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Clinical Studies
Abstracts are presented below for clinical
studies on Gotu Kola.
Plant Phytonutrient Profile
1: J Ethnopharmacol. 2006 Nov 6; [Epub ahead of print]
Wound/healing activity of St. John's Wort (Hypericum perforatum L.) on chicken
embryonic fibroblasts.
Ozturk N, Korkmaz S, Ozturk Y.
Anadolu University, Faculty of Pharmacy, Department of Pharmacognosy, Tepebasi,
26470 Eskisehir, Turkey.
Wound/healing effect of St. John's Wort (Hypericum perforatum L.) extract was
evaluated by comparing with dexpanthenol and titrated extract of Centella
asiatica (TECA) on cultured chicken embryonic fibroblasts. Chicken embryonic
fibroblasts from fertilized eggs were incubated with the plant extract,
dexpanthenol and TECA. Using microscopical methods by staining cells, mitotic
ability, morphologic changes and collagen production in the cultured fibroblasts
were evaluated as parameters to approach its mechanism of action in wound
repair. Findings obtained in the present study indicated that Hypericum
perforatum extract exhibited a wound/healing activity whose mechanism of action
is similar to that of TECA. Wound/healing activity of Hypericum perforatum
extract seems to be mainly due to the increase in the stimulation of fibroblast
collagen production and the activation of fibroblast cells in polygonal shape,
which plays a role in wound repair by closing damaged area. The findings
demonstrated the wound/healing activity of Hypericum perforatum, which has
previously been based on ethnomedical data.
PMID: 17156955 [PubMed / as supplied by publisher]
2: Ceska Slov Farm. 2006 Sep;55(5):219/29.
[Plant metabolites as nootropics and cognitives]
[Article in Czech]
Cervenka F, Jahodar L.
Univerzita Karlova v Praze, Farmaceuticka fakulta v Hradci Kralove, Katedra
farmaceuticke botaniky a ekologie. frantisek.cervenka@faf.cuni.cz
Nowadays several millions of people suffer from Alzheimer's disease and other
types of dementia. Etiology of these diseases is not known very well. There
occur different levels of neurotransmitters, the level of acetylcholine in the
brain is decreased and pathological changes affect the brain tissue. Organic and
toxic damage of the brain, free radicals, and other changes participate in the
development of these diseases. Drugs as nootropics, cognitives, and
neuroprotectives are commonly used to treat these diseases. Some of these drugs
have often side and undesirable effects. In recent years some natural substances
(galanthamine, huperzine A, vinpocetine), and standardized plant extracts
(Ginkgo biloba L., Centella asiatica L.) Urban, Bacopa monniera L., Evolvulus
alsinoides L.) are often used. These plant preparations produce fewer
undesirable effects and the same effectiveness as the classic therapy, or these
preparations are used as a supplement to the classic therapy.
Publication Types:
English Abstract
Research Support, Non/U.S. Gov't
Review
PMID: 17128592 [PubMed / indexed for MEDLINE]
3: Ir Med J. 2006 Jul/Aug;99(7):219; author reply 219/20.
Comment on:
Ir Med J. 2005 Nov/Dec;98(10):250/1.
Night eating syndrome (NES).
Tan JW.
Publication Types:
Comment
Letter
PMID: 16989019 [PubMed / indexed for MEDLINE]
4: Evid Based Complement Alternat Med. 2006 Sep;3(3):349/57.
Centella asiatica (L.) Leaf Extract Treatment During the Growth Spurt Period
Enhances Hippocampal CA3 Neuronal Dendritic Arborization in Rats.
Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S.
Centella asiatica (CeA) is a creeping plant growing in damp places in India and
other Asian countries. The leaves of CeA are used for memory enhancement in the
Ayurvedic system of medicine, an alternative system of medicine in India. In
this study, we have investigated the effect during the rat growth spurt period
of CeA fresh leaf extract treatment on the dendritic morphology of hippocampal
CA3 neurons, one of the regions of the brain concerned with learning and memory.
Neonatal rat pups (7 days old) were fed with 2, 4 or 6 ml kg(/1) body weight of
fresh leaf extract of CeA for 2, 4 or 6 weeks. After the treatment period the
rats were killed, their brains were removed and the hippocampal neurons were
impregnated with silver nitrate (Golgi staining). Hippocampal CA3 neurons were
traced using a camera lucida, and dendritic branching points (a measure of
dendritic arborization) and intersections (a measure of dendritic length) were
quantified. These data were compared with data for age/matched control rats. The
results showed a significant increase in the dendritic length (intersections)
and dendritic branching points along the length of both apical and basal
dendrites in rats treated with 4 and 6 ml kg(/1) body weight per day of CeA for
longer periods of time (i.e. 4 and 6 weeks). We conclude that the
constituents/active principles present in CeA fresh leaf extract have a neuronal
dendritic growth stimulating property; hence, the extract can be used for
enhancing neuronal dendrites in stress and neurodegenerative and memory
disorders.
PMID: 16951719 [PubMed / in process]
5: Int J Low Extrem Wounds. 2006 Sep;5(3):169/80.
A review of the microcirculation in skin in patients with chronic venous
insufficiency: the problem and the evidence available for therapeutic options.
Wollina U, Abdel/Naser MB, Mani R.
Department of Dermatology, Hospital Dresden/Friedrichstadt, Academic Teaching
Hospital of the Technical University of Dresden, Germany. wollina/uw@khdf.de.
Impairment of the cutaneous microcirculation is a major predisposing factor in
inflammation and ulceration in patients with chronic venous insufficiency (CVI).
Increase of capillary filtration rate predisposes to the formation of edema.
Local lymphedema is a complication of CVI, often underdiagnosed. This review is
focused on CVI but excludes the complication of ulceration. Treatment of
microcirculatory dysfunction can be done by pharmacologic intervention or
compression therapy or using a combination of both. This review is focused on
drugs that have been evaluated by randomized prospective controlled trials. The
following compounds are discussed: horse chestnut seed extracts, flavonoids, red
vine leaves extracts, total triterpenic fraction of Centella asiatica (L),
prociadins, calcium dobesilate, and pentoxifylline. The microcirculatory effects
of compression therapy using bandages or stockings are also reviewed. The major
microcirculatory effects that have been shown are the reduction of capillary
filtration rate and improvements in levels of transcutaneous partial pressures
of oxygen and carbon dioxide (TcPO(2) and TcPCO(2)). Available data suggest that
a combination of pharmacologic and compression therapy may have some additive
effects.
Publication Types:
Review
PMID: 16928673 [PubMed / indexed for MEDLINE]
6: Int J Low Extrem Wounds. 2006 Sep;5(3):137/43.
Effect of Centella asiatica L (Umbelliferae) on normal and
dexamethasone/suppressed wound healing in Wistar Albino rats.
Shetty BS, Udupa SL, Udupa AL, Somayaji SN.
Department of Biochemistry, Melaka Manipal Medical College, India.
somashekarshetty@yahoo.com
Centella asiatica is a reputed medicinal plant used in the treatment of various
skin diseases in the Indian system of medicine. The objective of the study
presented in this article was to evaluate the wound/healing potential of the
ethanolic extract of the plant in both normal and dexamethasone/suppressed wound
healing. The study was done on Wistar albino rats using incision, excision, and
dead space wounds models. The extract of C asiatica significantly increased the
wound breaking strength in incision wound model compared to controls (P < .001).
The extract/treated wounds were found to epithelize faster, and the rate of
wound contraction was significantly increased as compared to control wounds (P <
.001). Wet and dry granulation tissue weights, granulation tissue breaking
strength, and hydroxyproline content in a dead space wound model also increased
at statistically significant levels as shown. The extract of the leaves had the
effect of attenuating the known effects of dexamethasone healing in all wound
models (P < .001, P < .05). The results indicated that the leaf extract promotes
wound healing significantly and is able to overcome the wound/healing
suppressing action of dexamethasone in a rat model. These observations were
supported by histology findings.
PMID: 16928669 [PubMed / indexed for MEDLINE]
7: Trop Biomed. 2005 Dec;22(2):165/70.
In vitro screening of five local medicinal plants for antibacterial activity
using disc diffusion method.
Zaidan MR, Noor Rain A, Badrul AR, Adlin A, Norazah A, Zakiah I.
Bioassay Unit, Herbal Medicine Research Centre, Institute for Medical Research,
Kuala Lumpur.
Medicinal plants have many traditional claims including the treatment of
ailments of infectious origin. In the evaluation of traditional claims,
scientific research is important. The objective of the study was to determine
the presence of antibacterial activity in the crude extracts of some of the
commonly used medicinal plants in Malaysia, Andrographis paniculata, Vitex
negundo, Morinda citrifolia, Piper sarmentosum, and Centella asiatica. In this
preliminary investigation, the leaves were used and the crude extracts were
subjected to screening against five strains of bacteria species, Methicillin
Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella
pneumoniae, Pseudomonas aeruginosa and Escherichia coli, using standard protocol
of Disc Diffusion Method (DDM). The antibacterial activities were assessed by
the presence or absence of inhibition zones and MIC values. M. citrifolia, P.
sarmentosum and C. asiatica methanol extract and A. paniculata (water extract)
have potential antibacterial activities to both gram positive S. aureus and
Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested
showed antibacterial activities to gram negative E. coli and K. pneumoniae,
except for A. paniculata and P. sarmentosum which showed activity towards P.
aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding
forms a basis for further studies on screening of local medicinal plant extracts
for antibacteria properties.
PMID: 16883283 [PubMed / in process]
8: Phytochemistry. 2006 Sep;67(18):2041/9. Epub 2006 Jul 28.
The effect of methyl jasmonate on triterpene and sterol metabolisms of Centella
asiatica, Ruscus aculeatus and Galphimia glauca cultured plants.
Mangas S, Bonfill M, Osuna L, Moyano E, Tortoriello J, Cusido RM, Pinol MT,
Palazon J.
Laboratorio de Fisiologia vegetal, Facultad de Farmacia, Universidad de
Barcelona, Avda. Diagonal 643, E/08028 Barcelona, Spain.
Considering that exogenously applied methyl jasmonate can enhance secondary
metabolite production in a variety of plant species and that 2,3/oxidosqualene
is a common precursor of triterpenes and sterols in plants, we have studied
Centella asiatica and Galphimia glauca (both synthesizing triterpenoid secondary
compounds) and Ruscus aculeatus (which synthesizes steroidal secondary
compounds) for their growth rate and content of free sterols and respective
secondary compounds, after culturing with or without 100 microM methyl
jasmonate. Our results show that elicited plantlets of G. glauca and to a higher
degree C. asiatica (up to 152/times more) increased their content of
triterpenoids directly synthesized from 2,3/oxidosqualene (ursane saponins and
nor/seco/friedelane galphimines, respectively) at the same time as growth
decreased. In contrast, the free sterol content of C. asiatica decreased
notably, and remained practically unaltered in G. glauca. However, in the case
of R. aculeatus, which synthesizes steroidal saponins (mainly spirostane type)
indirectly from 2,3/oxidosqualene after the latter is converted to the plant
phytosterol/precursor cycloartenol, while the growth rate and free sterol
content clearly decreased, the spirostane saponine content was virtually
unchanged (aerial part) or somewhat lower (roots) in presence of the same
elicitor concentration. Our results suggest that while methyl jasmonate may be
used as an inducer of enzymes involved in the triterpenoid synthesis downstream
from 2,3/oxidosqualene in both C. asiatica and G. glauca plantlets, in those of
C. asiatica and R. aculeatus it inhibited the enzymes involved in sterol
synthesis downstream from cycloartenol.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16876832 [PubMed / indexed for MEDLINE]
9: J Med Assoc Thai. 2005 Nov;88 Suppl 3:S131/40.
