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Effect of Centella asiatica L (Umbelliferae) on normal and dexamethasone-suppressed wound healing in Wistar Albino rats.

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.

Administration, Topical↗

Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats.

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.

Animals↗

Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes and rosmarinic acid from Centella asiatica.

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.

Apiaceae↗

Medicinal foodstuffs. XXVII. Saponin constituents of gotu kola (2): structures of new ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, from Centella asiatica cultivated in Sri Lanka.

Ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, were isolated from the aerial parts of Centella asiatica (L.) Urban cultivated in Sri Lanka together with madecassoside, asiaticoside, asiaticoside B, and sceffoleoside A. The chemical structures of centellasaponins B, C, and D were determined on the basis of chemical and physicochemical evidence to be madecassic acid 28-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, madasiatic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, and 3beta,6beta,23-trihydroxyolean-12-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, respectively.

Carbohydrate Sequence↗

[Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and centella asiatica in the treatment of patients with chronic venous insufficiency].

BACKGROUND: The aim of this comparative clinical study was to evaluate the efficacy of the association of alphatocopherol, rutin, melilotus officinalis, and centella asiatica with oral administration in patients with chronic venous insufficiency. METHODS: Thirty patients with chronic venous insufficiency have been randomized in two groups of fifteen subjects (control and treatment group). During the period of treatment the patients didn't wear elastocompressive stockings. The therapeutic efficacy and the clinical tolerability of this association have been valued with clinical-instrumental evaluations and by a control after 15 and 30 days. Functional bothers, cramps and the edema have been valued in function presence and of their gravity with a clinical-score between 0 and 4. RESULTS: At the end of the observation period, a significant improvement of the clinical simptomatology was obtained, characterised by a diminution of the sovrafascial edema. CONCLUSIONS: The present study confirms previous clinical experiences regarding the described treatment and suggests its application in chronic venous insufficiency.

Antioxidants↗

An improved HPLC method for quantitative determination of six triterpenes in Centella asiatica extracts and commercial products.

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 recovery rates ranged from 0.995 to 0.999 and from 98.39% to 100.02%, respectively. The qualitative and quantitative results are discussed.

Calibration↗

Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts. A preliminary study.

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.

Adult↗

[Effect of total glucosides of Centella asiatica on antagonizing liver fibrosis induced by dimethylnitrosamine in rats].

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.

Animals↗

Cloning and expression of a farnesyl diphosphate synthase in Centella asiatica (L.) Urban.

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.

Alkyl and Aryl Transferases↗

Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts in supportive periodontal therapy.

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.

Adult↗

Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts.

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.

Acanthaceae↗

Enhancement of the attachment on microcarriers and tPA production by fibroblast cells in a serum-free medium by the addition of the extracts of Centella asiatica.

The addition of ethanol extracts of Centella asiatica showed a remarkable enhancement of fibroblast cells attachment to Cytodex beads in serum-free (SF) medium. It also improves tPA production in both batch and perfusion cultivations. The optimal concentration for SF medium was determined as 2 ppm of the extracts when using Cytodex III. In batch cultivation a high specific tPA production rate was obtained, compared to that from 5% FBS containing medium. However, a fast specific growth rate was observed in 5% FBS medium. In perfusion cultivation a reasonably good cell density and tPA production was achieved at a perfusion rate of 2.4 x 10(6) (viable cell/ml) and 0.65 (micrograms/ml), respectively at 22 ml/min.

Cell Adhesion↗

Pharmacokinetics of the total triterpenic fraction of Centella asiatica after single and multiple administrations to healthy volunteers. A new assay for asiatic acid.

A new HPLC assay method was used to investigate the pharmacokinetics of asiatic acid after oral administration of the total triterpenic fraction of Centella asiatica in single doses (30 or 60 mg) and after a 7-day treatment (30 or 60 mg twice daily). Twelve healthy volunteers received each treatment following a randomized cross-over design with trials separated by a 3-week interval. The time of peak plasma concentration was not affected by dosage difference or by treatment scheme. Differences in peak plasma concentration and area under the concentration vs. time curve from 0 to 24 h (AUC0-24) calculated after 30 or 60 mg administration (single dose) were accounted for by the different dose regimen. However, after chronic treatment with both 30 and 60 mg, peak plasma concentrations, AUC0-24 and half-life were significantly higher than those observed after the corresponding single dose administration. This phenomenon could be explained by a metabolic interaction between asiatic acid and asiaticoside, which is transformed into asiatic acid in vivo.

