The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota

Abstract

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

Gut Microbiota May Mediate the Influence of Periodontitis on Prediabetes

“…Decreased diversity usually indicates loss of harmonious gut microbiota, with overgrowth of pathogenic bacteria and loss of beneficial bacteria. Correspondingly, we observed that bacteria enriched in the gut microbiota of the PD mice were mainly Proteobacteria, which include many potential enteropathogenic bacteria and lipopolysaccharideproducing bacteria, such as Deltaproteobacteria, Escherichia_ Shigella, and Enterobacteriaceae (Zhang et al 2020). Furthermore, several butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Eubacterium_fissicat-ena_group, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, Eubacterium_ventriosum_ group, Eubacterium_xylanophilum_group, Eubacterium_ nodatum_group, and Intestinimonas, were decreased in the gut microbiota of the PD mice.…”

Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier

“…Restoration of epithelial barrier function by anti-TNF therapy may reflect mucosal healing in the setting of a dampened immune system; however, pre-clinical studies have shown that TNF signaling also modulates TJ. Many studies have shown decreased levels of intestinal TJ-consisting proteins in animal models of IBD [ 40 ], obesity, and T2D [ 41 , 42 ], with increased permeability, suggesting that a leaky pathway is responsible for LGS.…”

“…Sci. 2021, 22, x 4 of 17 of IBD [40], obesity, and T2D [41,42], with increased permeability, suggesting that a leaky pathway is responsible for LGS. Epithelial cells bind each other with tight junction, adherens junction, and desmosome.…”

New Insights of Anti-Hyperglycemic Agents and Traditional Chinese Medicine on Gut Microbiota in Type 2 Diabetes

“…123 Furthermore, the hypoglycaemic effects of Scutellaria-Coptis were involved in regulating gut microbiota and alleviating intestinal mucosal barrier damage. 124 Scutellaria-Coptis significantly inhibited some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and increased the abundances of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. 124 The change of gut microbiota resulted in alleviating intestinal mucosa barrier damage by preventing the leakage of LPS and increasing the intestinal tight junction proteins claudin-1, occluding and ZO-1 in diabetic rats.…”