Gotu kola (centella asiatica), skin aging and cellulite: all 128 research papers in one place
Centella asiatica / gotu kola skin benefits: what the research says
All the research on the anti-cellulite, anti-ageing, skin healing and anti-stetch mark action of the four centella asiatica triterpenes
According to the research below, Gotu kola acts on all seven aspects of cellulite
Four triterpenes are responsible for Centella asiatica’s beneficial action on skin: asiatic acid, asiaticoside, madecassic acid, madecassoside
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All the research on the anti-cellulite, anti-ageing, skin healing and anti-stetch mark action of the four centella asiatica triterpenes
Gotu kola (Centella asiatica) is probably THE most important anti-cellulite, anti-ageing and skin healing herb, as it exerts a multifaceted action against all seven aspects of cellulite.
In the last few months we have made a huge effort and collated and summarised all 128 research papers on centella asiatica / gotu kola’s action relative to cellulite and skin health.
According to the research below, Gotu kola acts on all seven aspects of cellulite:
Boost circulation / reduce water retention
Fight free radical damage
Boost collagen/elastin production and thereby skin firmness and elasticity
Fight glycation
Stimulate lipolysis
Inhibit inflammation
Fight fibrosis
Four triterpenes are responsible for Centella asiatica’s beneficial action on skin:
Asiatic acid
Madecassic acid
Asiaticoside
Madecassoside
All the research on these four molecules is presented and summarised below, for your convenience.
You’re welcome :)
All 128 relevant research papers on centella asiatica’s action on skin aging and cellulite
This list includes all the currently available research and comprises a concise summary and research paper title.
Asiatic acid fights inflammation by inhibiting the notch signaling pathway. The Notch signaling pathway plays a critical role in inflammation, and its inhibition offers an avenue to treat inflammatory diseases, such as sepsis. Asiatic acid upregulates the Notch receptor (Notch3) and delta-like ligand (DLL4), inhibits Notch3 binding to the IL-6 promoter, regulates of mitochondrial function, decreases levels of interleukin-1β (IL-1β), IL-6; reduces liver, lung and kidney damage; and improves survival of mice with sepsis; and reduces lipopolysaccharide-stimulated expression of pro-inflammatory mediators, including nitric oxide, IL-1β and IL-6 in RAW 264.7 macrophages. (Source: Asiatic acid attenuates lipopolysaccharide-induced injury by suppressing activation of the Notch signaling pathway).
Repeated oral intake of centella asiatica results in higher levels of asiatic acid and madecassic acid (additive effect). As opposed to animal studies, where asiaticoside (AS) and madecassoside (MS) levels increase, in humans asiatic acid (AA) and madecassic acid (MA) increase in the bloodstream, thereby suggesting of metabolism of the glycoside (AS, MS) to the aglycone form (AA, MA). Levels in the bloodstream followed a dose-response relationship. Safety and tolerability evaluation illustrated that single and multiple doses were well tolerated and none of the volunteers discontinued their participation due to adverse effects during the study. (Source: Safety and Pharmacokinetics of Standardized Extract of Centella asiatica (ECa 233) Capsules in Healthy Thai Volunteers: A Phase 1 Clinical Study).
Six weeks of gotu kola supplementation improves stretch marks better than a popular commercial stretch mark cream. A centella asiatica supplement, standardised to 140mg active ingredients (asiatic acid, madecassic acid, asiaticoside and madecassoside) improved multiple markers or stretch marks in comparison to a stretch mark cream (which makes sense, as most such creams are highly diluted): skin thickness at the edge and in the middle of stretch marks, collagen content, skin perfusion (circulation), skin temperature, elasticity, overall appearance and number of stretch marks. (Source: Postpartum stretchmarks: repairing activity of an oral Centella asiatica supplementation).
Asiatic acid exerts a strong action on wound healing, blood vessel protection and against inflammation. Resveratrol and curcumin offer similar benefits, with some differences, implying a synergistic effect with the use of all three together (Source: Pharmacological Review on Asiatic Acid and Its Derivatives: A Potential Compound).
The combination of red vine leaf and gotu kola extracts protects blood vessels from oxidative damage more than the separate actives alone. Specifically, vitis vinifera and centella asiatica significantly reversed reactive oxygen species, nitric oxide and endothelial hyperpermeability triggered by H2O2. (Source: Combined Extract of Vitis vinifera L. and Centella asiatica Synergistically Attenuates Oxidative Damage Induced by Hydrogen Peroxide in Human Umbilical Vein Endothelial Cells).
Asiaticoside from Gotu Kola reverses senescence and prevents oxidative damage and reverses all markers of oxidation on endothelial cells. In a study of human umbilical vein endothelial cells (HUVECs) asiaticoside reversed all markers of oxidative stress and restored superoxide dismutase, nitric oxide and glutathione peroxidase after oxidative insult. Plus asiaticoside significantly reversed senescence-associated beta-galactosidase (SA-β-gal) activity. (Source: Asiaticoside Prevents Oxidative Stress and Apoptosis in Endothelial Cells by Activating ROS-dependent p53/Bcl-2/Caspase-3 Signaling Pathway).
Centella asiatica extract reduces erythema and accelerates healing after laser treatment for acne. In a 30-subject, double blind, randomised, placebo-controlled trial, topical application of a gel containing 0.05% centella asiatica standardised extract was found to improve erythema (skin reddening), skin crusting and general wound healing after acne scar removal procedure with ablative 2940 nm Er:YAG laser. (Source: The Effects of a Standardized Extract of Centella asiatica on Postlaser Resurfacing Wound Healing on the Face: A Split-Face, Double-Blind, Randomized, Placebo-Controlled Trial).
