An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation

https://doi.org/10.1016/j.apsb.2025.04.008

This new article publication from Acta Pharmaceutica Sinica B, discusses how an anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear.

This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis.

The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Keywords: Houttuynia cordata, Polysaccharides, H1N1, MRSA, Pneumonia, Complement, NLRP3, Treg/Th17 cell balance, Gut-lung axis

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525002400-ga1_lrg.jpg

This study uncovers HCPM alleviates severe pneumonia induced by H1N1–MRSA coinfection, and the mechanisms may be related to the Treg/Th17 balance in the gut–lung axis and NLRP3 inflammasome.

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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

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CiteScore: 24.3

Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy) 

JIF without self-citation: 13.8

ISSN 2211-3835

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Xinxing Li, Wenxin Ding, Yan Lu, Haiyan Zhu, Weilian Bao, Yang Liu, Jiaren Lyu, Lishuang Zhou, Hong Li, Jiyang Li, Daofeng Chen, An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation, Acta Pharmaceutica Sinica B,

Volume 15, Issue 6, 2025, Pages 3073-3091, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.04.008