Isobolographically additive anticonvulsant activity between Centella asiatica's
ethyl acetate fraction and some antiepileptic drugs.
Vattanajun A, Watanabe H, Tantisira MH, Tantisira B.
PhD Program of Inter/department of Physiology, Graduate School, Chulalongkorn
University, Bangkok, Thailand.
OBJECTIVE: To investigate interaction between orally given Centella asiatica's
ethyl acetate fraction (EACA) and intraperitoneally administered antiepileptic
drugs (AEDs), namely, phenytoin, valproate and gabapentin. MATERIAL AND METHOD:
Isobolographic analysis was used to evaluate the interaction between EACA and
AEDs in terms of protection of mice in the pentylenetetrazole test. Rotarod test
was used to evaluate neurotoxicity. RESULTS: When given alone, the median
effective dose of phenytoin, valproate and gabapentin were found to be 13, 104,
and 310 mg/kg BW, respectively, whereas the corresponding values in the presence
of EACA were 5, 29 and 79 mg/kg BW. Together with isobolographic analysis, the
results obtained indicated an additive effect among all combinations tested. In
relation to neurotoxicity, combination of gabapentin and EACA demonstrated a
broader margin between the effective dose and the neurotoxic dose while the
other two combinations did not. CONCLUSION: The present finding suggested a
potential of Centella asiatica to be developed as an adjunctive medication for
epileptic patients.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16858951 [PubMed / indexed for MEDLINE]
10: Mol Cell Biochem. 2007 Jan;294(1/2):55/63. Epub 2006 Jun 20.
Adriamycin induced myocardial failure in rats: Protective role of Centella
asiatica.
Gnanapragasam A, Yogeeta S, Subhashini R, Ebenezar KK, Sathish V, Devaki T.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600
025, Tamilnadu, India, devakit@yahoo.co.uk.
Generation of reactive oxygen species and mitochondrial dysfunction has been
implicated in adriamycin induced cardiotoxicity. Mitochondrial dysfunction is
characterized by the accumulation of oxidized lipids, proteins and DNA, leading
to disorganization of mitochondrial structure and systolic failure. The present
study was aimed to evaluate the efficacy of Centella asiatica on the
mitochondrial enzymes; mitochondrial antioxidant status in adriamycin induced
myocardial injury. Adriamycin (2.5 mg/kg body wt., i.p.) induced mitochondrial
damage in rats was assessed in terms of decreased activities (p< 0.05) of
cardiac marker enzymes (lactate dehydrogenase, creatine phosphokinase, amino
transferases), TCA cycle enzymes (isocitrate dehydrogenase, alpha/ketoglutarate
dehydrogenase, malate dehydrogenase, respiratory marker enzymes
(NADH/dehydrogenase, cytochrome/C/oxidase), mitochondrial antioxidant enzymes
(GPx, GSH, SOD,CAT) and increased (p< 0.05) level of lipid peroxidation.
Mitochondrial damage was confirmed by transmission electron microscopic
examination. Pre/co/treatment with aqueous extract of Centella asiatica (200
mg/kg body wt, oral) effectively counteracted the alterations in mitochondrial
enzymes and mitochondrial defense system. In addition, transmission electron
microscopy study confirms the restoration of cellular normalcy and accredits the
cytoprotective role of Centella asiatica against adriamycin induced myocardial
injury. Our results demonstrated elevated oxidative stress and mitochondrial
dysfunction in adriamycin treated rats. Moreover, on the basis of our findings
it may be concluded that the aqueous extract of C. asiatica not only possesses
antioxidant properties but it may also reduce the extent of mitochondrial
damage.
PMID: 16786185 [PubMed / in process]
11: Phytochemistry. 2006 Jun;67(11):1143/50. Epub 2006 May 2.
Immunosuppressive diacetylenes, ceramides and cerebrosides from Hydrocotyle
leucocephala.
Ramos F, Takaishi Y, Kawazoe K, Osorio C, Duque C, Acuna R, Fujimoto Y, Sato M,
Okamoto M, Oshikawa T, Ahmed SU.
Pharmacognosy Laboratory, Graduate School of Pharmaceutical Sciences, University
of Tokushima, Shomashi 1/78, Tokushima 770/8505, Japan.
Three C/17 diacetylenic compounds (1/3), one monoterpenoid (4), seven ceramides
(leucoceramides A/G, 5a/g), six cerebrosides (leucocerebrosides A/F, 6a/f) and
nine known compounds were isolated from the methanolic extract of Hydrocotyle
leucocephala. Their structures were established by spectroscopic methods. The
isolated compounds 1/3, 5a/g, 6a/f and 7 were shown to be active in the
lipopolysaccharide (LPS) induced cytokine production assay for IL/10, IL/12, and
TNF/alpha.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16631830 [PubMed / indexed for MEDLINE]
12: J Pharm Pharmacol. 2006 Apr;58(4):547/59.
Changes in brain biogenic amines and haem biosynthesis and their response to
combined administration of succimers and Centella asiatica in lead poisoned
rats.
Saxena G, Flora SJ.
Division of Pharmacology and Toxicology, Defence Research and Development
Establishment, Jhansi Road, Gwalior/474 002, India.
This study was designed to investigate the therapeutic potential of meso
2,3/dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA
(MiADMSA), individually or when administered in combination with an extract of
Centella asiatica against experimental lead intoxication in rats. Biochemical
variables indicative of alterations in the central nervous system and haem
biosynthesis were investigated to determine the toxicity in male Wistar rats.
Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10
days of treatment with DMSA and MiADMSA (50 mg kg(/1), i.p., once daily) alone
and in combination with C. asiatica (200 mg kg(/1), p.o., once daily).
Biochemical variables indicative of oxidative stress and brain biogenic amines,
along with lead concentration in blood and brain, were measured. Lead exposure
caused a significant depletion of blood and brain delta/aminolevulinic acid
dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis
pathway, and glutathione (GSH) level. These changes were accompanied by a marked
increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive
substances (TBARS), delta/aminolevulinic acid synthase (ALAS) and oxidized
glutathione (GSSG) activity in blood and brain. Significant depletion of brain
noradrenaline (norepinephrine, NE), 5/hydroxytryptamine (5/HT), dopamine (DA)
and acetylcholinesterase (AChE) also were observed following lead exposure. Also
seen was a significant depletion in brain glutathione peroxidase (GPx),
glutathione S/transferase (GST) and monoamine oxidase activity, as well as blood
and brain superoxide dismutase (SOD) activity. These biochemical changes were
correlated with an increased uptake of lead in blood and brain. Combined
administration of MiADMSA and C. asiatica was most effective in reducing these
alterations, including biogenic amines, besides reducing body lead burden,
compared with individual treatment with MiADMSA. Certain other biochemical
variables responded favourably to combination therapy and monotherapy with
MiADMSA. Thus, supplementation of C. asiatica during chelation could be
recommended for achieving optimum effects of chelation therapy.
Publication Types:
Comparative Study
PMID: 16597373 [PubMed / indexed for MEDLINE]
13: Planta Med. 2006 Mar;72(4):324/8.
Asiaticoside induces human collagen I synthesis through TGFbeta receptor I
kinase (TbetaRI kinase)/independent Smad signaling.
Lee J, Jung E, Kim Y, Park J, Park J, Hong S, Kim J, Hyun C, Kim YS, Park D.
Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Korea.
Skin aging appears to be principally related to a decrease in the levels of type
I collagen, the primary component of the skin dermis. Asiaticoside, a saponin
component isolated from Centella asiatica, has been shown to induce type I
collagen synthesis in human dermal fibroblast cells. However, the mechanism
underlying asiaticoside/induced type I collagen synthesis, especially at a
molecular level, remains only partially understood. In this study, we have
attempted to characterize the action mechanism of asiaticoside in type I
collagen synthesis. Asiaticoside was determined to induce the phosphorylation of
both Smad 2 and Smad 3. In addition, we detected the asiaticoside/induced
binding of Smad 3 and Smad 4. In a consistent result, the nuclear translocation
of the Smad 3 and Smad 4 complex was induced via treatment with asiaticoside,
pointing to the involvement of asiaticoside in Smad signaling. In addition,
SB431542, an inhibitor of the TGFbeta receptor I (TbetaRI) kinase, which is
known to be an activator of the Smad pathway, was not found to inhibit both Smad
2 phosphorylation and Type 1 collagen synthesis induced by asiaticoside.
Therefore, our results show that asiaticoside can induce type I collagen
synthesis via the activation of the TbetaRI kinase/independent Smad pathway.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16557473 [PubMed / indexed for MEDLINE]
14: Phytomedicine. 2006 Nov;13(9/10):668/76. Epub 2006 Feb 20.
Evaluation of anxiolytic properties of Gotukola//(Centella asiatica) extracts
and asiaticoside in rat behavioral models.
Wijeweera P, Arnason JT, Koszycki D, Merali Z.
Ottawa/Carleton Institute of Biology, University of Ottawa Institute of Mental
Health Research, Royal Ottawa Hospital, Canada.
The ayurvedic medicinal plant Gotukola (Centella asiatica) was evaluated for its
anxiolytic properties. Specifically, this study assessed the effects of:
Gotukola plant materials of different genotypic origin; hexane, ethyl acetate
and methanol extracts of Gotukola; and asiaticoside, a triterpenic compound
isolated from Gotukola. Various paradigms were used to assess the anxiolytic
activity, including the elevated plus maze (EPM), open field, social
interaction, locomotor activity, punished drinking (Vogel) and novel cage tests.
The EPM test revealed that Gotukola, its methanol and ethyl acetate extracts as
well as the pure asiaticoside, imparted anxiolytic activity. Furthermore, the
asiaticoside did not affect locomotor activity, suggesting these compounds do
not have sedative effects in rodents.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16488124 [PubMed / indexed for MEDLINE]
15: Arch Intern Med. 2006 Feb 13;166(3):370/1; author reply 371.
Comment on:
Arch Intern Med. 2005 Feb 14;165(3):296/301.
Studies on natural products.
Betz J, Costello R.
Publication Types:
Comment
Letter
PMID: 16476883 [PubMed / indexed for MEDLINE]
16: Ir Med J. 2005 Nov/Dec;98(10):250/1.
Comment in:
Ir Med J. 2006 Jul/Aug;99(7):219; author reply 219/20.
Night eating syndrome and Gotu Kola.
O'Brien B.
Publication Types:
Case Reports
Letter
PMID: 16445150 [PubMed / indexed for MEDLINE]
17: Phytomedicine. 2006 Feb;13(3):205/8. Epub 2005 Aug 15.
Herbal remedies for anxiety / a systematic review of controlled clinical trials.
Ernst E.