Steaming boosts the anti-inflammatory activity of centella asiatica; frying diminishes it. Specifically steaming of centella asiatica leaves boosts its lipoxygenase inhibition by 400%, as well as its hemolysis inhibition. Proteinase inhibition and protein denaturation inhibition, are also boosted by steaming, but to a lesser extent. Boiling has a less pronounced effect, while frying actually diminishes the anti-inflammatory activity of centella asiatica and other herbs. In general, the study authors stated that “steaming and boiling in contrast to frying protect the health-promoting properties of the leafy vegetables”. (Source: Influence of Boiling, Steaming and Frying of Selected Leafy Vegetables on the In Vitro Anti-inflammation Associated Biological Activities).
Centella asiatica facilitates the regular healing of surgical scars in subjects at high risk of keloids. The post-surgical use of centella asiatica extract supplements, standardised to 35% triterpenes, leads to improved scar tissue regularity and homogeneity after surgery and thereby helps prevent the creation of keloid scars on surgical wounds. (Source: Centella asiatica (Centellicum®) facilitates the regular healing of surgical scars in subjects at high risk of keloids).
Centella asiatica triterpene liposome extract inhibits the inflammatory activity of NF-kb and protects from atopic dermatitis. Topical application of 0.2% and 0.4% of centella asiatica triterpene liposome inhibits the infiltration of inflammatory cells and the expression of iNOS and COX-2, activity of NF-κB, and release of TNF-α, IL-1β, and IgE in a mouse model of atopic dermatitis. Furthermore, the same extract potently inhibits LPS-induced NO production as well as iNOS and COX-2 expression in macrophages and inhibits LPS-induced DNA binding activities of NF-κB. Histological analysis showed that the extract inhibits hyperkeratosis, proliferation of mast cells, and infiltration of inflammatory cells. (Source: Anti-inflammatory effect of Centella asiatica phytosome in a mouse model of phthalic anhydride-induced atopic dermatitis).
Review on the antioxidant and anti-inflammatory properties of asiatic acid. According to the review authors “asiatic acid possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases”. (Source: Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise).
Oral centella asiatica supplementation repairs post-pregnancy stretch marks better than a commercial anti-stretch mark cream. The daily oral consumption of 225mg of centella asiatica triterpenes for 6 weeks improves skin collagen, elasticity, microcirculation and temperature, as well as stretch mark skin thickness in comparison to both the Clarins stretch mark cream or a plain hydrating cream. Subjective evaluation of stretch mark visibility improved and number of visible stretch marks decreased. (Source: Postpartum stretch marks: repairing activity of an oral Centella asiatica supplementation (Centellicum®)).
Centella asiatica cream inhibits scar hyperpigmentation and overall scarring. Centella asiatica extract in cream improves scar development after a split-thickness skin graft (STSG), in relation to placebo applied to the donor site at least 2 weeks after epithelialization was completed. According to the study authors “there were significant differences in pigmentation parameter of the Vancouver Scar Scale and comparative total Vancouver Scar Scale scores between 4 and 12 weeks in the centella cream group” and that the “centella cream may prove to be an alternative product for hypertrophic scar amelioration”. (A Prospective Randomized, Controlled, Double-Blind Trial of the Efficacy Using Centella Cream for Scar Improvement).
Madecassoside inhibits acne-induced oxidative damage and inflammation & boosts skin hydration in an in-vitro model. According to this study, madecassoside significantly inhibits the pro-inflammatory cytokine IL-1b, TLR2 and nuclear translocation of NF-kB in Propionibacterium acne stimulated THP-1 human monocytic cells. In addition, madecassoside enhances skin hydration through increasing the key moisturizing contributors of aquaporin-3, loricrin and involucrin in HaCaT keratinocytes, as well as hyaluronan (HA) secretion in human dermal fibroblasts. The upregulation of HA synthases (HAS1, HAS2, HAS3) and inhibition to ROS formation accounted for the increment of HA content. (Source: Propionibacterium acnes related anti-inflammation and skin hydration activities of madecassoside, a pentacyclic triterpene saponin from Centella asiatica).
Topical multi-ingredient cream, including centella asiatica, reduces thigh fat in sedentary females. This seven subject, double-blind, placebo-controlled, within-group study showed that 28-day, twice daily topical application of an aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola , in combination with a hypocaloric diet and walking 150 minutes per week leads to reduced thigh circumference (1.2 vs 0.8 cm), skinfold thickness (3.7 vs 2.0 mm) and fat mass (100.0 g vs 57.3 g), in relation to placebo. (Source: Effects of a topical lotion containing aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola on thigh circumference, skinfold thickness, and fat mass in sedentary females).
Asiaticoside/hyaluronic acid niosomes penetrate into the dermis. Asiaticoside / hyaluronic acid niosomes penetrate through the stratum corneum and dermis in a larger amount than from asiaticoside niosomes or plain asiaticoside solution (Source: Dermal targeting of Centella asiatica extract using hyaluronic acid surface modified niosomes).
Titrated Extract of Centella asiatica and Astaxanthin inhibits inflammation in Atopic Dermatitis. Application of ointment 0.5% titrated extract of centella asiatica (TECA) combined with 0.5% astaxanthin (AST) 3 times a week for for 4 weeks produce inflammation inhibition in an atopic dermatitis model more than TECA or AST alone (the ointment inhibited the expression of iNOS and COX-2; NF-κB activity; and the release of TNF-α, IL-6 and IgE). (Source: Combination Effect of Titrated Extract of Centella asiatica and Astaxanthin in a Mouse Model of Phthalic Anhydride-Induced Atopic Dermatitis).
