Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis / 中国中药杂志

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

Effect of Iridoid-rich Fraction from Valeriana Jatamansi Jones on Neuron Pyroptosis in Rats with Acute Spinal Cord Injury / 中国康复理论与实践

Objective:To investigate the effects of iridoid-rich fraction from Valeriana jatamansi Jones (IRFV) on neuronal pyroptosis in rats with acute spinal cord injury, and to explain the related mechanism of neuroprotection. Methods:Twenty-four healthy male Sprague-Dawley rats were randomly divided into sham-operated group, model group and treatment group, with eight rats in each group. The model of spinal cord injury was established by using a medical aneurysm clip in the latter two groups. Only the lamina was removed without injury to the spinal cord in the sham-operated group. Four hours after the operation, the treatment group was given IRFV solution 10 mg/kg, the model group and the sham-operated group were given the same volume of sodium carboxymethyl cellulose (CMC-Na) solution, for seven days. The rats were sacrificed to detected the pathological changes and the residual area of spinal cord tissue through HE staining. The apoptosis of nerve cells of the spinal cord tissue at the perilesional area was detected by TUNEL fluorescent staining. The levels of interleukin (IL)-1 and IL-18 in serum were detected by ELISA Kit and the expression of NLRP3, Caspase-1 and GSDMD were detected by Western blotting. Results:Compared with the sham-operated group, the residual area of spinal cord tissue decreased (P < 0.05), and the positive rate of TUNEL staining, the level of IL-1 and IL-18, and the expression of pyroptosis-associated proteins (NLRP3, Caspase-1 and GSDMD) increased (P < 0.05) in the model group. Compared with the model group, the pathological condition of the spinal cord tissue improved and the residual area of the spinal cord tissue increased (P < 0.05); the positive rate of TUNEL staining, the level of IL-1 and IL-18 and the expression of NLRP3, Caspase-1 and GSDMD decreased (P < 0.05) in the treatment group. Conclusion:IRFV could attenuate the inflammatory response to exert neuroprotective effects, which may be related to the regulation of NLRP3/Caspase-1 signaling pathway to inhibit the neuronal pyroptosis in rats with acute spinal cord injury.

Effect of Huangqin Decoction on pyroptosis pathway of NLRP3/caspase-1 in mice with ulcerative colitis / 中国中药杂志

To explore the effect of Huangqin Decoction on ulcerative colitis(UC) pyroptosis, and to explain the mechanism of pyroptosis based on NOD-like receptor thermoprotein domain 3(NLRP3)/cysteine proteinase 1(caspase-1) pathway. The animal model of UC induced with 3% dextran sodium sulfate(DSS) was established. The experimental animals were divided into control group, model group, low-dose(4.55 g·kg~(-1)), medium-dose(9.1 g·kg~(-1)) and high-dose(18.2 g·kg~(-1)) Huangqin Decoction groups and salazosulfapyridine group(0.45 g·kg~(-1)). While modeling, intragastric administration was given for 7 consecutive days. On the 8 th day, the mice were euthanized, the colon length was collected, and the histopathological changes were observed by HE staining. The content of interleukin-18(IL-18) was observed by ELISA. The content of lactatedehydrogenase(LDH)was determined by microplate method. TUNEL assay kit was used to detect the cell death. The immunohistochemical staining was used to detect the expressions of NLRP3 and apoptosis-associated speck-like protein containing a CARD(ASC). Western blot was used to detect the expressions of interleukin-1β(IL-1β), caspase-1 and gasdermin D(GSDMD).The experimental study showed that compared with normal group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were significantly increased(P<0.05). Compared with model control group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were decreased, and these results were more significant in high-dose groups(P<0.05). The results of HE staining showed that Huangqin Decoction could improve the pathological changes of colon. Huangqin Decoction could inhibit UC cell pyroptosis, and the mechanism may be closely related to NLRP3/caspase-1 signaling pathway.