Cellulite, anti-aging & centella asiatica
The combination of asiatic acid + madecassic acid + madecassoside + asiaticoside comprises probably the most important anti-cellulite active known today, due to it's multiple action on cellulite, circulation, stretch marks, skin firming and anti-ageing.
The combination is found in the centella asiatica (gotu kola) plant and is known as TECA (titrated extract of centella asiatica) or TTFCA (total triterpenic fraction of centella asiatica) and multiple research papers have found that it helps firm and repair skin and connective tissue, fight glycation, protect blood vessel wall integrity, boost circulation, fight fat tissue inflammation, stimulate fat release and inhibit pigmentation.
Gotu kola / centella asiatica creams
For all those reasons, centella asiatica / gotu kola is of great importance as an active ingredient in anti-cellulite, anti-ageing, leg wellness, skin brightening, skin firming, stretch mark and under-eye creams.
[LipoTherapeia offers Celluence®, the only leg wellness / cellulite creams in the world with high concentrations of 40x natural actives, including 95% pure TECA from madagascan centella asiatica]
Gotu kola / Centella asiatica: the science
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 and procyanidins reduce capillary filtration rate and improve levels of partial pressures of oxygen and carbon dioxide in skin and 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
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 with may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids
[Source: Hemorrhoids and varicose veins: a review of treatment options]
The ayurvedic herb centella asiatica can be described as the ultimate "skin herb” and is well established as a skin firming and scar healing botanical for centuries
The ayurvedic herb Gotu kola (centella asiatica) is well-researched for it's connective tissue and blood vessel protecting action. Now a new study has shown that madecassic acid, one of the primary actives found in gotu kola, may help protect against damage of the retina caused by to hypoxia (low oxygen levels).
Retinal hypoxia, a common complication of diabetes, contributes to retinal damage which can ultimately lead to blindness. In this cell study scientists found that the addition of madecassic acid reduced cell damage in retinal cells and protected them from oxidation.
The authors suggest that madecassic acid could comprise a promising therapy to reverse the process and development of hypoxia-induced retinal endothelial cell dysfunction.
- Paper: Madecassic Acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress.
- Abstract: Madecassic acid (MA) is an abundant triterpenoid in Centella asiatica (L.) Urban. (Apiaceae) that has been used as a wound-healing, anti-inflammatory and anti-cancer agent. Up to now, the effects of MA against oxidative stress remain unclear. In this study, we investigated the effect of MA and its mechanisms on hypoxia-induced human Retinal Microvascular Endothelial Cells (hRMECs). hRMECs were pre-treated with different concentrations of MA (0-50μM) for 30min before being incubated under hypoxia condition (37°C, 5% CO2 and 95% N2). Cell apoptosis was evaluated with MTT assay and TUNEL staining, and the expression of apoptosis- and endoplasmic reticulum (ER) stress-related molecules was assessed with western blotting and RT-PCR analysis. Intracellular ROS level was evaluated using DCFH-DA. Intracellular malondialdehyde (MDA), dehydrogenase (LDH), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) were evaluated using related Kits. Activating transcription factor 4 (ATF4) nuclear translocation was assessed with western blotting analysis and immunofluorescence staining. MA significantly reduced oxidative stress in hypoxia-induced hRMECs, as shown by increased cell viability, SOD and GSH-PX leakage, decreased TUNEL- and ROS-positive cell ratio, LDH and MDA leakage, caspase-3 and -9 activity, and Bax/Bcl-2 ratio. In addition, MA also attenuated hypoxia-induced ER stress in hRMECs, as shown by reduced mRNA levels of glucose-regulated protein 78 (GRP78), C/EBP homologous transcription factor (CHOP), protein levels of cleaved activating transcription factor 6 (ATF6) and inositol-requiring kinase/endonuclease 1 alpha (IRE1α), phosphorylation of pancreatic ER stress kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α), cleaved caspase-12 and ATF4 translocation to nucleus. The current study indicated that the regulation of oxidative stress and ER stress by MA would be a promising therapy to reverse the process and development of hypoxia-induced hRMECs dysfunction.
Fighting inflammation and oxidative damage in the liver
Centella asiatica's protective effect on skin and connective tissue has been known for centuries and plenty of studies in the last few decades have confirmed the validity of this traditional knowledge.
Gotu kola / centella asiatica possesses antioxidant and anti-inflammatory properties, and in this new study published this month it was shown that centella exerts the same anti-inflammatory, antioxidant and overall protective effects in the liver too.
