Centella Asiatica Abstracts 1

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Centella asiatica
            (2007) Download

Apoptosis induction of Centella asiatica on human breast cancer cells
            (Babykutty et al., 2008) Download
The present study evaluated the ability of methanolic extract of Centella asiatica (Linn) Urban (Umbelliferae) to induce apoptosis in different cancer cell lines. MCF-7 cells emerged as the most sensitive cell line for in vitro growth inhibitory activity. C. asiatica extract induced apoptosis in MCF-7 cells as indicated by nuclear condensation, increased annexin staining, loss of mitochondrial membrane potential and induction of DNA breaks identified by TUNEL reactivity. It is possible that the use of C. asiatica extract as a component in herbal medicines could be justifiable.

The antiepileptic effect of Centella asiatica on the activities of Na/K, Mg and Ca-ATPases in rat brain during pentylenetetrazol-induced epilepsy
            (G et al., 2010) Download
BACKGROUND: To study the anticonvulsant effect of different extracts of Centella asiatica (CA) in male albino rats with reference to Na(+)/K(+), Mg(2+) and Ca(2+)-ATPase activities. MATERIALS AND METHODS: Male Wistar rats (150+/-25 g b.w.) were divided into seven groups of six each i.e. (a) control rats treated with saline, (b) pentylenetetrazol (PTZ)-induced epileptic group (60 mg/kg, i.p.), (c) epileptic group pretreated with n-hexane extract (n-HE), (d) epileptic group pretreated with chloroform extract (CE), (e) epileptic group pretreated with ethyl acetate extract (EAE), (f) epileptic group pretreated with n-butanol extract (n-BE), and (g) epileptic group pretreated with aqueous extract (AE). RESULTS: The activities of three ATPases were decreased in different regions of brain during PTZ-induced epilepsy and were increased in epileptic rats pretreated with different extracts of CA except AE. CONCLUSION: The extracts of C. asiatica, except AE, possess anticonvulsant and neuroprotective activity and thus can be used for effective management in treatment of epileptic seizures.


Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all
            (Gohil et al., 2010) Download
In recent times, focus on plant research has increased all over the world. Centella asiatica is an important medicinal herb that is widely used in the orient and is becoming popular in the West. Triterpenoid, saponins, the primary constituents of Centella asiatica are manly believed to be responsible for its wide therapeutic actions. Apart from wound healing, the herb is recommended for the treatment of various skin conditions such as leprosy, lupus, varicose ulcers, eczema, psoriasis, diarrhoea, fever, amenorrhea, diseases of the female genitourinary tract and also for relieving anxiety and improving cognition. The present review attempts to provide comprehensive information on pharmacology, mechanisms of action, various preclinical and clinical studies, safety precautions and current research prospects of the herb. At the same time, studies to evaluate the likelihood of interactions with drugs and herbs on simultaneous use, which is imperative for optimal and safe utilization of the herb, are discussed.

Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin
            (Haftek et al., 2008) Download
Skin ageing is a complex process determined by the genetic endowment of individual and environmental factors, such as sun exposure. The effects of skin ageing are mostly encountered in the superficial dermis and in the epidermis. We have previously demonstrated in vivo the beneficial effect of a topically applied formula of 5% vitamin C in the treatment of skin ageing. Another active compound, madecassoside extracted from Centella asiatica, known to induce collagen expression and/or to modulate inflammatory mediators, might thus prevent and correct some signs of ageing. A randomized double-blind study was carried out on photoaged skin of 20 female volunteers to investigate the effects of topically applied 5% vitamin C and 0.1% madecassoside on the clinical, biophysical and structural skin properties. After 6 months of treatment, we observed a significant improvement of the clinical score for deep and superficial wrinkles, suppleness, firmness, roughness and skin hydration. These results were corroborated by measurements of skin elasticity and semi-quantitative histological assessment of the elastic fibre network in the papillary dermis. Two-thirds of the subjects showed an improvement. The re-appearance of a normally structured elastic fibre network was observed. Our results revealed a functional and structural remodelling of chronically sun-damaged skin.


Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced parkinsonism in aged Sprague-Dawley rats
            (Haleagrahara and Ponnusamy, 2010) Download
Reactive oxygen species (ROS) play an important role in ageing and age-related neurodegenerative changes including Parkinson's disease (PD). PD is characterized by signs of major oxidative stress and mitochondrial damage in the pars compacta of the substantia nigra. Present study was designed to investigate whether the Centella asiatica extract (CAE) would prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in aged Sprague-Dawley rats. Adult, male Sprague-dawley rats of 300-350 g were divided into control, C. asiatica alone, MPTP alone (20 mg/kg, for 21 days) and MPTP with C. asiatica (300 mg/kg for 21 days) groups. Effect of aqueous extract of C. asiatica on oxidative biomarker levels in corpus striatum and hippocampus homogenate was examined. MPTP-challenged rats elicited a significant increase in lipid hydroperoxides (LPO) (p < 0.01), protein-carbonyl-content (PCC) (p < 0.01) and xanthine oxidase (XO) (p < 0.01) when compared with control rats. There was a significant decrease in total antioxidants (TA) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.01) and catalase (CAT) (p < 0.001) levels with MPTP treatment. Supplementation of CAE reduced LPO and PCC and significantly increased (p < 0.01) TA and antioxidant enzyme levels (p < 0.01) in corpus striatum and hippocampus. These results show that administration of C. asiatica was effective in protecting the brain against neurodegenerative disorders such as Parkinsonism.

Hepatotoxicity associated with the ingestion of Centella asiatica
            (Jorge and Jorge, 2005) Download
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.

Standardisation and Quality Evaluation of Centella asiatica Linn
            (Joseph et al., 2001) Download
Centella asiatica Linn. Is a well-known medicinal herb used in various types of diseases, it was noticed that the herb is being heavily adulterated with the cheaper substances. A critical stud of the authentic and maker samples (available in powder for) s carried out to study current status of the drug in the local market. Powder analysis of the market samples shoes fragments of sclerenchymatous net, which is a characteristic feature of some umbelliferous fruits. Occurrence of prismatic crystals of calcium oxalate and large number of starch grains shows that the powdered materials are heavily adulterated with some cheaper substances. Fluorescence analysis of authentic and market samples exhibits 23.28% and 12.34% -18.13% respectively and there is a difference in curde fibre content also. Moreover there is remarkable difference in the quantitative value of Asiatic acid (3.25% - 0.12%) which is one of the chief constituents of C. asiatica.

Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia
            (Krishnamurthy et al., 2009) Download
Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate- or beta-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre- and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygen-glucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia.

Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice
            (Kumar et al., 2011) Download
D-galactose induced neurotoxicity is well known model for studying aging and related oxidative damage and memory impairment. Aging is a biological process, characterized by the gradual loss of physiological functions by unknown mechanism. Centella asiatica, Indian pennywort has been documented in the treatment of various neurological disorders including aging. Therefore, present study has been conducted in order to explore the possible role of Centella asiatica against D-galactose induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. Chronic administration of D-galactose (100 mg/kg s.c.) for a period of six weeks significantly impaired cognitive task (both in both Morris water maze and elevated plus maze) and oxidative defense (Increased lipid peroxidation, nitrite concentration and decreased activity of superoxide dismutase, catalase and non-protein thiols) and impaired mitochondrial complex (I, II and III) enzymes activities as compared to sham group. Six weeks Centella asiatica (150 and 300 mg/kg, p.o) treatment significantly improved behavioral alterations, oxidative damage and mitochondrial enzyme complex activities as compared to contro l (D-galactose). Centella asiatica also attenuated enhanced acetylcholine esterase enzyme level in D-galactose senescence mice. Present study highlights the protective effect of Centella asiatica against D-galactose induced behavioral, biochemical and mitochondrial dysfunction in mice.

Evaluation of the effects of a preparation containing asiaticoside on periocular wrinkles of human volunteers
            (Lee et al., 2008) Download
Skin ageing is accompanied by wrinkle formation. In particular, periorbital wrinkle formation is a relatively early sign of skin ageing. We evaluated the effects of a preparation containing asiaticoside on the periorbital wrinkles of a group of volunteers. The effectiveness of the active compound, asiaticoside, in a base-cream preparation for the treatment of temporal periorbital wrinkles was tested on 27 female volunteers as follows: the women applied the cream twice a day to the region of interest for 12 weeks. Same women also applied a vehicle control cream to the periorbital skin around the other eye. Negative replicas were taken of the periorbital skin before treatment and 4, 8, and 12 weeks after application of the cream. The results were evaluated by semi-automated morphometry of the plastic replicas. After 12 weeks of treatment, there was a significant improvement of the periorbital wrinkles in majority of the volunteers who tested the cream. Of the 27 women examined with periocular wrinkles, 65% showed an improvement at the end of the treatment. In three cases, the improvement was 100% (disappearance of the crow's feet), 75% +/- 1.97 and 79% +/- 2.82. On six eyes, there was no significant change after the treatment. With 12 weeks of treatment with the asiaticoside-containing cream, most of the periorbital wrinkles were attenuated to some degree, and some women experienced a significant improvement of the periorbital wrinkles on one of their eyes.

