Abstract

BackgroundPulmonary fibrosis (PF) is a respiratory ailment that causes the substitution of healthy lung tissue with scar tissue due to collagen deposition and fibroblast proliferation. The incidence of PF increased with the successive waves of Coronaviruses and other viruses affecting the lungs. Therefore, the priority is moving toward treatment with medicinal plants for their active constituents. Salvia officinalis L. herbal drug (sage, family; Lamiaceae) is characterized by its strong antioxidative activity. This study aims to declare the effect of using sage ethanol extract (SOEE) as a protective agent from PF through an in vivo study on mercuric chloride (HgCl2)-induced lung fibrosis and in vitro evaluation of its anticancer, antiviral, and antioxidant activities concerning its phytoconstituents.ResultsTwelve compounds were isolated and identified as apigenin, luteolin, genkwanin, quercetin, hispidulin, luteolin-7-O-β- glucopyranoside, rutin, rosmarinic acid, caffeic acid, ferulic acid chlorogenic acid, and ellagic acid. The results of antioxidants indicated that SOEE exhibited the greatest efficacy as an antioxidant agent in the 1,1-Diphenyl-2-picrylhydrazyl assay with inhibitory concentration (IC50) 23.21 ± 1.17 µg/ mL followed by 1864.71 and 1793.80 µM Trolox equivalent/mg extract for ferric ion reducing antioxidant power and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS), respectively. SOEE showed notable cytotoxic activity against A549. Oral administration of SOEE at 69.4 and 173.5 mg/kg.bw afforded a noteworthy protective effect against HgCl2-induced pulmonary fibrosis. Also, lung superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were increased by SOEE. That was in parallel with working to reduce the malondialdehyde (MDA), necrosis factor kappa (NF-κB), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX-2) levels. The lung P53, Bcl-2, Bcl-XL, AKT, and vanin-1 gene expression was upregulated in SOEE-treated rats compared to HgCl2-treated rats.ConclusionSOEE reduces acute lung injury and can be used to inhibit the proliferation and migration of lung fibrotic cells. These activities may be related to its high antioxidant activity, which could result from the phenolic constituents. The authors recommended using sage in the treatment of lung diseases to protect from lung fibrosis. Additional animal and human experiments are needed for future research.Graphical abstract

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