The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro

Abstract

Using a validated explant model of in vitro cartilage damage, the effects of aqueous extracts of Withania somnifera (Ashwagandha) root and glucosamine sulphate (GlcS) were tested on the levels of nitric oxide (NO) and glycosaminoglycans (GAGs) secreted by knee cartilage from chronic osteoarthritis (OA) patients. W. somnifera extracts significantly decreased NO release by explants from one subset of patients (antiinflammatory response) and significantly increased levels of NO and GAGs released by explants from the second subset ('non-responders'). This is the first study showing direct, statistically significant, antiinflammatory effects of W. somnifera on human OA cartilage. It also confirmed that glucosamine sulphate exhibited statistically significant, antiinflammatory and chondroprotective activities in human OA cartilage. However, these beneficial effects of GlcS were observed in cartilage explants from 50% of patients tested ('responders'). In contrast, glucosamine significantly increased secretion of NO but not GAGs in explants from the second subset of OA patients ('non-responders'). Cartilage explants from the 11 OA patients gave differential responses to both drugs. Patient samples which responded to the antiinflammatory effects of W. somnifera did not always give a similar response to glucosamine, and vice versa. Thus, this in vitro model of human cartilage damage provides qualitative and statistically significant, quantitative pre-clinical data on antiinflammatory and chondroprotective activities of antiarthritic drugs.

Chlorinated withanolides from Withania somnifera

“…Previous research supports its pharmacological uses, confirming antioxidant, anti-inflammatory (Sumantran et al, 2008), immunomodulatory, anticarcinogenic, antibacterial (Owais et al, 2005), antiparkinsonism (Sankar et al, 2007) and antistress (Geetha and Harish, 2006) properties. Raw plant material and extracts of this species are currently sold as dietary supplements in the USA for increasing energy and endurance, strengthening immune function, and helping the body overcome imbalance.…”

Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee

“…Nutritional supplements of many types have been utilized for arthritis, and those containing glucosamine and chondroitin sulfate have been shown to provide pain relief [6]. Other supplements have been tried, but evidence in favor of their use is generally limited to anecdotal experience or in vitro effects [7,8]. …”

Prophylactic effect of <i>Withania somnifera</i> on inflammation in a non-autoimmune prone murine model of lupus

“…Elevated NO levels in the ascitic fluid and ROS production by peritoneal macrophages in the PT group were found to be decreased in WS1000 and WS500 groups. Sumantran et al (29) using an explant model of in vitro cartilage damage study on patients with osteoarthritis have also shown marked reduction in NO release when treated with WS root extract.…”