The objective of the present study was to evaluate structure–activity relationships of four sanshools on antioxidant activities. In vitro, hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), and hydroxy-γ-sanshool (HRS) had stronger antioxidant capacities than hydroxy-γ-sanshool (RS), attributed to the hydroxyl group. Furthermore, HRS had the greatest oxygen radical absorbance capacities (ORAC) and free radical scavenging (DPPH and ABTS) capacities, attributed to more cis-double bonds. Sanshools could effectively decrease the level of oxidative stress in colonic tissue and HCT-116 cells, including increased enzyme activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) and decreased concentrations of malondialdehyde (MDA). After intragastric administration of sanshool, HRS increased the the level of hepatic Total antioxidant capacity (T-AOC) and colon GSH-Px and SOD. Moreover, sanshools significantly increased Nrf2, HO-1 proteins and decreased Keap1 protein. The protective effect of HRS was much higher than HAS, HBS, and RS, apparently due to its amide and hydroxyl groups. The binding energies of Nrf2 with HAS, HBS, HRS, and RS were −5.17, −5.11, −5.75, and −4.16 kcal/mol, respectively. HRS is more easily combine with Nrf2. In summary, sanshools acted as substitutes for natural antioxidants, in which HRS has the greatest antioxidant activity. This study provided a basis for future research on relationships between structure and activity.
Hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), hydroxy-γ-sanshool (HRS), and γ-sanshool (RS) are the key components from theZanthoxylumgenus, processing a range of pharmacological activities. The present study investigated the protective capacities of four sanshools on a dextran sulfate sodium (DSS)-induced model of ulcerative colitis (UC). The results showed that sanshool administration alleviated the colitis symptoms by reducing body weight loss and disease activity index (DAI) score, increasing the colon length, and improving colonic injury and the change in immune organ weight. Furthermore, sanshools enhanced the antioxidant enzyme activities, and RS exhibited the lowest effect on the improvement in total antioxidative capacity (T-AOC) and antioxidant abilities compared to the other three sanshools. The p65 nuclear factor κB (p65 NFκB) signaling pathway was inhibited to prevent hyperactivation and decreased the production of inflammatory factors. The gut barrier function in DSS-induced mice was restored by increasing goblet cell number and levels of tight junction proteins (zonula occludens-1, occludin, and claudin-1), and the levels of protein in HAS and HRS groups were higher than that in the HBS group, significantly. The analysis of gut microbiota suggested that sanshool administration significantly boosted the abundance ofLachnospiraceae,Muribaculaceae,Oscillospiraceae, andAlistipesand reduced the level ofBuchnerain colitis mice. Collectively, the sanshool treatment could ameliorate colitis by resisting colon injury and regulating intestinal barrier dysfunction and gut microbiota dysbiosis; meanwhile, HRS and HAS have better improvement effects.Keywords:sanshool;colitis;intestinal barrier;p65;intestinal flora
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