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Background: Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis.Methods: AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800 mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot.Results: Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-α, IL-1 β, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1.Conclusion: KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug. [ABSTRACT FROM AUTHOR]

The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named "heilaohu", having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC 50 value of 9.37 μM. In the same line, nine compounds exhibited significant inhibition effects against TNF − α and IL-6 release in the LPS-induced RAW264.7 cells with IC 50 values ranging between 1.03 and 10.99 μM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF- k B and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies. [Display omitted] • Two undescribed sesquiterpenes were isolated from roots of K. coccinea. • Nine compounds exhibited significant anti-inflammation effects. • Compound 19 was good cytotoxic against RA-FLS cells with an IC 50 value of 9.37 μM. • The potential molecular mechanisms established by pharmacological network analysis. • Compound 19 suppressed inflammation by inhibiting the NF-κB and JAK2/STAT3 pathways. [ABSTRACT FROM AUTHOR]

Tujia ethnomedicine Xuetong (the stems of Kadsura heteroclita) have been widely used in folk for rheumatoid arthritis (RA), which can alleviate rheumatic pain through liquor soaking in folk. In this study, we aimed to evaluate the pharmacological effects and underlying mechanism of Xuetongsu (a key chemical component of Xuetong) on bone destruction. In our previous study, it was found that Xuetong extract can reduce adjuvant arthritic rats paw swelling and inhibit inflammatory factors in serum. Furthermore, Xuetongsu has been demonstrated to inhibit the proliferation of fibroblast-like synoviocytes, but its potential to inhibit bone destruction has not been explored. To address this, we employed the STRING database to predict protein interactions and utilized Autodock software to simulate the binding of Xuetongsu to target proteins. In this study, administration of Xuetongsu significantly alleviated paw swelling and bone destruction in C57BL/6 mice with collagen-induced arthritis (CIA). Mechanistic studies have indicated that Xuetongsu promotes apoptosis of mature osteoclasts in joint tissues by activating Caspase-3 and Bax, while inhibiting Bcl-2. Additionally, Xuetongsu inhibits osteoclast differentiation by suppressing RANKL, RANK, P -NF-κB, and NFATc1, and reduces bone resorption activity by inhibiting MMP-9, CTSK, and TRAP. Importantly, Xuetongsu exhibits good biocompatibility in major organs of mice. In summary, Xuetongsu has the potential to treat bone destruction by promoting apoptosis of mature osteoclasts, inhibiting osteoclast differentiation, and reducing bone resorption. This study reveals the pharmacological effects of Xuetongsu and its mechanism of action, which may contribute to the development of novel approaches for treating RA. [Display omitted] • Tujia ethnomedicine xuetong is widely used to treat RA and bone-related disease in folk. • Xuetongsu alleviates RA bone destruction by promoting osteoclasts apoptosis. • Xuetongsu inhibits osteoclast differentiation and bone resorption in CIA mice. [ABSTRACT FROM AUTHOR]

Four new dibenzocyclooctadiene lignans, named heilaohusus A-D (1 – 4), one new arylnaphthalene lignan named heilaohusu E (5), and seven known analogues (6 – 12) were isolated from the roots of Kadsura coccinea. Their structures and configurations were elucidated by a combination of HR-ESI-MS, 1H NMR, 13C NMR, HSQC, HMBC, NOESY and CD spectra. Among the known compounds, compounds 6 and 8 – 12 were isolated from this plant for the first time. All of compounds were evaluated for their cytotoxicity activities, compounds 3 , 6 and 7 showed weak cytotoxicity against four human cancer cell lines (HepG-2, HCT-116, BGC-823 and Hela) with IC 50 values range from 13.04 to 21.93 μ M. Compounds 1 and 7 demonstrated potential anti-RA (rheumatoid arthritis) activity against RA-FLS cell line with IC 50 values of 14.57 and 11.70 μ M, respectively. Unlabelled Image [ABSTRACT FROM AUTHOR]

Binglang, the fruit of Areca catechu L, has a long history as an important Chinese herbal medicine. Two new alkaloids (1 and 2), along with forty-one known compounds (3–43) were isolated from the dried fruit of Areca catechu L. The structures were elucidated on basis of the IR, UV, MS and 1D, 2D NMR spectroscopic data. Compounds 26 and 33 showed weak cytotoxicity against human gastric cancer cell line (BGC-823) with IC 50 of 15.91 μM and 20.13 μM, respectively. Unlabelled Image [ABSTRACT FROM AUTHOR]