DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis

Xu, Pengfei; Hong, Fan; Wang, Jialin; Wang, Jing; Zhao, Xia; Wang, Sheng; Xue, Tingting; Xu, Jianlin; Zheng, Xiaohui; Zhai, Yonggong

doi:10.1016/j.bbagen.2017.07.013

Cited by 55 publications

(39 citation statements)

References 51 publications

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“…Increasing studies have demonstrated the relationship between microbiota and host homeostasis [70]. In our previous studies, dietary lipid adsorbent-montmorillonite (DLA-M) and the traditional Chinese medicine Danshensu Bingpian Zhi (DBZ) both showed antiobesity effects in high-fat diet-fed mice by improving the microbiota composition [49,71]. Recently, studies demonstrated that melatonin was also prebiotic that alleviated dyslipidemia and weanling stress [37,38,45].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Hong

Pan

et al. 2020

Cells

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Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light–12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.

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Section: Discussionmentioning

confidence: 99%

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Hong

Pan

et al. 2020

Cells

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“…The potential targets of DBZ by in silico study not only revealed an effect on angiogenesis but also identified, previously observed, multiple pharmacological activities of DBZ. In our previous studies, DBZ was found to be a PPARγ agonist, by in silico prediction (PPARγ was ranked in the top 5% in the target list of DBZ), which was validated experimentally (Xu et al, ). In this study, for instance, based on our predicted results, we also found that the platelet activation pathway was involved and P2Y 12 receptors (P2RY12) were ranked in the top 5% in the target list of DBZ.…”

Section: Discussionmentioning

confidence: 84%

Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris

Liao

Han

Zheng

et al. 2019

British J Pharmacology

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Background and Purpose Tanshinol borneol ester (DBZ) is a novel synthetic compound derived from Dantonic®, a botanical drug approved in 26 countries outside the United States for angina pectoris and currently undergoing FDA Phase III clinical trial. Here, we investigated the angiogenic effects of (S)‐DBZ and (R)‐DBZ isomers in vitro and in vivo. Experimental Approach A network pharmacology approach was used to predict molecular targets of DBZ. The effects of DBZ isomers on proliferation, migration, and tube formation of human endothelial cells were assessed. For in vivo approaches, the transgenic Tg (vegfr2:GFP) zebrafish and C57BL/6 mouse Matrigel plug models were used. ELISA and western blots were used to quantitate the release and expression of relevant target molecules and signalling pathways. Key Results DBZ produced a biphasic modulation on proliferation and migration of three types of human endothelial cells. Both DBZ isomers induced tube formation in Matrigel assay and a 12‐day co‐culture model in vitro. Moreover, DBZ promoted Matrigel neovascularization in mice and partially reversed the vascular disruption in zebrafish induced by PTK787. Mechanistically, DBZ enhanced the cellular levels of VEGF, VEGFR2, and MMP‐9, as well as activating Akt and MAPK signalling in endothelial cells. Selective inhibition of PI3K and MEK significantly attenuated its angiogenic effects. Conclusions and Implications These data reveal, for the first time, that DBZ promotes multiple key steps of angiogenesis, at least in part through Akt and MAPK signalling pathways, and suggest it may be potentially developed further for treating myocardial infarction and other cardiovascular diseases.

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“…In a recent study, we reported that DBZ (danshensu bingpian zhi), a putative PPARγ agonist, simultaneously prevented HFD-induced obesity-related metabolic syndrome and gut dysbiosis. It also has antiatherosclerotic effects that involve inflammation suppression and the promotion of reverse cholesterol transport through concurrent partial activation of both PPARγ and LXRs [4,205,206]. Drugs for treating dyslipidemia via activating PPARα, especially represented by fibrates, are also widely used.…”

Section: Discussionmentioning

confidence: 99%

The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development

Hong

Zhai

2018

IJMS

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Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer’s disease and ulcerative colitis. The three PPAR isoforms (α, β/δ and γ) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPARα is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia. The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks. In this review, we summarize 84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases and provide a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development.

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DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis

Cited by 55 publications

References 51 publications

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris

The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development

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