Renovation of Intestinal Barrier by Polydatin in Experimentally Induced Ulcerative Colitis: Comparative Ultrastructural Study with L-Carnosine

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with intestinal epithelial barrier impairment. Polydatin (PD), a natural product isolated from <i>Polygonum cuspidatum</i>, is known to have an anti-inflammatory, antioxidant, and antiapoptotic effect. We attempted to compare the protective impact of PD pretreatment on alterations to the intestinal epithelial barrier and the colonic wall’s ultrastructure accompanying ulcerative colitis to other conventional drugs in practice, primarily L-carnosine, which has not been addressed before. The rats were divided into 5 groups; 3 of them were treated with sulphasalazine (500 mg/kg), L-carnosine (30 mg/kg), and PD (45 mg/kg). All groups were administered their respective drugs 3 days before the UC was induced by acetic acid intra-rectally, and the treatment was continued until the 11th day. The disease activity index (DAI) was estimated, and a macroscopic scoring was established for the harvested colonic tissue. The tissues were extracted and processed for hematoxylin and eosin staining, caspase-3 immunohistochemical staining, electron microscopy, and biochemical analysis evaluating proinflammatory markers (IL-1β, TNF-α, and IL-6), myeloperoxidase (MPO), oxidative stress, and lipid peroxidation. Histopathological examination of colonic tissue showed that PD pretreatment effectively restored mucosal epithelial cells, intercellular tight junctions, goblet cells, and maintained the intestinal epithelial and endothelial barriers. PD suppressed MPO, proinflammatory markers, and malondialdehyde but enhanced superoxide dismutase and glutathione levels. It also hampered apoptosis, as evidenced by a reduction in caspase-3 expression. PD showed a significantly better response in preserving the intestinal epithelial barrier against acetic acid-induced colitis as compared to sulphasalazine and L-carnosine. These findings demonstrate the therapeutic role of PD for patients with UC.

Polydatin alleviates DSS‐ and TNBS‐induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3

“…The results showed that polydatin could significantly improve the main symptoms of the two colitis models, such as diarrhea, bloody stool, weight loss, shortened colon length, and histopathological changes. These results are consistent with the reported effect of polydatin on DSS and similar DNBS‐induced colitis (Lv et al, 2018; Ebrahim & Elsherbini, 2021; Yao et al, 2011; Liu et al, 2018). Drugs for clinical treatment of colitis, such as 5‐aminosalicylic acid, steroids and immunosuppressants, have shown therapeutic effects on DSS or TNBS‐induced colitis models (Yousefi‐Ahmadipour et al, 2020; Khan et al, 2021; Panés & Gisbert, 2019), indicating that IBD animal models have been successful in the study of colitis drugs.…”

“…In view of the preventive or therapeutic effects of polydatin on DSS-and TNBS-induced colitis in mice, we have reason to believe that polydatin may be a candidate drug for the treatment of IBD. (Chen et al, 2021;Peritore et al, 2021;Lv et al, 2018;Ebrahim & Elsherbini, 2021;Yao et al, 2011;Liu et al, 2018). However, the effect of regulating Th17/Treg balance to protect colitis has not been studied.…”

“…The distortion of the Th17/Treg balance in favor of the pro‐inflammatory Th17 side is hence believed to contribute to exacerbation of IBD. Polydatin has been reported to improve DSS or DNBS‐induced colitis through anti‐inflammatory, antioxidant, and anti‐apoptotic effects, and its mechanism involves Sonic hedgehog pathway, NF‐κB pathway, SIRT‐1/Nrf2 pathway, and MAPK pathway (Chen et al, 2021; Peritore et al, 2021; Lv et al, 2018; Ebrahim & Elsherbini, 2021; Yao et al, 2011; Liu et al, 2018). However, the effect of regulating Th17/Treg balance to protect colitis has not been studied.…”

“…Many studies have shown that polydatin has a wide range of pharmacological activities, such as anti‐fibrosis, anti‐tumor, anti‐atherosclerotic diseases, anti‐hepatitis, protection against multi‐organ ischemia–reperfusion injury and dementia‐related disorders, and so on (Li et al, 2018; Sun & Wang, 2020; Wu et al, 2020; Jin et al, 2020; Chen, Niu, et al, 2020; Liu et al, 2020; Tang, 2021). In the past decade, it has been reported that polydatin can improve dextran sulfate sodium (DSS) or dinitro‐benzene sulfonic acid (DNBS)‐induced colitis by anti‐inflammation, anti‐oxidation and anti‐apoptosis, and its mechanism of action involves the Sonic hedgehog pathway, the nuclear factor kappa B (NF‐κB) pathway, the sirtuin 1/nuclear factor erythroid 2‐related factor 2 (SIRT‐1/Nrf2) pathway, and the mitogen‐activated protein kinase (MAPK) pathway (Chen et al, 2021; Peritore et al, 2021; Lv et al, 2018; Ebrahim & Elsherbini, 2021; Yao et al, 2011; Liu et al, 2018). However, it is rarely reported that polydatin regulates Th17/Treg balance and its molecular mechanism to alleviate colitis.…”

Recent Advances in Traditional Chinese Medicine for Treatment of Podocyte Injury

“…Various studies have shown that PD has pharmacological effects on ischemia-reperfusion injuries of kidneys, heart, cerebra, lungs and other organs (Sun and Wang, 2020). Furthermore, it is also known to have anti-inflammatory, antioxidative, anti-apoptotic, hepatoprotective and immunoregulatory effects (Ebrahim and Elsherbini, 2021). Zheng et al demonstrated that PD stabilizes mitochondrial morphology, and attenuates mitochondrial malfunction in both KK-Ay mice and HG-induced cells through suppressing Drp1 expression (Zheng et al, 2017).…”