withaferin-a and Osteoarthritis

The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity.. This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study.. Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound.. Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Humans; Molecular Structure; Neoplasms; Nervous System; Osteoarthritis; Phytotherapy; Plant Extracts; Stress, Physiological; Withania

Withaferin A (WFA), a highly oxygenated withanolide is used for anti-osteoporotic, fracture healing, obesity control as medicine and dietary supplement in Ayurveda and Unani medicine but its potential remains to be investigate for the osteoarthritis studies. In the present study, chondro-protective effects of WFA, under in vitro and in vivo conditions were evaluated. In-vitro pharmacological activity of WFA was tested on rat articular chondrocytes through MTT, DPPH, different staining, FACS and translation studies. In-vivo studies of WFA were evaluated through monosodium iodoacetate (MIA) induced osteoarthritis studies. DPPH assay, alcian blue and toluidine blue staining indicated the chondrogenic potential of WFA. Similarly, WFA enhance chondrogenesis through up-regulation of SOX9 protein. In addition, WFA reduced the ROS generation, mitochondrial depolarization and apoptosis induced by inflammatory cytokines IL-1β and TNF-α. Furthermore, WFA treatment in MIA treated rats alleviated cartilage erosion and improvement in sub-chondral bone micro-architecture by decrease in Tissue volume (∼32%), and trabecular bone pattern factor (∼28%). Taken together, our study provides convincing evidence for the candidature of WFA (10 mg kg

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Bone and Bones; Cartilage, Articular; Cell Differentiation; Cells, Cultured; Chondrogenesis; Disease Models, Animal; Female; Gene Expression Regulation; Iodoacetates; Osteoarthritis; Rats, Sprague-Dawley; Up-Regulation; Withanolides

Increasing evidence supports the role of microRNAs (miRNA) in the regulation of inflammation in various human disorders. Several recent studies have demonstrated that microRNA-25 (miR-25) has multiple functions, and it affects the expression of inflammatory mediators. Withaferin A (WFA), a natural compound derived from the medicinal plant Withania somnifera, has shown the potential to be an effective drug for arthritis treatment in several preclinical and clinical studies. We investigated the role of miR-25 in the WFA-mediated up-regulation of cyclooxygenase-2 (COX-2) expression in rabbit articular chondrocytes. WFA induced COX-2 expression in a dose-dependent manner as analyzed by western blot analysis and immunofluorescence staining in rabbit articular chondrocytes. WFA up-regulated miR-25 expression as determined by real-time PCR. Overexpression of miR-25 in the presence of WFA increased the expression of COX-2 compared to that observed with just WFA treatment alone, as indicated by western blot analysis and Real-time PCR. Moreover, silencing of miR-25 by anti-miR25 inhibited COX-2 expression in a dose-dependent manner. Since miR-25 up-regulation by WFA treatment induced the expression of COX-2 in rabbit articular chondrocytes, these findings collectively suggest that miR-25 mediates the WFA-induced inflammatory responses in chondrocytes.

Topics: Animals; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Dose-Response Relationship, Drug; Gene Expression; Joints; MicroRNAs; Molecular Targeted Therapy; Osteoarthritis; Phytotherapy; Rabbits; Up-Regulation; Withania; Withanolides