Centella asiatica (Linn.) Urban (Umbelliferae) which is also known as ‘pegaga’ is highly consumed and eaten raw as ‘ulam’ in Malaysia. C. asiatica is used in traditional medicines to treat various health conditions such as rheumatism, inflammation, syphilis, skin diseases and diarrhoea. Various reports exhibited that the crude extracts and isolated bioactive compounds of C. asiatica possessed a broad range of pharmacological activities such as anti-oxidant, anti-diabetic, anti-tumor, wound healing, anti-microbial, anti-inflammatory, immunomodulatory, hepatoprotective and memory enhancing properties. The pharmacological validation on anti-microbial and immunomodulatory of C. asiatica is very limited and several existence review papers related for this plant had not been focused for both activities. This review therefore attempts to combine the existing literature to offer immense scope for researchers engaged in validation of the traditional claims and bioactivities of this plant related with anti-microbial and immunomodulatory potential.
Centella ; Complex Mixtures ; Inflammation ; Malaysia ; Memory ; Plants ; Rheumatic Diseases ; Syphilis, Cutaneous ; Wound Healing

PURPOSE: In our previous study, we demonstrated that both titrated extract of Centella asiatica (TECA) and astaxanthin (AST) have anti-inflammatory effects in a 5% phthalic anhydride (PA) mouse model of atopic dermatitis (AD). The increasing prevalence of AD demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of the ointment form of TECA, AST and a TECA + AST combination in a mouse model of AD to see whether a combination of the reduced doses of 2 compounds could have a synergistic effect. METHODS: An AD-like lesion was induced by the topical application of 5% PA to the dorsal ear and back skin of an Hos:HR-1 mouse. After AD induction, TECA (0.5%), AST (0.5%) and the TECA (0.25%) + AST (0.25%) combination ointment (20 μg/cm2) were spread on the dorsum of the ear or back skin 3 times a week for 4 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclocxygenase (COX)-2, and nuclear factor (NF)-κB activity. We also measured the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and immunoglobulin E (IgE) in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). RESULTS: PA-induced skin morphological changes and ear thickness were significantly reduced by TECA, AST and TECA + AST treatments, but these inhibiting effects were more pronounced in the TECA + AST treatment. TECA, AST and the TECA+AST reatments inhibited the expression of iNOS and COX-2; NF-κB activity; and the release of TNF-α, IL-6 and IgE. However, the TECA+AST treatment showed additive or synergistic effects on AD. CONCLUSIONS: Our results demonstrate that the combination of TECA and AST could be a promising therapeutic agent for AD by inhibiting NF-κB signaling.
Animals ; Blotting, Western ; Centella ; Dermatitis ; Dermatitis, Atopic ; Ear ; Enzyme-Linked Immunosorbent Assay ; Immunoglobulin E ; Immunoglobulins ; Inflammation ; Interleukin-6 ; Interleukins ; Mice ; Nitric Oxide Synthase Type II ; Prevalence ; Skin ; Tumor Necrosis Factor-alpha

OBJECTIVES: Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed. METHODS: Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression. CONCLUSIONS The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.
Animals ; Cells, Cultured ; Centella ; chemistry ; Collagen Type IV ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Mesangial Cells ; drug effects ; metabolism ; Rats ; Signal Transduction ; Smad Proteins ; metabolism ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.
Animals ; Centella ; chemistry ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; chemically induced ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Transforming Growth Factor-beta Type I ; metabolism ; Receptor, Transforming Growth Factor-beta Type II ; metabolism ; Signal Transduction ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVES: The aim of this study was to assess the antiplaque and antigingivitis effectiveness of aqueous single-phase and oil-water two-phase mouthrinses, containing bamboo salt, magnolia bark, and Centella asiatica extracts, in Korean adults. METHODS: In this double-blinded clinical trial, a total of thirty-four participants aged over 19 years were randomly allocated to three experimental groups: 1) control group; 2) aqueous single-phase mouthrinse (ASM) group, and; 3) oil-water two-phase mouthrinse (OTM) group. The experimental mouthrinses all contained sodium fluoride, and the ASM and OTM contained additional ingredients of bamboo salt, magnolia bark, and Centella asiatica extracts. For the OTM, 50% essential oil was added to create an oil-water two-phase mouthrinse. A two-week randomized crossover design with a two-week washout period was applied. Following a complete dental prophylaxis, participants were instructed to use the prescribed mouthrinse twice daily for two weeks as an adjunct to their usual mechanical oral hygiene procedures. Pre- and post-experiment clinical examinations were performed to measure the plaque index (PI) and bleeding on probing (BOP) for the full mouth. Paired t-test was applied to compare the intergroup differences for all clinical variables. RESULTS: Compared to the control group, ASM showed a significantly reduced BOP (P<0.05). However, there was no statistically significant difference in the effects of the three mouthrinses on reducing the PI. CONCLUSIONS: The results of this study indicate that the use of an aqueous, single-phase mouthrinse containing bamboo salt, magnolia bark and Centella asiatica extracts could help alleviate gingivitis.
Adult ; Centella* ; Cross-Over Studies ; Dental Prophylaxis ; Gingivitis* ; Hemorrhage ; Humans ; Magnolia* ; Mouth ; Oral Hygiene ; Sodium Fluoride

