Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut-microbiota-related tryptophan metabolites.

BACKGROUND: Barberry plants can be considered as useful additives and functional compounds in various industries, especially in the food industry. Berberine (BBR), the most important functional compound in the barberry roots, has recently been used to treat obesity, diabetes, and atherosclerosis. Gut microbiota and the intestinal barrier play an important role in the development of glucolipid metabolism disorders (GLMDs). However, the association of gut microbiota metabolism disorder and the intestinal barrier dysfunction effect of BBR in GLMDs remains elusive. RESULTS: The results showed that administration of BBR could increase the number of colonic glands and goblet cell mucus secretion, improve the intestinal barrier function, and reduce the serum glycolipid level in GLMD hamsters. Interestingly, BBR was metabolized into 12 metabolites by gut microbiota, and the main metabolic pathways were oxidation, demethylation, and hydrogenation. In addition, BBR significantly improved the species diversity and uniformity of gut microbiota and promoted the proliferation of beneficial microbiota. Furthermore, the levels of tryptophan metabolites, such as indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-pyruvic acid, and indole-3-acetic acid were significantly altered by BBR. Both the intestinal tight junction proteins and intestinal immune factors were altered by BBR. CONCLUSION: BBR could alleviate intestinal barrier dysfunction of GLMDs by modulating gut microbiota and gut-microbiota-related tryptophan metabolites, which may be one of the pharmacological mechanisms for the treatment of GLMDs. © 2022 Society of Chemical Industry.

Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats.

Background: It has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear. Methods: A diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro. Results: In the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely. Conclusions: In the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.

Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology. METHODS: HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology. RESULTS: The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP. CONCLUSIONS: In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

Berberine improves neurogenic contractile response of bladder detrusor muscle in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma has been used to treat diabetes mellitus for more than 1400 years in China. Berberine, one of the main alkaloids of Coptidis Rhizoma, is a principal antidiabetic component of Coptidis Rhizoma. To investigate the effects of berberine on impaired neurogenic contractility of detrusor muscle from urinary bladder of rats with early stage diabetes. MATERIALS AND METHODS: The detrusor muscle strips were isolated from urinary bladders of streptozotocin-induced diabetic rats, 5% sucrose-induced diuretic rats or normal rats, and were placed in organ bath. The contractions induced by electrical field stimulation (EFS), carbachol, KCl, adenosine triphosphate, and the effects of berberine on those contractions were measured. RESULTS: The EFS- or KCl-induced contraction of detrusor muscle was significantly decreased in diabetic rats as compared with diuretic or normal rats. Atropine and suramin inhibited EFS-induced contraction. In diabetic rats, the atropine sensitive components were decreased in EFS-induced contraction of detrusor muscle, and the adenosine triphosphate-induced contraction was significantly increased. The carbachol-induced contrations were not different among groups. Berberine significantly potentiated EFS-induced contractions of detrusor muscle both from normal and diabetic rats, but the potentiated effect of BBR was more sensitive to atropine in diabetic rats. Berberine also potentiated adenosine triphosphate-induced contraction of detrusor muscle, but did not change carbachol- or KCl-induced contraction. CONCLUSION: The neurogenic contraction of urinary bladder detrusor muscle is decreased while purinergic contraction of bladder detrusor muscle is increased in rats with early stage diabetes. Berberine increases the neurogenic contractile response to EFS possibly via both presynaptic increasing neurotransmitters release and postsynaptic potentiation of purinergic transmitter-regulated response in rat urinary bladder detrusor; and in diabetic rats, berberine increases neurogenic contractile response mainly via the presynaptic increasing acetylcholine release.