Curculigoside exerts significant anti‑arthritic effects in�vivo and in�vitro via regulation of the JAK/STAT/NF‑κB signaling pathway

Abstract

The present study aimed to investigate the anti-arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro , as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-12 and IL-17A. Furthermore, indices of the thymus and spleen were determined. The anti-proliferative effects of curculigoside were detected with Cell Counting kit-8 assays in rheumatoid arthritis-derived fibroblast-like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)-κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen-induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF-α, IL-1β, IL-6, IL-10, IL-12 and IL-17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration-dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)-κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti-arthritic effects in vivo and in vitro , and the molecular mechanism may be associated with the JAK/STAT/NF-κB signaling pathway.

JAK3 and TYK2 Serve as Prognostic Biomarkers and Are Associated with Immune Infiltration in Stomach Adenocarcinoma

“…Moreover, NF- κ B suppression can inhibit tumor cell growth and promote cell apoptosis in cholangiocarcinoma [ 33 ]. Increasing evidence has also highlighted the significant role of JAK/STAT/NF- κ B signaling pathway in the immune response, axial spondyloarthritis, type 2 diabetes, metabolic disorders, and cancers [ 34 – 38 ]. Thus, JAK3 and TYK2 may exert functions in STAD via JAK-STAT and NF- κ B signaling pathway.…”

JAK/STAT pathway in pathology of rheumatoid arthritis (Review)

“…The JAK/STAT signaling pathway not only regulates cytokine signaling but is also implicated in the production of anti-inflammatory cytokines, thereby having a key role in the signaling related to neuropoietic cytokines (36,37). This pathway provides a similar role in the pathogenesis of RA, whereby JAK molecules can activate specific immune cells and induce the expression of pro-inflammatory cytokines, with regulation being achieved through JAK1 and JAK3 through cytokine binding (38).…”

“…Medication used in the treatment of RA includes: synthetic disease-modifying anti-rheumatic drugs (DMARDs), biologic agents such as TNF-α inhibitors, interleukin inhibitors (IL-6 inhibitor), B cell-depleting agents, targeted synthetic disease-modifying anti-rheumatic drugs (tDMARDs) such as Janus kinase inhibitors (JAKinibs), along with symptomatic, considered to be fast-acting drugs i.e. nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (38,42,43).…”

Therapeutic Anabolic and Anticatabolic Benefits of Natural Chinese Medicines for the Treatment of Osteoporosis

“…They are native to the tropical and subtropical regions of Asia, Africa, South America, and Oceania (Nie et al, 2013). Curculigo orchioides Gaertn (CO, “Xian Mao”), one of curculigo species, is used to relieve the symptoms of limb weakness, lumbar and knee joint arthritis, and diarrhea in Chinese medicine (Tan et al, 2019). Recent studies have found that CO also appears to have antioxidant properties and anticancer potential, and may be used as an antiosteoporotic herb (Cao et al, 2008; Ramchandani et al, 2014; Hejazi et al, 2018).…”