Complementary Medicine Peninsula Medical School, Universities of Exeter
Plymouth, UK. edzard.ernst@pms.ac.uk
Anxiety is a prominent indication for herbal medicine. This systematic review
was therefore aimed at summarising the evidence for or against the anxiolytic
efficacy of such treatments. Six databases were searched for all randomised
clinical trials testing herbal monopreparations in the alleviation of anxiety.
Seven such studies and one systematic review were located. Eight different
herbals were studied. The herbal medicines, which, according to these data are
associated with anxiolytic activity in humans, are Piper methysticum and Bacopa
monniera. Only for kava were independent replications available. It was
concluded that there is a lack of rigorous studies in this area and that only
kava has been shown beyond reasonable doubt to have anxiolytic effects in
humans.
Publication Types:
Review
PMID: 16428031 [PubMed / indexed for MEDLINE]
18: J Appl Toxicol. 2006 May/Jun;26(3):213/22.
Effect of Centella asiatica on arsenic induced oxidative stress and metal
distribution in rats.
Gupta R, Flora SJ.
Division of Pharmacology and Toxicology, Defence Research and Development
Establishment, Gwalior, India.
Concomitant oral supplementation of Centella asiatica (100, 200 or 300 mg
kg(/1), orally once daily) during arsenic exposure (20 ppm in drinking water for
4 weeks) was investigated in rats for its protective value. The animals exposed
to arsenic (III) showed a significant inhibition of delta/aminolevulinic acid
dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an
increase in zinc protoporphyrin (ZPP) level in blood. Hepatic and renal
glutathione (GSH) decreased, while oxidized glutathione (GSSG) and
thiobarbituric acid reactive substance (TBARS) levels increased significantly in
the liver, kidney and brain. The activities of brain superoxide dismutase (SOD)
and catalase decreased marginally on arsenic exposure. Concomitant
administration of Centella asiatica showed a significant protective action on
inhibited blood ALAD activity and restored the blood GSH level, whereas most of
the other blood biochemical parameters remained unchanged on Centella asiatica
supplementation. Interestingly, most of the hepatic biochemical variables
indicative of oxidative stress showed protection. There was, however, a
significant protection observed in the altered kidney GSSG level and hepatic and
brain TBARS. Only a marginal beneficial effect of Centella asiatica on blood and
liver arsenic concentration was noted, particularly at the highest dose studies
(300 mg kg(/1)). No effect of Centella asiatica on most of the altered renal
biochemical parameters was noted. The results thus lead to the conclusion that
simultaneous supplementation of Centella asiatica significantly protects against
arsenic/induced oxidative stress but does not influence the arsenic
concentration in these organs. It can thus be suggested that co/administration
of Centella asiatica protects animals from arsenic/induced oxidative stress but
exhibits no chelating property. Further studies are recommended for determining
the effect of co/administration of Centella asiatica during chelation therapy
with a thiol chelator. Copyright 2006 John Wiley & Sons, Ltd.
PMID: 16389662 [PubMed / indexed for MEDLINE]
19: Dakar Med. 2005;50(2):77/81.
[Healing activity of methanolic extract of the barks of Spathodea campanulata
Beauv (Bignoniaceae) in rat experimental burn model]
[Article in French]
Sy GY, Nongonierma RB, Ngewou PW, Mengata DE, Dieye AM, Cisse A, Faye B.
Laboratoire de Pharmacologie, Faculte de Medecine et Pharmacie, Universite
Cheikh Anta Diop, BP 5005, Dakar, Senegal. guatayoro_sy@yahoo.fr
Spathodea campanulata Beauv. (Bignoniaceae) is widely distributed through Africa
and found in particular in Cameroon and Senegal. It is used in traditional
herbal medicine for the treatment of ulcers, filaria, gonorrhea, diarrhea and
fever. S. campanulata was also known in Cameroon traditional medicine to have a
healing activity in burn wounds. The aim of the present study was to assess the
burn healing effectiveness of the methanolic extract of the barks of S.
campanulata ointment (MEBSCO) in comparison to those of Centella asiatica and
Peru's balm in experimental burn model in rats. Experimental burn was made in
rat under chloral anaesthesia with electric iron (200 degrees C) on the right
and left side of the medianus line. Topical applications of MEBSCO (2%, 10% and
49%) dose/dependently decreased the score damage of the burn site. Treatment
with 10% and 49% of MEBSCO varied the score damage from 5 to 1 +// 0.4 and 5 to
0.2 +// 0.5 (p < 0.05, n = 5) respectively, at day 15 after experimental burn.
As well as C. asiatica (1%) and Peru's balm (1%) ointments, MEBSCO (10% and 49%)
induced a complete burn healing on the 19/20th post burn day. This study shows
for the first time, the burn healing effectiveness of MEBSCO in experimental
burn model. It also provides a rational use of the S. campanulata barks in
traditional medicine to promote burn healing.
Publication Types:
English Abstract
PMID: 16295762 [PubMed / indexed for MEDLINE]
20: Asian Pac J Cancer Prev. 2005 Jul/Sep;6(3):396/400.
Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus
extracts.
Punturee K, Wild CP, Kasinrerk W, Vinitketkumnuen U.
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai 50200, Thailand.
Centella asiatica (CA) and Rhinacanthus nasutus (RN )have been used for
treatment of various illnesses, but the mechanisms of action remain largely
unknown. This study focused on the influence of CA and RN extracts on
cell/mediated and humoral immune responses. In human peripheral blood
mononuclear cells (PBMCs), CA (water extract) and RN (water and ethanol
extracts) significantly increased proliferation and the production of IL/2 and
TNF/alpha. In contrast, an ethanol extract of CA inhibited human PBMC
mitogenesis and the production of IL/2 and TNF/alpha. BALB/c mice treated with
CA extracts (100 mg/kg bw) showed higher responses to both primary and secondary
antibodies against BSA when compared with non/treated group. Only the secondary
antibody response was increased in RN extract/treated mice. The present study
revealed immunomodulating activity of CA and RN extracts with regard to both
non/specific cellular and humoral immune responses. The data available to date
suggest that they may have chemopreventive or anticancer potential.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16236006 [PubMed / indexed for MEDLINE]
21: Physiol Behav. 2005 Nov 15;86(4):449/57. Epub 2005 Oct 6.
Centella asiatica treatment during postnatal period enhances learning and memory
in mice.
Rao SB, Chetana M, Uma Devi P.
Department of Radiobiology, Kasturba Medical College, Manipal 576104, India.
Present investigation was planned to evaluate the nootropic effect of Centella
asiatica. Three months old male Swiss albino mice were injected orally with
graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous
extract for 15 days to select an effective dose for nootropic studies. Animals
were tested in radial arm maze to assess the learning and memory performance.
Based on these results, mice were treated orally with 200 mg/kg of C. asiatica
for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect
was evaluated on the 31st day and 6 months p.p. The behavioral (open field,
dark/bright arena, hole board and radial arm maze tests), biochemical
(acetylcholine esterase activity) and histological studies (dendritic
arborization) were carried out. Performance of juvenile and young adult mice was
significantly improved in radial arm maze and hole board tests, but locomotor
activity did not show any change compared to control. Treatment resulted in
increased acetylcholine esterase activity in the hippocampus. Dendritic
arborization of hippocampal CA3 neurons was also increased in terms of
intersections and branching points, both at one month and 6 months. Results of
the present investigation show that treatment during postnatal developmental
stage with C. asiatica extract can influence the neuronal morphology and promote
the higher brain function of juvenile and young adult mice.
PMID: 16214185 [PubMed / indexed for MEDLINE]
22: Zhong Yao Cai. 2005 Jun;28(6):492/6.
[Effects of total triterpenes of Centella asiatica on the corticosterone levels
in serum and contents of monoamine in depression rat brain]
[Article in Chinese]
Chen Y, Han T, Rui Y, Yin M, Qin L, Zheng H.
Pharmacy School, Shanghai Jiao Tong University, Shanghai.
OBJECTIVE: To investigate the possible effect of antidepressant effect of total
triterpentes of Centella asiatica. METHODS: The corticosterone levels in serum
were measured by fluorescence spectroscopy. The contents of monoamine
neurotransmitters and their metabolites in rats cortex, hippocamopus and
thalamus were evaluated by using HPLC with electrochemical detector. RESULTS:
Significant reduction of the corticosterone level in serum and increase of the
contents of 5/HT, NE, DA and their metabolites 5/HIAA, MHPG in rat brain were
observed. CONCLUSION: The antidepressant effect of total triterpenes of Centella
asiatica may be involved in ameliorating the function of HPA axis and increasing
the contents of monoamine neurotransmitters.
Publication Types:
English Abstract
Research Support, Non/U.S. Gov't
PMID: 16209267 [PubMed / indexed for MEDLINE]
23: Biomed Chromatogr. 2006 Feb;20(2):151/3.
Identification of triterpenoid compounds of Centella asiatica by thin/layer
chromatography and mass spectrometry.
Bonfill M, Mangas S, Cusido RM, Osuna L, Pinol MT, Palazon J.
Laboratorio de Fisiologia vegetal, Facultad de Farmacia, Universidad de
Barcelona, Avda. Diagonal 643, E/08028 Barcelona, Spain. mbonfill@ub.edu
The identification of the four principal triterpenoid components of Centella
asiatica has been achieved by TLC on silica gel plates and mass spectrometry, as
a modification of the method described in the European Pharmacopoeia (5th edn).
A combination of ethyl acetate and methanol as the mobile phase was found to be
successful in separating these compounds from the rest of the main components of
the extract. The spots were detected with anisaldehyde solution. The separated
compounds were confirmed by MALDI /TOF mass spectrometry. Copyright (c) 2005
John Wiley & Sons, Ltd.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16206136 [PubMed / indexed for MEDLINE]
24: Phytother Res. 2005 Jul;19(7):605/11.
Modification of gamma ray induced changes in the mouse hepatocytes by Centella
asiatica extract: in vivo studies.
Sharma R, Sharma J.
Department of Zoology, University of Rajasthan, Jaipur 302004, India.
Radhasharma13@yahoo.com
Ionizing radiation, besides causing direct damage also generates reactive oxygen
species that are capable of inducing damage to various organs. Pretreatment with
Centella asiatica 1 h prior to irradiation at a dose rate of 100 mg/kg body
weight was found to be effective against radiation induced damage in the liver.
The number of normal hepatocytes was higher in the Centella asiatica pretreated
group in comparison with the irradiated only group. The number of binucleated
cells and abnormal hepatocytes was less in comparison with the animals
irradiated without Centella asiatica pretreatment.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16161023 [PubMed / indexed for MEDLINE]
25: J Environ Biol. 2005 Jan;26(1):79/89.
Toxicity and accumulation of lead and chromium in Hydrocotyle umbellata.
Yongpisanphop J, Kruatrachue M, Pokethitiyook P.
Department of Biology, Faculty of Science, Mahidol University, Bangkok 10400,
Thailand.
