Effect of 1-Deoxynojirimycin on insulin resistance in prediabetic mice based on next-generation sequencing and intestinal microbiota study

Diabetes mellitus (DM) is a serious metabolic disease characterized by persistent hyperglycemia, with a continuously increasing morbidity and mortality. Although traditional treatments including insulin and oral hypoglycemic drugs maintain blood glucose levels within the normal range to a certain extent, there is an urgent need to develop new drugs that can effectively improve glucose metabolism and diabetes-related complications. Notably, accumulated evidence implicates that the gut microbiota is unbalanced in DM individuals and is involved in the physiological and pathological processes of this metabolic disease. In this review, we introduce the molecular mechanisms by which the gut microbiota contributes to the development of DM. Furthermore, we summarize the preclinical studies of bioactive natural products that exert antidiabetic effects by modulating the gut microbiota, aiming to expand the novel therapeutic strategies for DM prevention and management.

Section: Natural Products Targeting the Gut Microbiota In Dmmentioning

confidence: 97%

Section: Microbiota In Dmmentioning

confidence: 99%

Preclinical Studies of Natural Products Targeting the Gut Microbiota: Beneficial Effects on Diabetes

Jiang

Sun

Zhou

2022

“…Therefore, advocating a healthy lifestyle and searching for effective glucose-lowering drugs to reduce the risk of diabetes are critical. Currently, based on ancient herbal formulas and modern pharmacological validation, multiple natural products, including polyphenols, flavonoids, and alkaloids, have been applied to ameliorate hyperglycemia. − Flavonoids are the major active components isolated from M. nigra L. In this research, the plasma glucose, plasma insulin, HOMA-IR index, and lipoprotein profile data suggested that TFM treatment is effective in reducing the levels of blood lipids and plasma glucose and thus markedly ameliorates insulin resistance in prediabetes mice.…”

Section: Discussionmentioning

confidence: 79%

“…The total identified In order to further confirm the results, the seven compositions with top peak areas in HPLC were identified by MS and NMR spectroscopy. Six of them belonged to flavonoids, and they mainly included morin (6), quercetin (8), kuwanon C (20), sanggenon C (23), nigrasin K (26), and sanggenon A (29). Another compound was identified as oxyresveratrol (3), a polyphenol.…”

Section: ■ Resultsmentioning

confidence: 99%

Ameliorating Effect of the Total Flavonoids of Morus nigra L. on Prediabetic Mice Based on Regulation of Inflammation and Insulin Sensitization

Ren

Sun

Guo

et al. 2022

Self Cite

Prediabetes is a critical stage characterized by insulin resistance. Morus nigra L., an edible plant, is widely used in food and nutritive supplements and exhibits various pharmacological activities; however, its therapeutic effects and mechanisms on prediabetes have rarely been reported. In this research, the major components of total flavonoids of M. nigra L. (TFM) were identified, and TFM treatment was found to reduce prediabetes progressing to type 2 diabetes mellitus (T2DM) from 93.75 to 18.75%. The microbiota and next-generation sequencing combined with western blotting in vivo and in vitro demonstrated that TFM and its components ameliorated insulin resistance mediated by the suppressor of cytokine signaling and protein tyrosine phosphatase 1B, which benefited by maintaining intestinal homeostasis and restraining plasma levels of inflammatory factors. This study confirmed the T2DM prevention effect of TFM and revealed the underlying mechanism, setting the stage for the design of functional foods for diabetes prevention.

“…10 Du 11 found that the water-soluble alkaloids in mulberry twigs can effectively alleviate the tissue and organ lesions of diabetic mice induced by alloxan, promote the synthesis of liver glycogen and muscle glycogen, and reduce the blood sugar value of diabetic mice. Consequently, the Mulberry Twig Alkaloid Tablet was approved as a marketed drug (Z20200002) by National Medical Products Administration (NMPA) in March 2020 for the treatment of T2DM, 12 and it is clinically comparable to acarbose with lower side effects. 13 In the early research stage, our group studied the different extraction fractions (water, ethyl acetate, n-butanol, petroleum ether) of the mulberry twig extract and found that there may be α-glucosidase inhibitors with better activity except for polyhydroxypiperidine alkaloids in mulberry twigs, which were mainly distributed in ethyl acetate and petroleum ether extracts.…”

Section: Introductionmentioning

confidence: 99%

Rapid Screening of Nonalkaloid α-Glucosidase Inhibitors from a Mulberry Twig Extract Using Enzyme-Functionalized Magnetic Nanoparticles Coupled with UPLC-MS/MS

Feng

Xiang

Han

et al. 2022

Mulberry twigs are an important source of α-glucosidase inhibitors. To date, research studies on α-glucosidase in mulberry twigs have mainly focused on alkaloids such as 1-deoxynojirimycin (DNJ). Preliminary studies have shown that there may be more active nonalkaloid α-glucosidase inhibitors in mulberry twigs. In this study, we immobilized α-glucosidase on Fe3O4@SiO2 for the first time and rapidly screened four nonalkaloid α-glucosidase inhibitors (kuwanon G, kuwanon C, kuwanon H, and morusin) using ligand fishing technology with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) from the mulberry twig extract of Jialing 20, the excellent artificial triploid variety of mulberry cultivated extensively in Southwest China. The half maximal inhibitory concentrations (IC50) of kuwanon H and kuwanon G were 2.82 ± 0.68 and 2.83 ± 0.31 μM, respectively, with better inhibition activity than that of DNJ (with an IC50 of 7.04 ± 0.82 μM). Meanwhile, the molecular docking results showed that the action sites of these two isopentenyl flavonoids on α-glucosidase were different from that of DNJ. In brief, this work is beneficial to discovering new α-glucosidase inhibitors from mulberry twigs quickly and accurately and provides a theoretical basis for the mulberry twig extract as a functional food or a natural hypoglycemic drug source, as well as a reference for directional breeding of mulberry, which greatly improves the exploitation and utilization value of mulberry twigs as an agricultural byproduct in the fields of agricultural production, functional food, and natural medicine.