Curcumin attenuates the progression of hemorrhoids through the inhibition of angiogenesis via miR-190a-5p/TGFBR2
Background: Hemorrhoids are common diseases of the anorectal system and are usually accompanied by vascular proliferation and edema. Curcumin is a natural molecule with potential anti-inflammatory, antitumor and antioxidant effects. This study aimed to explore the effect and molecular mechanism of curcumin in alleviating angiogenesis in rat hemorrhoids. Methods: A rat model of hemorrhoids was established via glacial acetic acid induction. Human venous endothelial cells were collected to perform cell experiments. The rats received curcumin at 25, 50, or 100 mg/kg/d. The rats were scored for perianal symptoms and inflammation levels, and the expression of angiogenesis-related factors was evaluated by immunofluorescence. Bioinformatics analysis, dual-luciferase, RT?qPCR and Western blotting were used to verify the molecular mechanism of curcumin in the treatment of hemorrhoids. Results: Curcumin inhibited angiogenesis in endothelial cells and relieved the symptoms of hemorrhoids in rats. The study revealed that the expression of miR-190a-5p was significantly downregulated in hemorrhoids, whereas curcumin promoted the expression of miR-190a-5p. The results revealed that miR-190a-5p could inhibit angiogenesis and inflammation in endothelial cells by targeting TGFBR2, thereby alleviating the development of hemorrhoids. Mechanistically, curcumin inhibits the expression of TGFBR2 by upregulating miR-190a-5p, effectively blocking the angiogenesis ability of endothelial cells and thereby attenuating the progression and development of hemorrhoids in rats. Conclusion: Curcumin effectively inhibits angiogenesis in endothelial cells and relieves inflammation and the progression of hemorrhoids by regulating the miR-190a-5p/TGFBR2 molecular pathway. Overall design: This study included a total of 6 human samples, comprising 3 hemorrhoid tissue samples (hemorrhoid group) and 3 normal control tissue samples (control group). Both the case and control group samples were pathologically confirmed, and the baseline characteristics, such as age and sex, were not significantly different between the two groups (p > 0.05) on the basis of statistical tests to minimize the interference of confounding factors on the results. For construction of the sequencing library, the TruSeq Small RNA Sample Prep Kit (Illumina, San Diego, USA) was used, which strictly followed the manufacturer's protocol. After the quality control of the library was passed, high-throughput sequencing was performed using the Illumina HiSeq 2000/2500 platform in single-end mode, with a read length of 50 bp. Differential expression analysis of the miRNAs was conducted using an independent sample t test. The screening criteria for differentially expressed miRNAs were as follows: |log2(fold change)| > 1 (i.e., fold change > 2 or < 0.5) and p value < 0.05.