Centella Gel

Centella asiatica

Centella asiatica known as Gotu Kola is a medicinal plant that has been used in folk medicine for hundreds of years as well as in scientifically oriented medicine. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecassoside, asiatic and madecassic acids. Centella asiatica is effective in improving treatment of small wounds, hypertrophic wounds as well as burns, psoriasis and scleroderma. The mechanism of action involves promoting fibroblast proliferation and increasing the synthesis of collagen and intracellular fibronectin content and also improvement of the tensile strength of newly formed skin as well as inhibiting the inflammatory phase of hypertrophic scars and keloids. Research results indicate that it can be used in the treatment of photoaging skin, cellulite and striae (1)

Skin Cancer

Asiatic Acid can act as a natural chemoprotective agent against UVB-mediated injury in normal human dermal fibroblasts (NHDFs) through alteration in the expression of specific miRNAs. AA induces apoptosis in SK-MEL-2 human melanoma cells, and it also induces apoptosis through ROS generation, alteration of the Bax/BCL-2 ratio, and caspase-3 activation in SK-MEL-2 human melanoma cells. (1)

Park et al. suggested that role of AA may be a good candidature for the treatment for skin cancer. (2) They also reported that AA induces apoptosis in melanoma cells through increasing the levels of ROS. AA also showed a protective effect against OGD/R-injured PC12 cells, and the possible mechanisms were related to eliminating free radicals and inhibiting cell apoptosis.

Skin

Centella asiatica is effective in treatment of skin conditions, prevention of hypertrophic scar, Keloids and wrinkles. (3,4) The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecassoside, asiatic and madecassic acids. The action has been demonstrated both for the extracts as well as triterpene compounds in a large number of scientific reports involving in vitro and in vivo experiments. (5,6 ) The terpenoids (TTF) cause a significant increase in the percentage of collagen and cell layer fibronectin. The most beneficial effects are the stimulation of scar maturation by the production of type I collagen, decrease in the inflammatory reaction and myofibroblast production. (7) The triterpenoid components were also able to stimulate glycosaminoglycan, especially hyaluronic acid synthesis. Photo-aging - Centella asiatica has been used as an effective anti- photoaging agent, mainly due to enhancement of type I collagen, which amount in skin decreases with age. (8)

The mechanism of action involves promoting fibroblast proliferation and increasing the synthesis of collagen as well as acidic mucopolysaccharides, increasing intracellular fibronectin content and mitotic activity in the germ layer, significantly improving the tensile strength of newly formed skin as well as by inhibiting the inflammatory phase of hypertrophic scars and keloids. Centella asiatica is a common ingredient of cosmetics applied on photoaging skin also in cellulite and striae. (9)

In a study on Centella asiatica extract in cream for the prevention of scar development of the split- thickness skin graft (STSG). There were significant differences in pigmentation parameter of VSS and comparative total VSS scores between 4 and 12 weeks in Centella cream group. The effect of Centella cream on scar development of a STSG operation may be attainable in terms of better pigmentation. Centella cream may prove to be an alternative product for hypertrophic scar amelioration. The gel formulation provided significantly better healing outcome than the ointment and cream formulations. (10)

Venous insufficiency

One of primary effects of Centella asiatica (CA) was postulated to be on connective tissues by strengthening the weakened veins. (11) It was postulated that CA might assist in the maintenance of connective tissue. In the treatment of scleroderma, it might also assist in stabilising connective tissue growth, reducing its formation as it reportedly stimulated the formation of hyaluronidase and chondroitin sulfate, as well as exerted a balancing effect on the connective tissue. (12) CA was reported to act on the connective tissues of the vascular wall, being effective in hypertensive microangiopathy and venous insufficiency and decreasing capillary filtration rate by improving microcirculatory parameters. (13,14)

A single-blind, placebo-controlled, randomised study was performed on the effects of different doses of the total triterpenic fraction of Centella asiatica (TTFCA) in patients with venous hypertensive microangiopathy (VHM). VHM is a microcirculatory syndrome associated with chronic venous insufficiency and hypertension. This condition is characterised at the microcirculatory level by increased skin flow at rest and on standing an important decrease of venoarteriolar (or venivasomotor) response.

TTFCA has demonstrated and important activity on the microcirculatory alterations present in venous incompetence and hypertension. This compound acts at the metabolic level, since TTFCA has been shown to modulate collagen synthesis by cultured fibroblasts. Alterations in collagen metabolism have been documented in the vein wall of patients with venous hypertension. Moreover, TTFCA action on endothelial cells, shown both by in vitro studies and by in vivo normalisation of endotheliemia in patients with venous hypertension could be important for therapeutic purposes in venous diseases. Our study shows that the effects of TTFCA are highly significantly different from placebo effects on all microcirculatory parameters we have studied.

In conclusion, TTFCA is useful for the treatment of VHM. Furthermore, because of its action on the vein wall, TTFCA can prevent the progression of the disease. (15)

Varicose Veins

The effects were studied of the total triterpenic fraction of Centella asiatica on serum levels of the uronic acids and lysosomal enzymes involved in mucopolysaccharide metabolism (beta- glycuronidase, beta-N-acetylglucosaminidase, arylsulfatase) in patients with varicose veins.