The aquatic plant, Hydrocotyle umbellata, was studied for its toxicity and
accumulation of lead (Pb) and chromium (Cr) in a synthetic solution. Plants were
cultured in a modified Hoagland's nutrient solutions supplemented with 20, 40,
60, 80, and 100 mg Pb/l as lead nitrate [Pb(NO3)2] and 2, 4, 6, 8, and 10 mg
Cr/l as potassium dichromate (K2Cr2O7). They were separately harvested after 3,
6, 9, and 12 days. Plants exposed to Pb and Cr showed significant decreases in
the biomass productivity and total chlorophyll content when the exposure time
and metal concentration were increased. The accumulation of Pb and Cr in the
plants was significantly increased, but it was not linear with the exposure time
and metal concentration. Both metals were accumulated higher in the roots than
in the shoots. The bioconcentration factor of Pb was higher than that of Cr at
the same exposure time, indicating a higher accumulation potential of Pb than Cr
in H. umbellata. Toxicity symptoms of both metals showed a reduction in the
production of new plantlets, withering of petioles, and change in color of roots
from light green to dark brown. Pb caused leaf chlorosis, whereas Cr caused leaf
necrosis. The toxicity symptoms increased when the exposure time and metal
concentration were increased.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16114465 [PubMed / indexed for MEDLINE]
26: J Pharm Pharmacol. 2005 Sep;57(9):1221/9.
Centella asiatica accelerates nerve regeneration upon oral administration and
contains multiple active fractions increasing neurite elongation in/vitro.
Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG.
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson
Park Road, Portland OR 97239, USA.
Axonal regeneration is important for functional recovery following nerve damage.
Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been
used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that
Centella asiatica ethanolic extract (100 microg mL/1) elicits a marked increase
in neurite outgrowth in human SH/SY5Y cells in the presence of nerve growth
factor (NGF). However, a water extract of Centella was ineffective at 100 microg
mL/1. Sub/fractions of Centella ethanolic extract, obtained through silica/gel
chromatography, were tested (100 microg mL/1) for neurite elongation in the
presence of NGF. Greatest activity was found with a non/polar fraction (GKF4).
Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less
than GKF4. Thus, Centella contains more than one active component. Asiatic acid
(AA), a triterpenoid compound found in Centella ethanolic extract and GKF4,
showed marked activity at 1 microM (microg mL/1). AA was not present in GKF10 to
GKF13, further indicating that other active components must be present. Neurite
elongation by AA was completely blocked by the extracellular/signal/regulated
kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague/Dawley rats
given Centella ethanolic extract in their drinking water (300/330 mg kg/1 daily)
demonstrated more rapid functional recovery and increased axonal regeneration
(larger calibre axons and greater numbers of myelinated axons) compared with
controls, indicating that the axons grew at a faster rate. Taken together, our
findings indicate that components in Centella ethanolic extract may be useful
for accelerating repair of damaged neurons.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non/P.H.S.
Research Support, U.S. Gov't, P.H.S.
PMID: 16105244 [PubMed / indexed for MEDLINE]
27: Int J Food Sci Nutr. 2005 Jun;56(4):287/91.
Phenolic contents and antioxidant activity of some food and medicinal plants.
Bajpai M, Pande A, Tewari SK, Prakash D.
Nutraceutical Chemistry, National Botanical Research Institute, Lucknow, India.
To identify promising sources of antioxidants, some food and medicinal plants
were studied for total phenolic contents and antioxidant activity. The leaves,
bark and fruits of Terminalia arjuna, Terminalia bellerica, Terminalia chebula
and Terminalia muelleri, the leaves and fruits of Phyllanthus emblica, and the
seeds of Syzygium cumini were found to have high total phenolic contents
(72.0/167.2 mg/g) and high antioxidant activity (69.6/90.6%). Leaves of
Eucalyptusglobulus were a rich source of rutin, Moringa oleifera for kaempferol,
aerial parts of Centella asiatica for quercetin, fruits of T. bellerica and T.
chebula for gallic acid, and bark of T. arjuna, leaves and fruits of T.
bellerica and bark, leaves and fruits of T. muelleri for ellagic acid.
PMID: 16096138 [PubMed / indexed for MEDLINE]
28: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003229.
Phlebotonics for venous insufficiency.
Martinez MJ, Bonfill X, Moreno RM, Vargas E, Capella D.
Hospital de la Santa Creu i Sant Pau, Iberoamerican Cochrane Center, Service of
Epidemiology, Sant Antoni M. Claret, 171, Barcelona, Spain, 08041.
mmartinezz@hsp.santpau.es
BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by
inadequate blood flow through the veins, usually in the lower limbs. It can
result in considerable discomfort with symptoms such as pain, itchiness and
tiredness in the legs. Sufferers may also experience swelling and ulcers.
Phlebotonics are a class of drugs that are often used to treat CVI. OBJECTIVES:
To assess the efficacy of oral or topical phlebotonics. SEARCH STRATEGY: We
searched the Cochrane Peripheral Vascular Diseases Group trials register (April
2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library
Issue 2, 2005), MEDLINE (January 1966 to April 2005), EMBASE (January 1980 to
April 2005) and reference lists of articles. We also contacted pharmaceutical
companies. SELECTION CRITERIA: Randomised, double blind, placebo/controlled
trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium
dobesilate, chromocarbe, centella asiatica, disodium flavodate, french maritime
pine bark extract, grape seed extract and aminaftone in CVI patients at any
stage of the disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently
extracted data and assessed trial quality. The effects of treatment were
estimated by relative risk (RR) or by standardised mean differences (SMD) by
applying a random effects statistical model. Sensitivity analyses were also
performed. MAIN RESULTS: Fifty/nine RCTs of oral phlebotonics were included, but
only 44 trials involving 4413 participants contained quantifiable data for the
efficacy analysis: 23 of rutosides, ten of hidrosmine and diosmine, six of
calcium dobesilate, two of centella asiatica, one of french maritime pine bark
extract, one of aminaftone and one of grape seed extract. No studies evaluating
topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the
inclusion criteria.Outcomes included oedema, venous ulcers, trophic disorders,
subjective symptoms (pain, cramps, restless legs, itching, heaviness, swelling
and paraesthesias), global assessment measures and side effects. The results of
many variables were heterogeneous. Phlebotonics showed some global benefit (i.e.
oedema reduction) (relative risk 0.72, 95% confidence interval 0.65 to 0.81).
The benefit for the remaining CVI signs and symptoms must be evaluated by
phlebotonic group. There were no quantifiable data on quality of life. AUTHORS'
CONCLUSIONS: There is not enough evidence to globally support the efficacy of
phlebotonics for chronic venous insufficiency. There is a suggestion of some
efficacy of phlebotonics on oedema but this is of uncertain clinical relevance.
Due to the limitations of current evidence, there is a need for further
randomised, controlled clinical trials with greater attention paid to
methodological quality.
Publication Types:
Meta/Analysis
Review
PMID: 16034893 [PubMed / indexed for MEDLINE]
29: Exp Gerontol. 2005 Aug/Sep;40(8/9):707/15.
Emerging role of Centella asiatica in improving age/related neurological
antioxidant status.
Subathra M, Shila S, Devi MA, Panneerselvam C.
Department of Biochemistry, Dr AL Mudaliar PG Institute of Basic Medical
Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Free radicals have been hypothesized to play an important role in ageing
process. There exists an imbalance between free radical production and
antioxidant defense mechanism, which may lead to cell death during ageing. Our
study was designed to determine whether extract of Centella asiatica, an
antioxidant, when administered orally (300 mg/kg body weight/day) for 60 days
would prevent age/related changes in antioxidant defense system, lipid
peroxidation (LPO) and protein carbonyl (PCO) content in rat brain regions such
as cortex, hypothalamus, striatum, cerebellum and hippocampus. Aged rats
elicited a significant decline in the antioxidant status and increased the LPO
and PCO as compared to control rats in all five regions studied. The increase in
LPO and PCO contents were (64%, 34%) in cortex, (86%, 30%) in cerebellum, (51%,
47%) in striatum, (77%, 27%) in hypothalamus and (58%, 45%) in hippocampus,
respectively, in aged rats as compared to young rats. Supplementation of C.
asiatica was effective in reducing brain regional LPO and PCO levels and in
increasing the antioxidant status. Thus, C. asiatica by acting as a potent
antioxidant exerted significant neuroprotective effect and proved efficacious in
protecting rat brain against age related oxidative damage.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16026958 [PubMed / indexed for MEDLINE]
30: J Int Acad Periodontol. 2005 Jul;7(3):70/9.
Adjunctive periodontal treatment with Centella asiatica and Punica granatum
extracts in supportive periodontal therapy.
Sastravaha G, Gassmann G, Sangtherapitikul P, Grimm WD.
Department of Oral Medicine and Periodontics, Faculty of Dentistry, Mahidol
University, Bangkok, Thailand. sgrindwit@yahoo.com
BACKGROUND: Centella asiatica and Punica granatum are medicinal plants that have
been reported to promote tissue healing and modulate host responses. Preliminary
study revealed positive clinical effects of an innovative preparation from the
two herbal extracts in the form of biodegradable chips as a subgingival adjunct
to scaling and root planing. The purpose of this research was to evaluate
further augmenting efficacy the combined herbal preparation may have among
maintenance patients in comparison to standard supportive periodontal therapy
(SPT), with additional monitoring of certain inflammatory markers. METHODS:
Fifteen patients in the recall programme who had completed conventional
periodontal therapy with remaining probing pocket depths of 5/8 mm were
enrolled. After baseline examination and collection of gingival crevicular fluid
(GCF) samples, SPT was provided and the target teeth in the test group received
subgingival delivery of the medicated chips. The clinical parameters, which
included probing pocket depth (PD), attachment level (AL), bleeding index (BI),
gingival index (GI) and plaque index (PI) were recorded and GCF samples were
collected at baseline, 3 and 6 months. RESULTS: The results showed significant
improvement of PD, AL, and GI at 3 and 6 months and of BI at 6 months in the
test group as compared to control. No significant differences in PI were found
between the two treatment modalities at all subsequent visits. The test group
also showed statistically greater reduction of IL/1beta at both 3 and 6 months
and lower IL/6 concentration, which almost reached the level of significance at
6 months. CONCLUSION: The results indicate that adjunctive local delivery of
extracts from C. asiatica in combination with P. granatum significantly improved
clinical signs of chronic periodontitis and IL/1beta level in maintenance
patients.
Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non/U.S. Gov't
PMID: 16022023 [PubMed / indexed for MEDLINE]
31: Rev Enferm. 2005 May;28(5):67/70.
[Topical chemotherapy for the treatment of burns]
[Article in Spanish]
Salas Campos L, Fernandes Mansilla M, Martinez de la Chica AM.
D.U.E. Hospital General Vall d'Hebron.
A burn is a tissue lesion which provokes different alterations that vary from
topical erythema to total destruction of the structures affected. A burn always
produces an alteration in the skin, a lesion in the corneal strata is sufficient
to cause the skin to lose its capacity to act as a barrier. The objective the
treatment for a burn has is to produce epithelization as soon as possible in
order to prevent infection and to reduce functional and esthetic aftereffects.
Infection is the main cause of death due to burns due to the growth of
endogenous flora or due to external contamination. The use of topical
chemotherapy is fundamental to prevent infections when there are deep and
superficial burns or extensive intermediary burns. Centella asiatica extract has
proven to be efficient in helping, maintaining and regularizing cicatrisation of
skin affected by burns. Its usage combined with an antibiotic agent such as
neomycin covers the bacterial spectrum for gram/positive or /negative
microorganisms, guaranteeing an anti/infectious efficiency for this extract.
