TY - JOUR
T1 - Prevention of articular cartilage degeneration in a rat model of monosodium iodoacetate induced osteoarthritis by oral treatment with Withaferin A
AU - Choudhary, Dharmendra
AU - Adhikary, Sulekha
AU - Ahmad, Naseer
AU - Kothari, Priyanka
AU - Verma, Ashwni
AU - Trivedi, Prabodh Kumar
AU - Mishra, Prabhat Ranjan
AU - Trivedi, Ritu
N1 - Publisher Copyright:
© 2017
PY - 2018/3
Y1 - 2018/3
N2 - 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−1 day−1) as a potential agent for the treatment of cartilage degenerative diseases like osteoarthritis.
AB - 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−1 day−1) as a potential agent for the treatment of cartilage degenerative diseases like osteoarthritis.
KW - Cartilage
KW - Chondrocytes
KW - Interleukin-1β
KW - Monosodium iodoacetate
KW - Osteoarthritis
UR - http://www.scopus.com/inward/record.url?scp=85040225363&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2017.12.113
DO - 10.1016/j.biopha.2017.12.113
M3 - Article
C2 - 29331761
AN - SCOPUS:85040225363
SN - 0753-3322
VL - 99
SP - 151
EP - 161
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -