Ginkgetin alleviates LPS-induced inflammatory damage in macrophages of mouse model via inhibiting IκB-α degradation / 中国药理学通报

Aim To explore the anti-inflammatory effect of natural compound Ginkgetin on lipopolysaccharide-induced mouse primary peritoneal macrophages and the underlying mechanism, in order to provide a theoretical basis for the development of clinical drug candidates. Methods MTT test kit was used to detect the cytotoxicity of Ginkgetin on mouse primary peritoneal macrophages; ELISA and RT-qPCR methods were used to detect the anti-inflammatory effect of different concentrations of Ginkgetin on LPS-induced cell inflammation injury model; Western blot was used to detect the anti-inflammatory mechanism of ginkgo flavonoids. Results Compared with LPS stimulation group, Ginkgetin treatment group produced a concentration-dependent anti-inflammatory effect, which could be attributed to the fact that Ginkgetin could inhibit LPS-induced activation of NF-κB signaling pathway. MTT results also showed that ginkgo flavonoids had little toxicity to mouse primary peritoneal macrophages. Conclusions Ginkgelin alleviates LPS-induced inflammatory injury of mouse primary peritoneal macrophages by inhibiting the activation of NF-κB signaling pathway. It is expected to be a natural monomer antiinflammatory drug candidate.

Tanshinone IIA inhibits LPS induced inflammation of RAW264.7 cells by regulating TLR4/IκB-α/NF-κB signaling pathway / 中国药理学通报

Aim To establishan inflammatory model of mouse monocyte macrophages ( RAW264. 7) using li-popolysaccharide (LPS), and to investigate the antiinflammatory activity and mechanism of tanshinone II-A (Tan IIA). Methods Cell viability was determined by CCK-8 method. Cell migration was detected by Tr-answell apparatus. TNF-α, IL-6, IL-1 p, MCP-1 content in cell supernatant was analyzed using ELISA method. The protein expression of MMP-2, MMP-9, TLR4, κB-α, p-κB-α, NFκB and p-NFκB in RAW264.7 cells was investigated by Western blot. Results Tan IIA significantly inhibited .the secretion of TNF-α, IL-6, IL-1β and MCP-1 in LPS induced RAW264.7 cell culture medium , and significantly down-regulated the expression of matrix metalloprotein-ase-2 (MMP-2), MMP-9, TLR4, p-κB-α and p-NFκB , inhibited IκB-α phosphorylation and NFκB entry into the nucleus and activation. Conclusion Tan IIA can inhibit the release of inflammatory factors through the regulation of TLR4/IκB-α/NFκB signaling pathway.

Schisandrin C alleviates atherosclerosis and inflammation in ApoE-/-mice fed with arterial high-fat diet / 中国药理学通报

Aim To investigate the effects of schisandrin C on arterial inflammation and atherosclerosis of ApoE-/-mice fed with high-fat diet. Methods ApoE-/-mice were divided into high fat diet group (HFD) and high fat diet group + schisandrin group (HFD + Sch C). High fat diet and Sch C were given at the same time. After 12 weeks, mice were executed and arterial tissues were collected. RT-q PCR and Western blot were respectively used to detect the expressions of IL-6, TNF-α, ICAM-1, β-actin and the phosphorylation and expression of IκB-α in arteries. Oil red O staining and biochemical kit were respectively used to detect the lipid changes in aortic root and the blood lipid levels. Results Compared with HFD group, the area of atherosclerotic plaque in HFD + Sch C was reduced (P < 0. 05), but Sch C did not affect blood lipid levels. Compared with HFD group, the mRNA expression of TNF-α, IL-6 and ICAM-1 and the phosphorylation of IκB-α of arterial tissue in HFD + Sch Cgroup decreased (P < 0. 05). Conclusions Sch C could effectively alleviate atherosclerosis induced by high-fat diet in ApoE-/-mice, accompanied by alleviation of arterial inflammation.

Breviscapine reduces intestinal ischemia reperfusion via inhibiting IκB-α/NF-κB/ICAM-1 pathway in a rat model / 实用医学杂志

Objective To investigate the effects of breviscapine injection on intestinal injury induced by intestine ischemia-reperfusion(IIR). Methods 48 males SD rats with 8-week old were randomly divided into 4 groups:Sham,intestine ischemia-reperfusion(IIR),EB+IIR,TP+IIR. Breviscapine injection 20 mg/(kg·d) was given intraperitoneally in EB + IIR group. TPCA-1(12 mg/kg)was given intravenously 30 min before surgery in TP+IIR group. Rats were subjected to superior mesenteric artery occlusion consisting of 45 min of ischemia and 6 h of reperfusion;sham laparotomy served as controls. Intestine pathology was assayed by H&E staining. Con-centrations of TNF-α,IL-1β,and IL-6 in intestinal mucosa were determined by ELISA. The protein expressions of IκB-α,NF-κB ,ICAM-1of intestine tissue were assayed by western blot. Results IIR induced serious intesti-nal injury ,evidenced as poor intestine pathology ,elevation of TNF-α,IL-1β,and IL-6 levels in intestinal mu- cosa,accompanied with IκB-α/NF-κB/ICAM-1 pathway activation. However,breviscapine injection pretreatment could inhibit IκB-α/NF-κB/ICAM-1 pathway activation,leading to reduction of TNF-α,IL-1β,and IL-6 concen-trations in lung,finally attenuate ALI induced by IIR. Conclusion Breviscapine injection pretreatment could atten-uate inflammation in intestine after IIR injury via inhibiting IκB-α/NF-κB/ICAM-1signaling pathway.