Publication Types:
English Abstract
PMID: 15981974 [PubMed / indexed for MEDLINE]
32: Arch Pharm Res. 2005 Apr;28(4):502/8.
Advanced formulation and pharmacological activity of hydrogel of the titrated
extract of C. asiatica.
Hong SS, Kim JH, Li H, Shim CK.
Department of Pharmaceutics, College of Pharmacy, Seoul National University,
Seoul 151/742, Korea.
Titrated extract of Centella asiatica (TECA) contains three principal
ingredients, asiaticoside (AS), asiatic acid (AA), and madecassic acid (MA).
These components are known to be clinically effective on systemic scleroderma,
abnormal scar formation, and keloids. However, one problem associated with
administration of TECA is its low solubility in aqueous as well as oil medium.
In this study, various nonionic surfactants and bile salts as anionic surfactant
were tested and screened for solubilizing TECA with a view to developing topical
hydrogel type of ointment which is stable physicochemically, and has better
pharmacological effects. When TECA was incorporated into various nonionic
surfactant systems, labrasol had the most potent capacity for solubilizing TECA.
In cases of bile salt systems, Na/deoxycholate (Na/DOC) had foremost
solubilizing capacity, even more than labrasol. In differential scanning
calorimetric study, the peaks of AA, MA, AS and Na/DOC disappeared at the
coprecipitate of 1% TECA and 1% Na/DOC, suggesting the optimum condition of
Na/DOC for solubilizing TECA. When the physicochemical stability of hydrogel
containing this mixture was assessed, it was stable at room temperature for at
least one month. Pharmacologically it significantly decreased the size of wound
area at the 9th day when applied to the wound area of rat dorsal skin. Taken
together, solubility of TECA was dramatically improved by using nonionic and
anionic surfactant systems, and Na/DOC was found to be the most effective
solubilizer of TECA in formulating a TECA/containing hydrogel typed ointment.
Moreover this gel was considered to be applicable to clinical use for wound
healing effect.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15918527 [PubMed / indexed for MEDLINE]
33: Mol Cells. 2005 Apr 30;19(2):294/9.
Cloning and expression of a farnesyl diphosphate synthase in Centella asiatica
(L.) Urban.
Kim OT, Ahn JC, Hwang SJ, Hwang B.
Department of Biology and Institute of Plant Resources, Chonnam National
University, Gwangju 500/757, Korea.
A cDNA encoding farnesyl diphosphate synthase (FPS; EC2.5.1.1/EC2.5.1.10) was
isolated from Centella asiacita (L.) Urban, using degenerate primers based on
two highly conserved domains. A full/length cDNA clone was subsequently isolated
by rapid amplification of cDNA ends (RACE) PCR. The sequence of the CaFPS (C.
asiatica farnesyl diphosphate synthase) cDNA contains an open reading frame of
1029 nucleotides encoding 343 amino acids with a molecular mass of 39.6 kDa. The
deduced CaFPS amino acid sequence exhibits 84, 79, and 72%, identity to the FPSs
of Artemisia annua, Arabidopsis thaliana, and Oryza sativa, respectively.
Southern blot analysis suggested that the C. asiatica genome contains only one
FPS gene. An artificially expressed soluble form of the CaFPS was identified by
SDS/PAGE. It had high specific activity and produced farnesyl diphosphate as the
major isoprenoid.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 15879717 [PubMed / indexed for MEDLINE]
34: Int J Low Extrem Wounds. 2003 Mar;2(1):25/39.
Plant medicines of Indian origin for wound healing activity: a review.
Biswas TK, Mukherjee B.
Department of Sharira Kriya, J. B. Roy State Ayurvedic Medical College and
Hospital.
Research on wound healing drugs is a developing area in modern biomedical
sciences. Scientists who are trying to develop newer drugs from natural
resources are looking toward the Ayurveda, the Indian traditional system of
medicine. Several drugs of plant, mineral, and animal origin are described in
the Ayurveda for their wound healing properties under the term Vranaropaka. Most
of these drugs are derived from plant origin. Some of these plants have been
screened scientifically for the evaluation of their wound healing activity in
different pharmacological models and patients, but the potential of most remains
unexplored. In a few cases, active chemical constituents were identified. Some
Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon,
Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa,
Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica,
Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental
models. This paper presents a limited review of plants used in Ayurvedic
medicine.
PMID: 15866825 [PubMed]
35: Plant Cell Rep. 2005 Jul;24(5):304/11. Epub 2005 Apr 15.
Cloning of a cDNA probably encoding oxidosqualene cyclase associated with
asiaticoside biosynthesis from Centella asiatica (L.) Urban.
Kim OT, Kim MY, Huh SM, Bai DG, Ahn JC, Hwang B.
Department of Biology, Chonnam National University, Gwangju, 500/757, South
Korea.
A homology/based PCR method was used to clone a cDNA encoding oxidosqualene
cyclase from Centella asiatica, which produces a large quantity of triterpene
saponins such as asiaticoside and madecassoside. Sequence analysis of one clone
found sequences related to beta/amyrin synthase. An open reading frame in the
full/length clone was named CabAS (Centella asiatica putative beta/amyrin
synthase). On the basis of amino acid sequence, CabAS appears to be an enzyme
(beta/amyrin synthase) that synthesizes beta/amyrin. Southern analysis showed
that the C. asiatica genome contains one copy of the CabAS gene. Northern blot
analysis demonstrated that the CabAS gene is expressed in leaves with no
detectable transcript in other plant tissues, consistent with the organ/specific
accumulation of the asiaticoside. Up/regulation of expression of CabAS by methyl
jasmonate in leaves was also demonstrated.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15834571 [PubMed / indexed for MEDLINE]
36: Rev Esp Enferm Dig. 2005 Feb;97(2):115/24.
Hepatotoxicity associated with the ingestion of Centella asiatica.
[Article in English, Spanish]
Jorge OA, Jorge AD.
Gastroenterology Department, Hospital Espanol, Mendoza, Argentina.
oliverjorge@lanet.com.ar
BACKGROUND: Hepatotoxicity due to herbal remedies is being increasingly
recognized. Centella asiatica (Centella asiatica Linn Urban) is commercialized
for multiple conditions. Its active principles are pentacyclic triterpenic
saponosides (asiaticoside, madecassoside). CLINICAL CASE STUDIES: We present
three women (61, 52 and 49 years old) who developed jaundice after taking
Centella asiatica for 30, 20 and 60 days. Respective laboratory tests: ALT:
1193, 1694 and 324 U/L; ALP: 503, 472 and 484 U/L; bilirubin: 4.23, 19.89 and
3.9 mg/dl. The first patient also had ASMA 1/160 and AMA 1/320. Respective
pathological diagnoses: granulomatous hepatitis with marked necrosis and
apoptosis; chronic hepatitis with cirrhotic transformation and intense
necroinflammatory activity, and granulomatous hepatitis. All patients improved
with Centella asiatica discontinuation, and ursodeoxycholic acid 10 mg/kg/day.
The first patient took Centella asiatica again, with recurrence of the damage.
The second one had taken this herb a year before. CONCLUSIONS: Many plants
synthesize hepatotoxic compounds. Germander, Skullcap and Glycyrrhizin contain
di/ or triterpenic active principles, which can produce hepatic injury by
promoting apoptosis and altering cell membranes. We hypothesize that these
mechanisms may have resulted in injuries associated with Centella asiatica. The
presence of autoantibodies and granulomas also favors an immune/mediated
mechanism. Ursodeoxycholic acid has anti/apoptotic properties, but we cannot
rule out that Centella asiatica discontinuation alone may have resulted in
patient improvement.
Publication Types:
Case Reports
PMID: 15801887 [PubMed / indexed for MEDLINE]
37: Electrophoresis. 2005 Feb;26(3):648/60.
Precision improvement for the analysis of flavonoids in selected Thai plants by
capillary zone electrophoresis.
Suntornsuk L, Anurukvorakun O.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University,
Bangkok, Thailand. pylll@mahidol.ac.th
A capillary zone electrophoresis (CZE) method for the analyses of kaempferol in
Centella asiatica and Rosa hybrids and rutin in Chromolaena odorata was
developed. The optimization was performed on analyses of flavonoids (e.g.,
rutin, kaempferol, quercetin, myricetin, and apigenin) and organic carboxylic
acids (e.g., ethacrynic acid and xanthene/9/carboxylic acid) by investigation of
the effects of types and amounts of organic modifiers, background electrolyte
concentrations, temperature, and voltage. Baseline separation (R(s) = 2.83) of
the compounds was achieved within 10 min in 20 mM NaH2PO4 / Na2HPO4 (pH 8.0)
containing 10% v/v ACN and 6% v/v MeOH using a voltage of 25 kV, a temperature
of 30 degrees C, and a detection wavelength set at 220 nm. The application of
the corrected migration time (t(c)), using ethacrynic acid as the single marker,
was efficient to improve the precision of flavonoid identification (% relative
standard deviation (RSD) = 0.65%). The method linearity was excellent (r2 >
0.999) over 50/150 microg/mL. Precision (%RSD < 1.66%) and recoveries were good
(> 96% and %RSDs < 1.70%) with detection and quantitation limits of 2.23 and
7.14 microg/mL, respectively. Kaempferol in C. asiatica and R. hybrids was 0.014
g/100 g (%RSD = 0.59%) and 0.044 g/100 g (%RSD = 1.04%), respectively, and rutin
in C. odorata was 0.088 g/100 g (%RSD = 0.06%).
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15690438 [PubMed / indexed for MEDLINE]
38: Planta Med. 2004 Dec;70(12):1150/4.
Inhibitory effects of Centella asiatica water extract and asiaticoside on
inducible nitric oxide synthase during gastric ulcer healing in rats.
Guo JS, Cheng CL, Koo MW.
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong,
Hong Kong.
In this study, the effects of Centella asiatica water extract (CE) and its
active constituent, asiaticoside (AC), on the expression and activity of
inducible nitric oxide synthase (iNOS) during gastric ulcer healing in rats were
investigated. CE was prepared from Centella asiatica dry plant and the
concentration of AC in CE was quantitatively determined with the use of high
performance liquid chromatography analysis. Different concentrations of CE (0.10
g/kg and 0.25 g/kg) and AC (5 mg/kg and 10 mg/kg) were orally administered to
rats with acetic acid/induced gastric ulcers. They were found to reduce the size
of the ulcers at days 1, 3 and 7 after ulcer induction in a dose/dependent
manner, with a concomitant attenuation of iNOS activity and protein expression
at the ulcer tissues. The levels of nitrite and nitrate (NO(X)/), the stable
end/products of nitric oxide (NO), in the gastric ulcer tissues were also
decreased. N/[3/(aminomethyl)benzyl]acetamidine (1400W), a highly selective
inhibitor of iNOS, was found to produce similar but more potent inhibition on
iNOS activity at a dose of 0.1 mg/kg. These findings indicate that CE and AC
have an anti/inflammatory property that is brought about by inhibition of NO
synthesis and thus facilitates ulcer healing.
