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Paeoniflorin,the Main Monomer Component of Paeonia lactiflora,Exhibits Anti-inflammatory Properties in Osteoarthritis synovial inflammation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 433-442页

作者： CHEN Pu ZHOU Jun RUAN An-min MA Yu-feng WANG Qing-fu Department of Orthopaedic Surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China Department of Orthopaedic Surgery Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Department of Orthopaedic Surgery Beijing Longfu HospitalBeijing 100010China

Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental ***:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)*** counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial ***:Twenty-six co-targeted genes were *** enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and *** docking results showed that PF was well docking with ***-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA *** PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF

关键词： paeoniflorin osteoarthritis synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora

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Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis

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Chinese Journal of Natural Medicines 2022年第6期20卷 458-472页

作者： ZHANG Yan TANG Li-Dong WANG Jian-Ying WANG Hao CHEN Xiao-Yun ZHANG Lei YUAN Ying School of Traditional Chinese Materia Medica Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Innovation Center of TCM Health Service Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key Laboratory of Formulated Chinese Medicines Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Longhua Hospital affiliated to Shanghai University of TCM Rheumatoid DepartmentShanghai 200232China

Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune *** is known that aucubin(AU)exerts anti-inflammatory activity,but its effects and mechanisms in RA are *** study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in *** fibroblast-like synoviocyte cells from patients with RA(HFLS-RA),RAW264.7 cells,and MC3T3-E1 cells were used to evaluate the effects of AU on migration,invasion,apoptosis,osteoclast differentiation and *** was used to observe nuclear translocation of nuclear factor(NF)-/cB,the double luciferase reporter gene method was used to observe NF-/cB-p65 activity in AU-treated MC3T3-E1 ***-qPCR was used to measure expression of bone metabolism and inflammation-related genes,and western blot was used to measure bone metabolism and NF-a:B protein expression ***-induced arthritis(CIA)rat model was used for pharmacodynamics *** indexes were measured in the ankle and knee,histological staining and Micro-computed tomography were performed on the ankle ***,inflammatory factor gene expression and the levels of NF-/cB-related proteins were detected as in *** effectively inhibited HFLS-RA cell migration and invasion,promoted apoptosis,and inhibited RAW264.7 cell differentiation into osteoclasts,as well as inhibited NF-/cB-p65 activity in MC3T3-E1 ***,AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors,effectively inhibited the expression of p-lKKafi,p-lA:Ba,and p-p65 *** vivo,AU relieved joint inflammation,reduced related inflammatory factors,and inhibited NF-/cB *** could be used to treat RA-related synovial inflammation and bone destruction through the NF-/cB pathway.

关键词： Aucubin Collagen-induced arthritis synovial inflammation Bone erosion NF-/cB signaling pathway

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Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway

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Chinese Journal of Integrative Medicine 2023年第2期29卷 137-145页

作者： MA Rui-jiao Maharajan Kannan XIA Qing ZHANG Shan-shan TU Peng-fei LIU Ke-chun ZHANG Yun Biology Institute Qilu University of Technology(Shandong Academy of Sciences)Jinan 250103China Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province Jinan 250103China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Objective: To investigate the anti-angiogenic activity of Kunxian Capsule(KX) extract and explore the underlying molecular mechanism using zebrafish. Methods: The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization(hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 μg/m L of KX extract, *** 24-h post exposure(hpe), mortality and malformation(%), intersegmental vessels(ISV) formation, and m RNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase(PI3K), protein kinase B(AKT),extracellular signal-regulated kinases(ERKs), mitogen-activated protein kinase(MAPK), vascular endothelial growth factor(VEGF) and fibroblast growth factor(FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein(SIV) after 24 hpe. Results: The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV(P<0.01) and SIV formation(P<0.05). Besides, the m RNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT,thereby inhibiting the m RNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors(VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also downregulated by KX treatment in zebrafish larvae. Conclusion: KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VE

关键词： angiogenesis rheumatoid arthritis synovial inflammation osteoporosis Chinese medicine

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Expression of β-1,4-galactosyltransferase Ⅰ in a surgically-induced rat model of knee osteoarthritic synovitis

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Chinese Medical Journal 2010年第21期123卷 3067-3073页

作者： WANG You-hua NI Xiao-hui XU Da-wei CAI Hao WANG Hai-rong SUN Fa-mi SHEN Ai-guo Department of Orthopaedics Affiliated Hospital of Nantong University Nantong Jiangsu 226001 China Department of Immunology Medical College Nantong University Nantong Jiangsu 226001 China

Background There are few reports of a biological role for glycosyltransferases in the infiltration of osteoarthritic synovitis. The aim of this research was to investigate the expression and cellular location of β-1,4-galactosyltransferase Ⅰ （β-1,4-GaIT-Ⅰ） in a surgically-induced rat model of knee osteoarthritis （OA）, and explore the role of β-1,4-GalT-Ⅰ in the pathogenesis of *** Male Sprague-Dawley rats were randomly divided into three groups： OA group, sham group and normal group. The model of OA was established in the right knees of rats by anterior cruciate ligament transaction （ACLT） with partial medial meniscectomy. Fibroblast-like synoviocytes （FLSs） obtained from normal rat synovial tissue were *** expression of β-1,4-GalT-Ⅰ mRNA in the synovial tissue, articular cartilage and FLSs treated with tumor necrosis factor-α （TNF-α） were assayed by real-time PCR. Western-blotting and immunohistochemisty were used to observe the expression of β-1,4-GalT-Ⅰ at the protein level. Double immunofluorescent staining was used to define the location of the β-1,4-GalT-Ⅰ with macrophage-like synoviocytes, FLSs, neutrophils, and TNF-α in the OA synovium. The alteration of TNF-α in FLSs which were treated with lipopolysaccharide （LPS） and β-1,4-GalT-Ⅰ-Ab were detected by enzyme-linked immunosorbent assay （ELISA）.Results The mRNA and protein expression of β-1,4-GalT-Ⅰ increased in synovial tissue of the OA group compared with the normal and sham groups at two and four weeks after the surgery, however, no significant difference appeared in the articular cartilage. Immunohistochemistry also indicated that the β-1,4-GalT-Ⅰ expression in OA synovium at four weeks after surgery increased sharply compared with the control group. β-1,4-GalT-Ⅰ co-localized with macrophage-like synoviocytes, FLSa, neutrophils and TNF-α in rat OA synovitis. Moreover, in vitro β-1,4-GalT-Ⅰ mRNA in FLSs was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELIS

关键词： β-1,4-galactosyltransferase Ⅰ osteoarthritis synovial inflammation tumor necrosis factor-α rat

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