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Introduction Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury. Objectives This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs. Methods A literature search was carried out regarding our topic with the keywords of “atherosclerosis” or “Nrf2/HO-1” or “vascular endothelial cells” or “oxidative stress” or “Herbal medicine” or “natural products” or “natural extracts” or “natural compounds” or “traditional Chinese medicines” based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed. Results These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies. Conclusion Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

HIF-1α is an important factor regulating oxygen balance in mammals, and its expression is closely related to various physiological and pathological conditions of the body. Because HIF-1α plays an important role in the occurrence and development of cancer and other diseases, it has become an enduring research hotspot. At the same time, natural medicines and traditional Chinese medicine compounds have amazing curative effects in various diseases related to HIF-1 subtype due to their unique pharmacological effects and more effective ingredients. Therefore, in this article, we first outline the structure of HIF-1α and the regulation related to its expression, then introduce various diseases closely related to HIF-1α, and finally focus on the regulation of natural medicines and compound Chinese medicines through various pathways. This will help us understand HIF-1α systematically, and use HIF-1α as a target to discover more natural medicines and traditional Chinese medicines that can treat related diseases.

Huxinyue Duan,* Qing Zhang,* Jia Liu, Ruolan Li, Wei Peng, Chunjie Wu School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Peng; Chunjie WuSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu, 611137, People’s Republic of ChinaTel +86-028-61801001Email pengwei@cdutcm.edu.cn; wucjcdtcm@163.comObjective: This study was aimed to investigate the potential active components, targets and mechanisms of silkworm excrement (SE) in the treatment of type 2 diabetes mellitus (T2D) based on THE network pharmacology combined with experimental verification.Methods: Firstly, the inhibitory effects of SE on α-glucosidase were measured in vitro. Then, the potential active components and potential targets of SE and the targets of T2D were collected and screened using bioinformatics databases. Then, the R language, Cytoscape, Perl software were used to screen and visualize important components, targets, biological processes and signaling pathways. Finally, the predicted results by network pharmacology were verified via glucose absorption assay, oil red O staining assay and Western blot assay.Results: Our results showed SE effectively inhibited the activities of α-glucosidase. The results of network pharmacology suggested there were 33 potential active ingredients and 42 potential targets in SE. The molecular pathways of SE against T2D were further predicted, including response to insulin-like growth factor receptor binding, protein serine/threonine kinase activity, and MAP kinase activity. KEGG pathway analyses predicted potential targets were involved in multiple signaling pathways, such as insulin signaling pathway, insulin resistance pathway and AMPK signaling pathway. In IR HepG2 cells, SE treatments increased glucose consumption and decreased lipogenesis. The insulin resistance (IR)-related AMPK/PI3K/AKT signaling was further studied and the results showed SE could significantly up-regulate the phosphorylation levels of AMPK, PI3K, and Akt proteins in IR-HepG2 cells.Conclusion: Our results suggested AMPK/PI3K/Akt signaling is an important way for the anti-type 2 diabetic activity of silkworm excrement by using an integrated approach based on network pharmacology combined with experimental verification.Keywords: α-glucosidase, insulin resistance, network pharmacology, silkworm excrement, type 2 diabetes

Atherosclerosis, a chronic multifactorial disease, is closely related to the development of cardiovascular diseases and is one of the predominant causes of death worldwide. Normal vascular endothelial cells play an important role in maintaining vascular homeostasis and inhibiting atherosclerosis by regulating vascular tension, preventing thrombosis and regulating inflammation. Currently, accumulating evidence has revealed that endothelial cell apoptosis is the first step of atherosclerosis. Excess apoptosis of endothelial cells induced by risk factors for atherosclerosis is a preliminary event in atherosclerosis development and might be a target for preventing and treating atherosclerosis. Interestingly, accumulating evidence shows that natural medicines have great potential to treat atherosclerosis by inhibiting endothelial cell apoptosis. Therefore, this paper reviewed current studies on the inhibitory effect of natural medicines on endothelial cell apoptosis and summarized the risk factors that may induce endothelial cell apoptosis, including oxidized low-density lipoprotein (ox-LDL), reactive oxygen species (ROS), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α), homocysteine (Hcy) and lipopolysaccharide (LPS). We expect this review to highlight the importance of natural medicines, including extracts and monomers, in the treatment of atherosclerosis by inhibiting endothelial cell apoptosis and provide a foundation for the development of potential antiatherosclerotic drugs from natural medicines.