Asiaticoside enhances wound healing by 40%. Asiaticoside hydrogel formulation enhances wound healing 15% faster than a commercial cream and > 40% faster than untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected. (Source: Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits).
Centella asiatica extract increases telomerase activity by 880%, thereby preserving telomere length and consequently preventing cellular aging. Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging‑related diseases. Environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti‑aging modulator that can play a role in the treatment of aging‑related diseases. Centella asiatica extract increases telomerase activity by 880% compared to the untreated cells (oleanolic acid also increases it by 590%) in human peripheral blood mononuclear cells (PBMCs). (Source: Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives.).
Centella asiatica Extract inhibits atopic dermatitis inflammation. Treatment with Centella asiatica extract inhibits the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory HaCaT cells, stimulated by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Furthermore, oral and topical administration also inhibits allergic inflammation (TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9) associated with atopic dermatitis. (Source: Inhibitory Effect of Centella asiatica Extract on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice).
Asiaticoside induces elevation of antioxidant levels in new healing wounds. Topical application of 0.2% asiaticoside twice daily for 7 days on wounds leads 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%). 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. (Source: Asiaticoside-induced elevation of antioxidant levels in healing wounds).
Nano-doses of of asiaticoside boosts burn wound repair via VEGF-mediated angiogenesis. Some reports published from 1967 to 1999 describe the use of ointments containing high doses (0.1 to 0.2%, w/w) Centella asiatica herb extracts to enhance wound repair. In this study it was found that the application of asiaticoside at miniscule doses of 0.00000001% and 0.000000000001% (w/w) facilitated burn wound repair. According to this one study, the topical application of such low doses of asiaticoside increased monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and interleukin (IL)-1beta levels in burn wound exudates. 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. (Source: Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism).
Asiaticoside enhances skin wound healing. In conclusion, recent findings suggest that of C. asiatica extract (MF) possess wound healing properties. A standardised 2.4% methanol asiaticoside extract boosts fibroblast and keratinocyte cell migration and enhances the proliferative and remodeling process of wound healing. (Source: In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica).
Asiatic acid, madecassic acid and asiaticoside stimulate collagen I synthesis equally. Asiatic acid, madecassic acid, and asiaticoside, terpenoids with an ursane skeleton, were tested separately and in combination on skin human fibroblast collagen I synthesis in vitro. In the absence of ascorbic acid, the mixture as well as each individual component stimulated collagen I synthesis to a similar extent. In the presence of ascorbic acid, the level of collagen I secretion was higher for each individual component and for the mixture. A comparison of asiaticoside and asiatic acid shows that the sugar moiety of the molecule does not seem to be necessary for this biological activity. (Source: Influence of asiatic acid, madecassic acid, and asiaticoside on human collagen I synthesis).
Asiaticoside inhibits scarring by markedly inhibiting TGF-Β1 and enhancing the expression of inhibitory Smad7. Asiaticoside inhibits scarring by markedly inhibiting tgf-β1 and by enhancing the expression of inhibitory Smad7, while it has no effect on the expression of Smad2 (Source: Effects of asiaticoside on the expression of Smad protein by normal skin fibroblasts and hypertrophic scar fibroblasts).
Asiaticoside reduces periocular wrinkles. In this placebo controlled study, twice a day application of an asiaticoside cream for 12 weeks on the area around the eye led to: significant improvement in 65% of the volunteers (three of them showed 100% (disappearance of the crow's feet), 75% and 79% improvement), while 22% of the volunteers experienced no improvement. (Source: Evaluation of the effects of a preparation containing asiaticoside on periocular wrinkles of human volunteers).
Centella asiatica extract improves hand flexibility and signs and symptoms of Dupuytren palmar fibromatosis by collagen remodulation. Oral daily intake of 150 mg of centella triterpenes for 8 weeks in Dupuytren palmar fibromatosis patients improved signs and symptoms like pain, mobility, thickness and ultrasound echogenicity, particularly ultrasound echogenicity at elastosonography. Furthermore, hand grip improved by 15% (as opposed to 6% on the placebo group). After 8 weeks diclofenac had been used as a rescue medication by 50% of the controls and only 14% of 14 subjects on supplementation. Supplementation with centella asiatica appeared to improve signs and symptoms and hand flexibility, possibly by collagen remodulation. The supplement made the palmar aponeurosis softer, more elastic (less echogenic) and mobile, with a better function in only 8 weeks. Oxidative stress was significantly reduced with the supplement, with non-significant variations in controls. “The use of Centellicum® in the early phases of PFM may avoid a full scarring/keloidal evolution of palmar fibrosis and palmar retraction”. (Source: Effects of collagen remodulation with Centella asiatica (Centellicum®) in Dupuytren palmar fibromatosis: a pilot supplement study).
An 0.1% madecassoside and 5% vitamin C cream results in a significant improvement of the clinical score for deep and superficial wrinkles, suppleness, firmness, roughness and skin hydration and skin elasticity, repairing the elastic fibre network in the papillary dermis, after six months of treatment. The study authors state that their "results revealed a functional and structural remodelling of chronically sun-damaged skin". Given the extremely low amount of madecassoside acid in the cream (for reasons of cost-cutting, as madecassoside is 10x more expensive then vitamin C), even more impressive results should be expected with a more significant 1% madecassoside concentration. (Source: Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin).