PMID: 15643549 [PubMed / indexed for MEDLINE]
39: Cancer Lett. 2005 Jan 31;218(1):81/90.
Asiatic acid induces apoptosis in SK/MEL/2 human melanoma cells.
Park BC, Bosire KO, Lee ES, Lee YS, Kim JA.
College of Pharmacy, Yeungnam University, Gyongsan 712/749, South Korea.
Asiatic acid (AA) is a pentacyclic triterpene found in Centella asiatica. In the
present study, the mechanism of anticancer effect of AA on skin cancer was
investigated. AA decreased viability and induced apoptosis in human melanoma
SK/MEL/2 cells in a time/ and dose/dependent manner. AA also markedly increased
intracellular reactive oxygen species (ROS) level and enhanced the expression of
Bax but not Bcl/2 protein in the cells. In addition, AA/induced activation of
caspase/3 activity in a dose/dependent manner. Pretreatment with Trolox, an
antioxidant, significantly blocked the induction of Bax and activation of
caspase/3 in AA/treated cells. Furthermore, Ac/DEVD/CHO, a specific caspase/3
inhibitor, and Trolox prevented the AA/induced apoptosis. AA did not elevate p53
nuclear protein levels that are present in a mutant form in SK/MEL/2 cells.
These results suggest that AA/induced apoptosis may be mediated through
generation of ROS, alteration of Bax/Bcl/2 ratio and activation of caspase/3,
but p53/independent. These results further suggest that AA may be a good
candidate for the therapeutic intervention of human skin cancer.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15639343 [PubMed / indexed for MEDLINE]
40: Biol Pharm Bull. 2005 Jan;28(1):173/5.
Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes
and rosmarinic acid from Centella asiatica.
Yoshida M, Fuchigami M, Nagao T, Okabe H, Matsunaga K, Takata J, Karube Y,
Tsuchihashi R, Kinjo J, Mihashi K, Fujioka T.
Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
The antiproliferative constituents in the MeOH extract from the aerial parts of
Centella asiatica were investigated. Activity/guided fractionation of MeOH
extract resulted in the isolation of ursolic acid lactone, ursolic acid, pomolic
acid, 2alpha,3alpha/dihydroxyurs/12/en/28/oic acid, 3/epimaslinic acid, asiatic
acid, corosolic acid, and rosmarinic acid. Antiproliferative activity of the
isolated compounds against human gastric adenocarcinoma (MK/1), human uterine
carcinoma (HeLa), and murine melanoma (B16F10) cells was estimated.
PMID: 15635187 [PubMed / indexed for MEDLINE]
41: Ai Zheng. 2004 Dec;23(12):1599/604.
[Asiaticoside inducing apoptosis of tumor cells and enhancing anti/tumor
activity of vincristine.]
[Article in Chinese]
Huang YH, Zhang SH, Zhen RX, Xu XD, Zhen YS.
Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and
Peking Union Medical College, Beijing 100050, P.R. China.
BACKGROUND & OBJECTIVE: Asiaticoside (ATS), a triterpene extracted from Centella
asiatica (L.) Urban, a traditional Chinese herb, possesses good wound healing
activities because of its stimulative effect on collagen synthesis. Recently,
the anti/tumor effect of asiaticiside has been reported. This study was to
examine the induction of apoptosis in cancer cells, and the enhancement of
vincristine (VCR) cytotoxicity by asiaticoside. METHODS: MTT assay was used to
evaluate inhibitory effect of asiaticoside combined with vincristine on
proliferation of several cancer cell lines, including KB, KBv200, MCF/7, and
MCF/7/ADM. Cell cycle, and apoptosis of KB cells were analyzed by flow
cytometry; apoptosis induction was also proved by electrophoresis,and
morphologic assessment; the expression of apoptosis/, and cell cycle/related
proteins were determined by Western blot. RESULTS: The IC(50) values of
asiaticoside for KB, KBv200, MCF/7, and MCF/7/ADM cells detected by MTT assay
were (1.11+//0.13) mg/ml, (1.82+//0.08) mg/ml, (1.58+//0.15) mg/ml, and
(3.25+//0.46) mg/ml, respectively. Multidrug resistant KBv200, and MCF/7/ADM
cancer cells displayed similar sensitivity to asiaticoside as their parental
counterparts (KB, and MCF/7 cells). Moreover, asiaticoside induced apoptosis in
KB cells. At sub/cytotoxicity concentration, asiaticoside showed synergistic
effect with vincristine in these 4 cell lines. The apoptosis rates were much
higher in asiaticoside plus vincristine groups than in vincristine or
asiaticoside groups. Bcl/2 phosphorylation levels were higher in the combination
groups than in vincristine or asiaticoside alone groups. The activated caspase/3
protein was only presented in the combination groups. Asiaticoside plus
vincristine enhanced S/G(2)/M arrest, up/regulated Cyclin B1 protein expression,
and down/regulated P34(cdc2) protein expression in KB cells. CONCLUSION:
Asiaticoside, as a biochemical modulator, may induce apoptosis,and enhance
anti/tumor activity of vincristine in cancer cells, might be useful in cancer
chemotherapy.
Publication Types:
English Abstract
Research Support, Non/U.S. Gov't
PMID: 15601545 [PubMed / indexed for MEDLINE]
42: Life Sci. 2004 Dec 17;76(5):585/97.
Protective effect of Centella asiatica on antioxidant tissue defense system
against adriamycin induced cardiomyopathy in rats.
Gnanapragasam A, Ebenezar KK, Sathish V, Govindaraju P, Devaki T.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai/ 600
025, Tamilnadu, India.
Increased oxidative stress and antioxidant deficit have been suggested to play a
major role in adriamycin induced cardiomyopathy and congestive heart failure due
to multiple treatments with adriamycin. In this study the cardio protective
effect of Centella asiatica on myocardial marker enzymes and antioxidant enzymes
in adriamycin induced cardiomyopathy was investigated in rats. The rats
administered with adriamycin (2.5 mg/kg body wt, i.p) caused myocardial damage
that was manifested by the elevation of serum marker (LDH, CPK, GOT and GPT)
enzymes and showed significant changes in the antioxidant enzymes (SOD, CAT,
GPx, GST). Pre/co/treatment with Centella asiatica(200 mg/kg of body wt/oral)
extract significantly prevented these alterations and restored the enzyme
activities to near normal levels. These findings demonstrate the cardio
protective effect of Centella asiatica on antioxidant tissue defense system
during adriamycin induced cardiac damage in rats.
PMID: 15556170 [PubMed / indexed for MEDLINE]
43: Int J Dermatol. 2004 Nov;43(11):801/7.
Asiaticoside induction for cell/cycle progression, proliferation and collagen
synthesis in human dermal fibroblasts.
Lu L, Ying K, Wei S, Fang Y, Liu Y, Lin H, Ma L, Mao Y.
From the State Key Laboratory of Genetic Engineering, Institute of Genetics,
School of Life Science, Fudan University, Shanghai, China. luluo@vip.163.com
Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation
and extracullar matrix synthesis in wound healing. The precise mechanism,
however, in molecular and gene expression levels still remains partially
understood. Using cDNA microarray technology, the alternation of genes
expression profiles was determined in a human dermal fibroblast in vitro in the
presence of asiaticoside (30 microg/ml). Fifty/four genes, with known functions
for cell proliferation, cell/cycle progression and synthesis of the
extracellular matrix, were significantly up/regulated in our "whole/genes nest"
expression profile at various timepoints. Furthermore, mRNA levels and protein
productions of certain genes responsible for extracellular matrix (ECM)
synthesis (e.g. encoding type I and type III collagen proteins) were evaluated
by Northern blot and radioimmunoassay, respectively. As a result, there is a
close correlation among the gene profile, mRNA and protein production in the
cells response to asiaticoside stimulation. This information could be used for
exploring the target genes in response to asiaticoside in fibroblasts.
PMID: 15533060 [PubMed / indexed for MEDLINE]
44: J Ethnopharmacol. 2004 Dec;95(2/3):183/9.
Thai medicinal plants modulate nitric oxide and tumor necrosis factor/alpha in
J774.2 mouse macrophages.
Punturee K, Wild CP, Vinitketkumneun U.
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang
Mai 50200, Thailand.
Centella asiatica (CA) and Rhinacanthus nasutus (RN) are Thai medicinal plants
traditionally used to treat a variety of disorders including inflammatory
conditions and infections. Nitric oxide (NO) produced from activated macrophages
plays a role in both inflammatory and anti/inflammatory processes. This study
examined whether CA and RN modulate the production of NO and tumour necrosis
factor/alpha (TNF/alpha) by J774.2 mouse macrophages. Expression of the
inducible nitric oxide synthase (iNOS) and TNF/alpha genes was also analysed.
With CA (water extract) NO production was increased in a dose/dependent manner.
An increase also occurred when CA was administered with lipopolysaccharide
(LPS), a known macrophage activator. In contrast, an ethanol extract of CA had
no effect on NO, and when administered with LPS the extract suppressed
production. With RN, neither water nor ethanol extracts alone had an effect on
NO, although when the ethanol extract of RN was used in combination with LPS,
production was increased. TNF/alpha secretion was correlated with NO production
and increases were associated with an elevation in TNF/alpha mRNA. The only
effect on iNOS gene expression was an inhibition with the CA ethanol extract in
the presence of LPS, consistent with the reduction in NO under these conditions.
These studies show that CA and RN extracts can either increase or decrease NO
production by macrophages and that these effects are predominantly mediated
through an effect on TNF/alpha expression. These data contribute to a better
mechanistic understanding of the medicinal properties of these Thai plants.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15507334 [PubMed / indexed for MEDLINE]
45: Food Chem Toxicol. 2004 Dec;42(12):1987/97.
Inhibitory effects of Centella asiatica on azoxymethane/induced aberrant crypt
focus formation and carcinogenesis in the intestines of F344 rats.
Bunpo P, Kataoka K, Arimochi H, Nakayama H, Kuwahara T, Bando Y, Izumi K,
Vinitketkumnuen U, Ohnishi Y.
Department of Molecular Bacteriology, Graduate School of Medicine, The
University of Tokushima, Tokushima 770/8503, Japan.
Effects of the water extract of Centella asiatica Linn. on formation of
azoxymethane (AOM)/induced aberrant crypt foci (ACF) and intestinal
tumorigenesis in male F344 rats were investigated. Treatment with the extract
significantly decreased the number of larger ACF (with four or more crypts per
focus) in the large intestine in the early stage, while the number of methylated
DNA adducts was not decreased compared with that in the AOM/treated group. In
the post/initiation stage, the extract significantly decreased the total number
of ACF and the number of larger ACF, accompanied by a decrease in the
5/bromo/2'/deoxyuridine/labeling index and an increase in the induction of
apoptotic cells in the colonic mucosa. The incidences of neoplasms, the numbers
of adenocarcinomas in the small intestines and entire intestines, and sizes of
neoplasms in the entire intestines in rats fed C. asiatica extract at a dose of
10 mg/kg were smaller than those in rats given AOM alone (p < 0.05). The extract
at a dose of 100 mg/kg significantly reduced the multiplicity of neoplasms in
the small intestine (p < 0.05). These results suggest that inhibition of the
formation of AOM/induced ACF by C. asiatica extract is associated with
modification of cell proliferation and induction of apoptosis in colonic crypts
and that the extract has a chemopreventive effect on colon tumorigenesis.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15500935 [PubMed / indexed for MEDLINE]
46: Br J Dermatol. 2004 Sep;151(3):571/8.
