Deciphering the anti-constipation effects of leaf extracts from Globularia alpym on loperamide as laxative through in vitro, in silico and in vivo experimental model
摘要
Many plants act as natural anti-constipation agents due to their specific compounds that work as laxatives and promote bowel movements. This study focuses on the investigation into the Globularia alypum plant’s ability to relieve constipation induced by loperamide (Lop) in rats. The aqueous extract of G. alypum leaves (GA) was subjected to physico-chemical analyses and in vitro anti-oxidative assays. GA in vivo effects on intestinal transit, oxidative stress markers and tissues’ structure were evaluated. Dominant chemicals of GA were selectively tested for their interaction to inflammatory factors (IL-6 and TNF- α) receptors through in silico study. Our results revealed that GA contains 19 bioactive components. At 20 µg/ml, GA did reduce the half of both DPPH radical and ferric ions. In vivo experimentation, proved that GA ameliorates intestinal transit and restores the oxidative stress equilibrium in both kidney and colon organs. Among the studied components of GA, oleuropein and verbascoside have the best binding affinities to both tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) receptors, with Gibb’s free energies ranging from – 6.6 and – 6.8 kcal. They present interactions with 4 or more hydrogen bonds into the site of action of IL-6 receptor. Furthermore, no relevant histological abnormalities were induced by both doses of the extract. Overall, these findings support the potential use of GA extract as a laxative and antioxidant agent, as well as a modulator of inflammatory pathways.