Chlorogenic acid ameliorates intestinal inflammation via miRNA-microbe axis in db/db mice.

Chlorogenic acid improves diabetic symptoms, including inflammation, via the modulation of the gut microbiota. However, the mechanism by which the microbiota is regulated by chlorogenic acid remains unknown. In this study, we firstly explored the effects of chlorogenic acid on diabetic symptoms, colonic inflammation, microbiota composition, and microRNA (miRNA) expression in db/db mice. The results showed that chlorogenic acid decreased body weight, improved glucose tolerance and intestinal inflammation, altered gut microbiota composition, and upregulated the expression level of five miRNAs, including miRNA-668-3p, miRNA-467d-5p, miRNA-129-1-3p, miRNA-770-3p, and miRNA-666-5p in the colonic content. Interestingly, the levels of these five miRNAs were positively correlated with the abundance of Lactobacillus johnsonii. We then found that miRNA-129-1-3p and miRNA-666-5p promoted the growth of L. johnsonii. Importantly, miRNA-129-1-3p mimicked the effects of chlorogenic acid on diabetic symptoms and colonic inflammation in db/db mice. Furthermore, L. johnsonii exerted beneficial effects on db/db mice similar to those of chlorogenic acid. In conclusion, chlorogenic acid regulated the gut microbiota composition via affecting miRNA expression and ameliorated intestinal inflammation via the miRNA-microbe axis in db/db mice.

Chlorogenic acid improves glucose tolerance, lipid metabolism, inflammation and microbiota composition in diabetic db/db mice.

Introduction: Chronic and acute chlorogenic acid (CGA) can improve glucose tolerance (GT) and insulin sensitivity (IS). However, whether acute administration of CGA has beneficial effects on hepatic lipid metabolism and cecal microbiota composition remains unclear. Methods: In the current study, diabetic db/db mice were administered CGA or metformin, and db/m mice were used as controls to explore the effects of CGA on hepatic lipid metabolism, including fatty acid oxidation and transportation and triglyceride (TG) lipolysis and synthesis. Moreover, alterations in the inflammatory response and oxidative stress in the liver and gut microbe composition were evaluated. Results: The results showed that CGA decreased body weight and improved glucose tolerance and insulin resistance, and these effects were similar to those of metformin. CGA decreased hepatic lipid content by increasing the expression of CPT1a (carnitine palmitoyltransferase 1a), ACOX1 (Acyl-CoA oxidase 1), ATGL (adipose triglyceride lipase), and HSL (hormone-sensitive lipase) and decreasing that of MGAT1 (monoacylglycerol O-acyltransferase 1), DGAT1 (diacylglycerol O-acyltransferase), DGAT2, CD36, and FATP4 (fatty acid transport protein 4). Additionally, CGA restored the expression of inflammatory genes, including TNF-α (tumor necrosis factor-alpha), IL-1ß (interleukin-1beta), IL-6, and IL-10, and genes encoding antioxidant enzymes, including SOD1 (superoxide dismutases 1), SOD2 (superoxide dismutases 2), and GPX1 (glutathione peroxidase 1). Furthermore, CGA improved the bacterial alpha and beta diversity in the cecum. Moreover, CGA recovered the abundance of the phylum Bacteroidetes and the genera Lactobacillus, Blautia, and Enterococcus. Discussion: CGA can improve the antidiabetic effects, and microbes may critically mediate these beneficial effects.

Study on Baohe Pills Regulating Intestinal Microecology and Treating Diarrhea of High-Fat and High-Protein Diet Mice.

Objective: To investigate the effects of Baohe pills on intestinal microorganisms and enzyme activities in mice with a high-fat and high-protein diet. Methods: 45 KM male mice were randomly divided into the control group, the high-fat and high-protein diet group, and the Baohe pill intervention group. The mice in the high-fat and high-protein diet group and the Baohe pill intervention group were fed with the self-made high-fat and high-protein diet as the sole food source of the mice, and the mice in the control group were fed with the normal diet. Starting from the 7th day of the feed intervention, mice in the Baohe pill intervention group were given 0.28 g/mL of Baohe pill decoction twice a day at the dose of 6.67 g/(kg·day), each time of 0.35 mL for 6 days. Mice in the control group and the high-fat and high-protein diet group were given the same amount of distilled water by gavage. The general state of mice in each group was observed, and the changes of intestinal microorganisms and intestinal enzyme activities were analyzed by culturable microorganism technology and intestinal functional enzyme detection technology. Results: The excrement of mice fed with a high-fat and high-protein diet was relatively thin and wet, and the Baohe pill intervention could not improve the symptoms well. In the high-fat and high-protein diet group, the number of bacteria, Escherichia coli, Lactobacillus, and Bifidobacterium, was significantly lower than that in the control group (P < 0.01). Baohe pills could obviously increase the high-fat, high-protein diet for the number of culturable microorganisms in mice, the total number of bacteria, and the number of Bifidobacteria in the most significant (P < 0.01), but the number of bacteria, Escherichia coli, and the Lactobacillus are still significantly lower than the control group (P < 0.01). In terms of enzyme activity, both contents and mucosa, the Baohe pill could improve the activities of amylase, protease, sucrase, and lactase in high-fat and high-protein diet mice, which were significantly different from the control group (P < 0.05). In terms of microbial activity, the intestinal contents of high-fat and high-protein mice were lower than those of the control group, while the intestinal mucosa was higher than that of the control group, but the difference was not significant (P > 0.05). Baohe pills could improve the intestinal contents and intestinal mucosal microbial activity of mice, and the difference was significant in the high-fat and high-protein diet group (P < 0.05). Discussion. A high-fat and high-protein diet can destroy the physiological balance of the body, which is mainly reflected in the disturbance of intestinal flora and the decrease of some enzyme activities and microbial activity. Baohe pills can restore the number of intestinal flora to a certain extent and improve the activities of various digestive enzymes including protease and amylase.

Use of Chlorogenic Acid against Diabetes Mellitus and Its Complications.

Chlorogenic acid (CA) is a phenolic compound commonly found in human plant-based diets. CA is the main component of many traditional Chinese medicine preparations, and in recent years, it has been found to have hypoglycemic, hypolipidemic, anti-inflammatory, antioxidant, and other pharmacological properties. Specifically, CA relieves the effects of, and prevents, diabetes mellitus (DM). In addition, CA is also beneficial against complications arising from DM, such as diabetic nephropathy (DN), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Herein, we review the use of CA in the prevention and treatment of DM and its complications, providing a background for further research and medical uses.

Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.

Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.