trans-δ-Viniferin inhibits Ca2+-activated Cl− channels and improves diarrhea symptoms

Bioactivity, bioavailability, and gut microbiota transformations of dietary phenolic compounds: implications for COVID-19

“…Moreover, COVID-19 patients exhibited intestinal dysbiosis characterized by a decrease in the diversity and abundance of gut microbiota [ 58 , 194 ], which could represent a potential target for the use of PC ( Figure 2 ). Supporting this hypothesis, resveratrol [30] and certain resveratrol oligomers [188] have been demonstrated to alleviate diarrhea induced by rotavirus in animal models. The inhibition of epithelial Ca 2+ -activated Cl – channels contributes to the anti-secretory and anti-motility protective effects of these PC [188] ( Figure 2 ).…”

“…Supporting this hypothesis, resveratrol [30] and certain resveratrol oligomers [188] have been demonstrated to alleviate diarrhea induced by rotavirus in animal models. The inhibition of epithelial Ca 2+ -activated Cl – channels contributes to the anti-secretory and anti-motility protective effects of these PC [188] ( Figure 2 ).…”

The diverse roles of TMEM16A Ca2+-activated Cl− channels in inflammation

“…Recent studies have reported that the approved drugs anthelmintics niclosamide and nitazoxanide, which are well tolerated with mild side effects in the clinic, inhibit TMEM16A channels and are promising for treating airway inflammatory diseases such as asthma, COPD, and CF [96,156]. In addition, many natural compounds, such as shikonin from the dried root of Lithospermum erythrorhizon [42], trans-d-viniferin from Vitis amurensis Rup [89], and plumbagin from Plumbago zeylanica L. [44], inhibit TMEM16A channels, and are used to treat secretory diarrhea in animal models. These compounds are widely used with mild side effects, and thus may be clinically useful for the treatment of secretory diarrhea.…”

“…Ousingsawat et al reported that the rotavirus toxin NSP4, which is known to activate PLC to increase [Ca 2+ ] i [87], activated TMME16A Cl À channels in colonic epithelial cells and TMEM16A-overexpressing HEK293 cells [43]. TMEM16A inhibition by many compounds such as red wine extract [88], trans-delta-viniferin [89], and shikonin [42] relieved rotaviral diarrhea. Therefore, rotaviral endotoxin induces excessive fluid secretion by activating TMEM16A Cl À channels in colonic epithelial cells.…”

“…The TMEM16A Ca 2+ -activated Cl À channel exerts diverse cellular functions in inflammatory diseases. For example, TMEM16A overexpression in airway and intestinal epithelial cells can result in excessive fluid secretion in inflammatory diseases such as allergic rhinitis [60,134,135] and infectious diarrhea [42][43][44]89]. In addition, increased TMEM16A expression level and activity in goblet cells contribute to goblet cell metastasis and mucus hypersecretion under inflammatory conditions [6,[60][61][62]65,66] and airway inflammatory diseases such as asthma [13].…”