Both asiaticoside and madecassoside stimulate fibroblast collagen secretion by 30% in 48 hours in culture, while only madecassoside is able to significantly increase collagen III secretion (Source: Comparative activity of asiaticoside and madecassoside on type I and III collagen synthesis by cultured human).
Asiaticoside reduces crow's feet (periorbital wrinkles) in double blind, placebo controlled study. Application of an asiaticoside cream twice a day for 12 weeks improved periorbital wrinkles on 65% of volunteers, with 12% experiencing complete wrinkle elimination and 23% not having a significant improvement. With the addition of the other three triterpenes and an increase in concentration, even more impressive results should be expected. (Source: Evaluation of the effects of a preparation containing asiaticoside on periocular wrinkles of human volunteers).
Centella overcomes cortisone's wound-healing suppression and significantly promotes wound healing. Extract-treated wounds were found to epithelise faster, the rate of wound contraction significantly increases and wet and dry granulation tissue weights, granulation tissue breaking strength, and hydroxyproline content in a dead space wound model also increase. In summary, the extract of the centella asiatica leaf extract has the effect of attenuating the known effects of dexamethasone healing in all wound models. (Source: Effect of Centella asiatica L (Umbelliferae) on normal and dexamethasone-suppressed wound healing in Wistar Albino rats).
Centella asiatica accelerates wound healing and hyaluronic acid / collagen synthesis. Titrated extract of centella asiatica (TECA) increases dry weight, DNA, total protein, collagen, glycosaminoglycans and uronic acid in treated wounds, as well as levels of hydroxyproline, showing an increased remodeling of the collagen matrix in the wound. Asiatic acid and asiaticoside was found to be the most active of the 3 triterpenes, with asiaticoside exerting a preferential stimulation of collagen synthesis, at low doses only. (Source: Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds).
Centella asiatica acts on multiple phases of wound repair. Centella asiatica extract increases 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 is observed in extract-treated skin, as indicated by the high stability of acid-soluble collagen and increase in aldehyde content and tensile strength. The extract treated wounds is found to epithelialise faster and the rate of wound contraction is higher, as compared to control wounds. (Source: Effects of Centella asiatica extract on dermal wound healing in rats).
Gotu kola extract protects skin cells from UV-B radiation. Specifically TECA treatment decreases UVB toxicity and increases keratinocyte viability by upregulating 46 genes and downregulating 26 genes functionally related to the inhibition of apoptosis and cell proliferation (Source: Centella asiatica protects against UVB-induced HaCaT keratinocyte damage through microRNA expression changes).
Centella may help against psoriasis, a hyperproliferative skin disorder, by inhibiting excessive keratinocyte replication, mainly via the action of its two constituent triterpenoid glycosides, madecassoside and asiaticoside (Source: In vitro keratinocyte antiproliferant effect of Centella asiatica extract and triterpenoid saponins).
Asiaticoside increases levels of collagen type I, while at the same time avoiding fibrosis. Specifically, asiaticoside induces collagen synthesis via its multipronged involvement in Smad signaling via a TGFbeta-independent pathway. This allows asiaticoside to boost collagen I synthesis without the fibrotic effects seen in collagen I synthesis via the TGFbeta pathway. (Source: Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling).
Centella may reduce hair loss by increasing the size and hair growth capacity of hair follicle dermal papillae, and by boosting the expression of the hair growth-related signature genes in those cells. (Source: Titrated extract of Centella asiatica increases hair inductive property through inhibition of STAT signalling pathway in three-dimensional spheroid cultured human dermal papilla cells).
Asiaticoside boosts the expression of fifty genes(!), related to fibroblast proliferation, cell cycle progression and synthesis of extracellular matrix (ECM), with a close correlation between gene profile, mRNA and protein production in the response of the cells to asiaticoside stimulation. (Source: Dermal fibroblast-associated gene induction by asiaticoside shown in vitro by DNA microarray analysis).
Gotu kola extract reduces the development of atopic dermatitis, by inhibiting NF-κB signaling in macrophage cells. Specifically TECA (titrated extract of centella asiatica) inhibits hyperkeratosis, mast cells and infiltration of inflammatory cells and the expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE and lipopolysaccharide (LPS). (Source: Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model).
Centella asiatica extract facilitates the wound healing process in both incision and burn wounds with asiatic acid being the most potent component in that respect (Source: Wound healing activities of different extracts of Centella asiatica in incision and burn wound models: an experimental animal study).
Centella asiatica protects skin fibroblasts from senescence, caused by H202-induced oxidative stress (stress-induced premature senescence / SIPS), by protecting DNA replication (Source: Centella asiatica extracts modulate hydrogen peroxide-induced senescence in human dermal fibroblasts).
Asiaticoside reduces hypertrophic scar formation, by downregulating TGF-beta1 and TIMP1 and by increasing TGF-beta3, thereby balancing collagen type I synthesis / breakdown equilibrium. Asiaticoside does not affect MMP1, MMP2 and TIMP2 or type III collagen in hypertrophic scars. (Source: Effect of asiaticoside on the expression of transforming growth factor-beta mRNA and matrix metalloproteinases in hypertrophic scars).
Asiaticoside accelerates wound healing and fights keloid scar formation, by decreasing fibroblast proliferation and type I and type III collagen in keloids and by inhibiting both TGF-βRI and TGF-βRII and Smad7. However, asiaticoside does not influence the expression of Smad2, Smad3, Smad4. (Source: Asiaticoside suppresses collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts).
