Asiaticoside

Arch Dermatol Res. 2011 Oct;303(8):563-72.

Asiaticoside suppresses collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts.[Pubmed: 21240513 ]

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.
METHODS AND RESULTS:
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.
CONCLUSIONS:
Taken together, these results suggest that Asiaticoside could be of potential use in the treatment and/or prevention of hypertrophic scars and keloids.

Phytother Res. 2013 Aug;27(8):1136-42.

Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide-treated rat through up-regulation of heme oxygenase-1.[Pubmed: 22972613 ]

Asiaticoside (AS), a triterpenoid isolated from Centella asiatica, has been found to exhibit antioxidant and anti-inflammatory activities in several experimental animal models. However, the underlying mechanisms remain elusive.
METHODS AND RESULTS:
In this study, we provide experimental evidences that AS dose-dependently inhibited lipopolysaccharide (LPS)-induced fever and inflammatory response, including serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, liver myeloperoxidase (MPO) activity, brain cyclooxygenase-2 (COX-2) protein expression and prostaglandin E2 (PGE2 ) production. Interestingly, AS increased serum IL-10 level, liver heme oxygenase-1 (HO-1) protein expression and activity. Furthermore, we found that the suppressive effects of AS on LPS-induced fever and inflammation were reversed by pretreatment with ZnPPIX, a HO-1 activity inhibitor. In summary, our results suggest that AS has the antipyretic and anti-inflammatory effects in LPS-treated rat.
CONCLUSIONS:
These effects could be associated with the inhibition of pro-inflammatory mediators, including TNF-α and IL-6 levels, COX-2 expression and PGE2 production, as well as MPO activity, which might be mediated by the up-regulation of HO-1.

2018 Feb;17(2):2893-2900.

Effect of asiaticoside on endothelial cells in hypoxia‑induced pulmonary hypertension[Pubmed: 29257311]

Pulmonary hypertension (PH) is a chronic progre-ssive disease with limited treatment options. The exact etiology and pathogenesis of PH remain to be elucidated, however there is novel evidence that implicates abnormal endothelial cells (ECs) apoptosis and dysfunction of ECs to be involved in the initiation of PH. Asiaticoside (AS) is a saponin monomer extracted from a medicinal plant called Centella asiatica, which had a preventing effect of hypoxia‑induced pulmonary hypertension (hypoxic PH) by blocking transforming growth factor‑β1/SMAD family member 2/3 signaling in our previous study. The present study demonstrated that AS can prevent the development of hypoxic PH and reverse the established hypoxic PH. AS may activate the nitric oxide (NO)‑mediated signals by enhancing the phosphorylation of serine/threonine‑specific protein kinase/eNOS, thus promoting NO production, and prevent ECs from hypoxia‑induced apoptosis. All these findings imply that AS may be a potential therapeutic option for hypoxic PH patients due to its effect on the vitality and function of endothelial cells.

J Ethnopharmacol. 1999 Apr;65(1):1-11.

In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica.[Pubmed: 10350364]

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

Int Immunopharmacol. 2015 May;26(1):181-7.

Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway.[Pubmed: 25835778]

Asiaticoside (AS), a triterpene glycoside isolated from Centella asiatica, has been shown to possess potent anti-inflammatory activity. However, the detailed molecular mechanisms of AS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in mice are scanty. The purpose of this study was to evaluate the effect of AS on LPS-induced mouse ALI via down-regulation of NF-κB signaling pathway.
METHODS AND RESULTS:
We investigated the efficacy of AS on cytokine levels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW 264.7 cells. The production of cytokine (TNF-α and IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The lung wet-to-dry weight ratios were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. To further study the mechanism of AS protective effects on ALI, the activation of NF-κB p65 subunit and the degradation of IκBα were tested by western blot assay. We found that AS treatment at 15, 30 or 45mg/kg dose-dependently attenuated LPS-induced pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS.
CONCLUSIONS:
Furthermore, our results suggested that AS suppressed inflammatory responses in LPS-induced ALI through inhibition of the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα, and might be a new preventive agent of ALI in the clinical setting.

Pharmacol Biochem Behav. 2008 May;89(3):444-9.

