1.Mechanism study on the improvement of lung injury in mice with in-fluenza A virus pneumonia by Shufeng Jiedu capsules based on regu-lating intestinal microflora
Yikun WU ; Hongmin GUO ; Yan LI ; Weige MU ; Shuyun HUANG ; Jiuling ZHU ; Zhu YANG ; Shuzhi ZHONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1351-1360
AIM:To study the improvement effect and possible mechanism of Shufeng Jiedu capsules(SFJDC)on viral pneumonia.METHODS:Forty-eight BALB/c mice were used to establish a viral pneumo-nia model by intranasal administration of influenza A virus H1N1.They were randomly divided into 4 groups,with twelve mice in each group.Except for the Model group,the treatment group was given oseltamivir(OSTW),low and high dose groups of Shufeng Jiedu capsules(SFJDC-L,SFJD-H)by gavage,take another 12 mice as the normal group,continu-ously administered for 7 days.The physical signs of each group of mice were observed during the ad-ministration process,and the daily body weight change rate and disease activity index was calculat-ed;After administration,lung,intestinal tissue,and intestinal contents were taken,and the pathological changes in mouse lung tissue were detected using hematoxylin eosin(HE)staining method,Alisin blue staining was used to detect goblet cells in the intes-tinal wall;RT-qPCR method for detecting viral load influenza(infA)and the expression of tumor necro-sis factor-a(TNF-α)and interleukin-6(IL-6)mRNA in mouse lung tissue;Detection of mouse gut mi-crobiota using 16S rRNA high-throughput sequenc-ing;ELISA method for detecting lipopolysaccharide(LPS),TNF-α and IL-6 level in mouse serum;The ex-pression of cyclic GMP AMP synthase(cGAS),inter-feron gene stimulating protein(STING),phospho-STING(p-STING),nuclear factor-κB(NF-κB)phos-pho-nuclear factor-κB(p-NF-κB)in lung tissue and ZO-1,Occludin in small small intestine was detected by Western Blotting.RESULTS:Compared with the model group,the lung index and viral load of mice in the Shufeng Jiedu capsules group were signifi-cantly reduced(P<0.01);significant reduction in lung tissue inflammation accompanied by TNF-α;The expression level of IL-6 mRNA decreased(P<0.01);The abundance of Firmicutes and Lachnospi-raceae in the intestine significantly increased(P<0.01),while the abundance of Bacteroidetes and Bacteroidaceae communities significantly de-creased(P<0.05 or 0.01);The number of goblet cells in the small intestine epithelium significantly increased(P<0.01);the levels of serum LPS and TNF-α,IL-6 were significantly reduced(P<0.01);The protein expression level of cGAS,p-STING,p-NF-κB significantly decreased in lung tissue(P<0.05 or 0.01),ZO-1,Occludin significantly decreased in small intestine(P<0.05).CONCLUSION:Shufeng Jie-du capsules reduces the inflammatory response of mice lung tissue,and its mechanism may be relat-ed to its regulation of intestinal flora,protection of intestinal mucosal barrier,and reduction the activa-tion of cGAS/STING/NF-κB signaling pathway ac-tived by LPS leakaging from the intestine.
2.Mechanism study on the improvement of lung injury in mice with in-fluenza A virus pneumonia by Shufeng Jiedu capsules based on regu-lating intestinal microflora
Yikun WU ; Hongmin GUO ; Yan LI ; Weige MU ; Shuyun HUANG ; Jiuling ZHU ; Zhu YANG ; Shuzhi ZHONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1351-1360
AIM:To study the improvement effect and possible mechanism of Shufeng Jiedu capsules(SFJDC)on viral pneumonia.METHODS:Forty-eight BALB/c mice were used to establish a viral pneumo-nia model by intranasal administration of influenza A virus H1N1.They were randomly divided into 4 groups,with twelve mice in each group.Except for the Model group,the treatment group was given oseltamivir(OSTW),low and high dose groups of Shufeng Jiedu capsules(SFJDC-L,SFJD-H)by gavage,take another 12 mice as the normal group,continu-ously administered for 7 days.The physical signs of each group of mice were observed during the ad-ministration process,and the daily body weight change rate and disease activity index was calculat-ed;After administration,lung,intestinal tissue,and intestinal contents were taken,and the pathological changes in mouse lung tissue were detected using hematoxylin eosin(HE)staining method,Alisin blue staining was used to detect goblet cells in the intes-tinal wall;RT-qPCR method for detecting viral load influenza(infA)and the expression of tumor necro-sis factor-a(TNF-α)and interleukin-6(IL-6)mRNA in mouse lung tissue;Detection of mouse gut mi-crobiota using 16S rRNA high-throughput sequenc-ing;ELISA method for detecting lipopolysaccharide(LPS),TNF-α and IL-6 level in mouse serum;The ex-pression of cyclic GMP AMP synthase(cGAS),inter-feron gene stimulating protein(STING),phospho-STING(p-STING),nuclear factor-κB(NF-κB)phos-pho-nuclear factor-κB(p-NF-κB)in lung tissue and ZO-1,Occludin in small small intestine was detected by Western Blotting.RESULTS:Compared with the model group,the lung index and viral load of mice in the Shufeng Jiedu capsules group were signifi-cantly reduced(P<0.01);significant reduction in lung tissue inflammation accompanied by TNF-α;The expression level of IL-6 mRNA decreased(P<0.01);The abundance of Firmicutes and Lachnospi-raceae in the intestine significantly increased(P<0.01),while the abundance of Bacteroidetes and Bacteroidaceae communities significantly de-creased(P<0.05 or 0.01);The number of goblet cells in the small intestine epithelium significantly increased(P<0.01);the levels of serum LPS and TNF-α,IL-6 were significantly reduced(P<0.01);The protein expression level of cGAS,p-STING,p-NF-κB significantly decreased in lung tissue(P<0.05 or 0.01),ZO-1,Occludin significantly decreased in small intestine(P<0.05).CONCLUSION:Shufeng Jie-du capsules reduces the inflammatory response of mice lung tissue,and its mechanism may be relat-ed to its regulation of intestinal flora,protection of intestinal mucosal barrier,and reduction the activa-tion of cGAS/STING/NF-κB signaling pathway ac-tived by LPS leakaging from the intestine.

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