Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage.Traditional treatments for OA are limited to alleviating various OA symptoms.There is a lack of ...Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage.Traditional treatments for OA are limited to alleviating various OA symptoms.There is a lack of drugs available in clinical practice that can truly repair cartilage damage.Here,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate A.In vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment.Binding prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 regulation.Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA rats.This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.展开更多
Three new lignan glucosides, baicalensinosides A-C (1-3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemica...Three new lignan glucosides, baicalensinosides A-C (1-3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofuran-type lignan glycoside with a mono-hydroxyl substitution at the 7'-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin (OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 mu mol/L, compounds 1-3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences(2022-I2M-2-002 and 2022-I2M-1e014,China)the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-JKCS-019,China).
文摘Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage.Traditional treatments for OA are limited to alleviating various OA symptoms.There is a lack of drugs available in clinical practice that can truly repair cartilage damage.Here,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate A.In vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment.Binding prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 regulation.Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA rats.This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.
基金supported by grants from National Natural Science Foundation of China(No.81361138020)
文摘Three new lignan glucosides, baicalensinosides A-C (1-3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofuran-type lignan glycoside with a mono-hydroxyl substitution at the 7'-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin (OPG) transcriptional activity assay using dual luciferase reporter detection. At 10 mu mol/L, compounds 1-3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
