Antiarthritic Potential of Comprehensively Standardized Extract of Alternanthera bettzickiana: In Vitro and In Vivo Studies

[Image: see text] Alternanthera bettzickiana is being used as a folk remedy for treating arthritis by conventional healers in Thailand. The current research was undertaken to explore the antiarthritic potential of A. bettzickiana ethanolic extract (ABEE). Plant characterization, molecular docking, and in vitro and in vivo (ABEE at 250, 500, and 1000 mg/kg was administered orally to rats once daily for 28 days) studies to explore the antiarthritic effect and enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) analyses were performed. Oxidative stress biomarkers (superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA)) in the serum and histopathological and radiographic assessment of joints were also carried out. Gallic acid, catechin, chlorogenic acid, sinapic acid, quercetin, and γ- and α-tocopherol were identified in high-performance liquid chromatography (HPLC). Molecular docking revealed a strong interaction between these compounds and cyclooxygenase (COX) enzymes. The extract significantly subdued paw swelling and arthritic scoring, inhibited cachexia, and considerably improved biochemical and hematological modifications. SOD and CAT levels increased and the MDA level decreased in ABEE-treated rats dose-dependently. Radiographic and histopathological analyses also supported the antiarthritic effect of ABEE, which was linked with the downregulation of nuclear factor (NF)-kB, COX-2, interleukin (IL)-6, tumour necrosis factor (TNF)-α, and IL-1β and upregulation of IL-10, I-kB, and IL-4 as compared to disease control rats. Results suggested that A. bettzickiana possessed antiarthritic potential, supporting its folkloric use for treating rheumatoid arthritis.