Specifically, gotu kola reduced malondialdehyde (MDA), a marker of lipid oxidation, significantly increased the levels of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase and catalase, and may have provided direct antioxidant protection against reactive oxygen species (ROS) too.
Furthermore, centella significantly reduced a host of inflammatory markers, including interleukin (IL)‑1β, IL‑2, IL‑6, IL‑10, IL‑12 and TNF‑alpha, among others!
The authors of the study concluded that "centella asiatica may be useful in preventing liver damage"
Clearly centella is not just an active for anti-cellulite creams or circulation-boosting supplements, and possesses diverse beneficial properties for multiple tissues and organs in the body. In addition to it's inclusion in creams and supplements, gotu kola can also be eaten as a salad or drunk as a herbal tea made with fresh or dried leaves.
- Paper: Protective effects of Centella asiatica leaf extract on dimethylnitrosamine‑induced liver injury in rats.
- Abstract: Oxidative stress in liver injury is a major pathogenetic factor in the progression of liver damage. Centella asiatica (L.) Urban, known in the United States as Gotu kola, is widely used as a traditional herbal medicine in Chinese or Indian Pennywort. The efficacy of Centella asiatica is comprehensive and is used as an anti‑inflammatory agent, for memory improvement, for its antitumor activity and for treatment of gastric ulcers. The present study investigated the protective effects of Centella asiatica on dimethylnitrosamine (DMN)‑induced liver injury in rats. The rats in the treatment groups were treated with Centella asiatica at either 100 or 200 mg/kg in distilled water (D.W) or with silymarin (200 mg/kg in D.W) by oral administration for 5 days daily following intraperitoneal injections of 30 mg/kg DMN. Centella asiatica significantly decreased the relative liver weights in the DMN‑induced liver injury group, compared with the control. The assessment of liver histology showed that Centella asiatica significantly alleviated mass periportal ± bridging necrosis, intralobular degeneration and focal necrosis, with fibrosis of liver tissues. Additionally, Centella asiatica significantly decreased the level of malondialdehyde, significantly increased the levels of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and catalase, and may have provided protection against the deleterious effects of reactive oxygen species. In addition, Centella asiatica significantly decreased inflammatory mediators, including interleukin (IL)‑1β, IL‑2, IL‑6, IL‑10, IL‑12, tumor necrosis factor‑α, interferon‑γ and granulocyte/macrophage colony‑stimulating factor. These results suggested that Centella asiatica had hepatoprotective effects through increasing the levels of antioxidant enzymes and reducing the levels of inflammatory mediators in rats with DMN‑induced liver injury. Therefore, Centella asiatica may be useful in preventing liver damage.
- In a study examining the would 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, the cells that produce collagen and elastin in the body, albeit via a different mechanism
- The connective tissue repair properties of centella make it an ideal anti-ageing, under-eye and anti-cellulite cream active ingredient
- Source: Testing Wound-healing Activity in T15 Fibroblast Cultures: A Morphometric Analysis.
- Abstract: The purpose was to evaluate the use of mouse T15 fibroblast cell cultures for the investigation of wound-healing activity. In order to investigate their mechanisms of action, the effects of drugs with wound-healing activities were compared by using morphometric analyses by microscopy after cell staining. A number of parameters were used to evaluate the effects of titrated extracts from centella asiatica and dexpanthenol (drugs that have been used in medical practice for their wound-healing activities) on cultured mouse T15 fibroblasts. These parameters were : the total number of cells ; the number of T15 cells in mitosis ; the percentages of fusiform, polygonal, round and vacuole-containing cells ; and the number of intracellular collagen granules. The results indicate that these two drugs exhibit wound-healing activities by activating fibroblast cells, and have cytoprotective effects, although their mechanisms of action on mouse T15 fibroblasts were different. On the basis of our findings, mouse T15 fibroblast cell cultures seem to be useful for the pharmacological screening of compounds with wound-healing activity.
- The medicinal herb centella asiatica / gotu kola is a south Asian plant known for centuries for it's connective tissue building and repair action
- The most important components of centella asiatica are asiatic acid, madecassic acid and asiaticoside
- In this study on human tissue cultures, a highly concentrated extract comprising solely the above natural chemicals was found to boost collagen synthesis, with increasing efficacy as the dose increased
- Out of the three, asiatic acid was found to be the only component responsible for collagen synthesis stimulation. However, all three components increased proline in collagen tissue, showing a supportive collagen stimulation action (proline is the most important aminoacid in collagen).
