Metabolic diseases have become major public health issues worldwide. Searching for effective drugs for treating metabolic diseases from natural compounds has attracted increasing attention. Quercetin, an important natural flavonoid, is extensively present in fruits, vegetables, and medicinal plants. Due to its potentially beneficial effects on human health, quercetin has become the focus of medicinal attention. In this review, we provide a timely and comprehensive summary of the pharmacological advances and clinical data of quercetin in the treatment of three metabolic diseases, including diabetes, hyperlipidemia, and nonalcoholic fatty liver disease (NAFLD). Accumulating evidences obtained from animal experiments prove that quercetin has beneficial effects on these three diseases. It can promote insulin secretion, improve insulin resistance, lower blood lipid levels, inhibit inflammation and oxidative stress, alleviate hepatic lipid accumulation, and regulate gut microbiota disorders in animal models. However, human clinical studies on the effects of quercetin in diabetes, hyperlipidemia, and NAFLD remain scarce. More clinical trials with larger sample sizes and longer trial durations are needed to verify its true effectiveness in human subjects. Moreover, another important issue that needs to be resolved in future research is to improve the bioavailability of quercetin. This review may provide valuable information for the basic research, drug development, and clinical application of quercetin in the treatment of metabolic diseases.

Purpose: Michael receptor molecules derived from plants are biologically active due to electrophilic groups in their structure. They can target nucleophilic residues on disease-related proteins, with significant therapeutic effects and low toxicity for many diseases. They provide a good option for relevant disease treatment. The aim of this study is to summarize the existing MAMs and their applications, and lay a foundation for the application of Michael receptor molecules in life science in the future.Methods: This review summarizes the published studies on Michael receptor molecules isolated from plants in literature databases such as CNKI, Wanfang Data, PubMed, Web of Science, ScienceDirect, and Wiley. Latin names of plants were verified through https://www.iplant.cn/. All relevant compound structures were verified through PubChem and literature, and illustrated with ChemDraw 20.0.Result: A total of 50 Michael receptor molecules derived from various plants were discussed. It was found that these compounds have similar pharmacological potential, most of them play a role through the Keap1-Nrf2-ARE pathway and the NF-κB pathway, and have biological activities such as antioxidant and anti-inflammatory. They can be used to treat inflammatory diseases and tumors.Conclusion: The Michael receptor molecule has electrophilicity due to its unsaturated aldehyde ketone structure, which can combine with nucleophilic residues on the protein to form complexes and activate or inhibit the protein pathway to play a physiological role. Michael receptor molecules can regulate the Keap1-Nrf2-ARE pathway and the NF-κB pathway. Michael receptor molecules can be used to treat diseases such as inflammation, cancer, oxidative stress, etc.

Globally, metabolic diseases are becoming a major public health problem. Herbal medicines are medicinal materials or preparations derived from plants and are widely used in the treatment of metabolic diseases due to their good curative effects and minimal side effects. Recent studies have shown that gut microbiota plays an important role in the herbal treatment of metabolic diseases. However, the mechanisms involved are still not fully understood. This review provides a timely and comprehensive summary of the interactions between herbal medicines and gut microbiota in metabolic diseases. Mechanisms by which herbal medicines treat metabolic diseases include their effects on the gut microbial composition, the intestinal barrier, inflammation, and microbial metabolites (e.g., short-chain fatty acids and bile acids). Herbal medicines can increase the abundance of beneficial bacteria (e.g., Akkermansia and Blautia), reduce the abundance of harmful bacteria (e.g., Escherichia–Shigella), protect the intestinal barrier, and alleviate inflammation. In turn, gut microbes can metabolize herbal compounds and thereby increase their bioavailability and bioactivity, in addition to reducing their toxicity. These findings suggest that the therapeutic effects of herbal medicines on metabolic diseases are closely related to their interactions with the gut microbiota. In addition, some methods, and techniques for studying the bidirectional interaction between herbal medicines and gut microbiota are proposed and discussed. The information presented in this review will help with a better understanding of the therapeutic mechanisms of herbal medicines and the key role of gut microbiota.