Breviscapine reduces intestinal ischemia reperfusion via inhibiting IκB-α/NF-κB/ICAM-1 pathway in a rat model / 实用医学杂志

Objective To investigate the effects of breviscapine injection on intestinal injury induced by intestine ischemia-reperfusion(IIR). Methods 48 males SD rats with 8-week old were randomly divided into 4 groups:Sham,intestine ischemia-reperfusion(IIR),EB+IIR,TP+IIR. Breviscapine injection 20 mg/(kg·d) was given intraperitoneally in EB + IIR group. TPCA-1(12 mg/kg)was given intravenously 30 min before surgery in TP+IIR group. Rats were subjected to superior mesenteric artery occlusion consisting of 45 min of ischemia and 6 h of reperfusion;sham laparotomy served as controls. Intestine pathology was assayed by H&E staining. Con-centrations of TNF-α,IL-1β,and IL-6 in intestinal mucosa were determined by ELISA. The protein expressions of IκB-α,NF-κB ,ICAM-1of intestine tissue were assayed by western blot. Results IIR induced serious intesti-nal injury ,evidenced as poor intestine pathology ,elevation of TNF-α,IL-1β,and IL-6 levels in intestinal mu- cosa,accompanied with IκB-α/NF-κB/ICAM-1 pathway activation. However,breviscapine injection pretreatment could inhibit IκB-α/NF-κB/ICAM-1 pathway activation,leading to reduction of TNF-α,IL-1β,and IL-6 concen-trations in lung,finally attenuate ALI induced by IIR. Conclusion Breviscapine injection pretreatment could atten-uate inflammation in intestine after IIR injury via inhibiting IκB-α/NF-κB/ICAM-1signaling pathway.

Effects of heat shock protein 70 activator SW02 on lipopolysaccharide-induced expression of inducible nitric oxide synthase in macrophages / 中国药理学通报

Aim To observe the effects of heat shock protein 70 ( Hsp70 ) activator SW02 on lipopolysaccha-ride( LPS)-induced expression of inducible nitric oxide synthase ( iNOS ) and LPS-induced production of nitric oxide ( NO ) in macrophages. Methods RAW264. 7 cells were stimulated by LPS, and were divided into DMSO,DMSO+LPS(1 mg·L-1),SW02,and SW02+LPS ( 1 mg · L-1 ) groups. The protein expression was detected by Western blot. NO concentration was measured by Griess kit. The iNOS mRNA was detected by real-time PCR. The NF-κB binding to iNOS promot-ers was measured by chromatin immunoprecipitation ( ChIP ) assays. Results SW02 significantly blocked the protein and mRNA expression of iNOS as well as the production of NO in LPS-stimulated RAW264 . 7 cells(P0. 05 , SW02 +LPS group vs DMSO+LPS group ) and nuclear translocation of NF-κB ( P > 0. 05 , SW02 + LPS group vs DMSO + LPS group) . However,SW02 reduced the NF-κB binding to iNOS promoters inside the cell( P<0. 05,SW02+LPS group vs DMSO+LPS group) . Conclusion These re-sults show that SW02 prevents iNOS expression and NO induction likely through attenuation of the NF-κB bind-ing to iNOS promoters in macrophages.

Regulatory effect of a Chinese medicine prescription Hu Qi Shan on the telomerase activity in hepatic precancerous lesions in rats / 中国比较医学杂志

Objective To explore the possible mechanism of action of telomerase in hepatic precancerous lesions, and the regulatory effect of a Chinese medicine prescription HU Qi Shan ( HQS) and its principal drug mistletoe alkali on the telomerase activity in rat liver tissues.Methods Rat model of hepatic precancerous lesions was established by Solt-Farber two-step protocol.The model rats were randomly divided into 5 groups, including the model group, high-dose HQS [8 g/(kg· d)] group, low-dose HQS [4 g/(kg· d)] group, and mistletoe alkali[8 mg/(kg· d)] group.γ-Glutamy-transpeptidase (γ-GT) was analyzed by immunohistochemistry.AFP was detected by immunofluorescence technique.The telomerase activity was detected using a quantitative telomerase detection kit.The expression of NF-κB P65 was detected by immunohistochemistry.The cytoplasmic protein IκB-αwas detected by western blotting.Results After treated with HQS and mistletoe alkali, the areas ofγ-GT-positive foci and number of AFP-positive cells in the liver tissus were significantly decreased than those of the model group ( P<0.05 for both) , the telomerase activity was decreased, the number of NF-κB P65-positive cells was also decreased ( P <0.05 ) , whereas the intracytoplasmic expression of IκB-αproteins was significantly increased ( P <0.05 ) .Conclusions HQS and mistletoe alkali can suppress the telomerase activity.Its possible mechanism may be through inhibition of the over-expressed apoptosis-related genes such as NF-κB P65 and increase the expression of IκB-αdecreasing the telomerase activity.