- Due to it's connective tissue growth and repair activity, gotu kola is ideal for use in skin anti-aging and anti-cellulite creams and supplements.
- Source: Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica
- Abstract: The drug "Titrated Extract from Centella asiatica" (TECA), used for its stimulating properties on the healing of wounds, is a mixture of 3 terpenes extracted from a tropical plant: asiatic acid (30%, w/w), madecassic acid (30%, w/w) and asiaticoside (40%, w/w). The effects of TECA and its individual components were checked on human foreskin fibroblast monolayer cultures. TECA increased the collagen synthesis in a dose-dependent fashion whereas a simultaneous decrease in the specific activity of neosynthesized collagen was observed. Asiatic acid was found to be the only component responsible for collagen synthesis stimulation. TECA and all three terpenes increased the intracellular free proline pool. This effect was independent of the stimulation of collagen synthesis.
- 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 (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)
- These are the types of gotu kola extract to look for when taking centella asiatica orally (food supplements) or topically (creams)
- High quality, concentrated extracts, such as the above, do help in wound / burn / hypertrophic scar healing, facial skin anti-ageing, body and face skin firming, under eye bags, cellulite reduction and water retention / poor circulation, as multiple studies, included the one mentioned below, have shown.
- The main mode of action of gotu kola is in the repair of connective tissue, which is implicated in all the health / aesthetic problems mentioned above. For this reason, centella is one of the key actives we use for treatments at our clinic and in our anti-cellulite / leg wellness creams.
- Source: Centella asiatica in dermatology: an overview
- Abstract: Centella asiatica is a medicinal plant that was already used as a 'panacea' 3000 years ago. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecasosside, asiatic acid and madecassic acid. We have conducted an overview to summarize current knowledge on the results of scientific in vitro and in vivo experiments focused on the improvement of the healing process of small wounds, hypertrophic scars and burns by C. asiatica. In this paper, we discuss the data on constituents, recommended preparations and the potential side effects of C. asiatica.
- Comment: Centella asiatica / gotu kola extract is well-known for it's skin whitening properties and this study confirms that madecassoside, one of the 4 main triterpenes in centella "significantly reduces UV-induced melanin index at 8 weeks after topical application". Madecassoside achieves that, at least partially, by blocking multiple markers of inflammation on skin.
- Source: Madecassoside inhibits melanin synthesis by blocking ultraviolet-induced inflammation.
- Abstract: Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.), is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV)-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.
- Source: Asiatic acid inhibits pulmonary inflammation induced by cigarette smoke.
- Abstract: Asiatic acid (AA) is one of the major components of Titrated extract of Centella asiatica (TECA), which has been reported to possess antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the protective effect of AA on pulmonary inflammation induced by cigarette smoke (CS). AA significantly attenuated the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF) of CS exposure mice. AA also decreased ROS production and NE activity, and inhibited the release of proinflammatory cytokines in BALF. AA reduced the recruitment of inflammatory cells and MCP-1 expression in lung tissue of CS exposure mice. AA also attenuated mucus overproduction, and decreased the activation of MAPKs and NF-kB in lung tissue. Furthermore, AA increased HO-1 expression and inhibited the reduced expression of SOD3 in lung tissue. These findings indicate that AA effectively inhibits pulmonary inflammatory response, which is an important process in the development of chronic obstructive pulmonary disease (COPD) via suppression of inflammatory mediators and induction of HO-1. Therefore, we suggest that AA has the potential to treat inflammatory disease such as COPD.
- Source: Anti-inflammaging and antiglycation activity of a novel botanical ingredient from African biodiversity (Centevita™).
- Abstract: PURPOSE: The aim of this study was to investigate the topical efficacy of a new purified extract from Madagascar, Gotu Kola (Centella asiatica [L.] Urban), both on human explants and on human volunteers, in relation to skin wrinkling and skin protection against ultraviolet light exposure. The extract, with a peculiar content of biologically active molecules, was investigated as a novel anti-inflammaging and antiglycation agent. Its typical terpenes, known as collagen synthesis promoters, represent at least 45% of the extract. It also contains a polyphenolic fraction cooperating to the observed properties. METHODS: C. asiatica purified extract was assayed on human skin explants maintained alive, and several parameters were evaluated. Among the most relevant, the thymine dimerization was evaluated by immunostaining. Malondialdehyde formation was evaluated as free-radical scavenging marker by enzyme-linked immunosorbent assay. The expression of interleukin-1α was observed by enzyme-linked immunosorbent assay as well. The product was further evaluated as an antiglycation agent, being glycation quantified by the advanced glycation product carboxymethyl lysine. C. asiatica purified extract was also evaluated as an antiwrinkling agent in a single-blind, placebo-controlled study. Formulated in a simple oil-in-water emulsion, the extent of wrinkling was assessed by skin replicas, skin firmness, skin elasticity, and collagen density measurements. RESULTS: C. asiatica purified extract could protect DNA from ultraviolet light-induced damage, decreasing the thymine photodimerization by over 28% (P<0.05). A reduced (26%, P<0.01) expression of interleukin-1α was also observed, supporting its anti-inflammatory potential. C. asiatica purified extract showed in vitro a total inhibition of carboxymethyl lysine formation induced by the glycating agent methylglyoxal. A clear epidermal densification of collagen network in the papillary dermis was observed. These in vitro data have been confirmed by clinical results. CONCLUSION: These results qualify C. asiatica purified extract as an antiaging ingredient, addressing skin damage caused by inflammaging and glycation by relying on the synergy of triterpens and polyphenolics.
- Source: Centella asiatica in cosmetology
- Abstract: 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.
- Source: Matrix metalloproteinase, hyaluronidase and elastase inhibitory potential of standardized extract of Centella asiatica.
- Abstract: CONTEXT: Centella asiatica (L.) Urban (Apiaceae), a valuable herb described in Ayurveda, is used in the indigenous system of medicine as a tonic to treat skin diseases. OBJECTIVE: Centella asiatica methanol extract and its ethyl acetate, n-butanol and aqueous fraction, were subjected for the evaluation of skin care potential through the in vitro hyaluronidase, elastase and matrix metalloproteinase-1 (MMP-1) inhibitory assay. MATERIALS AND METHODS: The C. asiatica plant was extracted with methanol and fractionated with ethyl acetate, n-butanol and water. The enzymatic activities were evaluated using ursolic acid and oleanolic acid as standards. Isolate molecule asiaticoside was quantified in the crude extract and fractions through high-performance liquid chromatography (HPLC) and structural was characterized by liquid chromatography-mass spectroscopy (LC-MS) and ¹H nuclear magnetic resonance (NMR). Isolated compound was also evaluated for in vitro enzyme assays. RESULTS: Extract exhibited anti-hyaluronidase and anti-elastase activity with IC₅₀ of 19.27 ± 0.37 and 14.54 ± 0.39 µg/mL, respectively, as compared to ursolic acid. Centella asiatica n-butanol fraction (CAnB) and isolated compound showed significant hyaluronidase (IC₅₀ = 27.00 ± 0.43 and 18.63 ± 0.33 µg/mL) and elastase (IC₅₀ = 29.15 ± 0.31 and 19.45 ± 0.25 µg/mL) inhibitory activities, respectively, and also showed significant MMP-1 inhibition (p < 0.05 and p < 0.01). DISCUSSION AND CONCLUSION: n-Butanol fraction was found to be most effective among the all fractions from which asiaticoside was isolated and further quantified by HPLC. This work concludes that the asiaticoside from C. asiatica may be a prospective agent for skin care.
- Source: Asiaticoside, a component of Centella asiatica, inhibits melanogenesis in B16F10 mouse melanoma
- Abstract: Melanogenesis is the process of generating pigmentation via melanin synthesis and delivery. Three key enzymes, tyrosinase, tyrosinase‑related protein 1 (TRP1) and TRP2, metabolize melanin from L‑tyrosine. Melanin synthesizing enzymes are regulated by microphthalmia‑associated transcription factor (MITF). The titrated extract of Centella asiatica (TECA) contains the major components asiatic acid, asiaticoside and madecassic acid. The present study revealed that TECA reduces the melanin content in melanocytes. Moreover, the asiaticoside contained in TECA modulated melanogenesis by inhibiting tyrosinase mRNA expression. The decrease in tyrosinase mRNA levels was mediated through MITF. Uniquely, asiaticoside inhibited MITF by decreasing its DNA binding affinity. In conclusion, the results of the present study indicate that asiaticoside treatment may have beneficial effects in hyperpigmentation diseases or for skin whitening.
- Source: Triterpene Composition and Bioactivities of Centella asiatica
- Abstract: 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 (5% solution). 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.
- Source: Asiatic acid isolated from Centella asiatica inhibits TGF-β1-induced collagen expression in human keloid fibroblasts via PPAR-γ activation.