Antidepressant-like effect of asiaticoside in mice.[Pubmed: 18325568 ]

METHODS AND RESULTS:
In the present study, the potential antidepressant properties of Asiaticoside were investigated in male mice in three tests -- splash test in the unpredictable chronic mild stress (CMS) model, tail suspension test (TST), forced swimming test (FST) -- with clomipramine being a positive control. In the splash test, Asiaticoside (10 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly augmented the frequency of grooming behavior in stressed mice. In the tail suspension test, Asiaticoside (10, 20 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly decreased immobility time. In the forced swimming test, Asiaticoside (10, 20 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly decreased immobility time.
CONCLUSIONS:
These results suggest that Asiaticoside may have antidepressant-like action.

Phytomedicine. 2010 Aug;17(10):811-9.

Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice.[Pubmed: 20171071 ]

Asiaticoside (AS), a triterpenoid product isolated from Centella asiatica, has been described to exhibit anti-in fl ammatory activities in several inflammatory models. However, the effects of AS on liver injury are poorly understood.
METHODS AND RESULTS:
The present study was undertaken to investigate whether AS is efficacious against Lipopolysaccharide (LPS) /D-galactosamine (D-GalN)-induced acute liver injury in mice and its potential mechanisms. AS (5, 10 and 20 mg/kg/d) was pretreated orally once daily for 3 days before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, plasma levels of Tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic tissue TNF-alpha and caspase-3 activity were measured. Besides, western blotting analysis of phospho-p38 mitogen-activated protein kinase (phospho-p38 MAPK), phospho-c-jun N-terminal kinase (phospho-JNK) and phospho-extracellular signal regulated kinase (phospho-ERK) were determined. As a result, AS showed significant protection as evidenced by the decrease of elevated aminotransferases, hepatocytes apoptosis and caspase-3, alleviation of mortality and improvement of liver pathological injury in a dose-dependent manner. Further, we found that AS dose-dependently reduced the elevation of phospho-p38 MAPK, phospho-JNK, phospho-ERK protein and TNF-alpha mRNA expression in liver tissues and plasma TNF-alpha.
CONCLUSIONS:
These results suggest that AS has remarkable hepatoprotective effects on LPS/D-GalN-induced liver injury and the possible mechanism is related to inhibition of TNF-alpha and MAPKs.

J Neurosci Res. 1999 Nov 1;58(3):417-25.

Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity.[Pubmed: 10518115]

Asiaticoside (AS) derivatives were tested for potential protective effects against Abeta-induced cell death. Of the 28 AS derivatives tested, asiatic acid (AA), Asiaticoside 6 (AS6), and SM2 showed strong inhibition of Abeta-induced death of B103 cells at 1 microM.
METHODS AND RESULTS:
The three AS derivatives were further tested for their effects on free radical injury and apoptosis. All three AS derivatives reduced H(2)O(2)-induced cell death and lowered intracellular free radical concentration, but AA showed the strongest protection. In contrast, SM2 was the most effective blocker of staurosporine-induced apoptosis. These results suggest that the three AS derivatives block Abeta toxicity by acting through different cellular mechanisms. When applied to hippocampal slices, AA, SM2, and AS6 did not alter n-methyl-D-aspartic acid (NMDA) or non-NMDA receptor-mediated synaptic transmission, paired-pulse facilitation or induction of long-term potentiation in the field CA1.
CONCLUSIONS:
These results indicate that the three AS derivatives do not alter physiological properties of the hippocampus at the concentration that blocks Abeta-induced cell death. Therefore AS6, AA, and SM2 can be regarded as reasonable candidates for a therapeutic Alzheimer's disease drug that protects neurons from Abeta toxicity.

Ai Zheng. 2004 Dec;23(12):1599-604.

Asiaticoside inducing apoptosis of tumor cells and enhancing anti-tumor activity of vincristine.[Pubmed: 15601545]

