10. Molecules. 2011 Jan 28;16(2):1310-22. Triterpene composition and bioactivities of Centella asiatica. Hashim P, Sidek H, Helan MH, Sabery A, Palanisamy UD, Ilham M. Halal Products Research Institute, Universiti Putra Malaysia, Putra Infoport, 43400 UPM Serdang, Selangor, Malaysia. puziahashim@hotmail.com

 

Leaves of Centella asiatica (Centella) were analysed for their triterpene composition and bioactivity such as collagen enhancement, antioxidant, anticellulite and UV protection capacity properties. Triterpenes of Centella were measured using HPLC-PAD on an Excil ODS 5 mm (C18) column for the simultaneous determination of asiatic acid, madecassic acid, asiaticoside and madecassoside. Centella was found to contain significant amounts of madecassoside (3.10 ± 4.58 mg/mL) and asiaticoside (1.97 ± 2.65 mg/mL), but was low in asiatic and madecassic acid. The highest collagen synthesis was found at 50 mg/mL of Centella  extracts. The antioxidant activity of Centella (84%) was compared to grape seed extract (83%) and Vitamin C (88%). Its lipolytic activity was observed by the release of glycerol (115.9 µmol/L) at 0.02% concentration. Centella extracts exhibited similar UV protection effect to OMC at 10% concentration. In view of these results, the potential application of Centella in food and pharmaceutical industries is now widely open. PMID: 21278681  [PubMed - indexed for MEDLINE]

 

9. Exp Dermatol. 2008 Nov;17(11):946-52. Epub 2008 May 21.  Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin.  Haftek M, Mac-Mary S, Le Bitoux MA, Creidi P, Seité S, Rougier A, Humbert P.  Université Lyon 1, EA4169 Laboratory for Dermatological Research, Edouard Herriot Hospital, Lyon, France. haftek@univ-lyon1.fr 

 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.  PMID: 18503551  [PubMed - indexed for MEDLINE]  

8. Eur J Pharmacol. 2008 Apr 28;584(2-3):415-23. Epub 2008 Feb 21.  Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism.  Kimura Y, Sumiyoshi M, Samukawa K, Satake N, Sakanaka M.  Division of Biochemical Pharmacology, Department of Basic Medical Research, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, 791-0295, Japan. yokim@m.ehime-u.ac.jp 

 Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) C. asiataica herb extracts to enhance wound repair. Lower doses at which burn wound repair is enhanced by such topical applications have not been established yet. We found that the application of asiaticoside at low doses of 10(-8) to 10(-12)% (w/w) facilitated burn wound repair. To clarify the accelerating mechanisms of asiaticoside on burn wound repair, we examined the effects of asiaticoside on the levels of various cytokines produced at the site of the burn wound. The topical application of a low dose (10 pg, 1 ng, or 100 ng/wound area) of asiaticoside increased monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and interleukin (IL)-1beta levels in burn wound exudates. Asiaticoside (10 pg to 100 ng/ml) enhanced MCP-1 production in HaCaT cells, but it had no direct effect on VEGF production. Furthermore, asiaticoside (10 pg to 100 ng/ml) increased the IL-1beta production  in THP-1 macrophages with MCP-1, but it had no effect on IL-1beta production without MCP-1 or with lipopolysaccharide (LPS). These findings suggest that the enhancement of burn wound healing by asiaticoside might be due to the promotion of angiogenesis during skin wound repair as a result of the stimulation of VEGF production caused by the increase in MCP-1 expression in keratinocytes and the increase in IL-1beta expression in macrophages induced cooperatively by asiaticoside plus MCP-1.  PMID: 18353310  [PubMed - indexed for MEDLINE] 

7. 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] 

6. Rev Enferm. 2005 May;28(5):67-70.  [Topical chemotherapy for the treatment of burns].  [Article in Spanish]  Salas Campos L, Fernándes Mansilla M, Martínez 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.  PMID: 15981974  [PubMed - indexed for MEDLINE] 

5. 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.  PMID: 15918527  [PubMed - indexed for MEDLINE] 

4. Phytomedicine. 2001 May;8(3):230-5.  In vitro keratinocyte antiproliferant effect of Centella asiatica extract and triterpenoid saponins.  Sampson JH, Raman A, Karlsen G, Navsaria H, Leigh IM.  The Centre for Bioactivity Screening of Natural Products, King's College London,  UK. 

