Antinociceptive, Anti-inflammatory, and Chondroprotective Activities of Cryptolepis buchanani Extract and the Efficacy of Its Oil Formulation in the Symptomatic Treatment of Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a more costly disease than rheumatoid arthritis in economic terms due to its higher prevalence. Approximately one-third of direct OA costs is allotted for medications. In Thailand, there are many herbs used in traditional and folk medicine for relieving joint pain such as Thao En On or Cryptolepis buchanai. Therefore, the present study aimed to investigate and evaluate the analgesic and anti-inflammatory activities of the methanol extract of stems of C. buchanani (CBE) in animal models as well as its chondroprotective activity in cartilage explants. CBE significantly reduced the acetic acid-induced writhing response in mice. It also inhibited the edema formation in both ethyl phenylpropiolate (EPP)-induced rat ear edema and carrageenan-induced rat paw edema. In cartilage explants, CBE significantly reduced the sulfated glycosaminoglycan (s-GAG) and hyaluronan (HA) released into the culture media while the cartilage matrix molecules such as uronic acid and collagen were reserved within the cartilage tissues. It also suppressed the matrix metalloproteinase-2 (MMP-2) activity without adverse effects on cell viability. To validate the clinical efficacy of C. buchanani, a randomized, double-blind, active controlled trial was performed to compare the efficacy of C. buchanani oil formulation (CBO) to 1% indomethacin (IDM) solution in symptomatic treatment of OA of knee for 4 weeks in 169 OA patients. The clinical assessments included visual analog scale (VAS) score for assessing joint’s pain and stiffness, Lequesne’s functional index (LI), time for climbing up 10 steps, as well as physician’s and patients’ overall opinion on improvement which were evaluated weekly until 4 weeks. After 4 weeks of treatment, all clinical parameters of both groups were significantly improved with no difference between groups. In per protocol analysis, the difference between groups was not significant for all assessment except for the morning stiffness. IDM significantly improved the morning stiffness better than that of CBO. The numbers of responders according to total pain reduction and to overall opinion on improvement of both groups were similar. The most common adverse events were pruritus and rash at the application sites with significantly higher occurrence in IDM group than CBO group. In conclusion, CBE shows analgesic, anti-inflammatory, and chondroprotective effects in this preliminary study. In addition, CBO demonstrates clinical efficacy on the treatment of symptomatic OA of knee comparable to IDM solution with lower rate of adverse events. Therefore, C. buchanani may be useful as an alternative treatment of OA. Further investigations of the mechanism of actions and to uncover the active compound(s) of C. buchanani are warranted.