Therapeutic potential of zinc oxide/berberine nanoparticles in mitigating acute respiratory distress syndrome: in vivo and in silico approaches

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BACKGROUND: Inflammation and oxidative stress strongly contribute to the pathophysiology of acute respiratory distress syndrome (ARDS), which is a life-threatening pulmonary disease. Zinc oxide/berberine nanoparticles (ZnO/Ber-NPs) have been shown to have a protective effect against COVID-19 because of their antioxidant, anti-inflammatory, and antiviral properties. Hence, this study aimed to investigate the therapeutic action of ZnO/Ber NPs against ARDS. ARDS was induced by a combination of lipopolysaccharides and nicotine (LPS + Nt). METHODS: Male mice were induced with LPS + Nt alternately for 14 days and then orally administered berberine (Ber) (1.24 mg/kg), ZnO NPs (2.06 mg/kg), a ZnO NP + Ber mixture (3.3 mg/kg), or ZnO/Ber NPs (3.3 mg/kg). Assessment of (1) prooxidant and antioxidant (enzymatic and nonenzymatic) parameters, (2) inflammatory and anti-inflammatory markers (TNF-α, IL-1β, IFN-ɣ, NF-kB and IL-10), (3) lung lesion parameters, triggering receptor expressed on myeloid cells-1 (TREM-1), myeloperoxidase enzyme (MPO) and angiotensin-converting enzyme-2 (ACE II), (4) and apoptotic markers (Bax and p53) were performed via standardized methods. In addition, ZnO, Ber, and ZnO/Ber NPs were examined for their bioactivities against the following proteins GPx, code: 2R37, SOD protein, code: 1PL4, ACE2 protein, code: 6M1D, TREM1 protein, code: 1Q8M and MPO protein, code: 6WYZ. RESULTS: The results demonstrated that LPS + Nt administration significantly elevated oxidative stress, proinflammatory, lung lesion, and proapoptotic parameters while reducing antioxidant and ACE II levels in the lung. Treatments, especially ZnO/Ber NPs, significantly attenuated the oxidative stress and inflammation associated with ARDS, as indicated by the restoration of antioxidant enzyme activities, decreased lipid peroxidation, and proinflammatory TNF-α and IFN-ɣ levels. ZnO/Ber NPs significantly decreased TREM-1 and MPO in association with elevated ACE II. In addition, ZnO/Ber NPs decreased the expression of apoptotic markers and decreased the number of alveolar inflammatory infiltrates to the minimal score. Molecular docking analysis revealed that ZnO/Ber NPs showed the strongest binding with all tested receptors. CONCLUSION: ZnO/Ber NPs exhibit antioxidant, anti-apoptotic, and anti-inflammatory effects and act as therapeutic candidates against ARDS.

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