 Psoriasis is a hyperproliferative skin disorder estimated to be present in 1-3% of most populations. Conventional therapy using corticosteroids, Vitamin D analogs and cytotoxic agents eg psoralens is associated with low success rate and many side effects. Traditional plant remedies may provide leads for new treatments. A rapid-throughput, in vitro bioassay has been utilised to examine plants for inhibitory effects on the growth of SVK-14 keratinocytes. Centella asiatica, a reputed anti-psoriatic herb, has been compared against the psoralen-containing seeds of Psoralea corylifolia and the synthetic anti-psoriatic agent dithranol (anthralin). Aqueous extracts of Psoralea corylifolia and Centella asiatica inhibited keratinocyte replication with IC50 values of 18.4 +/- 0.6 microg/ml and 209.9 +/- 9.8 mg/ml respectively prior to treatment with polyvinylpolypyrrolidone (PVPP) and 36.3 +/- 3.3 mg/ml and 238.0 +/- 2.5 mg/ml respectively after PVPP treatment of the extracts. The effect produced by C. asiatica is thus unlikely to be due to phenolic compounds. It may, however, be due to its two constituent triterpenoid glycosides madecassoside and  asiaticoside which had IC50 values of 8.6 +/- 0.6 microM respectively. These values were comparable to their concentrations in the crude extract and to the IC50 of dithranol (5.1 +/- 0.4 microM). These results suggest that the potential  use of C. asiatica extracts as a topical anti-psoriatic agent is worthy of further investigation.  PMID: 11417919  [PubMed - indexed for MEDLINE] 

3. Int J Cosmet Sci. 2000 Jun;22(3):201-6.  Topical formulation of a new plant extract complex with refirming properties. Clinical and non-invasive evaluation in a double-blind trial.  Martelli L, Berardesca E, Martelli M.  Department of Dermatology, IRCCS Policlinico S. Matteo, Università di Pavia, 27100 Pavia, Italy. 

 We tested an OTC formulation versus placebo in a double-blind trial to evaluate its ability to improve elasticity and firmness of the skin. The clinical non-invasive evaluation in 20 volunteers shows: 1. No adverse reactions such as itching or irritation 2. Efficacy and cosmetic acceptibility of the test cream 3. An increase in electrical capacitance (moisture content) even though without statistical significance. This result is not surprising because the patients had  healthy skin and were relatively young (aged 20-25) 4. A very significant improvement in the biomechanical properties (extensibility and firmness) of the skin. This increase was statistically significant (P < 0.02) The main components  of the cream (boswellic acids, Sylibin and Centella asiatica extracts) were formulated as complexes with lyso-phospholipids and soya bean non-saponifiable lipids.  PMID: 18503475  [PubMed - in process] 

2. J Ethnopharmacol. 1999 Apr;65(1):1-11.  In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica.  Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN.  Pharmacology Division, Central Drug Research Institute, Lucknow, India. gshukla@zoo.uvm.edu1 

 The activity of asiaticoside, isolated from Centella asiatica, has been studied in normal as well as delayed-type wound healing. In guinea pig punch wounds topical applications of 0.2% solution of asiaticoside produced 56% increase in hydroxyproline, 57% increase in tensile strength, increased collagen content and  better epithelisation. In streptozotocin diabetic rats, where healing is delayed, topical application of 0.4% solution of asiaticoside over punch wounds increased  hydroxyproline content, tensile strength, collagen content and epithelisation thereby facilitating the healing. Asiaticoside was active by the oral route also  at 1 mg/kg dose in the guinea pig punch wound model. It promoted angiogenesis in  the chick chorioallantoic membrane model at 40 microg/disk concentration. These results indicate that asiaticoside exhibits significant wound healing activity in normal as well as delayed healing models and is the main active constituent of Centella asiatica.  PMID: 10350364  [PubMed - indexed for MEDLINE] 

1. Phytother Res. 1999 Feb;13(1):50-4.  Asiaticoside-induced elevation of antioxidant levels in healing wounds.  Shukla A, Rasik AM, Dhawan BN.  Pharmacology Department, Central Drug Research Institute, Lucknow, India. gshukla@zoo.uvm.edu 

 Asiaticoside derived from the plant Centella asiatica is known to possess good wound healing activity. Enhanced healing activity has been attributed to increased collagen formation and angiogenesis. Since antioxidants have been reported to play a significant role in the wound healing process we studied the effect of asiaticoside on the levels of certain antioxidants in the wound so as to explore the possible involvement of such a mechanism in the asiaticoside induced wound healing. Asiaticoside application (0.2%, topical) twice daily for 7 days to excision-type cutaneous wounds in rats led to increased enzymatic and non-enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%), glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly formed tissues. It also resulted in a several fold decrease in lipid peroxide levels (69%) as measured in terms of thiobarbituric acid reactive substance. However, continued application for 14 days showed no significant difference in these antioxidants compared with their values in vehicle treated wound tissue. It appears from the present study that asiaticosides enhanced induction of antioxidant levels at an initial stage of healing which may be an important contributory factor in the healing properties of this substance.  PMID: 10189951  [PubMed - indexed for MEDLINE] 

Advanced skin care research on Gotu Kola (centella asiatica) has shown that it is an effective ingredient for: collagen production, to reduce fine lines and wrinkles, reducing stretch marks care, in scar care, and for wound healing support.

Centella Asiatica research