Qing Zhang,1 Hu-Xinyue Duan,1 Ruo-Lan Li,1 Jia-Yi Sun,2 Jia Liu,1 Wei Peng,1 Chun-Jie Wu,1 Yong-Xiang Gao3 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People’s Republic of China; 2Innovation Research Institute, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People’s Republic of China; 3School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People’s Republic of ChinaCorrespondence: Chun-Jie WuSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People’s Republic of ChinaTel +86-28-61801001Email wucjcdtcm@163.comYong-Xiang GaoSchool of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People’s Republic of ChinaTel +86-28-61801001Email gaoyxcdtcm@126.comBackground and Objectives: Guizhi-Shaoyao-Zhimu decoction (GSZD) is often applied to control rheumatoid arthritis (RA), gout, osteoarthritis, etc. In this study, bioinformatic analysis and experimental verification were used to uncover the integral mechanism profile of GSZD against RA.Materials and Methods: The chemical compositions of GSZD were identified by UPLC-QTOF-MS/MS. MH7A cell model was established to screen active compounds in GSZD, and potential targets of these compounds were predicted through online database retrieval. The differential expression genes (DEGs) in synovial tissue of RA patients and normal controls were retrieved from the GEO database. DEGs and the predicated compounds targets were overlapped, and the overlapped genes were subsequently enriched by GO and KEGG analysis. The pathways with significant enrichments were further experimentally verified.Results: A total of 19 constituents were identified from GSZD, and 11 compounds showed obviously antiproliferative effects on MH7A cells with IC50 < 100 μg/mL. Bioinformatic analysis indicated that IL-1β, IL-6, MAPK8, JAK2, CXCL8, and CASP3 were the main targets of GSZD, and the integral pharmacological mechanisms profile of GSZD might be related to anti-inflammation and proapoptosis. GSZD can promote the loss of mitochondrial membrane potential (MOMP) and induce apoptosis in MH7A cells. Furthermore, in vitro experiments showed GSZD can not only downregulate mRNA expressions of IL-1β (p< 0.05), IL-6 (p< 0.05), MMPs (p< 0.05) and CCL5 (p< 0.05) but also inhibit the nuclear transcription of NF-κB. GSZD also reduced the expressions of Bcl-2 (p< 0.05), JAK2 (p< 0.05), STAT-3 (p< 0.05), whereas increase Bax (p< 0.05), Caspase-3 (p< 0.05) and caspase-9 (p< 0.05).Conclusion: Collectively, inducing synovial fibroblast apoptosis and inhibiting inflammatory response are two important ways for GSZD to RA, and our study proved bioinformatic analysis combined with experimental verification is a feasible method to explore the drug targets and mechanism of actions of TCMs.Keywords: apoptosis, anti-inflammatory, bioinformatic analysis, rheumatoid arthritis, Guizhi-Shaoyao-Zhimu decoction

Objectives Postoperative intestinal obstruction is a common postoperative complication with typical symptoms of abdominal pain, vomiting, abdominal distension and constipation. The principal aim of this paper is to provide a full-scale review on the categories and characteristics of postoperative intestinal obstruction, pathophysiology, effects and detailed mechanisms of compounds and monomers from traditional Chinese medicine for treating postoperative intestinal obstruction. Moreover, the possible development and perspectives for future research are also analyzed. Methods Literature regarding postoperative intestinal obstruction as well as the anti-pio effect of aqueous extracts and monomers from traditional Chinese medicine in the last 20 years was summarized. Key findings To date, approximately 30 compounds and 25 monomers isolated from traditional Chinese medicine including terpenes, alkaloids, polysaccharides, flavonoids, phenylpropanoids and quinones, have exerted significant antipio effect. This paper reviews the effective doses, models, detailed mechanisms, and composition of these traditional Chinese medicine compounds, as well as the structure of these monomers. Moreover, challenges existed in the current investigation and further perspectives were discussed as well, hoping to provide a reference for future clinical treatment of postoperative intestinal obstruction and the development of new drugs. Conclusions Above all, the convincing evidence from modern pharmacology studies powerfully supported the great potential of traditional Chinese medicine in the management of postoperative intestinal obstruction. Regrettably, less attention was currently paid on the mechanisms of traditional Chinese medicine compounds and monomers with antipio effect. Consequently, future study should focus on monomer-mechanism and structure–function relationship.

Zanthoxylum bungeanum pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy-α-sanshool (HAS) is the most important active ingredient of Z. bungeanum pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H2O2-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H2O2-stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H2O2-induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H2O2-stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H2O2-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H2O2-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.