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Objective: To predict the action targets of anti-acute lung injury active ingredients of Xuebijing Injection, and investigate the “multi-components, multi-targets, and multi-pathways” mechanism. Methods: Reverse molecular docking was used to forecast its targets of 38 main active components of Xuebijing Injection. The relevant targets of acute lung injury were searched through literature mining and multiple databases and compared with the predicted component targets. The protein interaction network was constructed by Cytoscape software, and topological analysis was performed to screen the key targets of anti-acute lung injury of Xuebijing Injection. And GO enrichment analysis and KEGG analysis were carried out on the key targets through DAVID database. Results: The network analysis indicated that 38 active ingredients affected 143 key target proteins directly or indirectly, involved in 71 biological processes, 29 cellular components, 40 molecular function, and 25 KEGG pathways. These active compounds might participate in regulating the processes of gene, protein, external stimulus, and interfering the mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3-kinase (PI3K)-Akt, and other signaling pathways to play a role in resisting to acute lung injury. Conclusion: The anti-acute lung injury effect of Xuebijing Injection showed the characteristics of traditional Chinese medicine in multi-components, multi-targets, and multi-pathways. This research provides a scientific basis for elucidation of the anti-acute lung injury pharmacological mechanism of Xuebijing Injection.
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OBJECTIVE: To study the protective effect of moxibustion for tripterygium-induced premature ovarian failure (POF) and its underlying mechanisms in rats. METHODS: Forty-five female SD rats were randomly divided into normal control, POF model and moxibustion groups (n＝15/group). The POF model was induced by intragastric administration of Triptolide (40 mg/kg), once daily for 6 weeks. From the 4th week after modeling, moxibustion was given at "Guanyuan" (CV 4) and bilateral "Sanyinjiao" (SP 6) for 10 min, once daily for 3 weeks. Pathological changes of ovary tissues were determined by hematoxylin-eosin (HE) staining. The serum estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), interleukin-6 (IL-6) and interleukin-1 β (IL-1 β) contents were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of phosphatidyl inositol 3- kinase (PI 3 K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR) proteins of the ovarian tissue were detected by Western blot. RESULTS: After modeling, HE staining showed that the numbers of ovarian follicles and follicular granulocytes and corpora luteum layers were decreased, and the number of corpora atretica was increased in the model group. The content of serum E2 was markedly decreased and those of serum LH, FSH, IL-6 and IL-1 β were markedly increased in the model group (P<0.01), and the expression levels of ovarian p-PI 3 K, p-Akt and p-mTOR were markedly increased after modeling relevant to the control group (P<0.01). Following moxibustion, the pathological damage of ovarian tissue was improved, the contents of serum LH, FSH, IL-6, IL-1 β, and the levels of p-PI 3 K, p-Akt and p-mTOR proteins in the ovarian tissue were significantly decreased (P<0.05, P<0.01), and the content of serum E2 was markedly increased (P<0.05) in comparison with the model group. CONCLUSION: Moxibustion can improve POF in POF rats, which may be related to its actions in inhibiting PI 3 K/Akt/mTOR signaling, down-regulating serum IL-6, IL-1 β, and regulating serum hormones.
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Objective To explore effect of irregular chemotatic factor fractalkine(FKN),phosphatidyl inositol 3 kinase and nuclear factor?κB(NF?κB)on interleukin?6(IL?6)expression in peripheral blood monocytes and the effect of valsartan intervention,so as to research the signal conduc?tive mechanism of FKN impacting on IL?6. Methods Peripheral blood monocytes were isolated from fresh blood of healthy volunteers by the densi?ty gradient centrifugation. The extractive peripheral blood monocytes were divided into seven groups:the control group,the FKN group,the LY294002 group(PI3K inhibitors),the PDTC group(NF?κB inhibitors),the FKN+valsartan group,the FKN+LY294002 group,and the FKN+PDTC group,the latter two were pretreated by LY294002 and PDTC respectively before FKN inducing PBMC cells. The IL?6 expression in cell me?dium was measured in each group by ELISA at 12 hours and 24 hours after PBMC treatment. Results After 12 hours of culture,compared with the control group,the expression of IL?6 in the FKN group was decreased(P0.05). Compared with the FKN group,the expression of IL?6 was decreased in the FKN+valsartan group(P0.05). Conclusion FKN can adjust the expression of peripheral blood PBMC IL?6 in a two?way pattern, inhibiting the expression of IL?6 by PI3K pathway and promoting the expression of IL?6 by NF?κB pathway,overall,FKN can inhibit the expression of IL?6. Valsartan can increase FKN to inhibit the expression of IL?6.
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Objective To explore the effect of QizhiJiangtang Capsule on the insulin resistance (IR)in the diabetic rats,and to clarify the action mechanism.Methods The diabetes rat models were induced by high fat diet combined with STZ injection.The successful models of the rats were randomly divided into diabetes group (DM), ShenqiJiangtang Granule group (SQ)and high (QJH),middle-(QJM),low (QJL)doses of QizhiJiangtang Capsule groups;at the same time control group (NC)was established. The drug concentrations in high, middle and low-doses of QizhiJiangtang Capsules groups were 1.35, 0.68, and 0.34 g · kg-1 respectively;and the concentration of ShenqiJiangtang Granule was 0.27 g·kg-1.After the diabetic model was established successfully, the rats were treated for 8 weeks on the basis of drug dose.Then the levels of fasting blood glucose (FBG),fasting insulin (FINS),insulin resistance index (IRI)and biochemical indexes related to lipid metabolism of the rats were measured using blood glucose detector and automatic biochemistry analyser.The gene expression of insulin receptor substrate-1 (IRS-1),phosphatidyl inositol 3-kinase (PI3K),and glucose transporter 4 (GLUT4)in liver tissue were examined by Real Time PCR.The levels of tumor necrosis factorα(TNF-α)and adiponectin (ADPN)in serum were detected using ELISA.Results Compared with control group,the levels of FBG,FINS and IRI of the rats in diabetes group were significantly increased (P<0.05 or P<0.01 );the serum total cholesterol (TC), triglyceride (TG)and low density lipoprotein (LDL)levels were significantly increased (P<0.05 ), while the serum high-density lipoprotein (HDL)level was significantly decreased (P<0.05);the mRNA expression levels of IRS-1,PI3K and GLUT4 in liver tissue were decreased (P<0.05);the level of serum TNF-αwas increased (P<0.05),but the ADPN level was decreased (P<0.05).Compared with diabetes group,the FBG level and IRI of the rats in QizhiJiangtang Capsule and ShenqiJiangtang Granule groups were significantly decreased (P<0.01);the levels of FINS of the rats middle and high doses of in QizhiJiangtang Capsule groups and ShenqiJiangtang Granule group were significantly decreased (P<0.05);the levels of serum TC,TG and LDL of the rats in middle dose of QizhiJiangtang Capsule group and ShenqiJiangtang Granule group were significantly decreased (P<0.05 or P<0.01),but the HDL level was increased (P<0.05);the mRBA expression lvels of IRS-1,PI3K and GLUT4 inliver tissue were increased (P<0.05);the levels of serum TNF-αof the rats in middle dose of QizhiJiangtang Capsule group and Shenqijiangtang Granule group were significantly decreased (P<0.05),but the serum ADPN levels were increased (P<0.05 ). Conclusion QizhiJiangtang Capsule can significantly improve the IR in the diabetic rats,and the pharmacological mechanisms are related to adapting the blood lipid component and insulin signal transduction pathways.