- Abstract: Keloids are fibroproliferative disorders characterized by exuberant extracellular matrix deposition and transforming growth factor (TGF)-β/Smad pathway plays a pivotal role in keloid pathogenesis. Centella asiatica extract has been applied in scar management for ages. As one of its major components, asiatic acid (AA) has been recently reported to inhibit liver fibrosis by blocking TGF-β/Smad pathway. However, its effect on keloid remains unknown. In order to investigate the effects of AA on cell proliferation, invasion and collagen synthesis, normal and keloid fibroblasts were exposed to TGF-β1 with or without AA. Relevant experiments including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay, Transwell invasion assay, enzyme-linked immunosorbent assay, Western blot, quantitative polymerase chain reaction and RNA interference assay were conducted. As a result, keloid fibroblasts showed higher responsiveness to TGF-β1 stimulation than normal fibroblasts in terms of invasion and collagen synthesis. AA could suppress TGF-β1-induced expression of collagen type I, inhibit Smad 2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) expression, while elevate Smad 7 protein level. Noteworthy, the effects of AA on keloid fibroblasts could be abrogated by PPAR-γ antagonist GW9662 and by silencing of PPAR-γ. The present study demonstrated that AA inhibited TGF-β1-induced collagen and PAI-1 expression in keloid fibroblasts through PPAR-γ activation, which suggested that AA was one of the active constituents of C. asiatica responsible for keloid management, and could be included in the arsenal for combating against keloid.
- Source: Madecassoside isolated from Centella asiatica herbs facilitates burn wound healing in mice.
- Abstract: The current study was designed to investigate the effect of madecassoside, the major triterpene in CENTELLA ASIATICA, on burn wound healing and its possible mechanism of action. An oral administration of madecassoside (6, 12, 24 mg/kg) facilitated wound closure in a time-dependent manner and reached its peak effect, nearly completely wound closure, on day 20 in the group receiving the highest dose of 24 mg/kg of madecassoside. Further histopathological analysis revealed that madecassoside alleviated infiltration of inflammatory cells as well as enhanced epithelisation resulting from dermal proliferation of fibroblasts. Madecassoside at higher doses (12 and 24 mg/kg) decreased nitric oxide (NO) levels and malondialdehyde (MDA) content in the burn skin tissue. However, reduced glutathione (GSH) and hydroxyproline levels were increased in the same skin tissue. In addition, madecassoside promoted skin angiogenesis IN VIVO, correlating with our findings IN VITRO that it stimulated endothelial cell growth in a rat aortic ring assay. These data suggest that madecassoside has significant wound-healing activity and is one of the major reasons for the use of C. ASIATICA herbs in the successful treatment of burn injury. Moreover, the results from the present study indicate that the effect of madecassoside on wound healing may involve several mechanisms including antioxidative activity, collagen synthesis and angiogenesis.
- Source: Medicinal plants and their natural components as future drugs for the treatment of burn wounds: an integrative review.
- Abstract: Burn wound healing is a complicated process including inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Several biochemicals are involved in burn healing process including antioxidants, cytokines and liver and kidney damage biomarkers. Although several preparations are available for the management of burn wound, there is still a necessity of researching for efficacious medicine. The aim of the present study was to evaluate herbal preparations and their phytochemical constituents for burn wound management. For this purpose, electronic databases including Pubmed, Scirus, Scopus and Cochrane library were searched from 1966 to July 2013 for in vitro, in vivo or clinical studies which examined the effect of any herbal preparation on different types of burn wound. Only 3 human studies were found to include in this review. In contrast, there were 62 in vivo and in vitro studies that show the need for more clinical trials to prove the plant's potential to cure burn wound. Among single herbal preparations, Allium sativum, Aloe vera, Centella asiatica and Hippophae rhamnoides showed the best burn wound healing activity. Flavonoids, alkaloids, saponins and phenolic compounds were active constituents present in different herbs facilitating wound closure. Glycosides including madecassoside and asiaticoside and proteolytic enzymes were among the main active components. Phytochemicals represented positive activity at different stages of burn wound healing process by various mechanisms including antimicrobial, anti-inflammatory, antioxidant, collagen synthesis stimulation, cell proliferative and angiogenic effect. Overall, several herbal medicaments have shown marked activity in the management of wounds-especially burn wounds-and therefore can be considered as an alternative source of treatment. Furthermore, various natural compounds with verified burn-induced wound healing potential can be assumed as future natural drugs.
- Source: Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats.