Dermal fibroblast/associated gene induction by asiaticoside shown in vitro by
DNA microarray analysis.
Lu L, Ying K, Wei S, Liu Y, Lin H, Mao Y.
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of
Life Science, Fudan University, Shanghai 200433, People's Republic of China.
luluo@vip.163.com
BACKGROUND: Asiaticoside, isolated from Centella asiatica, promotes fibroblast
proliferation and extracellular matrix (ECM) synthesis in wound healing. The
precise mechanism, however, in molecular and gene expression levels is still
unclear. OBJECTIVE: Using cDNA microarray technology, the alteration of gene
expression profiles was determined for human dermal fibroblasts in vitro in the
presence of asiaticoside (30 microg mL(/1)). Fifty/four genes, with known
functions for cell proliferation, cell cycle progression and synthesis of ECM,
were significantly upregulated in our 'genome/nest' expression profile at
various time points. Furthermore, the mRNA levels and protein production of
certain genes responsible for ECM synthesis (e.g. encoding type I and type III
collagen proteins) were evaluated by Northern blot and radioimmunoassay,
respectively. RESULTS: We found that there is a close correlation between the
gene profile, mRNA and protein production in the response of the cells to
asiaticoside stimulation. CONCLUSIONS: This information could be used for
exploring the response of the target genes to asiaticoside in fibroblasts.
PMID: 15377342 [PubMed / indexed for MEDLINE]
47: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Aug;24(8):731/4.
[Effect of total glucosides of Centella asiatica on antagonizing liver fibrosis
induced by dimethylnitrosamine in rats]
[Article in Chinese]
Ming ZJ, Liu SZ, Cao L.
Department of Pharmacy, School of Medicine, Suzhou University, Jiangsu (215007).
mingzj4451@sina.com
OBJECTIVE: To investigate the anti/liver fibrosis effect of total glucosides of
Centella asiatica (GCA) in experimental rats. METHODS: Rat liver fibrosis model
was induced by injecting dimethylnitrosamine (DMN) intraperitoneally for 6
weeks. Rats were randomly divided into 6 groups, the normal group, the model
group, the positive control group treated by colchicine, and the three GCA
groups treated by high, moderate and low dosage of GCA through gastrogavage
started simultaneously with the modeling. At the end of the experiment, levels
of serum total protein (TP), albumin (ALB), alanine transaminase (ALT),
aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) were
measured, and the pathology of liver tissue was observed. RESULTS: The liver
function in the GCA groups was improved, the levels of serum ALT, AST, HA were
significantly lower than those in the model group (P < 0.05). Histopathological
observation showed that GCA has significant anti/liver fibrosis effect.
CONCLUSION: GCA has significant preventive and therapeutic effect on DMN induced
liver fibrosis in rats.
Publication Types:
English Abstract
Research Support, Non/U.S. Gov't
PMID: 15366600 [PubMed / indexed for MEDLINE]
48: Plant Cell Rep. 2004 Nov;23(5):339/44. Epub 2004 Aug 14.
Stimulation of asiaticoside accumulation in the whole plant cultures of Centella
asiatica (L.) urban by elicitors.
Kim OT, Kim MY, Hong MH, Ahn JC, Hwang B.
Department of Biology, Chonnam National University, Gwangju, 500/757, South
Korea.
The effects of a number of different elicitors on asiaticoside production in
whole plant cultures of Centella asiatica were studied, including yeast extract,
CdCl(2), CuCl(2) and methyl jasmonate (MJ). Only MJ and yeast extract stimulated
asiaticoside production//1.53 and 1.41/fold, respectively. Maximum asiaticoside
production was achieved following treatment with 0.1 mM MJ (116.8 mg/l). The
highest asiaticoside production (342.72 mg/l) was obtained after 36 days of
elicitation in cultures treated with 0.1 mM MJ and 0.025 mg/l
1/phenyl/3/(1,2,3/thidiazol/5/yl)urea (TDZ). Interestingly, MJ not only
stimulated the production of asiaticoside but also had an important role in the
senescence of C. asiatica. Although asiaticoside content did not change when TDZ
was added to medium containing an elicitor, TDZ did increase shoot growth of C.
asiatica. We discuss the interactive roles of MJ and TDZ in secondary metabolic
production and biomass in whole plants of C. asiatica.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15316748 [PubMed / indexed for MEDLINE]
49: Asia Pac J Clin Nutr. 2004 Aug;13(Suppl):S72.
Antioxidative behaviour of Malaysian plant extracts in model and food oil
systems.
Jaswir I, Hassan TH, Said MZ.
Department of Biotechnology, Faculty of Science, International Islamic
University Malaysia, Jalan Gombak 53100 Kuala Lumpur, Malaysia.
Background / 'Pegaga' (Centella Asiatica) and 'limau purut' (Citrus hystrix) are
two types of plant traditionally used in Malaysian local dishes. Recent studies
showed that pegaga and limau purut leaves not only can be used as food
ingredients, but also can benefit human health. Objective / To investigate the
antioxidative behaviour of the crude extracts of pegaga leaves, and limau purut
leaves, peels, and stems in a linoleic acid model system and in palm olein
system. Design / Antioxidant activity of these local plants were analyzed using
an oxygen consumption method and by differential scanning calorimetry (DSC). The
antioxidant activity of these plants were then compared to the activity of
rosemary and sage, two types of antioxidant commonly found in the market.
Outcomes / From the analysis using oxygen consumption method, it was found that
among the samples evaluated, pegaga leaves had the longest time to reach the 50%
oxygen in the chamber, with 90 min, meaning that this sample had the highest
level of antioxidant activity. This was followed by the extracts of limau purut
leaves (85 min), peels (60 min), and stems (39 min). Results from the DSC
analysis showed that addition of pegaga leaves and limau purut samples to the
palm olein in the system reduced the oxidation as evidenced by longer T(o) of
antioxidants/treated samples. Statistical analysis from this study showed that
there was no significant difference between T(o) of pegaga leaves and those of
rosemary and sage. This meant that the antioxidant activity of pegaga leaves was
comparable to the activities of rosemary and sage. Conclusion / The finding from
this study indicated that all samples used in this study had very good potential
to be explored as sources of natural antioxidants.
PMID: 15294565 [PubMed / as supplied by publisher]
50: J Agric Food Chem. 2004 Aug 11;52(16):5183/6.
Total phenolics and antioxidant activities of fenugreek, green tea, black tea,
grape seed, ginger, rosemary, gotu kola, and ginkgo extracts, vitamin E, and
tert/butylhydroquinone.
Rababah TM, Hettiarachchy NS, Horax R.
Department of Food Science, University of Arkansas, 2650 North Young Avenue,
Fayetteville, Arkansas 72704, USA.
The total phenolics and antioxidant activities of fenugreek, green tea, black
tea, grape seed, ginger, rosemary, gotu kola, and ginkgo extracts, vitamin E,
and tert/butylhydroquinone, were determined. Grape seed and green tea were
analyzed for their phenolic constituents using high/performance liquid
chromatography. The total phenolics of the plant extracts, determined by the
Folin/Ciocalteu method, ranged from 24.8 to 92.5 mg of chlorogenic acid
equivalent/g dry material. The antioxidant activities of methanolic extracts
determined by conjugated diene measurement of methyl linoleate were 3.4/86.3%.
The antioxidant activity of the extracts using chicken fat by an oxidative
stability instrument (4.6/10.2 h of induction time) followed a similar trend in
antioxidant activity as determined by the Folin/Ciocalteu method. Seven
phenolics in grape seed and green tea extracts were identified that ranged from
15.38 to 1158.49 and 18.3 to 1087.02 mg/100 g of extract, respectively. Plant
extracts such as green tea and grape seed extracts can be used to retard lipid
oxidation in a variety of food products.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15291494 [PubMed / indexed for MEDLINE]
51: Phytomedicine. 2004;11(4):361/5.
Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and
Centella asiatica.
Jayathirtha MG, Mishra SH.
Pharmacy Department, The M.S. University of Baroda, Kalabhavan, Vadodara 390
001, India.
An attempt has been made to assess the immunomodulatory activity of methanol
extracts of whole plant of E. alba (1.6% wedelolactone) and C. asiatica (0.18%
of asiaticoside) at five dose levels (dose/response relationship) ranging from
100 to 500 mg/kg body wt. using carbon clearance, antibody titer and
cyclophosphamide immunosuppression parameters. In the case of E. alba, the
phagocytic index and antibody titer increased significantly and the F ratios of
the phagocytic index and WBC count were also significant. Regression analysis
showed linearity in patterns of the dose/response relationship, greatest in the
case of the phagocytic index, moderate in the WBC count and lowest in the
antibody titer. For C. asiatica, significant increases in the phagocytic index
and total WBC count were observed and the F ratio of the phagocytic index was
also significant. Regressed values revealed maximum linearity in the case of the
phagocytic index, moderate linearity in the total WBC count and lowest linearity
in the antibody response.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15185851 [PubMed / indexed for MEDLINE]
52: J Ethnopharmacol. 2004 Jul;93(1):105/8.
Cardioprotective activity of Hydrocotyle asiatica L. in ischemia/reperfusion
induced myocardial infarction in rats.
Pragada RR, Veeravalli KK, Chowdary KP, Routhu KV.
Pharmacology Division, Department of Pharmaceutical Sciences, Andhra University,
Visakhapatnam 530003, Andhra Pradesh, India. rajeswararaopragada@rediffmail.com
The alcoholic extract of Hydrocotyle asiatica Linn. (Hydrocotyle asiatica L.)
whole plant was evaluated for cardioprotective activity against
ischemia/reperfusion induced myocardial infarction in rats. Cardioprotective
activity was studied by measuring infarct size and estimating lipid peroxide
levels in serum and heart tissue. A lead II electrocardiogram was monitored at
various intervals throughout the experiment. A dose (100/1000 mg kg(/1))
dependent reduction in percent left ventricle necrosis (PLVN) as well as in
lipid peroxide levels was observed in rats treated with alcoholic extract of
Hydrocotyle asiatica L. orally for 7 days compared to control animals. The study
strongly suggests the cardioprotective activity of Hydrocotyle asiatica L. in
limiting ischemia/reperfusion induced myocardial injury.
Publication Types:
Comparative Study
PMID: 15182913 [PubMed / indexed for MEDLINE]
53: Zhong Yao Cai. 2003 Dec;26(12):870/3.
[Effect of total triterpenes from Centella asiatica on the depression behavior
and concentration of amino acid in forced swimming mice]
[Article in Chinese]
Chen Y, Han T, Qin L, Rui Y, Zheng H.
School of Pharmacy, Second Military Medical University, Shanghai 200433.
