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.
Highlights
Type 2 diabetes (T2D) has become a major threat to human health
Clinical studies found that proinflammatory factors such as interleukin-6 (IL-6) and C-reactive protein (CRP) were significantly higher for the population who developed diagnosed diabetes over the follow-up period, and to some degree, these indicators could be used as powerful predictors of type 2 diabetes (T2D) [5, 6]
Diabetic rats were further randomly divided into 5 groups (n 7 per group): a diabetes control group (DC group), a diabetes with high-dose Scutellaria-Coptis group (DHSC group), a diabetes with middle-dose ScutellariaCoptis group (DMSC group), a diabetes with low-dose Scutellaria-Coptis group (DLSC group), and a diabetes with metformin group (DME group). is animal study was approved by the experimental animal ethics committee of Chengdu University of T
Summary
Type 2 diabetes (T2D) has become a major threat to human health. In recent years, accumulating evidence has indicated that chronic inflammation plays a significant role in the occurrence and development of T2D, and anti-inflammatory administration is a potential approach to treatment [2,3,4]. Clinical studies found that proinflammatory factors such as interleukin-6 (IL-6) and C-reactive protein (CRP) were significantly higher for the population who developed diagnosed diabetes over the follow-up period, and to some degree, these indicators could be used as powerful predictors of T2D [5, 6]. Experimental studies have confirmed that inflammatory cytokines could inhibit the phosphorylation of insulin receptor substrate proteins and promote the M1-like polarity shift of islet macrophages, causing insulin resistance (IR) and islet dysfunction [7, 8].
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