Taohong Siwu Decoction Ameliorates Ischemic Stroke Injury Via Suppressing Pyroptosis

Abstract

Objective: Taohong Siwu decoction (THSWD) is one of the classic prescriptions for promoting blood circulation and removing blood stasis, and it has a good therapeutic effect on ischemic stroke. We sought to explore the therapeutic effects of THSWD on pyroptosis in rats with middle cerebral artery occlusion-reperfusion (MCAO/R).Methods: MCAO/R model of rats were established by suture-occluded method. MCAO/R rats were randomly divided into five groups, which were model group, nimodipine group, THSWD high, medium and low dose group (18, 9, and 4.5 g/kg, respectively), rats of sham group without thread embolus. All rats were treated by intragastric administration for 7 days. We detected the level of inflammatory factors. NLRP3 and Caspase-1 were detected by immunofluorescence. Western blot was used to detect NLRP3, Caspase-1, ASC, and GSDMD in penumbra. Also, the expression of TXNIP, HMGB1, toll-like receptors (TLR4), NF-κB, and MAPK were detected.Results: THSWD treatment improved the behavioral function and brain pathological damage. These results showed that the levels of TNF-α, TGF-β, IL-2, IL-6, IL-1β, and IL-18 were significantly reduced in THSWD treatment groups. THSWD could significantly decrease the expression levels of NLRP3, Caspase-1, Caspase-1 p10, ASC, TXNIP, GSDMD, HMGB1, TLR4/NFκB, p38 MAPK, and JNK in penumbra.Conclusion: Our results showed that THSWD could reduce the activation level of NLRP3 inflammatory corpuscle, down-regulate GSDMD, and inhibit pyroptosis in MCAO/R rats. These may be affected by inhibiting HMGB1/TLR4/NFκB, MAPK signaling pathways.

Rhamnocitrin Ameliorates Ovarian Fibrosis Via PPARγ/TGF-β1/Smad Pathway to Repair Ovarian Function in Polycystic Ovary Syndrome Rats Running Title：rhamnocitrin Ameliorates Ovarian Fibrosis in Polycystic Ovary Syndrome Rats

“…For PPARγ inhibitor treatment, rats were injected intraperitoneally with T0070907 (10 mg/kg, Sigma-Aldrich, St Louis, MO, USA) once daily in accordance with the previous study [28]. For PPARγ agonist treatment, rats were treated with GW1929 (15 mg/kg, Sigma-Aldrich) by oral gavage once daily according to previous study [29]. The drugs were administered for 21 consecutive days, meanwhile control group and PCOS group were given the same volume of normal saline.…”

Traditional Chinese Medicine for adjuvant treatment of breast cancer: Taohong Siwu Decoction

“…THSWD is traditionally used in gynecology, the effective rate of treating primary dysmenorrhea is more than 90% [ 20 ], and it can be used for postpartum blood stasis [ 21 ], uterine bleeding [ 22 ], etc. It is widely used in internal medicine such as coronary heart disease [ 23 , 24 ], ischemic stroke [ 25 ], etc.…”

Thioredoxin interacting protein, a key molecular switch between oxidative stress and sterile inflammation in cellular response

“…Ischemic stroke models were used to demonstrate the protective effects of natural and herbal medicine via inhibitory effect on TXNIP expression. Taohong Siwu decoction (THSWD), a traditional Chinese medicine could inhibit the expression of TXNIP thereby improved neurobehavioral outcome, inhibited NLRP3-inflammasome activation and pyroptosis following ischemic reperfusion injury in rat[ 96 ]. Treatment with THSWD attenuated activation of NLRP3-inflammasome evident by lower level of caspase-1, IL-1β, TNFα, IL-6, HMGB1 and IL-18.…”