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Objective:To investigate the protective effect of quercetin （Qu） on articular cartilage of knee osteoarthritis and its mechanism by inhibiting p38 mitogen activated protein kinase （MAPK） signaling pathway. Method:Through the network pharmacology technology，we scientifically predicted and analyzed the target factors and signal pathways of Qu in the protection of articular cartilage in patients with osteoarthritis. We selected a prediction pathway closely related to osteoarthritis and validated it by cell experiment <italic>in vitro</italic>. The best intervention concentration of the drug was selected by cell counting kit-8 （CCK-8） method. The osteoarthritis and its closely related inflammatory factors interleukin（IL）-1<italic>β</italic> and tumor necrosis factor（TNF）-<italic>α</italic> were detected by enzyme linked immunosorbent assay（ELISA）. The expression of related mRNA and protein in p38 signal pathway after Qu intervention were detected by quantitative real time polymerase chain reaction（Real-time PCR） and Western blot. Result:It was predicted that MAPK signal pathway was closely related to osteoarthritis by network pharmacology，and p38 MAPK pathway，which was most closely related to osteoarthritis，was selected for study. The results showed that 100 μmol·L<sup>-1</sup> Qu had the most obvious effect in decreasing the expression of related inflammatory factors，inhibited the expression of p38，phosphorylated（p）-p38，matrix metalloproteinase-13（MMP-13），A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-4（ADAMTS-4） in the pathway，and promoted the expression of CollagenⅡ. Conclusion:Qu could decrease the expression of cartilage inflammatory factors in the prevention and treatment of osteoarthritis，and the effect can be well developed by intervening and inhibiting p38 MAPK pathway related factor expression level. All the results show that Qu can decrease osteoarthritis inflammatory factors and protect articular cartilage in patients with osteoarthritis.
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Objective: To investigate the protective effect and mechanism of Pterocarya hupehensis Skan extract on liver injury induced by concanavalin A (conA). Methods:Forty C57BL/6 male mice were randomly divided into 5 groups: normal group, model group, and groups of low-, medium- and high-dose extract, with 8 mice in each group. Except for the normal group that received intravenous injection of normal saline, the other mice were injected with conA (12 mg/kg) for replication of the immunological liver injury model. The treatment groups were intragastrically administered with corresponding concentrations of extract. After 12 hours, the mice were subjected to eyeball extraction and dissection of liver tissue to prepare HE stained sections. The liver index was collected and calculated. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also detected. The content of STAT-3 and the level of phosphorylation in liver tissue were also tested. Results: HE staining showed that the liver tissue of the model group was significantly damaged compared with the normal group, and that of the treatment groups were ameliorated. Compared with the model group, each treatment group had reduced liver index and serum ALT, AST, IL-6 and TNF-α levels (P<0.05 or P<0.01). Significant phosphorylation of STAT-3 was observed in the model group, but it was inhibited in the treatment groups. Conclusion: The extract of Pterocarya hupehensis Skan can effectively treat immunological liver injury induced by conA, which may be related to the inhibition of phosphorylation of STAT-3.
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Objective:To observe the therapeutic effect and mechanism of Cangxi Tongbi capsule on knee osteoarthritis (KOA) model rats. Method:Sixty 4-week-old SPF healthy male SD rats were randomly divided into blank group, model group, dimethyl sulfoxide (DMSO) group, Cangxi Tongbi capsule group, SB203580 group and Cangxi Tongbi capsule combined with SB203580 group. In addition to the normal group, the modified Hulth method was used to establish the koa model. After the model was established successfully, the Cangxi Tongbi capsule group was given 0.25 g·kg-1 Cangxi Tongbi capsule solution by gavage every day, the SB203580 group was given 0.015 g·kg-1 SB203580 solution by gavage, the Cangxi Tongbi capsule combined with SB203580 group was given a mixed solution containing 0.015 g·kg-1 SB203580 and 0.25 g·kg-1 Cangxi Tongbi capsule by gavage, the DMSO group was given 1% DMSO solution by gavage, the model group and blank group were given normal saline by gavage The stomach was killed and the material was taken after 4 weeks of drug intervention. The expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α（TNF-α）in the supernatant of peripheral blood were detected by ELISA. p38, p-p38, matrix metalloproteinase-13(MMP-13), Collagen Ⅱ mRNA and protein in p38 MAPK signal pathway were detected by Real-time fluorescence quantification PCR （Real-time PCR） and Western blot, and the localization expression of p-p38 was detected by immunohistochemistry. Result:Compared with normal group，the expression levels of p38，p-p38，MMP-13 in articular cartilage of the model group were up-regulated (P<0.01), the expression levels of CollagenⅡ was down-regulated (P<0.01). The contents of IL-1β and TNF-α in serum were significantly increased (P<0.01). Compared with model group, the expression levels of p38，p-p38，MMP-13 in articular cartilage of the Cangxi Tongbi capsule group, SB203580 group and Cangxi Tongbi capsule combined with SB203580 group were down-regulated (P<0.01), the expression levels of CollagenⅡ was up-regulated (P<0.01). The contents of IL-1β and TNF-α in serum were significantly decreased (P<0.01). Conclusion:Cangxi Tongbi capsule can effectively protect the cartilage of KOA rats, and its mechanism may be related to the targeted blocking of p38 MAPK signal pathway.