Asiaticoside (ATS), a triterpene extracted from Centella asiatica (L.) Urban, a traditional Chinese herb, possesses good wound healing activities because of its stimulative effect on collagen synthesis. Recently, the anti-tumor effect of asiaticiside has been reported. This study was to examine the induction of apoptosis in cancer cells, and the enhancement of vincristine (VCR) cytotoxicity by Asiaticoside.
METHODS AND RESULTS:
MTT assay was used to evaluate inhibitory effect of Asiaticoside combined with vincristine on proliferation of several cancer cell lines, including KB, KBv200, MCF-7, and MCF-7/ADM. Cell cycle, and apoptosis of KB cells were analyzed by flow cytometry; apoptosis induction was also proved by electrophoresis,and morphologic assessment; the expression of apoptosis-, and cell cycle-related proteins were determined by Western blot. The IC(50) values of Asiaticoside for KB, KBv200, MCF-7, and MCF-7/ADM cells detected by MTT assay were (1.11+/-0.13) mg/ml, (1.82+/-0.08) mg/ml, (1.58+/-0.15) mg/ml, and (3.25+/-0.46) mg/ml, respectively. Multidrug resistant KBv200, and MCF-7/ADM cancer cells displayed similar sensitivity to Asiaticoside as their parental counterparts (KB, and MCF-7 cells). Moreover, Asiaticoside induced apoptosis in KB cells. At sub-cytotoxicity concentration, Asiaticoside showed synergistic effect with vincristine in these 4 cell lines. The apoptosis rates were much higher in Asiaticoside plus vincristine groups than in vincristine or Asiaticoside groups. Bcl-2 phosphorylation levels were higher in the combination groups than in vincristine or Asiaticoside alone groups. The activated caspase-3 protein was only presented in the combination groups. Asiaticoside plus vincristine enhanced S-G(2)/M arrest, up-regulated Cyclin B1 protein expression, and down-regulated P34(cdc2) protein expression in KB cells.
CONCLUSIONS:
Asiaticoside, as a biochemical modulator, may induce apoptosis,and enhance anti-tumor activity of vincristine in cancer cells, might be useful in cancer chemotherapy.

Life Sci. 2004 Mar 19;74(18):2237-49.

The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats.[Pubmed: 14987949 ]

METHODS AND RESULTS:
In this study, the healing effects of Centella asiatica water extract (CE) and Asiaticoside (AC), an active constituent of CE, on acetic acid induced gastric ulcers (kissing ulcers) in rats were examined. CE was prepared from Centella asiatica dry plant and the concentration of AC in CE was quantitatively determined with the use of high performance liquid chromatography analysis. Different concentrations of CE and AC were orally administered to rats with kissing ulcers. They were found to reduce the size of the ulcers at day 3 and 7 in a dose-dependent manner, with a concomitant attenuation of myeloperoxidase activity at the ulcer tissues. Epithelial cell proliferation and angiogenesis were on the other hand promoted. The expression of basic fibroblast growth factor, an important angiogenic factor, was also upregulated in the ulcer tissues in rats treated with CE or AC.
CONCLUSIONS:
These results further suggest the potential use of Centella asiatica and its active ingredient as anti-gastric ulcers drugs.

Pharmacol Biochem Behav. 2006 Oct;85(2):339-44.

Anxiolytic-like effect of asiaticoside in mice.[Pubmed: 17059844]

The putative anxiolytic activity of Asiaticoside was examined in male mice by using a number of experimental paradigms of anxiety, with diazepam being as a positive anxiolytic control.
METHODS AND RESULTS:
In the elevated plus-maze test, diazepam (1 and 2 mg/kg) or Asiaticoside (5 or 10 mg/kg) increased the percentage of entries into open arms and of time spent on open arms. In the light/dark test, as with 1 mg/kg diazepam, Asiaticoside (10 and 20 mg/kg) increased the time spent in the light area and the movement in the light area without altering the total locomotor activity of the animals. In the hole-board test, Asiaticoside at 10 mg/kg significantly increased head-dipping counts and duration as well as diazepam (0.3 mg/kg).
CONCLUSIONS:
Thus, these findings indicated that Asiaticoside exhibited an anxiolytic-like effect. Further studies will be required to assess the generality of present findings to other species and behavioural paradigms.

Exp Toxicol Pathol. 2011 Sep;63(6):519-25.

Protective effects of asiaticoside on septic lung injury in mice.[Pubmed: 20471230 ]

Asiaticoside (AS), a major triterpenoid saponin component isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities.
METHODS AND RESULTS:
The present study aimed to determine the protective effects and the underlying mechanisms of AS on septic lung injury induced by cecal ligation and puncture (CLP). Mice were pretreated with the AS (45 mg/kg) or AS as well as GW9662 at 1h before CLP, the survival, lung injury, inflammatory mediators and signaling molecules, and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined 24 h after CLP. The results showed that AS significantly decreased CLP-induced the mortality, lung pathological damage, the infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. Moreover, AS inhibited CLP-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Interestingly, the expression of PPAR-γ protein in lung tissue was up-regulated by AS. Furthermore, GW9662 (the inhibitor of PPAR-γ) significantly reversed these beneficial effects of AS in septic mice.
CONCLUSIONS:
These findings suggest that AS could effectively protect from septic lung injury induced by CLP and the underlying mechanisms might be related to up-regulation of PPAR-γ expression to some extent, which inhibits MAPKs and NF-κB pathway.