47-of Natural Medicines

[ABSTRACT] Background: Acute lung injury (ALI) is a critical illness in clinical with high incidence and mortality, and is characterized by inflammatory injury to the lung endothelial and epithelial barriers. Furthermore, safe and effective drugs for the treatment of ALI are not available. In our previous study, we found that Jinyinqingre oral liquid (JYQR), which is a preparation of traditional Chinese medicine made by the Taihe Hospital affiliated to Hubei University of Medicine, has shown remarkable efficacy against inflammation related hepatitis and cholecystitis in clinic. However, whether JYQR plays a role in ALI/ARDS disease has not been reported and its anti-inflammatory mechanism remains unclear. In the present study, we investigated the role and molecular mechanisms of JYQR against ALI using mice model of Lipopolysaccharide (LPS)-induced ALI and RAW264.7 cells model. Methods: The ALI mouse model was induced by intratracheal infusion of LPS solution (5 mg/kg). In the JYQR-treatment group, the male C57B/6 mice were intragastrically administered with JYQR at doses of (high), 8 (mid) and 4 (low) g/kg for 7 days before the LPS challenge. In the positive control group, the mice were pretreated with dexamethasone (5 mg/kg, i.p.) for 3 days before the LPS stimulate. Then, the mean pulmonary arterial pressure (MPAP) and pleural thickness were measured by ultrasound 20 h after LPS treatment and the mice were sacrificed. Histopathological changes in lung tissues were assessed by Hematoxylin-eosin staining (HE staining) and Immunohis-tochemistry (IHC). The pro-inflammatory cytokine levels (IL-1β, TNF-α and IL-6) and total protein in mouse bronchoalveolar lavage fluid (BALF) were detected by ELISA and BCA assays, respectively. The expressions of phosphor-nuclear factor kappa B (p-NF-κB) p65, NOD-like receptor family pyrin domain containing 3 (NLRP3) and gasdermin D (GSDMD) in mouse lungs were detected by Western blotting and immunostaining. Additionally, we measured the expression changes of proinflammatory cytokine levels and the protein expression of p-NF-κB, NLRP3 and GSDMD in LPS-challenged RAW264.7 model with or without JYQR. Results: JYQR pretreatment significantly ameliorated the LPS-induced lung histological changes, total BALF protein, MPAP, and pleural thickness, indicating that JYQR played a protective role in LPS-induced ALI. The mechanism mechanism study showed that JYQR pretreatment significantly inhibited NF-κB activation, and downregulated the expression of the downstream proteins NLRP3/GSDMD expression and proinflammatory cytokine levels in mice and RAW2647 cells. Therefore, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. Conclusions: JYQR protected LPS-induced ALI in mice, and its mechanism is highly related to the down-regulation of the NF-κB/NLRP3/GSDMD inflammatory pathway. [KEY WORDS] Jinyinqingre oral liquid (JYQR); Acute lung injury (ALI); Lipopolysaccharide (LPS); inflammation; NF-κB/NLRP3/ GSDMD pathway [Document code] A [Article ID] 2095-6975(2023)08-0001-13