Senkyunolide I (SI) is a natural phthalide that has drawn increasing interest for its potential as a cardio-cerebral vascular drug candidate. In this paper, the botanical sources, phytochemical characteristics, chemical and biological transformations, pharmacological and pharmacokinetic properties, and drug-likeness of SI are reviewed through a comprehensive literature survey, in order to provide support for its further research and applications. In general, SI is mainly distributed in Umbelliferae plants, and it is relatively stable to heat, acid, and oxygen, with good blood–brain barrier (BBB) permeability. Substantial studies have established reliable methods for the isolation, purification, and content determination of SI. Its pharmacological effects include analgesic, anti-inflammatory, antioxidant, anti-thrombotic, anti-tumor effects, alleviating ischemia–reperfusion injury, etc. Pharmacokinetic parameters indicate that its metabolic pathway is mainly phase Ⅱ metabolism, and it is rapidly absorbed in vivo and widely distributed in the kidneys, liver, and lungs.

Oxidative stress is one of the major mechanisms implicated in endotoxin‐induced acute lung injury. Seabuckthorn paste (SP), a traditional Tibetan medicine with high content of polyphenols and remarkable antioxidant activity, is commonly used in treating pulmonary diseases. In the present study, the protective effects and possible underlying mechanisms of SP on lipopolysaccharide‐ (LPS‐) induced acute lung injury in mice were investigated. It was found that body weight loss, lung tissue microstructure lesions, transvascular leakage increase, malondialdehyde augmentation, and the reduction of superoxide dismutase and glutathione peroxidase levels caused by LPS challenge were all consistently relieved by SP treatment in a dose‐dependent manner. Moreover, accumulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) in lung nuclei caused by SP treatment was observed. Our study demonstrated that SP can provide significant protection against LPS‐induced acute lung injury through maintaining redox homeostasis, and its mechanism involves Nrf2 nuclear translocation and activation.

Purpose: Endothelial-to-mesenchymal transition (EndMT) is an important mechanism underlying cardiac fibrosis. The anti-ischemic drug trimetazidine (TMZ) is reportedly useful in ventricular remodeling and associated with NADPH oxidase (NOX) 2. This study aimed to investigate the possible effect of TMZ on cardiac fibrosis exerted via the inhibition of NOX2-mediated EndMT. Methods: A cardiac fibrosis model was established in Sprague-Dawley rats through a subcutaneous injection of isoproterenol (ISO, 5 mg/kg/d). Echocardiographic parameters, myocardial fibrosis, NOX2 expression and EndMT were assessed. An in vitro model of EndMT was developed using human umbilical vein endothelial cells (HUVECs) via treatment with transforming growth factor-β (TGF-β) at 10 ng/mL for 24 h. HUVECs were administrated with TMZ or TMZ and lentivirus, the expression of EndMT and related proteins was observed by wound healing assay, immunoblotting, and immunofluorescence. Results: Rats injected with ISO exhibited severe interstitial cardiac fibrosis and perivascular fibrosis, decreased left ventricular ejection fraction, and increased NOX activity. TMZ treatment mitigated cardiac fibrosis, ameliorated left ventricular dysfunction, and reduced NOX activity. In addition, TMZ effectively inhibited EndMT in ISO-treated rat hearts and TGF-β-treated HUVECs, as manifested by increased CD31 expression, decreased α-SMA expression, and suppressed cell migration. Compared with the control group, the expression of NOX2, nuclear factor-κB (NF-κB), and Snail was increased in vivo and in vitro but decreased with TMZ treatment. Furthermore, the overexpression of NOX2 by lentivirus abolished the protective effects of TMZ on TGF-β-induced EndMT. Conclusion: TMZ may ameliorate EndMT and ISO-induced cardiac fibrosis through the NOX2/NF-κB/Snail pathway. The findings of the study may provide new insights into the potential role of TMZ in the pathophysiology of cardiac fibrosis.