Ethnopharmacological and scientific validation of Caryota mitis Lour fruit peel for osteoarthritis and gout management.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine in Vietnam has long utilized Caryota mitis Lour fruit peel to relieve joint pain, back pain, and inflammation. Despite its widespread use, scientific validation of its therapeutic effects remains limited. The application of the fruit peel in disease treatment is largely based on anecdotal evidence, highlighting the need for rigorous scientific research to substantiate its efficacy and elucidate its mechanisms of action.

AIM OF THE STUDY: This study aimed to investigate the immunomodulatory effects, including anti-xanthine oxidase activity, reactive oxygen species (ROS) inhibition, and anti-inflammatory properties, alongside cartilage-protective effects such as in vitro chondrocyte proliferation, chondrogenic activity, and in vivo osteoarthritis treatment. Furthermore, phytochemical profiling was conducted to identify bioactive compounds in the fruit peel extract.

METHODS: Active compounds were extracted using various chromatographic techniques. Cytotoxicity and chondrogenic assays were performed on human chondrocytes to assess cellular responses. A model of LPS-induced RAW264.7 macrophages was used to evaluate nitric oxide (NO), interleukin-6 (IL-6), and interleukin-10 (IL-10) secretion, as well as ROS inhibition. Xanthine oxidase inhibition assays were conducted to assess the impact on uric acid production. In vivo efficacy was examined using a CFA-induced osteoarthritis mouse model, with histological analysis and biomarker quantification to assess cartilage regeneration and anti-inflammatory effects. The phytochemical profile was analysed using LC-MS/MS and molecular networking, while the chemical structures of isolated compounds were confirmed through spectral analysis.

RESULTS: All extracts-including crude ethanol (CME), hexane (CMH), chloroform (CMC), ethyl acetate (CMEA), and methanol (CMM)-significantly enhanced chondrocyte proliferation at concentrations below 1 μg/mL. At 0.1 μg/mL, CME, CMC, and CMEA strongly promoted cartilage formation. Additionally, CME, CMH, and CMEA exhibited potent immunomodulatory effects by reducing intracellular ROS, inhibiting xanthine oxidase activity, and suppressing inflammatory mediators such as NO and IL-6. In vivo, osteoarthritis-induced mice treated with CME exhibited significant cartilage regeneration, as evidenced by Safranin O staining and histopathological evaluation. The extract reduced ankle joint swelling, suppressed inflammatory cytokines, and improved cartilage integrity, demonstrating comparable efficacy to diclofenac treatment. Phytochemical analysis identified 18 bioactive compounds, primarily flavonoids and anthraquinones, in the fruit peel. Among them, emodin and esculetin, isolated from the CMEA fraction, demonstrated significant anti-inflammatory and xanthine oxidase inhibitory activities.

CONCLUSION: This study provides the first pharmacological validation of Caryota mitis fruit peel in joint disease management. The extracts exhibited immunomodulatory effects, cartilage-protective properties, and xanthine oxidase inhibition, supporting their potential role as a natural alternative to NSAIDs for osteoarthritis and gout. These findings underscore the need for further clinical research to facilitate the integration of Caryota mitis into modern phytotherapy.