In this study, we investigated the lipid metabolism regulatory activity of a novel metformin derivative (MD568) and its potential mechanism of action in obese rats with type 2 diabetes mellitus (T2DM). Previous gene chip analysis of 3T3‐L1 cells have shown that MD568 regulates the transcription of genes involved in the peroxisome proliferator‐activated receptor (PPAR) signalling pathway, fatty acid metabolism, and glycerolipid metabolism. In this study, obese T2DM rats were treated with MD568 (200 mg/kg) for 8 weeks. Results showed that MD568 significantly reduced the body weight gain, plasma glucose, insulin, total cholesterol, triglyceride, and low‐density lipoprotein cholesterol levels. MD568 treatment also improved the insulin resistance of obese T2DM model rats. In particular, in white adipose tissue, MD568 inhibited the excessive volume increment of adipose cells by down‐regulating the protein levels of CCAAT/enhancer‐binding protein‐α (C/EBP‐α) and PPAR‐γ, as well as the transcription of their target lipid metabolism‐related genes. In the liver, MD568 inhibited hepatic fatty lesions and interfered with hepatic gluconeogenesis by regulating the expression of lipid metabolism‐related genes and glycogen‐related kinases. In conclusion, our results suggest that the newly synthesized MD568 affects the maintenance of lipid homeostasis in obese type 2 diabetic rats.

Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., 13C NMR, 1H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC50) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties.

Anemarrhena asphodeloides BUNGE is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides BUNGE. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet β cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides BUNGE by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic β cells through reducing IL-1β (interleukin-1β) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

Pu‐erh tea is believed to be a beneficial beverage for health due to its many kinds of pharmacological effects. Nevertheless, detailed information related to differences in metabolites of Pu‐erh raw tea from different geographical origins remains scarce. In this study, 43 elements were found in water‐soluble components of Pu‐erh raw tea by highly sensitive ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (U‐HPLC/Q‐TOF‐MS). The characteristic groups of 29 metabolites from nondestructive proton nuclear magnetic resonance (1H‐NMR) spectroscopy were assigned. The variables contributed largely to the origin classification, mainly including valine, threonine, chlorogenic acid, quinic acid, epiafzelechin, and gallic acid ester, were screened out by sparse partial least squares discriminant analysis (sPLS‐DA) method. This study provided a feasible and rapid technique for distinguishing Pu‐erh tea from different areas by 1H‐NMR combined with sPLS‐DA.

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