Abstract
Impaired intestinal barrier plays an important role in the pathogenesis of hypertension primarily through promoting the development of chronic low-grade inflammation. Baicalin is the major flavonoid component of Scutellaria baicalensis Georgi, a medicinal plant commonly used for the treatment of inflammatory intestinal disorders and hypertension in traditional Chinese medicine. However, it remains to be elucidated whether baicalin alleviates hypertension-associated intestinal barrier impairment. The current study thus investigated the effects of baicalin on the intestinal barrier integrity, the intestinal expression of genes encoding proinflammatory factors and tight junction proteins, the serum levels of the inflammatory markers, the amount of fecal short-chain fatty acids (SCFAs) and the abundance of SCFAs-producing bacteria in the spontaneously hypertensive rats (SHRs). The results showed that baicalin alleviated the pathological lesions in the ilium and the proximal colon in the SHRs. Baicalin treatment resulted in decreased ileal and colonic expression of proinflammatory genes in the SHRs. In addition, baicalin treatment attenuated hypertension-associated intestinal hyperpermeability and decreased the serum levels of inflammatory indicators such as high-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, and IL-6 in the SHRs. The protective effect of baicalin on the intestinal integrity was also supported by well-preserved intestinal ultrastructure and increased intestinal expression of genes encoding tight junction proteins such as zonula occludens-1 (ZO-1), cingulin, and occludin in the SHRs. Lastly, baicalin treatment increased the amount of fecal SCFAs and the abundance of SCFAs-producing bacteria in the SHRs. In conclusion, the work here provides for the first time the morphological, biochemical, and molecular evidence supporting the protective effects of baicalin on the intestinal integrity in the SHRs, which may help better understand the therapeutic effects of S. baicalensis Georgi in the treatment of hypertension.
Highlights
Hypertension is the leading risk factor for the development of cardiovascular diseases (Ahluwalia and Bangalore, 2017)
Measurement of the number of goblet cells, villi length and the thickness of tunica muscularis further revealed that the vehicle-treated spontaneously hypertensive rats (SHRs) was characterized by decreased number of goblet cells, reduced villi length, and decreased thickness of tunica muscularis compared to the vehicle-treated WKY controls, whereas baicalin treatment increased the number of goblet cells, the length of the villi, and the thickness of tunica muscularis compared to that from the vehicle-treated SHRs (Figures 1B–D)
These results indicate that baicalin treatment ameliorates the necrotic and ulcerative intestinal lesions and impairment of the mechanical intestinal barrier in the SHRs
Summary
Hypertension is the leading risk factor for the development of cardiovascular diseases (Ahluwalia and Bangalore, 2017). Intestinal barrier impairment has recently been noted as an important pathological element implicated in the progression of hypertension (Jaworska et al, 2017; Santisteban et al, 2017). Intestinal barrier impairment is implicated in the pathogenesis of chronic low-grade inflammation that perpetuates the hypertensive state, exacerbates hypertensive target organ damages, and promotes the development of resistant hypertension (Fukui, 2016; Solak et al, 2016). Therapeutic agents protecting the intestinal barrier integrity under hypertensive conditions may help better control the progression of hypertension. Whether baicalin is pharmacologically active at preserving the intestinal barrier integrity under hypertensive conditions remains to be investigated
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