OBJECTIVE: To evaluate the antidepressant activity of total triterpenes from
Centella asiatica in forced swimming test. METHODS: Mice were randomly divided
into control group, model group and treatment group. The effect of total
triterpenes from Centella asiatica on the immobility time in forced swimming
mice and concentration of amino acid in mice brain tissue was observed. RESULTS:
Imipramine and total triterpenes from Centella asiatica reduced the immobility
time and ameliorated the imbalance of amino acid levels. CONCLUSION: The total
triterpenes from Centella asiatica had antidepressant activity.
Publication Types:
English Abstract
Research Support, Non/U.S. Gov't
PMID: 15058206 [PubMed / indexed for MEDLINE]
54: Life Sci. 2004 Mar 19;74(18):2237/49.
The healing effects of Centella extract and asiaticoside on acetic acid induced
gastric ulcers in rats.
Cheng CL, Guo JS, Luk J, Koo MW.
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 21
Sassoon Road, Pokfulam, Hong Kong, China.
In this study, the healing effects of Centella asiatica water extract (CE) and
asiaticoside (AC), an active constituent of CE, on acetic acid induced gastric
ulcers (kissing ulcers) in rats were examined. CE was prepared from Centella
asiatica dry plant and the concentration of AC in CE was quantitatively
determined with the use of high performance liquid chromatography analysis.
Different concentrations of CE and AC were orally administered to rats with
kissing ulcers. They were found to reduce the size of the ulcers at day 3 and 7
in a dose/dependent manner, with a concomitant attenuation of myeloperoxidase
activity at the ulcer tissues. Epithelial cell proliferation and angiogenesis
were on the other hand promoted. The expression of basic fibroblast growth
factor, an important angiogenic factor, was also upregulated in the ulcer
tissues in rats treated with CE or AC. These results further suggest the
potential use of Centella asiatica and its active ingredient as anti/gastric
ulcers drugs.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 14987949 [PubMed / indexed for MEDLINE]
55: Altern Med Rev. 2003 Nov;8(4):359/77.
Nutritional support for wound healing.
MacKay D, Miller AL.
Thorne Research, Inc., PO Box 25, Dover, ID 83825, USA. duffy@thorne.com
Healing of wounds, whether from accidental injury or surgical intervention,
involves the activity of an intricate network of blood cells, tissue types,
cytokines, and growth factors. This results in increased cellular activity,
which causes an intensified metabolic demand for nutrients. Nutritional
deficiencies can impede wound healing, and several nutritional factors required
for wound repair may improve healing time and wound outcome. Vitamin A is
required for epithelial and bone formation, cellular differentiation, and immune
function. Vitamin C is necessary for collagen formation, proper immune function,
and as a tissue antioxidant. Vitamin E is the major lipid/soluble antioxidant in
the skin; however, the effect of vitamin E on surgical wounds is inconclusive.
Bromelain reduces edema, bruising, pain, and healing time following trauma and
surgical procedures. Glucosamine appears to be the rate/limiting substrate for
hyaluronic acid production in the wound. Adequate dietary protein is absolutely
essential for proper wound healing, and tissue levels of the amino acids
arginine and glutamine may influence wound repair and immune function. The
botanical medicines Centella asiatica and Aloe vera have been used for decades,
both topically and internally, to enhance wound repair, and scientific studies
are now beginning to validate efficacy and explore mechanisms of action for
these botanicals. To promote wound healing in the shortest time possible, with
minimal pain, discomfort, and scarring to the patient, it is important to
explore nutritional and botanical influences on wound outcome.
Publication Types:
Review
PMID: 14653765 [PubMed / indexed for MEDLINE]
56: J Int Acad Periodontol. 2003 Oct;5(4):106/15.
Adjunctive periodontal treatment with Centella asiatica and Punica granatum
extracts. A preliminary study.
Sastravaha G, Yotnuengnit P, Booncong P, Sangtherapitikul P.
Out/Patient Department, Faculty of Dentistry, Mahidol University, Bangkok,
Thailand.
BACKGROUND: Centella asiatica and Punica granatum are medicinal herbs that have
been reported to promote tissue healing and modulate host responses. The purpose
of this study was to investigate the effects of the combined extracts from C.
asiatica and P. granatum pericarp on periodontal healing following scaling and
root planing in adult periodontitis patients. METHODS: An innovative herbal
medicament was formulated in the form of biodegradable chips for subgingival
application. Twenty patients with initial pocket depth 5/8 mm were enrolled into
the study. After baseline examination, scaling and root planing of non/target
teeth, the target teeth received scaling and root planing followed by
subgingival delivery of medicated chips in the test group and unmedicated chips
in the placebo group. Probing pocket depth, attachment level, bleeding on
probing, gingival index, and plaque index were recorded at baseline, 3 and 6
months. RESULTS: The results showed significant improvements of pocket depth and
attachment level in the test sites when compared with the placebo sites at 3
months and with the placebo and control sites at 6 months. All treatment sites
exhibited a similar trend of decreasing plaque score. However, the test sites
seemed to show slightly better percentage of bleeding on probing. CONCLUSION:
The results indicate that local delivery with C. asiatica and P. granatum
extracts plus scaling and root planing significantly reduced the clinical signs
of chronic periodontitis.
Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non/U.S. Gov't
PMID: 14604059 [PubMed / indexed for MEDLINE]
57: Carbohydr Res. 2003 Oct 31;338(22):2393/402.
Structure and potential immunological activity of a pectin from Centella
asiatica (L.) Urban.
Wang XS, Dong Q, Zuo JP, Fang JN.
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological
Sciences, Chinese Academic of Sciences, 555 Zu/Chong/Zhi Road, Zhangjiang
Hi/Tech Park, Shanghai 201203, PR China.
S3A was a RG/I pectin isolated from Centella asiatica that contained Rha, Ara,
Gal, Glc and GalA in molar ratio of 1.0:0.6:1.5:0.2:1.1 and had been found to
have a backbone composed mainly of the disaccharide repeat unit,
//>4)/alpha/D/GalpA/(1//>2)/alpha/L/Rhap/(1//>. Based on methylation analysis,
NaIO4 oxidation, partial acid hydrolysis and lithium/treatment, the structural
features were elucidated. Side chains of S3A were predominantly linked to O/4 of
1,2,4/linked alpha/L/Rhap. The side chains are comprised of arabinosyl chains,
galactosyl chains, arabinogalactosyl chains and short glucosyl chains. A total
of 45% Rhap in the backbone was substituted by side chains. The arabinosyl
residues were mostly distributed in the arabinosyl side chains. According to the
immunological results of S3A and its degraded derivatives, S3A had no
immunological activity, but its derivatives had immuno/stimulating activities to
some extent.
PMID: 14572724 [PubMed / indexed for MEDLINE]
58: Planta Med. 2003 Aug;69(8):725/32.
Gene expression changes in the human fibroblast induced by Centella asiatica
triterpenoids.
Coldren CD, Hashim P, Ali JM, Oh SK, Sinskey AJ, Rha C.
Malaysia/MIT Biotechnology Partnership Program, Cambridge, MA, USA.
The molecular pathways underlying the diverse biological activity of the
triterpeniod compounds isolated from the tropical medicinal plant Centella
asiatica were studied with gene microarrays and real/time reverse transcription
polymerase chain reaction (real/time RT/PCR) to quantify the expression of 1053
human genes in human fibroblasts. Fibroblast cells grown in culture were used as
a model system to evaluate the stimulation of wound healing by titrated extract
from Centella asiatica (TECA) as well as by the four principal triterpenoid
components of Centella. TECA treatment effects the expression of genes involved
in angiogenesis and the remodeling of extracellular matrix, as well as diverse
growth factor genes. The extent of expression change of TNFAIP6, an
extracellular hyaluronan binding protein, was found to be largely
dose/dependent, to respond most strongly to the free acids asiatic acid and
madecassic acid, and to increase in expression over 48 hours of treatment. These
results show that Centella triterpenes evoke a gene/expression response
consistent with their prevailing medical uses in the treatment of connective
tissue disorders such as wound healing and microangiopathy. The identification
of genes modulated by these compounds provides the basis for a molecular
understanding of Centella's bioactivity, and opportunities for the quantitative
correlation of this activity with clinical effectiveness at a molecular level.
Publication Types:
Research Support, Non/U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 14531023 [PubMed / indexed for MEDLINE]
59: Clin Exp Pharmacol Physiol. 2003 May/Jun;30(5/6):336/42.
Effect of Centella asiatica on cognition and oxidative stress in an
intracerebroventricular streptozotocin model of Alzheimer's disease in rats.
Veerendra Kumar MH, Gupta YK.
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of
Medical Sciences, Ansari Nagar, New Delhi, India.
1. Centella asiatica, an Indian medicinal plant, has been described as
possessing central nervous system activity, such as improving intelligence. In
addition, we have demonstrated that C. asiatica has cognitive/enhancing and
anti/oxidant properties in normal rats. Oxidative stress or an impaired
endogenous anti/oxidant mechanism is an important factor that has been
implicated in Alzheimer's disease (AD) and cognitive deficits seen in the
elderly. 2. Intracerebroventricular (i.c.v.) streptozotocin (STZ) in rats has
been likened to sporadic AD in humans and the cognitive impairment is associated
with free radical generation in this model. Therefore, in the present study, the
effect of an aqueous extract of C. asiatica (100, 200 and 300 mg/kg for 21 days)
was evaluated in i.c.v. STZ/induced cognitive impairment and oxidative stress in
rats. 3. Male Wistar rats were injected with STZ (3 mg/kg, i.c.v.) bilaterally
on the days 1 and 3. Cognitive behaviour was assessed using passive avoidance
and elevated plus/maze paradigms on the days 13, 14 and 21. Rats were killed on
the day 21 for estimation of oxidative stress parameters (malondialdehyde (MDA),
glutathione, superoxide dismutase and catalase) in the whole brain upon
completion of the behavioural task. 4. Rats treated with C. asiatica showed a
dose/dependent increase in cognitive behaviour in both paradigms. A significant
decrease in MDA and an increase in glutathione and catalase levels were observed
only in rats treated with 200 and 300 mg/kg C. asiatica. 5. The present findings
indicate that an aqueous extract of C. asiatica is effective in preventing the
cognitive deficits, as well as the oxidative stress, caused by i.c.v. STZ in
rats.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 12859423 [PubMed / indexed for MEDLINE]
60: Pharmazie. 2003 Jun;58(6):381/4.
An improved HPLC method for quantitative determination of six triterpenes in
Centella asiatica extracts and commercial products.
Schaneberg BT, Mikell JR, Bedir E, Khan IA.
National Center for Natural Products Research, School of Pharmacy, The
University of Mississippi, MS 38677, USA.
An improved HPLC qualitative and quantitative method of six triterpenes
(asiaticoside, madecassoside, asiatic acid, madecassic acid, terminolic acid,
and asiaticoside/B) in Centella asiatica (raw plant material and preparations)
is described in this paper. After 50 minutes the six active triterpenes were
separated and detected in the methanolic extract at a limit of 0.01 microg/ml.
The method uses a Phenomenex Aqua 5mu C18 (200 A) column as the stationary
phase, a gradient mobile phase of water (0.1% TFA), acetonitrile (0.1% TFA), and
methyl tert/butyl ether (0.1% TFA), and UV detection at 206 nm. The correlation
coefficients for the calibration curves and the r
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