Natural compounds affecting diabetes through gut microbiota (Part 1)

EGCG is the main catechin in green tea. In vitro studies on obese db/db (type 2 diabetes model) mice showed that EGCG not only improved the parameters of diabetic mice but also increased the ratio of Firmicutes/Bacteroidetes at the phylum level and increased the relative abundance of Lactobacillus at the genus level. At the family level, EGCG increased the Christensenellaceae and decreased the Enterobacteriaceae and Proteobacteria ratios.In addition, EGCG alters the gut microbiota composition of obese patients by regulating the bile acid signaling pathway.Since obesity is closely related to diabetes, improvements in obesity provide insights into diabetes.

Curcumin is the active ingredient of the turmeric plant (Curcuma longa), with its main metabolite being tetrahydrocurcumin (THC). Studies have shown that THC can increase insulin secretion and GLP-1 expression in the pancreas, leading to a reduction in blood glucose compared to the control group. Additionally, THC restored gut ecological imbalance, including reducing the relative abundance of Proteobacteria and Actinobacteria, as well as the ratio of Firmicutes to Bacteroidetes. Notably, Actinobacteria has been shown to be negatively correlated with inflammatory responses in adults, such as glucose intolerance and insulin resistance.

Allicin is an active ingredient extracted from garlic leaves, known for its good pharmacological properties. A study in 2011 found thatthe water extract of allicin had a certain effect on reducing blood glucose, triglycerides, total lipids, total cholesterol, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in diabetic rats.In another study, obese model mice were provided with drinking water containing 0.1 mg/mL of allicin. Compared to the control group without allicin supplementation, the gut microbiota composition of these mice differed. The main difference in microbial composition was a decrease in the abundance of Lactobacillaceae in the experimental group, while the proportion of Ruminococcaceae increased.

Quercetin is a flavonoid found in fruits and vegetables that can affect the host's oxidative stress levels. In recent years,studies have found that quercetin has a positive effect on diabetes by influencing the gut microbiota.In male mice fed quercetin, indicators closely related to diabetes, including insulin, leptin, resistin, and glucagon levels, were significantly reduced. Quercetin increased the abundance of Akkermansia in the feces of mice and reduced the Firmicutes/Bacteroidetes ratio. Quercetin can restore gut barrier function, increase the concentration of beneficial metabolites (acetate, propionate, and butyrate) in the gut microbiota, and improve endotoxemia, gut-liver axis activation, and the expression of inflammatory cytokines.

In a study involving 45 participants, dihydroquercetin reduced insulin resistance in obese subjects and increased the proportion of Verrucomicrobia in their gut microbiota. In a mouse study, using a high-fat diet and STZ-induced type 2 diabetes,it was found that the application of dihydroquercetin reduced hyperlipidemia, increased the concentration of short-chain fatty acids, reduced the Firmicutes/Bacteroidetes ratio, decreased the proportions of Proteobacteria, Helicobacter pylori, and Ruminococcaceae, and increased the proportions of Bacteroidetes and Prevotella.

Capsaicin is a bioactive compound found in red chili peppers.It significantly inhibits the increase of fasting blood glucose and insulin levels in ob/ob (obese model) mice, improves glucose and insulin tolerance, and alters the diversity of the gut microbiota in mice.Among them, capsaicin significantly increased the Firmicutes/Bacteroidetes ratio, increased the proportion of Lactobacillus, and decreased the proportions of Bacteroides and Parabacteroides.

Betacyanin is an active ingredient of red dragon fruit (Hylocereus polyrhizus). It has been reported thatbetacyanin can improve adiposity, hepatic steatosis, and insulin resistance in mice fed a high-fat diet.In the same study, betacyanin also reduced the Firmicutes/Bacteroidetes ratio and induced a significant increase in the relative abundance of Akkermansia.

Pectin is a novel low-methoxy dietary fiber. In female non-obese diabetic mice,supplementation with pectin can prevent dysbiosis in the cecum and increase the types of bacteria that produce short-chain fatty acids in the cecum.

Matrine, a bitter compound, is derived from leguminous plants such as Sophora flavescens.It is commonly used to improve obesity and diabetes.In diabetic mice and intestinal secretion cell models, the glucose metabolism of diabetic mice fed with matrine significantly improved, and the secretion of insulin and GLP-1 (glucagon-like peptide-1) increased.

Berberine is the main pharmacological component of the traditional Chinese medicine Coptis chinensis. Research has shown that berberine can alleviate type II diabetes, demonstrating through 16S rRNA gene sequencing technology that berberine reduces the burden of exogenous antigens in the host and increases the levels of short-chain fatty acids in the intestine to alleviate inflammation. Berberine significantly increases the concentration of total short-chain fatty acids in the feces of mice on a high-fat diet, especially acetate and propionate.

Resveratrol is found in the buckwheat family, grapes, and peanuts. In db/db mice, resveratrol not only reverses the ecological imbalance characterized by lower proportions of Rickettsia, Bacteroides, Parabacteroides, Lactobacillus, Ochrobactrum, and Eubacterium but alsoimproves intestinal barrier function, intestinal permeability, and inflammation.In another study, resveratrol improved insulin sensitivity and induced the secretion of the intestinal incretin hormone GLP-1.

Hydroxytyrosol is a simple polyphenol found in extra virgin olive oil and is consideredbeneficial for metabolic disorders.

In PM2.5-induced obesity and insulin-resistant mice, hydroxytyrosol is associated with increased species richness of the gut microbiota and a reduced proportion of pathogenic bacteria, which can alleviate the progression of obesity and diabetes.

Danshensu B is a natural polyphenolic acid found in Salvia miltiorrhiza. When Danshensu B is injected into mice fed a high-fat diet, the expression levels of two genes, TLR4 and Myd88, the phosphorylation level of Jun N-terminal kinase, NF-κB p65 (an antibody), and insulin receptor substrates are all downregulated.It is speculated thatDanshensu B may alleviate diabetes by regulating the abundance of gut microbiota and the LPS/TLR4 signaling pathway.

Literature source:

[1] Liying He, Fang-Qing Yang, Pan Tang, et al. Regulation of the intestinal flora: A potential mechanism of natural medicines in the treatment of type 2 diabetes mellitus [J]. Biomedicine & Pharmacotherapy, (151) 2022.

[2] Liu Ming, Song Fengyuan, Li Fangtong, et al. Research progress on the interaction between natural products and gut microbiota [J]. Applied Chemistry, 2021, 38(4):9.

(The article is excerpted from popular science literature and does not provide any medical guidance.)

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