Pentacyclic triterpenes, mainly, asiatic acid, madecassic acid, asiaticoside, and madecassoside are the active constituents of Centella asiatica. A pentacyclic triterpene enriched C. asiatica extract (PRE) was prepared and standardized to contain a total pentacyclic triterpenes not less than 65% w/w. This work was focused on determination of antiinflammatory, antioxidant, and tyrosinase inhibitory activities of PRE and its stability. The PRE exhibited a satisfactory nitric oxide inhibitory effect, with an IC50 value of 64.6 µg/mL. In addition, the PRE inhibited tyrosinase enzyme activity with an IC50 value of 104.8 µg/mL. In contrast, the PRE possessed only weak antioxidant activity. The PRE was stable over a period of four months when stored as a dried powder but only in a well-closed container protected from light at 4 °C. An aqueous alcoholic solution of the PRE was stable at pH values of 5.8 and 7.0, but was not stable at a pH of 8.2. Preparations of the PRE in an aqueous solution should be performed in acidic or neutral conditions.
Alcoholics ; Centella* ; Humans ; Hydrogen-Ion Concentration ; Inhibitory Concentration 50 ; Monophenol Monooxygenase ; Nitric Oxide ; Pentacyclic Triterpenes

Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica acts as an antioxidant, reducing the effect of oxidative stress in vitro and in vivo. At the in vitro level, C. asiatica promotes dendrite arborisation and elongation, and also protects the neurons from apoptosis. In vivo studies have shown that the whole extract and also individual compounds of C. asiatica have a protective effect against various neurological diseases. Most of the in vivo studies on neuroprotective effects have focused on Alzheimer’s disease, Parkinson’s disease, learning and memory enhancement, neurotoxicity and other mental illnesses such as depression and anxiety, and epilepsy. Recent studies have embarked on finding the molecular mechanism of neuroprotection by C. asiatica extract. However, the capability of C. asiatica in enhancing neuroregeneration has not been studied much and is limited to the regeneration of crushed sciatic nerves and protection from neuronal injury in hypoxia conditions. More studies are still needed to identify the compounds and the mechanism of action of C. asiatica that are particularly involved in neuroprotection and neuroregeneration. Furthermore, the extraction method, biochemical profile and dosage information of the C. asiatica extract need to be standardised to enhance the economic value of this traditional herb and to accelerate the entry of C. asiatica extracts into modern medicine.
Centella ; Antioxidants

Traditionally, Centella asiatica leaf extracts are used to treat neurodegenerative diseases in India. Centella asiatica is reportedly used to enhance memory and treat dementia, but its promoting effect on neural stem cell differentiation has not been studied yet. In the present study, we investigated whether or not Centella asiatica leaf extracts act on neuronal precursor cells and neuronal cell lines to induce neuronal differentiation, neurite outgrowth, and neuroprotection. The neurogenesis-promoting potential of Centella asiatica leaf extracts was determined by differentiation assay on neural stem cells isolated from mouse embryos and PC12 cell lines. To understand the contribution of specific neural cell types towards increase after Centella asiatica treatment, neural stem cells were differentiated into various neural subtypes and checked by Western blotting using neural cell lineage-specific antibody markers. Neuroprotective activity of Centella asiatica was analyzed in PC12 cells exposed to 100 microM of H2O2. Cell growth was analyzed by MTT assay while cell death was analyzed by Western blotting detection of apoptosis-related proteins. Cells treated with Centella asiatica had significantly longer primary and secondary neurites as well as a higher number of neurites per cell compared to control cells. Expression levels of TUBBIII, TH, NF, and BDNF increased upon Centella asiatica treatment, suggesting that Centella asiatica has a neurogenesis-promoting effect. Centella asiatica also inhibited oxidative stress-induced neural cell damage through regulation of apoptosis- and cell cycle-related proteins. Thus, leaf extracts of Centella asiatica might promote neurogenesis, neuroregeneration, and neuroprotection in the context of neurodegenerative diseases.
Animals ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Cell Death ; Cell Line ; Centella* ; Dementia ; Embryonic Structures ; India ; Memory ; Mice ; Neural Stem Cells ; Neurites ; Neurodegenerative Diseases ; Neurogenesis* ; Neurons* ; Neuroprotective Agents ; PC12 Cells

The objective of the present study was to examine the effects of beta-glucan originating from Aureobasidium on full-thickness skin wound healing in diabetic C57BL/KsJ-db/ db mouse models. In the diabetic C57BL/KsJ-db/db model, test articles were topically applied twice a day for 20 days starting from 1 day after wounding. The results were compared to that of MadecassolTM ointment (madecassol; 1% Centella asiatica extracts) topically applied at a concentration of 100 mg/kg. Treatment with beta-glucan resulted in significant (p<0.01 or p<0.05) and dose-dependent decreases in wound size compared with that of vehicle control showing increased wound size (WS, %). In addition, 50% contraction time (CT50) was dramatically and dose-dependently reduced, and inflammatory cells in granulation tissues of the wound area were significantly (p<0.01 or p<0.05) and dosedependently reduced compared with that of vehicle control showing increased numbers of micro-vessels and fibroblasts as well as re-epithelialization. In the madecassol group, similar changes in inflammatory cells and fibroblasts with re-epithelialization were also observed, but madecassol did not influence angiogenesis. No meaningful changes in body weight were detected in all tested groups compared with the vehicle control. Therefore, these data suggest that beta-glucan has a beneficial effect on diabetic delayed skin wound healing and may be useful to manage incurable skin wounds in diabetic animals.
Animals ; Body Weight ; Centella ; Fibroblasts ; Granulation Tissue ; Mice* ; Re-Epithelialization ; Skin ; Wound Healing* ; Wounds and Injuries*

The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.
Animals ; Blood Glucose ; metabolism ; Centella ; chemistry ; Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; Disease Models, Animal ; Fibronectins ; metabolism ; Fibrosis ; Glucose Tolerance Test ; Hyperglycemia ; drug therapy ; pathology ; Insulin ; blood ; Insulin Resistance ; Islets of Langerhans ; drug effects ; pathology ; Male ; Pancreatic Diseases ; metabolism ; pathology ; prevention & control ; Pentacyclic Triterpenes ; pharmacology ; therapeutic use ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Inbred Strains