In vivo anti-rheumatoid arthritis activity and mechanistic insights of methanol extract of Zanthoxylum usambarense Engl.
摘要
This study aimed to determine the in vivo anti-rheumatoid arthritis potential and mechanistic insights of methanol extract of Zanthoxylum usamberense. Thirty rats were randomly classified into normal control, rheumatoid arthritis (RA) control, methotrexate control, and extract-treated (100, 200, and 300 mg/kg body weight) groups. RA was induced using complete Freund’s adjuvant. All treatments were administered orally for 21 days from day 8 post-induction of RA. On day 29, the rats were euthanized, and blood was drawn for hematological parameters analysis. The ankle joint tissue and liver were excised and utilized in gene expression and antioxidant assays, respectively. Phytochemical screening was undertaken using GC–MS and LC–MS. The effect of the extract significantly reduced levels of MDA, CRP, WBCs, and ESR; arthritis scores; ankle joint edema; and indices of spleen and thymus compared to RA control (p < 0.05). The extract also significantly enhanced activities of SOD and GPx and levels of RBCs and Hb relative to RA control (p < 0.05). Further, the extract significantly downregulated levels of NF-κB, IL-1β, IL-6, MMP-3, RANKL, and TNF-α genes, as well as upregulated expression of I-κBα, IL-4, and IL-10 genes compared to RA control (p < 0.05). The LC–MS analysis identified phytocompounds such as dihydroberberine, gamma-sanshool, laudanine, dihydrochelerythrine, ochotensine, and quercetin. The GC–MS screening identified phytochemicals such as methyl palmitate, sandaracopimara-8(14),15-diene, and stanozolol. These phytocompounds have been established to exert anti-rheumatoid arthritis effects. In conclusion, the extract exhibits potent anti-rheumatoid arthritis activity and may be a potential candidate in developing alternative agents against RA.
Graphical abstract