Targeted inhibition of STAT3 (Tyr705) by xanthatin alleviates osteoarthritis progression through the NF-κB signaling pathway.

The transcription factor, signal transducer, and stimulator of transcription 3 (STAT3) is a potential target in osteoarthritis (OA) treatment. Although xanthatin (XA), a biologically active substance derived from Xanthium strumarium L, specifically inhibits STAT3 phosphorylation at Tyr705, the mechanism underlying its inhibitory effect on OA progression remains unclear. In this study, our objective was to explore the therapeutic effects exerted by XA on OA and the underlying molecular mechanisms. The effects of XA treatment on mouse OA models subjected to destabilization of the medial meniscus using medial collateral ligament transection, as well as on interleukin-1ß (IL-1ß)-induced mouse chondrocytes, were examined. Histological changes in cartilage and subchondral bone (SCB), as well as changes in the expression levels of osteophytes, cartilage degeneration- and osteoclast differentiation-related factors, and the role of XA-related signaling pathways in human cartilage tissue, were studied using different techniques. XA inhibited STAT3 phosphorylation at Tyr705 and further attenuated the activity of nuclear factor-κB (NF-κB) in chondrocytes and osteoclasts. In vitro, XA administration alleviated pro-inflammatory cytokine release, extracellular matrix catabolism, and RANKL-mediated osteoclast differentiation. In vivo, intraperitoneal injection of XA exerted a protective effect on cartilage degeneration and SCB loss. Similarly, XA exerted a protective effect on human cartilage tissue by inhibiting the STAT3/NF-κB signaling pathway. Overall, our study elucidated the therapeutic potential of XA as a small-molecule inhibitor of STAT3-driven OA progression. This discovery may help enhance innovative clinical interventions against OA.

Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a classic type of osteoporosis that has gradually become a significant health problem worldwide. There is an urgent need for a safe alternative therapeutic agent considering the poor therapeutic strategies currently available for this disease. The roots and bark of the Morus australis tree (Moraceae) are used to make a traditional Chinese medicine known as "Morusin", and accumulating evidence has demonstrated its multiple activities, such as anti-inflammatory and anti-tumor effects. OBJECTIVE: In this study, we aim to explore the effect of Morusin on mouse osteoclasts and its mechanism. METHODS: In this study, we explored the inhibitory effects of Morusin on murine osteoclasts in vitro and its mechanism, and the protective effect of Morusin on an ovariectomy (OVX)-induced osteoporosis model in vivo. RESULTS: The results showed that Morusin prevented OVX-induced bone loss and dramatically decreased RANKL-induced osteoclastogenesis. Morusin interfered with RANKL-activated NF- κB, MAPK, and PI3K/AKT signaling pathways. The expression of three master factors that control osteoclast differentiation, c-Fos, NFATc1, and c-Jun, was reduced by Morusin treatment. Collectively, in vitro results indicated that Morusin has a protective effect on OVX-induced bone loss in a mouse model. CONCLUSION: Our data provide encouraging evidence that Morusin may be an effective treatment for PMOP.

A new iridoid compound from Patrinia rupestris (Pall.) Juss.

Extraction of roots of Patrinia rupestris (Pall.) Juss. gave a new iridoid compound, 1ß,3α-diethyloxy-7-hydromethyl-4-(3-methyl-butyryloxymethyl)-cyclopenta-4(4a),7(7a)-diene[c]pyran-6-one (1), together with a known compound, (1α,4aα, 6α,7ß,7aα)-[4a,5,6,7,7a-hexahydro-6,7-dihydroxy-1-(3-methyl-1-oxobutoxy) cyclopenta[c]pyran-4,7-diyl]bis(methylene) 3-methyl-butanoic acid ester (2). The structure of 1 was characterised by HRESIMS, IR, UV, 1-D NMR and 2-D NMR methods. Compound 2 was isolated from this genus for the first time.

Eremophilane-type sesquiterpene lactones from Ligularia hodgsonii Hook.

A dimeric eremophilane sesquiterpene lactone with a cyclobutane ring, biliguhodgsonolide (1) and an uncommon seco-sesquiterpene derivative, (4S,5S,6R,10R)-8,9-seco-12-hydroxyeremophil-7(11)-en-14,6;12,8-diolid-9-al (2), were isolated from the roots and rhizomes of Ligularia hodgsonii Hook. Their structures, including the absolute stereochemistry, were elucidated by spectroscopic data and CD analysis. The cyclobutane ring was confirmed by single-crystal X-ray diffraction.

[Progressing study in osteoblasts cultured in vitro].

With the development of cell culture technology in vitro, people have successfully cultivated osteoblast cells of typical characteristics from a number of animal skull, bone marrow, periosteum and bone tissues; studies have shown that these osteoblasts have good biological characteristics, can create bone tissue in different environments, can apply joint stand for the construction of tissue engineered bone, be implanted in the body to repair bone defects. In this article, the source of osteoblast, regulatory factor, composite graft and Chinese medicine research progress were reviewed.