Gut microbiota-mediated therapeutic effect of <i>Shengmai </i>formula (SMF)<i> </i>on sepsis in mice

HOU Jingyi; WU Jiawei; CAO Lijuan

doi:10.11665/j.issn.1000-5048.2023022701

Journal of China Pharmaceutical University > 2023 > 54(2): 218-225. > DOI: 10.11665/j.issn.1000-5048.2023022701

HOU Jingyi, WU Jiawei, CAO Lijuan. Gut microbiota-mediated therapeutic effect of Shengmai formula (SMF) on sepsis in mice[J]. Journal of China Pharmaceutical University, 2023, 54(2): 218-225. DOI: 10.11665/j.issn.1000-5048.2023022701

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Gut microbiota-mediated therapeutic effect of Shengmai formula (SMF) on sepsis in mice

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

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Received Date: February 26, 2023
Revised Date: March 20, 2023

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Abstract

To investigate the effects of Shengmai formula (SMF) on tissue damages, serum inflammatory factors and the proportion of innate immunocytes in peripheral blood, sepsis models using either intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) were established.The role of gut microbiota in septic mice during SMF treatment was further investigated.LPS-induced sepsis model was carried out 4 days after daily gavage administration with 0.3 g/kg, 0.6 g/kg, 1.2 g/kg SMF or intraperitoneal injection with 0.6 g/kg SMF.Survival rates of septic mice were determined.Histological evaluations of liver, lung and kidney were analyzed by H&E staining. Serum IL-6, TNF-α, Alanine transaminase (ALT), Aspartate aminotransferase (AST), Blood urea nitrogen (BUN) and Creatinine (Cr) levels were determined.LPS and CLP-induced sepsis models were established, and the proportion of monocytes, macrophages and neutrophils in peripheral blood were analyzed by flow cytometry after gavage administration or intraperitoneal injection of SMF.The therapeutic effects of SMF after antibiotics treatment were further determined, and the therapeutic effects of fecal microbiota from SMF-treated mice were investigated.The results show that LPS-induced sepsis caused death of mice, damages in liver, lung and kidney with increased infiltration of leukocytes and elevated levels of serum IL-6, ALT, AST, BUN and Cr, which were all reversed by gavage administration of SMF.Gavage administration of SMF could significantly reduce the proportion of peripheral macrophages in LPS model and monocytes, macrophages, neutrophils in CLP model.Intraperitoneal injection of SMF showed no therapeutic benefits in septic mice.Depletion of gut microbiota using antibiotics cocktail reversed the therapeutic effects of SMF on sepsis, indicating the involvement of gut microbiota.Fecal microbiota from SMF-treated donors was transplanted into pseudo-sterile recipients, and we found FMT could significantly ameliorate sepsis of recipients.These results showed that gavage administration of SMF reduced serum inflammatory factors and alleviated tissue damages in septic mice by regulating gut microbiota. This study provides a theoretical basis for the treatment of clinical sepsis with SMF.
- Shengmai formula (SMF),
- sepsis,
- tissue damages,
- inflammatory factors,
- immune regulation,
- gut microbiota

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