Madecassoside protects melanocytes and can help treat vitiligo, by inhibiting mitochondrial oxidative damage, reducing MMPs and activating autophagy (Source: Protective effect of madecassoside on H2O2-induced oxidative stress and autophagy activation in human melanocytes).
Asiatic acid inhibits weight gain caused by a high fat diet, improves insulin resistance, blood lipids and leptin levels, bone mineral density and adiponectin and confers antioxidant protection, at an intake of 20mg/kg of weight (Source: Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague-Dawley rats).
The Gotu kola active madecassoside accelerates burn wound healing via multiple mechanisms, due its antioxidative activity, stimulation of collagen synthesis and angiogenesis. In addition, madecassoside was found to decrease nitric oxide (NO) levels, malondialdehyde (MDA) content, infiltration of inflammatory cells in the burn skin tissue and to boost glutathione (GSH), hydroxyproline levels as well as enhanced epithelisation resulting from dermal proliferation of fibroblasts (Source: Madecassoside isolated from Centella asiatica herbs facilitates burn wound healing in mice).
Centella asiatica protects skin fibroblasts against UVB damage, by positively regulating cell proliferation and fighting apoptosis (Source: Titrated extract of Centella asiatica provides a UVB protective effect by altering microRNA expression profiles in human dermal fibroblasts).
Twice daily application of a centella asiatica cream containing 0.5% triterpenes inhibits inflammation, and improves epidermal hydration / reduces transepidermal water loss (TEWL) via improving epidermal barrier function (Source: Moisturizing and Antiinflammatory Properties of Cosmetic Formulations Containing Centella asiatica Extract).
Centella asiatica extract facilitates connective tissue and blood vessel repair, by effecting the expression of genes involved in angiogenesis, extracellular matrix remodeling and several other growth factor, especially that of the TNFAIP6, an extracellular hyaluronan binding protein (Source: Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids).
Asiaticoside promotes wound healing, by increasing skin cell migration rates, initial skin cell adhesion and normal human dermal fibroblast proliferation (Source: Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model).
Gotu kola and rutin improve chronic venous insufficiency, leg suprafascial oedema, water retention cramps, without the use of compression stockings, after just 30 days of treatment (Source: Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and centella asiatica in the treatment of patients with chronic venous insufficiency).
67% of Asiaticoside from topical gotu kola cream application gets absorbed into the epidermis and dermis, and after 48 hours a substantial amount of asiaticoside still remains inside the skin (Source: Development of a High-Performance Liquid Chromatographic Method for Asiaticoside Quantification in Different Skin Layers after Topical Application of a Centella asiatica Extract).
Centella highly significantly reduces vein wall catabolic enzymes, thereby improving varicose veins naturally (Source: Effects of Centella asiatica extract on mucopolysaccharide metabolism in subjects with varicose veins).
TTFCA Centella asiatica extract improves chronic venous insufficiency and microangiopathy, modulating the action of fibroblasts in the vein wall and stimulating collagen remodeling in and around the venous wall. TTFCA has a moderate in-vitro and in-vivo stimulating effect on collagen synthesis and, at higher dosages, an inhibition on the synthesis of collagen and acid mucopolysaccharides. The tissue-stimulating action of TTFCA is due to increased collagen production by each cells and it is not due to stimulation of fibroblast proliferation (this differentiates the action of TTFCA from cell growth factors). (Source: Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy).
TECA centella asiatica extract improves leg heaviness, oedema and water retention in lower legs (Source: Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs).
Asiaticoside reduces melanin and hyperpigmentation, by inhibiting tyrosinase and MITF (Source: Asiaticoside, a component of Centella asiatica, inhibits melanogenesis in B16F10 mouse melanoma).
Centella asiatica improves venous insufficiency, stretch marks and wound healing. Centella asiatica is a medicinal plant that has been in use since prehistoric times and is used in folk medicine to treat a wide range of indications. However, in contrast to other medicinal plants, centella asiatica and its triterpenes have been subjected to quite extensive experimental and clinical investigations. Studies conducted in accordance to standardised scientific criteria have shown it to have a positive effect in the treatment of venous insufficiency and stretch marks (striae) and wound healing. (Source: Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica).
Gotu kola extract TECA remodels collagen in a dose-dependent manner, with asiatic acid specifically being the only component of TECA responsible for collagen synthesis stimulation (Source: Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica).
Centella asiatica and vitamin B5 boost wound healing, by activating and protecting fibroblasts. In a study examining the wound healing activity of centella / gotu kola extract and dexpanthenol (a type of vitamin B5), it was found that both boost wound repair by activating and protecting fibroblasts, each via a different mechanism (Source: Testing Wound-healing Activity in T15 Fibroblast Cultures: A Morphometric Analysis).
Centella ointment improves burn wounds in less than 3 days, (both objective and subjective signs) and results in tissue re-epithelialization and complete healing, without any infection (Source: Partial-thickness burn wounds healing by topical treatment: A randomized controlled comparison between silver sulfadiazine and centiderm).
Centella asiatica / gotu kola: the 3000-year old "panacea" worth its reputation. The south Asian medicinal herb centella asiatica (gotu kola) has been used as a cure-all for thousands of years for the treatment of hypertrophic scars (which are very common in Asia), wound healing and burns. The main actives compounds of the herb are asiaticoside, madecasosside, asiatic acid and madecassic acid and together they are called TTFCA (total triterpenic fraction of centella asiatica) or TECA (titrated extract of centella asiatica) (Source: Centella asiatica in dermatology: an overview).
