Huashi Baidu Granules Treat Influenza Viral Pneumonia by Regulating Gut-Lung Axis
10.13422/j.cnki.syfjx.20261305
- VernacularTitle:基于肠-肺轴的化湿败毒颗粒治疗流感病毒性肺炎的作用机制
- Author:
Qijing LI
1
;
Hanhui HUANG
2
;
Yurong DENG
2
;
Ao'ao WANG
2
;
Jianliang LI
1
;
Jianhui SUN
2
;
Liyu HAO
2
;
Zongyuan LI
1
;
Guimin LIU
2
;
Hongmei LI
2
;
Luqi HUANG
3
Author Information
1. National Resource Center for Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China
2. Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China
3. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs， China Academy of Chinese Medical Sciences，Beijing 100700，China
- Publication Type:Journal Article
- Keywords:
Huashi Baidu Granules;
influenza A virus;
H1N1;
gut-lung axis;
NLRP3 inflammasome;
gut microbiota
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(23):59-69
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Huashi Baidu granules in treating influenza A （H1N1） virus infection based on the gut-lung axis. MethodsBALB/c mice were randomly assigned into a blank control group， a model control group， a positive control （oseltamivir phosphate capsules， 19.5 mg·kg-1） group， and a Huashi Baidu granules （17.81 g·kg-1） group. Mice in other groups except the blank control group were instilled nasally by H1N1 viral fluid for the modeling of influenza viral pneumonia and treated with corresponding drugs once daily by gavage for 5 consecutive days. The mouse lung index was calculated， and pathological changes in the lung and colon tissue were observed. Western blot was employed to quantify the expression levels of nucleotide-binding oligomeric domain-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific proteinase -1 （Caspase-1）， apoptosis-associated Speck-like protein containing a CARD （ASC）， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β， and colonic tight junction protein 1 （CLDN1）， and Occludin in the lung and colon tissue. Non-targeted metabolomics was employed to analyze the metabolic profiles of the lung tissue and intestinal contents. The 16S rRNA sequencing was performed to analyze the gut microbiota structure in intestinal contents. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the 5-hydroxytryptamine （5-HT） levels in the serum， lung tissue， and colon tissue. ResultsCompared with the blank control group， the model control group showed elevated lung index， marked inflammatory cell infiltration and alveolar structural destruction in the lung tissue， obvious inflammatory cell infiltration and mucosal epithelial damage in the colon tissue， upregulated protein levels of NLRP3 inflammasome pathway proteins NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in the lung and colon tissue （P<0.05， P<0.01）， downregulated protein levels of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Compared with the model control group， Huashi Baidu Granules reduced the lung index （P<0.01）， alleviated pathological damage in the lungs and colon， inhibited the expression of NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in lung and colon tissue （P<0.05， P<0.01）， and upregulated the expression of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Metabolomics analysis showed that Huashi Baidu Granules downregulated the 5-HT pathway and arachidonic acid metabolism pathway in the lung and colon tissue， while upregulating nucleotide metabolism and TCA cycle. Compared with the blank control group， the model control group exhibited elevated levels of 5-HT in the serum， lung tissue， and colon tissue （P<0.01）. The intervention with Huashi Baidu Granules lowered the levels of 5-HT in the serum （P<0.05） and the lung and colon tissue （P<0.01）. Huashi Baidu Granules increased the diversity of gut microbiota， enriched beneficial bacteria such as Blautia， and inhibited pathogenic bacteria such as Desulfovibrio. ConclusionHuashi Baidu Granules significantly alleviate lung inflammation and pathological damage in mice infected with influenza A （H1N1） virus， reshape the intestinal microecology， and repair the intestinal barrier. It may exert cross-organ regulation by inhibiting the cascade of "gutogenic 5-HT release-circulatory transport-pulmonary 5-HT receptor activation-NLRP3 inflammasome assembly." It exerts therapeutic effects on influenza viral pneumonia through the gut-lung axis. This study provides a modern biological interpretation for the TCM theories of interior-exterior relationship between the lung and large intestine and simultaneous treatment of the lung and intestine.