- Abstract: Centella asiatica was extracted by methanol. The assay content of triterpenes in the extract was 0.12 % asiatic acid, 0.54 % madecassic acid, 0.25 % asiaticoside and 1.02 % madecassoside. The extract was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) and formulated with Eudragit E100, glycerol, PEG 400, copovidone, ethanol and purified water. A clear yellowish solution (F1-F8) was obtained. The formulations had a pH of 5.5-6.0 with viscosity in the range of 20-60 mPa s, surface tension 20.3-24.6 mN m-1 and contact angle less than 20°. The amount of PEG 400 and copovidone affected the film and spreadability. The content of triterpenes in the spray formulation was close to 100 % compared to triterpenes in the extract. The skin irritation study indicated that the formulation was non-irritating in a rat model. An in vivo excision wound healing model showed that wound excision was completely healed after 14 days.
- Centella asiatica protects against UVB-induced HaCaT keratinocyte damage through microRNA expression changes.
- This study aimed to evaluate the protective effects of Centella asiatica (C. asiatica) against ultraviolet B (UVB) damage in human keratinocytes using microRNA (miRNA) expression profiling analysis. Titrated extract of C. asiatica (TECA) demonstrated low cytotoxicity in normal human HaCaT keratinocytes only at low doses (<5 µg/ml). UVB (50 mJ/cm2) irradiation significantly decreased cell viability, and TECA treatment decreased the UVB toxicity. By using miRNA microarrays, we determined that 72 miRNAs had an altered expression following TECA treatment in UVB-irradiated keratinocytes (46 upregulated and 26 downregulated). Using an miRNA target gene prediction tool and Gene Ontology (GO) analysis, we determined that miRNAs with altered expression were functionally related with the inhibition of apoptosis and cell proliferation. Overall, these results provide meaningful information to facilitate the understanding of TECA-mediated UVB protection in human keratinocytes.
- Source: The effect of Centella asiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast
- Abstract: Centella asiatica (Linn.) Urban is well known in promoting wound healing and provides significant benefits in skin care and therapeutic products formulation. Glycolic acid and vitamins also play a role in the enhancement of collagen and fibronectin synthesis. Here, we evaluate the specific effect of Centella asiatica (CA), vitamins, glycolic acid and their mixture preparations to stimulate collagen and fibronectin synthesis in cultured human fibroblast cells. The fibroblast cells are incubated with CA, glycolic acid, vitamins and their mixture preparations for 48 h. The cell lysates were analyzed for protein content and collagen synthesis by direct binding enzyme immunoassay. The fibronectin of the cultured supernatant was measured by sandwich enzyme immunoassay. The results showed that CA, glycolic acid, vitamins A, E and C significantly stimulate collagen and fibronectin synthesis in the fibroblast. Addition of glycolic acid and vitamins to CA further increased the levels of collagen and fibronectin synthesis to 8.55 and 23.75 μg/100 μg, respectively. CA, glycolic acid, vitamins A, E, and C, and their mixtures demonstrated stimulatory effect on both extra-cellular matrix synthesis of collagen and fibronectin in in vitro studies on human foreskin fibroblasts, which is beneficial to skin care and therapeutic products formulation.
- Source: Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress.
- Abstract: This study aimed to investigate the effect of madecassoside against oxidative stress-induced injury of endothelial cells. Hydrogen peroxide (H(2)O(2), 500 µmol/L) was employed as an inducer of oxidative stress in human umbilical vein endothelial cells (HUVECs). Cell apoptosis was detected by Hoechst 33258 staining and flow cytometry. Caspase-3 activity and mitochondria membrane potential were further examined. As a result, madecassoside (10, 30, 100 µmol/L) could reverse morphological changes, elevate cell viability, increase glutathione levels, and decrease lactate dehydrogenase and malondialdehyde levels caused by H(2)O(2) in a concentration-dependent manner. It attenuated apoptosis, preventing the activation of caspase-3 and the loss of mitochondria membrane potential, as well as the phosphorylation of p38 mitogen-activated protein kinase (MAPK) in HUVECs. These data suggested that madecassoside could protect HUVECs from oxidative injury, which was probably achieved by inhibiting cell apoptosis via protection of mitochondria membranes and downregulation of the activation of caspase-3 and p38 MAPK.
- Source: Titrated extract of Centella asiatica provides a UVB protective effect by altering microRNA expression profiles in human dermal fibroblasts.