During treatment with Centella asiatica extract (60 mg/day for three months), these levels fell progressively. At the end of treatment the serum uronic acid (231.8 +/- 51.5 micrograms/ml), beta- glycuronidase (1.2 +/- 0.05 microM/min/l), beta-N-acetylglucosaminidase (17.7 +/- 0.7 microM/min/l) and arysulfatase (0.042 +/- 0.003 microM/min/l) levels were highly significantly lower than the basal levels (p less than 0.01). The results of this trial provide an indirect confirmation of regulatory effects of the extract of Centella asiatica on metabolism in the connective tissue of the vascular wall. (16)

Centella asiatica extract containing 70% triterpenic acids (asiatic acid, madecassic acid, asiatoside) is impressive in treating cellulite, venous insufficiency of lower limbs, and varicose veins. It exerts normalising action on metabolism of connective tissue. It enhances tissue integrity by stimulating glycosaminoglycan (GAG) synthesis without promoting excessive collagen synthesis or cell growth. GAGs are major components of amorphous intercellular matrix (ground substance) in which collagen fibers are embedded. Net effect is normal tissue. Effect in venous insufficiency and varicose veins is to enhance connective tissue structure, reducing sclerosis and improving blood flow through affected limbs. (17,18)

Cellulite

Extracts of Centella asiatica have demostrated good results in the treatment of cellulite in a number of clinical studies. Bourguignon observed the action of the extract on several types of cellulite in 65 patients who had undergone other therapies without success. Over a period of three months, very good results were produced in 58%of the patients and satisfactory results in 20%. Other investigations have shown a similar success rate (approximately 80%).

The effect of centella in the treatment of cellulite appears to be related to its ability to enhance connective tissue structure and reduce sclerosis by acting directly on fibroblasts.

References

1 Bylka W, Znajdek-Awiżeń P, Studzińska-Sroka E, Brzezińska M. Centella asiatica in cosmetology. Postepy Dermatol Alergol. 2013;30(1):46-49. doi:10.5114/pdia.2013.33378

2 Yasurin P, et al. Review: The Bioavailability Activity of Centella asiatica. KMUTNB Int J Appl Sci Technol, Vol. 9, No. 1, pp. 1– 9, 2016

3 Park B, Bosire K, Lee E, et al. Asiatic Acid Induces Apoptosis in SK-MEL-2 Human Melanoma Cells. Cancer Lett. 2005, 218, 81–90.

4 Pittella F, Dutra RC, Junior DD, Lopes MT, Barbosa NR. Antioxidant and Cytotoxic Activities of Centella asiatica (L) Urb. Int J Mol Sci. 2009 Sep; 10(9): 3713–3721. doi: 10.3390/ijms10093713

5 Lu L, Ying K, Wei S, et al. Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysis. Br J Dermatol 2004; 151: 571-8.

6 Lu L, Ying K, Wei S, et al. Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human der- mal fibroblasts. Intern J Dermatol 2004; 43: 801-7.

7 WHO Monographs on selected medicinal plants. Vol. 1. World Health Organization, Geneva 1999.

8 Bosse JP, Papillon J, Frenette G, et al. Clinical study of a new antikeloid agent. Ann Plast Surg 1979; 3: 13-21.

9 Widgerow AD, Chait LA, Stals R, Stals PJ. New innovations in scar management. Aesth Plast Surg 2000; 24: 227-34.

10 Bylka W, Znajdek-Awiżeń P, Studzińska-Sroka E, Brzezińska M. Centella asiatica in cosmetology. Postepy Dermatol Alergol. 2013;30(1):46‐49. doi:10.5114/pdia.2013.33378

11 Jenwitheesuk K, Rojsanga P, Chowchuen B, Surakunprapha P. A Prospective Randomized, Controlled, Double-Blind Trial of the Efficacy Using Centella Cream for Scar Improvement. Evid Based Complement Alternat Med. 2018;2018:9525624. Published 2018 Sep 17. doi:10.1155/2018/9525624

12 Gray NE, Zweig JA, Caruso M, et al. Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice. Brain Behav. 2018;8(7):e01024. doi:10.1002/brb3.1024

13 Allegra C. Comparative Capillaroscopic study of certain bioflavonoids and total triterpenic fractions of Centella asiatica in venous insufficiency. Clin Ther 1981;99:507-13.

14 Darnis F, Orcel L, de Saint-Maur PP, Mamou P. Use of a titrated extract of Centella asiatica in chronic hepatic disorders. Sem Hop 1979;55:1749-50.

15 Cesarone MR, Laurora G, De Sanctis MT, Belcaro G. Activity of Centella asiatica in venous insufficiency. Minerva Cardioangiol 1992;40:137-43.

16 Gohil KJ, Patel JA, Gajjar AK. Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all. Indian J Pharm Sci. 2010;72(5):546‐556. doi:10.4103/0250-474X.78519

17 Incandela L, Belcaro G, De Sanctis MT, et al. Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model. Angiology. 2001;52 Suppl 2:S61‐S67.

18 Arpaia MR, Ferrone R, Amitrano M, Nappo C, Leonardo G, del Guercio R. Effects of Centella asiatica extract on mucopolysaccharide metabolism in subjects with varicose veins. Int J Clin Pharmacol Res. 1990;10(4):229‐233.