Madecassoside reduces hyperpigmentation caused by UV exposure, and reduces UV-induced melanin index within 8 weeks of topical application" by inhibiting UV ray induced melanin synthesis, melanosome transfer and multiple markers of skin inflammation (keratinocyte cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha) (Source: Madecassoside inhibits melanin synthesis by blocking ultraviolet-induced inflammation).
Gotu kola extract fights skin "inflammaging", inhibits oxidative damage and glycation and boosts collagen synthesis. A synergistic triterpene + polyphenolic extract of centella asiatica has been found to protecting DNA from UV-induced damage, decrease thymine photodimerization by over 28%, reduce expression of interleukin-1α by 26%, inhibit carboxymethyl lysine formation induced by the glycating agent methylglyoxal by 100% and densify the collagen network in the papillary dermis (Source: Anti-inflammaging and antiglycation activity of a novel botanical ingredient from African biodiversity - centevita).
Gotu kola treats photoaged skin, cellulite and striae (stretch marks), small wounds, hypertrophic wounds burns, psoriasis and scleroderma, by boosting fibroblast proliferation, collagen synthesis, intracellular fibronectin content and tensile strength of newly formed skin as well as inhibiting the inflammatory phase of hypertrophic scars and keloids (Source: Centella asiatica in cosmetology).
Madecassoside from centella asiatica improves keloid scars, by inhibiting keloid fibroblast proliferation via depolarising the mitochondrial membrane potential (Source: Madecassoside Induces Apoptosis of Keloid Fibroblasts via a Mitochondrial-Dependent Pathway).
Asiatic acid inhibits keloid scars by blocking TGF-beta and PAI-1 and by boosting Smad 7 and PPAR-gamma. Keloid fibroblasts show higher responsiveness to TGF-β1 stimulation than normal fibroblasts in terms of invasion and collagen synthesis. However, asiatic acid suppresses TGF-β1 induced expression of collagen type I, Smad 2/3 and plasminogen activator inhibitor-1 (PAI-1) and elevates Smad 7. Furthermore, its effects on keloid fibroblasts are cancelled by PPAR-γ inhibition. (Source: Asiatic acid isolated from Centella asiatica inhibits TGF-β1-induced collagen expression in human keloid fibroblasts via PPAR-γ activation).
Madecassoside and asiaticoside from gotu kola / centella asiatica are identified as major burn wound healing actives (Source: Medicinal plants and their natural components as future drugs for the treatment of burn wounds: an integrative review).
High concentration topical centella asiatica / gotu kola spray completes wound healing in 14 days. (Source: Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats).
Combination of Centella asiatica (gotu kola), glycolic acid and vitamins A, C and E stimulates collagen and fibronectin synthesis in fibroblasts (Source: The effect of Centella asiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast).
Madecassoside protects vein endothelial cells from oxidative injury. Madecassoside boosts cell viability and prevents apoptosis, activation of caspase-3, loss of mitochondria membrane potential and inhibits malondialdehyde levels caused by hydrogen peroxide in a concentration-dependent manner. (Source: Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress).
Venotonics, such as gotu kola, rutin, diosmin and pine bark extract reduce oedema, cramps, restless legs on lower legs. (Source: Phlebotonics for venous insufficiency).
The gotu kola molecule madecassoside suppresses hypertrophic scars and keloids by inhibiting excessive fibroblast migration. Keloid is a specific skin scar that expands beyond the boundaries of the original injury as it heals. The invasive nature of keloid and notable migratory activity of fibroblasts are a hallmark, which distinguishes keloids from other common scars. However, madecassoside pretreatment was found to considerably suppress keloid fibroblast migration and synthesis of F-actin filaments, thereby inhibiting the growth of keloids. (Source: Madecassoside suppresses migration of fibroblasts from keloids: involvement of p38 kinase and PI3K signaling pathways).
Madecassoside stimulates wound healing and collagen III formation. In contrast to what was previously thought, asiaticoside and, especially, madecassoside are the main actives in centella asiatica responsible for burn wound healing and collagen types I and III production (and not asiatic acid and madecassic acid) (Source: Identification of Major Active Ingredients Responsible for Burn Wound Healing of Centella asiatica Herbs).
TTFCA aids wound healing by boosting collagen and fibronectin synthesis in fibroblasts (Source: Effect of the triterpenoid fraction of Centella asiatica on macromolecules of the connective matrix in human skin fibroblast cultures).
Centella asiatica reduces leg heaviness, pain and oedema, review finds. In a meta-analysis of 8 randomised controlled trials assessing the efficacy of centella asiatica / gotu kola for chronic venous insufficiency (CVI) it was found that the herb significantly improves microcirculatory parameters, ankle swelling and other CVI signs such as leg heaviness, pain and oedema. (Source: A Systematic Review of the Efficacy of Centella asiatica for Improvement of the Signs and Symptoms of Chronic Venous Insufficiency).
Asiaticoside and Gotu kola extract fight fibrosis, by inhibiting transforming growth factor-β1 (TGF-beta1). (Source: Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts).