Centella asiatica Improves Physical Performance and Health-related Quality of Life in Healthy Elderly Volunteer
            (Mato et al., 2009) Download
Recently, oxidative stress has been reported to contribute an important role in the decline of physical function as age advances. Numerous antioxidants can improve both physical and psychological performances resulting in the increase of health-related quality of life (HQOL). Therefore, we hypothesized that Centella asiatica, a medicinal plant reputed for nerve tonic, strength improvement and antioxidant activity, could improve the physical performance and HQOL especially in the physical satisfaction aspect, of the healthy elderly volunteer. To test this hypothesis, a double-blind, placebo-controlled, randomized trial was performed. Eighty healthy elderly were randomly assigned to receive placebo or standardized extract of C. asiatica at doses of 250, 500 and 750 mg once daily for 90 days. The subjects were evaluated to establish baseline data of physical performance using 30-s chair stand test, hand grip test and 6-min walk test. The health-related quality of life was assessed using SF-36. These assessments were repeated every month throughout the 3-month experimental period using the aforementioned parameters. Moreover, 1 month after the cessation of C. asiatica treatment, all subjects were also evaluated using these parameters again. The results showed that after 2 months of treatment, C. asiatica at doses of 500 and 750 mg per day increased lower extremity strength assessed via the 30-s chair stand test. In addition, the higher doses of C. asiatica could improve the life satisfaction subscale within the physical function subscale. Therefore, the results from this study appear to support the traditional reputation of C. asiatica on strength improvement, especially in the lower extremities of the elderly. C. asiatica also possesses the potential to be a natural resource for vigor and strength increase, in healthy elderly persons. However, further research is essential.


Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts
            (Punturee et al., 2005) Download
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.

The anti-thrombotic active constituents from Centella asiatica
            (Satake et al., 2007) Download
The in vitro effects of a methanol extract from the aerial parts of Centella asiatica on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. 3,5-Di-O-caffeoyl quinic acid, 1,5-di-O-caffeoyl quinic acid, 3,4-di-O-caffeoyl quinic acid, 4,5-di-O-caffeoyl quinic acid, and chlorogenic acid, together with asiaticoside, kaempferol, quercetine, kaempferol-3-O-beta-D-glucoside and quercetin-3-O-beta-D-glucoside were all isolated from the methanol extract. Amongst these, only 3,5-di-O-caffeoylquinic acid showed significant inhibition of shear-induced platelet activation and dynamic coagulation. The reactive curve of the inhibitory effect on the platelet reaction and the dynamic coagulation showed a bell-shape.


Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro
            (Soumyanath et al., 2005) Download
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.

Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action
            (Soumyanath et al., 2012) Download
Centella asiatica (CA), commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD), we examined the effects of a water extract of CA (GKW) in the Tg2576 mouse, a murine model of AD with high beta-amyloid burden. Orally administered GKW attenuated beta-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated beta-amyloid, respectively. GKW prevented intracellular beta-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.

Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica
            (Wattanathorn et al., 2008) Download
AIMS OF THIS STUDY: Centella asiatica has a reputation to restore decline cognitive function in traditional medicine and in animal model. However, little evidence regarding the efficacy of Centella asiatica from systematized trials is available. Therefore, the present randomized, placebo-controlled, double-blind study investigated the effect of Centella asiatica on cognitive function of healthy elderly volunteer. MATERIALS AND METHODS: Twenty-eight healthy elderly participants received the plant extract at various doses ranging 250, 500 and 750 mg once daily for 2 months. Cognitive performance was assessed using the computerized test battery and event-related potential whereas mood was assessed using Bond-Lader visual analogue scales prior to the trial and after single, 1 and 2 months after treatment. RESULTS: The results showed that the high dose of the plant extract enhanced working memory and increased N100 component amplitude of event-related potential. Improvements of self-rated mood were also found following the Centella asiatica treatment. CONCLUSION: Therefore, the present findings suggest the potential of Centella asiatica to attenuate the age-related decline in cognitive function and mood disorder in the healthy elderly. However, the precise mechanism(s) underlying these effects still require further investigation.

