更新于：2024-11-01

胶原蛋白II x TNF-α

更新于：2024-11-01

基本信息

关联

项与胶原蛋白II x TNF-α 相关的药物

TE-2100

靶点

胶原蛋白II x TNF-α

作用机制

胶原蛋白II拮抗剂 [+1]

在研机构

免疫功坊股份有限公司

原研机构

免疫功坊股份有限公司

在研适应症

强直性脊柱炎 [+2]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

TE-2150

靶点

胶原蛋白II x TNF-α

作用机制

胶原蛋白II拮抗剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与胶原蛋白II x TNF-α 相关的临床结果

登录后查看更多信息

100 项与胶原蛋白II x TNF-α 相关的转化医学

登录后查看更多信息

0 项与胶原蛋白II x TNF-α 相关的专利（医药）

登录后查看更多信息

302

项与胶原蛋白II x TNF-α 相关的文献（医药）

2024-12-01·International Immunopharmacology

Wedelolactone alleviates inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway in osteoarthritis

Article

作者: Feng, Jianguo ; Shi, Houyin ; Cui, Yinxing ; You, Wei ; Yue, Jiaji ; Liang, Jianhui ; Sun, Weichao ; Sun, Wei ; Yi, Qian ; He, Qifei

Inflammation and extracellular matrix (ECM) degradation are two major factors involved in the pathogenesis of osteoarthritis (OA). Wedelolactone, a natural compound classified as a coumestan, is isolated from the medicinal plants Eclipta alba and Wedelia calendulacea. In this study, we assessed the protective effects of Wedelolactone on chondrocytes in OA. Our findings show that pretreatment with Wedelolactone effectively inhibited the IL-1β-induced upregulation of COX‑2, iNOS, TNF-α, and IL6 in chondrocytes, contributing to inflammation suppression. Moreover, pretreatment with Wedelolactone followed by IL-1β treatment significantly increased the expression of Collagen II and SOX9, while decreasing the expression of Adamts5, MMP1, MMP3, and MMP13, thereby promoting ECM protection. Through Network pharmacology Analysis, we identified 14 key targets that link Wedelolactone and OA. GO and KEGG pathway analysis suggested that Wedelolactone primarily impacted OA by targeting inflammatory responses, particularly the NF-κB signaling pathway. Further studies demonstrated Wedelolactone prevented IL-1β-induced activation of NF-κB signaling pathway by inhibiting the translocation of p65 and the preventing the degradation of IκBα in human chondrocytes. Molecular docking studies also indicated that Wedelolactone can directly bind to the NF-κB complex, thereby inhibited the nuclear localization of p65. In vivo experiments demonstrated that Wedelolactone can alleviate cartilage damage in DMM mice model. In summary, Wedelolactone appears to mitigate inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway, thereby alleviating OA progression. Our results suggested Wedelolactone may offer therapeutic advantages for OA treatment.

2024-11-01·International Immunopharmacology

Phillyrin: A potential therapeutic agent for osteoarthritis via modulation of NF-κB and Nrf2 signaling pathways

Article

作者: Zheng, Rukang ; Sun, Zeming ; Tan, Hongye ; Ma, Jiawei ; Zhang, Hanwen ; Wu, Yaosen ; Wang, Ze ; Jin, Zebin ; Sun, Yun

Osteoarthritis (OA) is the predominant cause of disability among elderly people worldwide and is characterized by cartilage degeneration and excessive bone formation. Phillyrin, derived from forsythia, is a key extract renowned for its pronounced antibacterial and anti-inflammatory effects. Forsythia, deeply integrated into traditional Oriental medicine, has historically been utilized for its various pharmacological effects, including antibacterial, anti-inflammatory, and hepato-protective properties. Nevertheless, the anti-inflammatory impact of phillyrin on the progression of osteoarthritis remains enigmatic. The objective of this research was to assess the anti-inflammatory and anti-aging properties of phillyrin in mouse chondrocytes induced by IL-1β, as well as to elucidate the fundamental mechanisms underlying the phenomenon at play. Additionally, the investigation extends to observing the impact of phillyrin by establishing a murine osteoarthritic model. The ultimate goal was to identify phillyrin as a potential antiosteoarthritic agent. This investigation employs a multifaceted approach. Initially, key action targets of phillyrin, along with its probable action pathways, were identified by molecular docking and network pharmacological techniques. These findings were subsequently confirmed through both in vivo and in vitro studies. Network pharmacological analysis revealed NFE2L2 (NRF2), NFKB1, TLR4, and SERPING1 as pivotal candidate targets for the treatment of osteoarthritis with phillyrin. Molecular docking revealed hydrogen bond interactions between phillyrin and Arg415, Arg483, Ser508, and Asn387 on the Nrf2 receptor, while electrostatic interactions occurred with residues Arg415 and Arg380. Experiments conducted in vitro indicated that phillyrin preconditioning hindered the IL-1β-induced expression of proinflammatory factors which included TNF-α, COX-2, IL-6, and iNOS. Furthermore, phillyrin counteracts the IL-1β-induced degradation of aggrecan and collagen II within the extracellular matrix (ECM). This protective action is caused by the inhibition of the NF-κB pathway by phillyrin. Additionally, the mitigation of chondrocyte aging by phillyrin was observed. Our investigation revealed that phillyrin mitigates inflammation and counteracts cartilage degeneration in osteoarthritis (OA) patients by suppressing inflammation in chondrocytes and impeding aging through suppression of the NF-κB pathway.

2024-11-01·Naunyn-Schmiedeberg's Archives of Pharmacology

Sappanone a alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis via activating the SIRT1/Nrf2 signaling pathway

Article

作者: Ma, Xing ; Qiu, Yusheng ; Zhang, Zhi ; Zhang, Nanzhi ; Li, Meng

Osteoarthritis (OA) is a common degenerative joint disease that cause pain and disability in adults. Chondrocyte ferroptosis is found to be involved in OA progression. Sappanone A has been found as an anti-inflammatory and antioxidative agent in several diseases. This study aims to investigate the effects of sappanone A on OA progression and chondrocyte ferroptosis. IL-1β-induced chondrocytes and destabilization of the medial meniscus (DMM)-induced rats were respectively used as the OA model in vitro and in vivo. The effects of sappanone A on inflammation, extracellular matrix (ECM) metabolism, and ferroptosis were determined. Our results showed that in IL-1β-induced chondrocytes, sappanone A suppressed the production of NO, PGE2, TNF-α, IL-6, iNOS, and COX2. Sappanone A also inhibited the expression of MMP3, MMP13, and ADAMTS5, while increasing collagen II expression. Moreover, sappanone A alleviated cytotoxicity and decreased the levels of intracellular ROS, lipid ROS, MDA, and iron, while increasing GSH levels. Additionally, sappanone A increased the protein expression of SLC7A11 and GPX4. Administration of ferroptosis activator reversed the inhibitory effects of sappanone A on IL-1β-induced inflammation and ECM degradation. More importantly, Sappanone A activated the Nrf2 signaling by targeting SIRT1. The inhibition of sappanone A on ferroptosis was greatly eliminated due to the addition of SIRT1 inhibitor. Furthermore, intra-articular injection of sappanone A mitigated cartilage destruction and ferroptosis in DMM-induced OA rats. In conclusion, sappanone A protects against inflammation and ECM degradation in OA via decreasing chondrocyte ferroptosis by activating the SIRT1/Nrf2 signaling. These findings deepen our understanding of chondrocyte ferroptosis in OA and highlight the therapeutic potential of sappanone A for OA.