Antifibrotic effect of <i>Centella asiatica</i> Linn and asiatic acid on arecoline‐induced fibrosis in human buccal fibroblasts

Adtani, Pooja; Narasimhan, Malathi; Punnoose, Alan M.; Kambalachenu, Himavanth Reddy

doi:10.1111/jicd.12208

Cited by 28 publications

(30 citation statements)

References 22 publications

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“…AA shows promising potential for the treatment of periodontitis. Further, AA exhibited an antifibrotic effect in primary human buccal fibroblasts induced by arecoline (Adtani et al, 2017 ). AA showed salvage of fibroblast morphology mediating inhibition of transforming growth factor-β1, collagen 1 type 2, and collagen 3.…”

Section: Asiatic Acid In Periodontitismentioning

confidence: 99%

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

et al. 2018

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Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics.

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Section: Asiatic Acid In Periodontitismentioning

confidence: 99%

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

et al. 2018

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“…Previous studies suggested that AA possessed a wide range of pharmacological properties, including antihepatofibric, neuroprotective, anti-inflammatory, anti-diabetic and antitumor activities ( 9 ). As for antitumor effect, AA was reported to induce apoptosis in hepatic and breast cancer cell lines and other tumor cells ( 10 , 11 ). The efficacy of AA was possibly attributed to the inhibition of nuclear factor-κB, p38 mitogen-activated protein kinase and extracellular signal-regulated kinase, as well as the change of Bcl-2 and caspase family proteins.…”

Section: Introductionmentioning

confidence: 99%

Asiatic acid inhibits proliferation, migration and induces apoptosis by regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K signaling pathway in human colon carcinoma cells

Hao

Huang

et al. 2018

Oncol Lett

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Previous studies have demonstrated that asiatic acid (AA), the major component of Centella asiatica, is able to meditate cytotoxic and anticancer effects on various types of carcinoma cells. In order to investigate the molecular mechanism that underlies the antitumor effect of AA, the present study investigated the effects of AA on proliferation, migration and apoptosis of SW480 and HCT116 colon cancer cells. Viability and changes in cell morphology in the cells were assessed by MTT assay and transmission electron microscopy, respectively. Colony formation analysis was used to observe proliferation of the single cell, and migratory ability of the cells was assessed by performing Transwell migration assay. Hoechst 33342 nuclear staining and flow cytometry were used to assess apoptosis in colon carcinoma cells. The expression of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70S6K signaling pathway and epithelial-mesenchymal transition (EMT) marker were analyzed by western blotting. The present study revealed that proliferation and migration of colon carcinoma cells were inhibited by AA in a dose-dependent and time-dependent manner. Numerous apoptotic bodies were observed, and G2/M and S phase progression were delayed in colon cancer cells treated with AA, but not in the control group. A number of phosphorylated proteins, including PI3K, Akt (Ser473), mTOR, ribosomal protein S6 kinase (p70S6K) downregulated, while the expression of Pdcd4 was upregulated following treatment with AA. Additionally, AA affects expression of EMT markers in a dose-dependent manner. On the basis of these results, it was concluded that AA inhibited proliferation, migration and induced apoptosis of colon cancer cells by regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K signaling pathway. These observations suggest that AA may be a potential therapeutic agent for the treatment of colon carcinoma.

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“…In the present study, ROS administered in the form of subcutaneously injected HOCl was used to induce SSc in a mouse model that has been widely used since 2009 (22). Preliminary experiments in SSc mice were also performed by assessing the effects of different doses of HOCl as described previously (7,20,(28)(29)(30), 300 µl was chosen as the optimal dose. This model mimicked the diffuse cutaneous form of human SSc, which exhibited increased collagen deposition, inflammatory infiltration in the lungs and autoimmune activation compared with control mice.…”

Section: Discussionmentioning

confidence: 99%

Asiatic acid prevents the development of interstitial lung disease in a hypochlorous acid‑induced mouse model of scleroderma

et al. 2018

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Interstitial lung disease is the most common complication of systemic sclerosis (SSc) and is associated with a high rate of mortality. Due to the complex pathogenesis of SSc, the therapies currently available remain limited. In the present study, the effect of asiatic acid (AA) on SSc-associated pulmonary fibrosis (PF) and its association with the transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway were evaluated. A hypochlorous acid (HOCl)-induced model of SSc was used to evaluate the therapeutic effect of AA on PF in SSc, where AA was administered to SSc mice by gavage. PF was alleviated in the AA-treated SSc mice groups when examined under light microscopy. In addition, there was a decrease in histopathological progression and collagen in the lungs. AA significantly reduced expression of type I collagen in the lungs of mice with SSc. It also significantly suppressed α-smooth muscle actin expression, which attenuated the conversion of fibroblasts into muscle fibroblasts. These AA-associated antifibrosis and anti-immune effects were mediated through the significant downregulation of advanced oxidation protein product, E-selectin, and anti-DNA topoisomerase-1 autoantibody levels in the serum. Furthermore, the expression levels of TGF-β1 and the phosphorylated-Smad2/3/Smad2/3 ratios in AA-treated SSc mice were similar to the control. The presence of pulmonary inflammation and fibrosis was confirmed in the HOCl-induced SSc mice and the results demonstrated that selective inhibition of reactive oxygen species prevented PF. By focusing on the classical TGF-β1/Smad2/3 signaling pathway, a mechanism of action of AA was identified to be associated with the inhibition of Smad2/3 activation through negative regulation of Smad2/3 phosphorylation.

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Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline‐induced fibrosis in human buccal fibroblasts

Abstract: CA and AA can be used as antifibrotic agents.

Cited by 28 publications

References 22 publications

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

Asiatic acid inhibits proliferation, migration and induces apoptosis by regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K signaling pathway in human colon carcinoma cells

Asiatic acid prevents the development of interstitial lung disease in a hypochlorous acid‑induced mouse model of scleroderma

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