Gotu Kola (Centella Asiatica) extract enhances phosphorylation of cyclic AMP response element binding protein in neuroblastoma cells expressing amyloid beta peptide
            (Xu et al., 2008) Download
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that shows cognitive deficits and memory impairment. Extract from the leaves of Gotu Kola (Centella Asiatica) have been used as an alternative medicine for memory improvement in Indian Ayurvedic system of medicine for a long time. Although several studies have revealed its effect in ameliorating the cognitive impairment in rat models of AD and stimulating property on neuronal dendrites of hippocampal region, the molecular mechanism of Gotu Kola on neuroprotection still remains to be elucidated. In this study, we report that phosphorylation of cyclic AMP response element binding protein (CREB) is enhanced in both a neuroblastoma cell line expressing amyloid beta 1-42 (Abeta) and in rat embryonic cortical primary cell culture. In addition, the contribution of two major single components to the enhanced CREB phosphorylatioin was examined. Furthermore, inhibitors were applied in this study revealing that ERK/RSK signaling pathway might mediate this effect of Gotu Kola extract. Taken together, we provide a possible molecular mechanism for memory enhancing property of Gotu Kola extract for the first time.

 


References

Babykutty, S., et al. (2008), ‘Apoptosis induction of Centella asiatica on human breast cancer cells’, Afr J Tradit Complement Altern Med, 6 (1), 9-16. PubMedID: 20162036
(2007), ‘Centella asiatica’, Altern Med Rev, 12 (1), 69-72. PubMedID: 17397269
G, V., et al. (2010), ‘The antiepileptic effect of Centella asiatica on the activities of Na/K, Mg and Ca-ATPases in rat brain during pentylenetetrazol-induced epilepsy’, Indian J Pharmacol, 42 (2), 82-86. PubMedID: 20711371
Gohil, K. J., J. A. Patel, and A. K. Gajjar (2010), ‘Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all’, Indian J Pharm Sci, 72 (5), 546-56. PubMedID: 21694984
Haftek, M., et al. (2008), ‘Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin’, Exp Dermatol, 17 (11), 946-52. PubMedID: 18503551
Haleagrahara, N. and K. Ponnusamy (2010), ‘Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced parkinsonism in aged Sprague-Dawley rats’, J Toxicol Sci, 35 (1), 41-47. PubMedID: 20118623
Jorge, O. A. and A. D. Jorge (2005), ‘Hepatotoxicity associated with the ingestion of Centella asiatica’, Rev Esp Enferm Dig, 97 (2), 115-24. PubMedID: 15801887
Joseph, G. V., S. Chaturvedi, and S. S. Deokule (2001), ‘Standardisation and Quality Evaluation of Centella asiatica Linn’, Anc Sci Life, 20 (4), 99-110. PubMedID: 22557022
Krishnamurthy, R. G., et al. (2009), ‘Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia’, J Neurosci Res, 87 (11), 2541-50. PubMedID: 19382233
Kumar, A., A. Prakash, and S. Dogra (2011), ‘Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice’, Int J Alzheimers Dis, 2011 347569. PubMedID: 21629743
Lee, J., et al. (2008), ‘Evaluation of the effects of a preparation containing asiaticoside on periocular wrinkles of human volunteers’, Int J Cosmet Sci, 30 (3), 167-73. PubMedID: 18452433
Mato, L., et al. (2009), ‘Centella asiatica Improves Physical Performance and Health-related Quality of Life in Healthy Elderly Volunteer’, Evid Based Complement Alternat Med, PubMedID: 19880441
Punturee, K., et al. (2005), ‘Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts’, Asian Pac J Cancer Prev, 6 (3), 396-400. PubMedID: 16236006
Satake, T., et al. (2007), ‘The anti-thrombotic active constituents from Centella asiatica’, Biol Pharm Bull, 30 (5), 935-40. PubMedID: 17473438
Soumyanath, A., et al. (2005), ‘Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro’, J Pharm Pharmacol, 57 (9), 1221-29. PubMedID: 16105244
Soumyanath, A., et al. (2012), ‘Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer’s Disease: Investigation of a Possible Mechanism of Action’, Int J Alzheimers Dis, 2012 381974. PubMedID: 22506133
Wattanathorn, J., et al. (2008), ‘Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica’, J Ethnopharmacol, 116 (2), 325-32. PubMedID: 18191355
Xu, Y., et al. (2008), ‘Gotu Kola (Centella Asiatica) extract enhances phosphorylation of cyclic AMP response element binding protein in neuroblastoma cells expressing amyloid beta peptide’, J Alzheimers Dis, 13 (3), 341-49. PubMedID: 18431001