[Acupuncture reduce colonic inflammation by suppressing oxidative stress and endoplasmic reticulum stress in rats with ulcerative colitis].

OBJECTIVE: To investigate the effect of manual acupuncture (MA) and electroacupuncture (EA) on histopathological changes, and levels of oxidative-stress related cytokines and key proteins of the endoplasmic reticulum stress (ERS) pathway in ulcerative colitis (UC) rats, so as to reveal their mechanisms underlying improvement of UC. METHODS: Twenty-eight male SD rats were randomly divided into control, model, EA and MA groups (n＝ 7 rats per group). The UC model was established by enema of mixture solution of 5% 2, 4, 6-trinitrobenzene sulfonic acid (TNBS, 100 mg/kg). Rats of the control group received intra-rectal perfusion of normal saline. After modeling, the left "Quchi"(LI11) and "Zusanli"(ST36) were stimulated with EA (2-4 mA，8 Hz/25 Hz) or MA for 20 min, once every other day for consecutive 2 weeks. The rats in the control and model group were just anesthetized and fixed. At the end of experiments, the colon tissue was collected for observing histopathological changes with H．E. staining. The contents of oxidative stress-related factors as superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (T-AOC) were detected by ELISA, and the expression levels of key proteins of ERS as phosphorylated inhibitor of nuclear factor kappa B kinase α (p-IκBα), phosphorylated p65 (p-p65), glucose regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK) and phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) by using Western blot. RESULTS: After modeling, the colon tissues showed severe swelling, disordered arrangement of intestinal mucosal cells, hemorrhage with infiltration of inflammatory cell and partial loss of colon villus, which was relatively milder in the EA and MA groups. The colonic lesion score was remarkably increased in the model group in contrast to the control group (P<0.01), and obviously reduced in both EA and MA groups relevant to the model group (P<0.01). The levels of SOD, CAT, GSH and T-AOC were all significantly decreased (P<0.01), and the content of MDA, and expression levels of p-IκBα， p-p65 and GRP78, p-PERK and p-eIF2α proteins were all significantly increased in the model group relevant to the control group (P<0.01). After the treatment, modeling-induced down-regulation of SOD, CAT and GSH in both EA and MA groups, and T-AOC in the EA group, and up-regulation of levels of MDA, p-IκBα， p-p65, GRP78, p-PERK and p-eIF2α in both groups were reversed (P<0.01, P<0.05). CONCLUSION: Both EA and MA treatment can obviously alleviate colonic inflammation in UC rats via inhibiting oxidative stress and ERS.

Asymmetric Construction of Spiro[thiopyranoindole-benzoisothiazole] Scaffold via a Formal [3 + 3] Spiroannulation.

An enantioselective formal thio[3 + 3] spiroannulation reaction of indoline-2-thiones to 1-azadienes has been developed by the use of a quinine-derived bifunctional tertiary amine-thiourea catalyst, which furnished a series of optically active spiro[thiopyranoindole-benzoisothiazole] heterocycles with a spiro quaternary C-N/C-S stereogenic centers in high yields with good to excellent diastereo- and enantioselectivities.