- Abstract: The titrated extract of Centella asiatica (TECA) is a reconstituted mixture comprising of asiatic acid, madecassic acid, asiaticoside and madecassoside, and is used as a therapeutic agent in wound healing and also as an anti-microbial, anticancer and anti-aging agent. Although these properties and the associated cell signaling pathways have been elucidated, the cellular mechanism of anti-photoaging upon ultraviolet (UV) exposure in normal human dermal fibroblasts (NHDFs) remains unknown. In this study, we investigated the photoprotective role of TECA via microRNA (miRNA) expression profiling analysis. Low dose of TECA did not exhibit toxicity and showed a protective effect against UVB irradiation in NDHFs. miRNA microarray experiments revealed that specific miRNAs were altered by TECA stimulation in UVB-irradiated NHDFs. Functional bioinformatic analysis showed that the putative target genes of the altered miRNAs were associated with the positive regulation of cell proliferation, anti-apoptosis, small GTPase- and Ras-mediated signal transduction and activation of MAPKK. Therefore, these results suggest that TECA may serve as a potential natural chemoprotective agent against UVB-mediated damage in NHDFs through changes in the expression of specific miRNAs.
- Source: Phlebotonics for venous insufficiency.
- Abstract: BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). 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 patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.
- Source: Moisturising and Antiinflammatory Properties of Cosmetic Formulations Containing Centella asiatica Extract.
- Abstract: Centella asiatica extract is a rich source of natural bioactive substances, triterpenoid saponins, flavonoids, phenolic acids, triterpenic steroids, amino acids and sugars. Thus, many scavenging free radicals, exhibit antiinflammatory activity and affect on the stratum corneum hydration and epidermal barrier function. The aim of the present study was to evaluate the in vivo moisturizing and antiinflammatory properties of cosmetic formulations (oil-in-water emulsion cream and hydrogel) containing different concentrations of Centella asiatica extract. The study was conducted over four weeks on a group of 25 volunteers after twice a day application of cosmetic formulations with Centella asiatica extract (2.5 and 5%, w/w) on their forearms. The measurement of basic skin parameters (stratum corneum hydration and epidermal barrier function) was performed once a week. The in vivo antiinflammatory activity based on the methyl nicotinate model of microinflammation in human skin was evaluated after four weeks application of tested formulations. In vivo tests formulations containing 5% of Centella asiatica extract showed the best efficacy in improving skin moisture by increase of skin surface hydration state and decrease in transepidermal water loss as well as exhibited antiinflammatory properties based on the methyl nicotinate model of microinflammation in human skin. Comparative tests conducted by corneometer, tewameter and chromameter showed that cosmetic formulations containing Centella asiatica extract have the moisturizing and antiinflammatory properties.
- Source: Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids
- Abstract: The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella's bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.
- Asiaticoside suppresses collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts.
- Asiaticoside (ATS) isolated from the leaves of Centella asiatica possesses strong wound-healing properties and reduces scar formation. However, the specific effects of asiaticoside on the formation of keloidal scars remain unknown. In the present study, we evaluated the in vitro effects of asiaticoside on the proliferation, collagen expression, and transforming growth factor (TGF)-β/Smad signaling of keloid-derived fibroblasts. Fibroblasts isolated from keloid tissue and normal skin tissues were treated with asiaticoside at different concentrations. Afterwards, they were subjected to RT-PCR and Western blot analyses. The inhibitory effects of asiaticoside on fibroblast viability were assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Asiaticoside decreased fibroblast proliferation in a time- and dose-dependent manner. It also inhibited type I and type III collagen protein and mRNA expressions. In addition, asiaticoside reduced the expression of both TGF-βRI and TGF-βRII at the transcriptional and translational level. Moreover, it increased the expression of Smad7 protein and mRNA. However, asiaticoside did not influence the expression of Smad2, Smad3, Smad4, phosphorylated Smad2, and phosphorylated Smad3. Taken together, these results suggest that asiaticoside could be of potential use in the treatment and/or prevention of hypertrophic scars and keloids.
- Madecassoside suppresses migration of fibroblasts from keloids: involvement of p38 kinase and PI3K signaling pathways.
- 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. Madecassoside, a triterpenoid saponin occurring in Centella asiatica herbs, possesses unique pharmacological properties to enhance wound-healing and diminish keloid formation. However, the effects of madecassoside on the formation of keloid scars have been poorly understood. Here, we focused on the potential of madecassoside on the migration of keloid-derived fibroblasts (KFs) and its mechanism. Primary KF, originating from human earlobe keloids, were purified and cultured, and then treated with madecassoside (10, 30, and 100μM). In both transwell migration assays and scratch-wound-closure assays, KF migration was considerably suppressed by madecassoside pretreatment. Furthermore, KFs treated with madecassoside showed decreased F-actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. By Western blot analysis, madecassoside was shown to remarkably attenuate the phosphorylation of cofilin, p38 MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT signaling, but only exhibited a minor effect on MMP-13 and little effect on ERK1/2 phosphorylation. It was concluded that madecassoside could be of great use in the treatment and/or prevention of hypertrophic scars and keloids.