TTFCA (total triterpenic fraction of centella asiatica) improves vein function, venous inflammation and venous hypertension in just 8 weeks, resulting in objective improvement (blood flow at rest, leg tissue oxygenation, removal of carbon dioxide from tissues, capillary permeability/filtration, reduced ankle swelling/oedema); and subjective improvement (feeling of heaviness, itching, puffiness, swelling sensation, restless lower extremity, pain, cramps, tiredness) as reported by patients. The studies showed that the higher dose of centella asiatica (120mg of TTFCA per day) offered the most impressive results. Higher doses producing better results, there were no side effects and the placebo group experienced no results at all. Furthermore, all the above changes were shown to protect diabetics from microangiopathy and progression to clinical stages. (Source 1: Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial; Source 2: Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model; Source 3: The microcirculatory activity of Centella asiatica in venous insufficiency. A double-blind study; Source 4: Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry; Source 5: Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA; Source 6: Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: a clinical, prospective, placebo-controlled, randomized, dose-ranging trial; Source 7: Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model; Source 8: Treatment of diabetic microangiopathy and edema with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled randomized study; Source 9: Activity of Centella asiatica in venous insufficiency; Source 10: TECA (Titrated Extract of Centella Asiatica): new microcirculatory, biomolecular, and vascular application in preventive and clinical medicine. A status paper.).
Asiaticoside from gotu kola prevents skin ageing and wrinkles and prevents the breakdown of elastin and hyaluronic acid in skin, by inhibiting hyaluronidase, elastase and MMP-1 (Source: Matrix metalloproteinase, hyaluronidase and elastase inhibitory potential of standardized extract of Centella asiatica).
Asiaticoside boosts type I collagen synthesis, via the Smad pathway but independently of TGF-beta receptor I kinase (TbetaRI kinase) (Source: Asiaticoside induces human collagen I synthesis through TGF-beta receptor I kinase (TbetaRI kinase)-independent Smad signaling).
Centella minimises ankle swelling / oedema in long haul flights and improves tissue oxygenation and vein-artery function (Source: Flight microangiopathy in medium-to long-distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica).
Gotu kola: the ideal scar / wound healing active. "As current aesthetic surgical techniques become more standardised and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results". This paper describes how tension is the initiating factor of hypertrophic scar formation or incomplete healing and also how the principal extracts of the centella asiatica plant (asiatic acid, madecassic acid and asiaticoside) have been documented in a large number of scientific reports to: aid wound healing; stimulate scar maturation; produce collagen type I; decrease inflammation; and reduce myofibroblast differentiation (Source: New innovations in scar management).
Centella protects veins from damage after deep vein thrombosis (postphlebitic syndrome (PPS), by preserving the integrity of the connective tissue to which endothelial cells are attached, and thereby reducing endothelial cell shedding into the bloodstream (Source: Centella Asiatica Triterpenic Fraction (CATTF) reduces the number of circulating endothelial cells in subjects with post phlebitic syndrome).
Asiaticoside affects the expression of 54 genes related to connective tissue function, "boosting "cell proliferation, cell-cycle progression and synthesis of the extracellular matrix", especially that of type I and type III collagen. This, in simple terms, means that collagen cells mature faster, multiply faster and produce more collagen and other connective tissue proteins. (Source: Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human dermal fibroblasts).
The collagen boosting, lipolytic, antioxidant and anti-cellulite properties of centella asiatica. In this study it was found that gotu kola extract stimulates collagen synthesis (better than vitamin C), lipolysis (better than that of caffeine), exhibits potent antioxidant / free radical scavenging activity (equal to that of grape seed extract and vitamin C) and exhibits similar UV protection effect to oligomeric cyanidins (Source: Triterpene Composition and Bioactivities of Centella asiatica).
TTFCA stabilises arterial plaques via increased collagen synthesis, thereby reducing the risk of thrombosis, artery rupture and embolization (Source 1: Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, randomized, placebo-controlled trial; Source 2: Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial).
Centella and pine bark combination helps prevent atherosclerosis, by halting the accumulation of arterial plaques and their progression to clinical stages, mainly via reducing oxidative stress (Source 1: Pycnogenol® and Centella asiatica to prevent asymptomatic atherosclerosis progression in clinical events; Source 2: Pycnogenol® and Centella asiatica in the management of asymptomatic atherosclerosis progression).
The combination of centella asiatica, esculoside caffeine and L-carnitine maximise lipolysis by inhibiting alpha-2 adrenoreceptors. In vitro tests demonstrated (a) a dramatic increase in the cyclic adenosine monophosphate (cAMP) content in human adipocytes, with a subsequent rise in the nonesterified fatty acids (NEFA) content of human adipocyte incubation medium, and (b) in vivo studies showed an actual potent slimming effect on human volunteers. Moreover, the combination antagonises the alpha(2)-adrenergic receptor that is known to reduce intracellular AMPc content and, subsequently, to down-regulate lipolysis. (Source: An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of slimming liposomes: an unexpected alpha(2)-adrenergic antagonism).
Gotu kola/centella asiatica can improve chronic venous insufficiency, lymphoedema and circulation impairment. Impaired skin microcirculation is a major contributing factor towards inflammation in patients with chronic venous insufficiency (CVI). Increase of capillary filtration rate predisposes to the formation of edema. Local lymphedema is a complication of CVI, often underdiagnosed. This paper, a review of randomised prospective controlled trials, shows that horse chestnut extract, flavonoids, total triterpenic fraction of centella asiatica (TTFCA) and procyanidins reduce capillary filtration rate and improve levels of partial pressures of oxygen and carbon dioxide in skin. The study found that combining with compression therapy may have some additive effects. (Source: A review of the microcirculation in skin in patients with chronic venous insufficiency: the problem and the evidence available for therapeutic options).
