Total saponins from Siraitiae Fructus alleviate lung and intestinal injuries in rats with acute lung injury and mice infected with the influenza virus by regulating cytokines and enhancing the mucosal barrier.

Siraitiae Fructus (SF), the dried fruit of Siraitia grosuenorii (Swingle) C. Jeffreyex A. M. Lu et Z. Y. Zhan g , a traditional medicinal and edible herb, is known for its properties in dissipating heat, moistening the lungs and intestines, and promoting defecation, which contains saponins, flavonoids, and polysaccharides. However, the effective substances of SF have not been fully identified. This study systematically evaluated therapeutic efficacy of aqueous extract of Siraitiae Fructus (SFE) and its three fractions: Siraitiae Fructus total saponins (SFTS), polysaccharides (SFP), low-polarity saponins (SFLS). In lipopolysaccharide (LPS)-induced acute lung injury (ALI) rats, both SFE and SFTS demonstrated significant protective effects against pulmonary and colonic tissue damage. SFTS is more advantageous in regulating IL-1β and IL-17A in serum, W/D and TNF-α in lung tissues, and IL-1β, IL-17A in colon tissues, compared with SFLS and SFP. Subsequent validation in influenza A virus (IAV)-infected mice confirmed SFTS's ability to improve survival rates while alleviating viral pneumonia and enterocolitis. The quantitative analysis revealed that Mogroside V (399.728 mg/g) and 11-O-Mogroside V (202.660 mg/g) constituted 60.23% of SFTS. In summary, Both SFE and SFTS could alleviate the lung and colon injury induced by LPS and IAV by restoring the mucosal barrier, reducing the immune response, and decreasing the expression of inflammatory cytokines in the systemic circulation, thereby exerting "lung-gut co-treatment" effect. This study provides a foundation for the further investigation on the effective substances of SF, and also supports the "Lung-gut axis" theory.