| Description: |
Asiaticoside, a biochemical modulator, which has antioxidant, anti-inflammatory, antipyretic, anxiolytic-like, anti-gastric ulcers, hepatoprotective, and antidepressant-like effects, it also exhibits significant wound healing activity in normal as well as delayed healing models. Asiaticoside suppressed collagen expression and TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts. It and its derivatives can be regarded as reasonable candidates for a therapeutic Alzheimer's disease drug that protects neurons from Abeta toxicity. |
| Targets: |
NF-kB | TNF-α | IL Receptor | p65 | IkB | TGF-β/Smad | p38MAPK | JNK | ERK | Caspase | COX | PGE | PPAR | NOS | Bcl-2/Bax | Beta Amyloid | IKK |
| In vitro: |
| 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. |
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| In vivo: |
| 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. |
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