Phlebitis ulcers heal with the aid of herbal cream consisting of gotu kola and other botanicals. This herbal compound, in combination with compression garments, significantly improved inflammation, healing time and pain in phlebitis, in relation to compression garments alone. Ivy extract in the cream contributed to pain reduction; horse chestnut, butcher's broom and grape seed extract reduced inflammation; and allantoin, gotu kola and hyaluronic acid aided sore healing. In patients who applied both the cream and the compression garment pain stopped in 72 hours, inflammation disappeared in one week, tissue swelling stopped in one week and healing was complete in 4 weeks. (Source: Multicentric study on a topical compound with lymph-draining action in the treatment of the phlebostatic ulcer of the inferior limbs).
Review paper suggests gotu kola for the treatment of varicose veins and hemorrhoids. The loss of vascular integrity is associated with the pathogenesis of varicose veins. Several botanical extracts (horse chestnut/aesculus, butcher's broom/ruscus, gotu kola, flavonoids and pine bark) have been shown to improve microcirculation, capillary flow and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate. Oral supplementation may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids (Source: Hemorrhoids and varicose veins: a review of treatment options).
Effects of Asiaticoside Treatment on the Survival of Random Skin Flaps in Rats
Antiobesity efficacy of asiatic acid: down-regulation of adipogenic and inflammatory processes in high fat diet induced obese rats.
Anti-aging potential and phytochemicals of Centella asiatica, Nelumbo nucifera, and Hibiscus sabdariffa extracts.
Burn wound healing properties of asiaticoside and madecassoside
Centella asiatica (L.) extract attenuates inflammation and improve insulin sensitivity in a coculture of lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes and RAW 264.7 macrophages
Propionibacterium acnes related anti-inflammation and skin hydration activities of madecassoside, a pentacyclic triterpene saponin from Centella asiatica
Madecassoside ameliorates bleomycin-induced pulmonary fibrosis in mice by downregulating collagen deposition
Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts
Asiatic acid ameliorates pulmonary fibrosis induced by bleomycin (BLM) via suppressing pro-fibrotic and inflammatory signaling pathways
Attenuation of methylglyoxal-induced glycation and cellular dysfunction in wound healing by Centella cordifolia
The Effects of a Standardized Extract of Centella asiatica on Postlaser Resurfacing Wound Healing on the Face: A Split-Face, Double-Blind, Randomized, Placebo-Controlled Trial
Efficacy and Safety of Centella Asiatica ( L.) Urb. on Wrinkles: A Systematic Review of Published Data and Network Meta-Analysis
Insights into antioxidant activities and anti-skin-aging potential of callus extract from Centella asiatica
Comparison of the effects of collagenase and extract of Centella asiatica in an experimental model of wound healing: an immunohistochemical and histopathological study.
Potential Antiaging Effects of DLBS1649, a Centella asiatica Bioactive Extract.
Asiaticoside Prevents Oxidative Stress and Apoptosis in Endothelial Cells by Activating ROS-dependent p53/Bcl-2/Caspase-3 Signaling Pathway.
Asiaticoside delays senescence and attenuate generation of ROS in UV‑exposure cells through regulates TGF-β1/Smad pathway
Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer
Preclinical Safety Assessment of Standardized Extract of Centella asiatica (L.) Urban Leaves
Asiaticoside initiates new growth in skin ulcers early stage of cicatrisation (wound healing).(Source: Asiaticoside; active constituent of Centella asiatica, initiating agent of the new growth in the early stage of cicatrization of skin ulcers (French)).
Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease
A Randomized, Active Comparator-controlled Clinical Trial of a Topical Botanical Cream for Skin Hydration, Elasticity, Firmness, and Cellulite
An integral topical gel for cellulite reduction: results from a double-blind, randomized, placebo-controlled evaluation of efficacy
Comparison of Centella with Flavonoids for Treatment of Symptoms in Hemorrhoidal Disease and After Surgical Intervention: A Randomized Clinical Trial
Asiaticoside attenuates bleomycin-induced pulmonary fibrosis in A2aR-/- mice by promoting the BMP7/Smad1/5 signaling pathway
Inhibition of Inflammatory Responses by Centella asiatica via Suppression of IRAK1-TAK1 in Mouse Macrophages
Anti-Inflammatory and Anti-Vascular Leakage Effects by Combination of Centella asiatica and Vitis vinifera L. Leaf Extracts
Role of Centella asiatica and ceramide in skin barrier improvement: a double blind clinical trial of Indonesian batik workers
Evaluation of the cutaneous wound healing potential of tamanu oil in wounds induced in rats
Development and Evaluation of the Wound Healing Effect of a Novel Topical Cream Formula Based on Ginkgo biloba Extract on Wounds in Diabetic Rats
Effects of Centella asiatica (L.) Urban extract in TNF-α levels
Evaluation of the Efficacy and Safety of a Compound of Micronized Flavonoids in Combination With Vitamin C and Extracts of Centella asiatica, Vaccinium myrtillus, and Vitis vinifera for the Reduction of Hemorrhoidal Symptoms in Patients With Grade II and III Hemorrhoidal Disease: A Retrospective Real-Life Study
A Systematic Review of the Effect of Centella asiatica on Wound Healing
Role of Cica ( Centella asiatica) in Skincare Formulations: Examination of a Popular Ingredient
Centella triterpenes cream as a potential drug for the treatment of hypertrophic scar through inhibiting the phosphorylation of STAT3: A network pharmacology analysis and in vitro experiments
Preparation, development, and scale-up of standardized pentacyclic triterpenoid-rich extract from Centella asiatica (L.) Urb. and study of its wound healing activity
Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis
Madecassoside modulates lipid metabolism in visceral adipocytes: exploring the browning, lipolysis, and lipogenesis mechanisms for potential obesity treatment
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