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Effects of Centella asiatica extract on dermal wound healing in rats.

Effects of oral and topical administration of an alcoholic extract of C. asiatica on rat dermal wound healing was studied. The extract increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, protein and collagen content of granulation tissues. Quicker and better maturation and crosslinking of collagen was observed in the extract-treated rats, as indicated by the high stability of acid-soluble collagen and increase in aldehyde content and tensile strength. The extract treated wounds were found to epithelialise faster and the rate of wound contraction was higher, as compared to control wounds. The results show that C. asiatica produced different actions on the various phases of wound repair.

Animals↗

Evaluation of topical formulations of aqueous extract of Centella asiatica on open wounds in rats.

Formulations (ointment, cream and gel) of aqueous extract of C. asiatica, when applied topically, thrice daily for 24 days on the open wounds in rats increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in collagen content and tensile strength. The treated wounds epithelialised faster and the rate of wound contraction was higher as compared to control wounds. The process of healing was better with gel formulation when compared to other two formulations.

Administration, Topical↗

Iron absorption from a traditional Sri Lankan weaning food and the enhancing effect of ascorbic acid in adult male volunteers.

OBJECTIVE: To study absorption of iron from Centella gruel and the enhancing effect of ascorbic acid in young adult males. DESIGN: An in vivo absorption study. SETTING: Faculty of Medicine, Galle. METHODS: The percentage of iron absorbed from the Centella gruel was measured using a double isotope technique with 55Fe and 59Fe on 10 healthy male volunteers. OUTCOME MEASURE: Percentage of iron absorption from the gruel with and without ascorbic acid. RESULTS: The mean iron absorption from each meal of Centella gruel was 2.2% (SEM 0.8). This increased to 5% (SEM 1.6) by addition of 50 mg ascorbic acid. When ingested with ascorbic acid, the bioavailable nutrient density (BND) of the weaning food was increased from 0.23 to 0.53 mg iron/1,000 kcal. To satisfy the daily physiological requirements of iron in infants and toddlers, it was calculated that apart from ascorbic acid supplementation, the total iron content also needs to be increased from 2.05 mg to 4.0 mg/meal. CONCLUSION: Centella gruel cannot provide the amount of iron to meet the BND for iron required by infants and toddlers, unless supplemented with an enhancer of iron absorption such as ascorbic acid and its total iron content is increased.

Adult↗

New innovations in scar management.

As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. With this in mind, a scar management program has been adopted based on the modalities of wound support, hydration, and hastened maturity, all factors gleaned from scientific evidence published over the past 25 years. Tension on a scar in one axis will result in a stretched scar, probably initiated by neutrophils and their neutral proteases [18,26]. Tension on a scar from many directions or intermittently will result in a hypertrophic scar, possibly initiated by lymphocytes but definitely related to a prolongation of the inflammatory process, with increased fibroblast activity and overabundant extracellular matrix secretion [24,26]. The common initiating factor is the tension on the scar, and the critical element needed to counteract this tension is scar support. Clinical experience has shown us that the most reliable way to support a scar is by using microporous tape. Hydration is a second beneficial influence on scar control and is the basis of the use of silicone sheeting and gel [7,29,36]. Alpha Centella cream has two main components. The first is an extract from the plant Bulbine frutescens. This increases hydration under the tape by leaving a layer of fatty vesicles of glycoprotein on the skin surface. This also has antibacterial properties. The second component is the principal terpenoids extracted from the Centella asiatica plant. These include asiatic acid, madecassic acid, and asiaticoside. Centella asiatica has been documented to aid wound healing in a large number of scientific reports [5,12,21,22,33,34,40]. The most beneficial effect appears to be the stimulation of maturation of the scar by the production of type I collagen [4,19] and the resulting decrease in the inflammatory reaction and myofibroblast production. Thus these components have been incorporated into the formulation of a scar management program. This publication reviews much of the available literature relating to scar management and describes the formulation and use of a scar management program based on this information.

Anti-Infective Agents↗

Phlebotonics for venous insufficiency.

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.

4-Aminobenzoic Acid↗

Precision improvement for the analysis of flavonoids in selected Thai plants by capillary zone electrophoresis.

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%).

Centella↗

Advanced formulation and pharmacological activity of hydrogel of the titrated extract of C. asiatica.

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.

Animals↗

Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells.

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.

Apoptosis↗

Thai medicinal plants modulate nitric oxide and tumor necrosis factor-alpha in J774.2 mouse macrophages.

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.

Acanthaceae↗