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  3. Synergistic effects of Lianhuaqingwen in combination with Oseltamivir and Baloxavir against seasonal influenza virus: In vitro and in vivo assessment

Synergistic effects of Lianhuaqingwen in combination with Oseltamivir and Baloxavir against seasonal influenza virus: In vitro and in vivo assessment

  • J Ethnopharmacol. 2025 Feb 10;338(Pt 2):119091. doi: 10.1016/j.jep.2024.119091.
Cheng Zhang 1,  Manhua Yuan 2,  Wenwan Rong 3,  Han Du 4,  Xuanxuan Li 4,  Tiannan Ji 5,  Jianxiong Li 5,  Bo Dai 6,  Zhenghai Ma 4,  Hui Qi 7,  Ning Zhang 2,  Jing Yang 2,  Xuefeng Duan 3,  Yuhai Bi 8
Affiliations

Affiliations

  • 1 College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China.
  • 2 CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China.
  • 3 CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 4 College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China.
  • 5 Department of Emergency, Department of Radiotherapy, The Fifth Medical Center of PLA General Hospital, Beijing, 100071, China.
  • 6 Department of Pharmacy, Air Force Medical Center, PLA, Beijing, 100142, China.
  • 7 Hebei Academy of Integrated Traditional Chinese and Western Medicine, National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China.
  • 8 CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: beeyh@im.ac.cn.
PMID: 39528119 DOI: 10.1016/j.jep.2024.119091
Abstract

Ethnopharmacological relevance: Lianhuaqingwen (LH), a traditional Chinese medicine, presents a broad-spectrum Antiviral effect and has been widely used to treat influenza. Given the potential rise of drug-resistant influenza viruses, it is necessary to develop new Antiviral drugs and explore combination therapies involving LH in tandem with existing antivirals such as Oseltamivir acid (Osel) or Baloxavir (Bal). These multidrug combinations could help effectively control the seasonal influenza epidemics and reduce the disease burden.

Aim of the study: This study aimed to evaluate the Antiviral effects of LH, alone and in combination with Osel or Bal, against human seasonal influenza viruses in vitro and in vivo models.

Materials and methods: The Antiviral efficacy of LH alone and LH in combination with Osel/Bal against seasonal influenza A viruses (IAVs) (H1N1 and H3N2 subtypes) and influenza B viruses (IBVs) (BV- and BY-lineages) was assessed in vitro using MDCK cells. The median effective concentration (EC50) was determined, and the drug synergies were analyzed. Additionally, the Antiviral activity of LH monotherapy and LH + Osel/Bal combination therapy were evaluated in vivo using an H1N1-infected BABL/c mouse model by monitoring changes in body weight, survival rate, lung viral titer, pathological damage, and inflammatory reaction.

Results: In vitro, LH alone and in combination with Osel/Bal exhibited Antiviral activity against both IAVs and IBVs. The addition of LH to Osel/Bal improved the therapeutic efficacy compared to Osel/Bal alone. In vivo, LH monotherapy reduced body weight loss and increased the survival rates of H1N1-infected mice. LH in combination with Osel/Bal resulted in lower virus titers, more effective relief of pathological damage, and comparable low expression of inflammatory factors in the lungs of H1N1-infected mice compared to the use of Osel/Bal alone. Transcriptomic analysis of the lungs revealed that LH + Osel/Bal significantly increased the expression of genes associated with Antiviral and anti-inflammatory effects.

Conclusions: This study evaluated the Antiviral effects of LH monotherapy and combination therapy with Osel/Bal against human seasonal influenza viruses in vitro and in vivo models. The results suggest that combining LH with Osel or Bal could enhance the Antiviral efficiency for influenza viruses compared to the monotherapy using any of these three drugs.

Keywords

Antiviral activity; Baloxavir; Lianhuaqingwen; Oseltamivir; Synergistic effect; Traditional Chinese medicine.

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