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Knee osteoarthritis (KOA) is a kind of joint disease characterized by progressive degeneration of articular cartilage, synovitis and pain. Its pathogenesis is not yet completely clear. Generally, it is believed that age, sex, obesity, trauma, inflammation, genetic susceptibility and other mechanical and biological factors together lead to the degradation and synthetic coupling imbalance of cartilage cells, extracellular matrix and subchondral bone. In recent years, signaling pathway has become a hot spot in the research of KOA chondrocyte proliferation and apoptosis, and the research of signal pathway in the pathogenesis and targeted therapy of KOA also began. It usually involves the expressions of cytokines, relevant genes and proteins in KOA chondrocyte. These researches mainly focus on the proliferation and apoptosis of chondrocytes, the synthesis and degradation of extracellular matrix, and the sclerosis of subchondral bone. More studies focus on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Literatures show that p38 MAPK signaling pathway can regulate the proliferation and apoptosis of chondrocytes, maintain the balance of extracellular matrix metabolism, regulate the production of matrix metalloproteinases and pro-inflammatory factors, participate in the degradation of collagen and proteoglycan, and play an important regulatory role in the pathological process of KOA. Traditional Chinese medicine(TCM) therapy under the guidance of holistic concept and dialectical treatment theory has a strong pertinence and remarkable curative effect, and can control the development of the disease fundamentally. Starting with the relationship between p38 MAPK and the pathogenesis of KOA, this paper summarizes the research progress of p38 MAPK signaling pathway in the diagnosis and treatment of KOA by TCM, and provides new targets for the clinical diagnosis and treatment of KOA.
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Objective:To analyze the effects of BANCR on proliferation,apoptosis,invasion and angiogenesis in human hepatocarcinoma cell line HepG2.Methods:The expression of BANCR was detected by quantitative real-time reverse transcription PCR (qRT-PCR).BANCR siRNA and Scramble was respectively transfected into human hepatocarcinoma cell line HepG2.Cell proliferation was detected by CCK-8.Flow cytometry was performed to analyze the apoptosis.Transwell assay was used to test the invasion.Angiogenesis was analyse by tube formation assay.Western blot was executed to check the expression of proliferating cell nuclear antigen (PCNA),caspase-3,matrix metalloprotein 9 (MMP-9),vascular endothelial growth factor(VEGF),acidic fibroblast growth factor (bFGF)and interferon-γ (IFN-γ).Results:The expression of BANCR in HepG2 was higher than L02 (P＜0.05).Compared with control group,the cell proliferation folds in BANCR siRNA was largely decreased.Besides,BANCR siRNA group had a higher apoptosis rate and less invasive cells (P＜0.05).Western blot showed that the expression level of caspase-3 and IFN-γwas obviously enhanced in BANCR siRNA group,and the expression of PCNA,MMP-9,Fn,Vimentin,VEGF and bFGF was distinctly surpressed in BANCR siRNA group compared to control group (P ＜ 0.05).Conclusion:siRNA interference of BANCR promotes apoptosis and represses proliferation,invasion and angiogenesis in human hepatocarcinoma cell line HepG2.
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OBJECTIVE@#To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism.@*METHODS@#Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1.@*RESULTS@#Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(<0.05). The high-dose of GBE possessed the most obvious treatment effect among them.@*CONCLUSIONS@#GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.