- Identification of Major Active Ingredients Responsible for Burn Wound Healing of Centella asiatica Herbs
- Centella asiatica herbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed. In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated. In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β(1) levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents of C. asiatica herbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P = 0.0446 for procollagen type III synthesis in vitro, P = 0.0057, for wound healing speed, and P = 0.0491 for wound healing pattern in vivo, correspondingly).
- Centella / gotu kola aids wound healing by boosting collagen and fibronectin production in collagen cells / fibroblasts
- Source: Effect of the triterpenoid fraction of Centella asiatica on macromolecules of the connective matrix in human skin fibroblast cultures.
- Abstract: The mechanism of action of the total triterpenoid fraction extracted from Centella Asiatica (TTFCA) was evaluated using human skin fibroblast cultures as the experimental system. In particular its influence on the biosynthesis of collagen, fibronectin and proteoglycans was considered. The presence of TTFCA (25 micrograms/ml) does not seem to affect cell proliferation, total protein synthesis or the biosynthesis of proteoglycans in a significant way. A statistically important increase was observed in the percentage of collagen and, as revealed by immunofluorescence measurements, in cell layer fibronectin. This effect on collagen and fibronectin may help to explain the action of TTFCA in promoting wound healing, and suggests an interesting working hypothesis for its action on basal endothelia.
- In this study asiaticoside, a natural chemical found in the herb gotu kola / centella asiatica, was found to boost the movement, adhesion and growth of collagen cells in wound sites, thereby accelerating wound healing
- Due to their connective tissue healing / repair action, asiaticoside-rich centella asiatica extracts, are ideal candidates for anti-ageing, wound healing, stretch mark and anti-cellulite, under eye care creams.
- Source: Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model
- Abstract: Wound healing proceeds through a complex collaborative process involving many types of cells. Keratinocytes and fibroblasts of epidermal and dermal layers of the skin play prominent roles in this process. Asiaticoside, an active component of Centella asiatica, is known for beneficial effects on keloid and hypertrophic scar. However, the effects of this compound on normal human skin cells are not well known. Using in vitro systems, we observed the effects of asiaticoside on normal human skin cell behaviors related to healing. In a wound closure seeding model, asiaticoside increased migration rates of skin cells. By observing the numbers of cells attached and the area occupied by the cells, we concluded that asiaticoside also enhanced the initial skin cell adhesion. In cell proliferation assays, asiaticoside induced an increase in the number of normal human dermal fibroblasts. In conclusion, asiaticoside promotes skin cell behaviors involved in wound healing; and as a bioactive component of an artificial skin, may have therapeutic value.
- 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.
- Multiple studies have shown that centella asiatica protects blood vessels from damage and stimulates their healing / repair, making it an identical active for use in supplements and topical creams against water retention, under-eye bags and cellulite.
- Source: A Systematic Review of the Efficacy of Centella asiatica for Improvement of the Signs and Symptoms of Chronic Venous Insufficiency.
- Abstract: We aimed to assess the efficacy of Centella asiatica for improvement of the signs and symptoms of chronic venous insufficiency (CVI). We searched 13 electronic databases including the Cochrane Central Register of Controlled Trials for randomised controlled trials assessing the efficacy of Centellaasiatica for CVI. Two review authors independently selected studies, assessed the risks of bias of included studies and extracted data. The treatment effects of similar studies were pooled whenever appropriate. Eight studies met the inclusion criteria. The pooling of data of similar studies showed that Centella asiatica significantly improved microcirculatory parameters such as transcutaneous partial pressure of CO2 and O2, rate of ankle swelling and venoarteriolar response. Three out of the eight studies did not provide quantitative data. However, these studies reported that patients treated with Centella asiatica showed significant improvement in CVI signs such as leg heaviness, pain and oedema. Our results show that Centella asiatica may be beneficial for improving signs and symptoms of CVI but this conclusion needs to be interpreted with caution as most of the studies were characterised by inadequate reporting and thus had unclear risks of bias, which may threaten the validity of the conclusions.