Baicalin tetrazole acts as anti-pneumocystis carinii pneumonia candidate in immunosuppressed rat model. (July 2019) - Chen, Lin
Abstract: The present study was aimed to synthesize and evaluate tetrazoles of baicalin against Pneumocystis carinii pneumonia in the rat model. Among the seven synthesized baicalin tetrazoles, one with trifloromethyl group in the aromatic ring was found to be most potent during the initial study. The mechanism of preventive effect of most potent compound4c against Pneumocystis carinii pneumonia was investigated in detail. The compound4c decreased the parasitic load by almost 99% in the rats. It significantly (P < 0.05) decreased mortality rate of the rats, prevented pulmonary tissue damage and aggregation of inflammatory cytokines. In Pneumocystis carinii infected rats compound 4c treatment inhibited production of interleukin-18, interleukin-1β and TNF-α significantly (P < 0.05) in the BALF and pulmonary tissues. Treatment of the pneumocystis carinii-infected rats with compound4c inhibited up-regulation of mRNA expression corresponding NLRP3, ASC and caspase-1. The compound4c treatment of the pneumocystis carinii-infected rats significantly (P < 0.02) suppressed the level of NLRP3 and ASC proteins. Moreover, the enhancement of caspase-1 activation by pneumocystis carinii-infection in rats was also suppressed by compound4c . The results from present study demonstrate that compound4c protects pneumocystis carinii induced pneumonia through suppression of inflammatory cytokines and NLRP3 activation. Therefore, compound4c can be of therapeutic importance for the treatment of pneumocystis carinii induced pneumonia. Graphical abstract: Image 1 Highlights: Baicalin tetrazoles with trifloromethyl group in the aromatic ring showed significant activity against Pneumocystis carinii. It decreased the parasitic load by almost 99% in the rats. It decreased mortality rate of the rats, prevented pulmonary tissue damage and aggregation of inflammatory cytokines. It inhibited production of interleukin-18, interleukin-1β and TNF-α. It inhibited up-regulation of mRNA expression corresponding NLRP3, ASC and caspase-1.