Administration, Oral↗

Protection against radiation-induced conditioned taste aversion by Centella asiatica.

Radiations are known to cause behavioural perturbations like conditioned taste aversion (CTA), performance decrement, learning, etc., even at very low doses. The manifestation of radiation-induced behavioural degradation has not been understood well and requires further studies. Therefore, the effects of low-dose whole-body 60Co gamma-irradiation in male rats were studied in terms of body weight and CTA learning. For CTA, the consumption of saccharin solution was considered as a parameter. To protect against the adverse effects of radiation, Centella asiatica (aqueous extract) was tested and compared with ondansetron, a standard antiemetic drug. A dose of 2 Gy incurred significant body weight loss [t(9)=9.00, P<.05] and induced CTA in rats [t(26)=9.344, P<.01]. Administration of C. asiatica (100 mg/kg bw ip, 2 Gy, -1 h) rendered significant radioprotection against radiation-induced body weight loss and CTA that became evident on the second postirradiation day [t(7)=0.917, P>>.05; t(7)=4.016, P>.05]. Ondansetron (1 mg/kg bw) elicited higher degree of protection against CTA [t(7)=3.641, P>.05] than C. asiatica [t(7)=7.196, P>.05] on the first postirradiation day, but on the second postirradiation day, both were equally effective [t(7)=3.38, P>.05; t(7)=4.01, P>.05]. In case of C. asiatica-treated animals, however, there was a consistently declining CTA from the second to the fifth postirradiation day whereas in ondansetron-treated animals it was inconsistent. Present investigation suggests that C. asiatica could be useful in preventing radiation-induced behavioural changes during clinical radiotherapy.

Animals↗

Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system.

Titrated extract of Centella asiatica (TECA), a drug used in treating systemic scleroderma, is poorly water-soluble. A conventional dosage form for the intramuscular injection of TECA, propylene glycol (PG)-based TECA solution, causes severe pain after intramuscular injection. To improve the solubility of TECA and reduce pain after injection, mixed micellar systems composed of 10% surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline, pH 7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from 0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85 from 0:10 to 4:6, followed by an abrupt decrease in size above the ratio of 6:4. Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the ratio of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the resultant droplet sizes were less than 2 microm. No significant changes were observed in the droplet sizes and asiaticoside contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remarkably lower than those of PG-based TECA solution and similar to that of saline solution, irrespective of dilution ratios. Most importantly, they markedly reduced the number of writhes compared with PG-based TECA solution after injection to mice. All of these results suggest that these three TECA micellar formulations prepared with Tween 20 and Tween 85 improved the solubility of TECA and reduced pain following injection, possibly due to the decrease in osmotic pressure. Thus, these micellar formulations composed of optimum ratios of Tween 20 and Tween 85 may have a potential as dosage forms for the intramuscular injection of a poorly water-soluble TECA.

Animals↗

Centella asiatica (L.) leaf extract treatment during the growth spurt period enhances hippocampal CA3 neuronal dendritic arborization in rats.

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.

Journal Article↗

A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects.

Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin (CCK) receptors. This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety. This double-blind, placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola (Centella asiatica) in healthy subjects. Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety. Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity, enhances elevated-plus maze performance, and attenuates the acoustic startle response (ASR). In this study, the authors evaluated the effects of Gotu Kola on the ASR in humans. Subjects were randomly assigned to receive either a single 12-g orally administered dose of Gotu Kola (N = 20) or placebo (N = 20). The results revealed that compared with placebo, Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment. Gotu Kola had no significant effect on self-rated mood, heart rate, or blood pressure. These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR. It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes.

Acoustic Stimulation↗

Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica.

The drug "Titrated Extract from Centella asiatica" (TECA), used for its stimulating properties on the healing of wounds, is a mixture of 3 terpenes extracted from a tropical plant: asiatic acid (30%, w/w), madecassic acid (30%, w/w) and asiaticoside (40%, w/w). The effects of TECA and its individual components were checked on human foreskin fibroblast monolayer cultures. TECA increased the collagen synthesis in a dose-dependent fashion whereas a simultaneous decrease in the specific activity of neosynthesized collagen was observed. Asiatic acid was found to be the only component responsible for collagen synthesis stimulation. TECA and all three terpenes increased the intracellular free proline pool. This effect was independent of the stimulation of collagen synthesis.

Cell Count↗