Pharmacological evaluation of Salvadora persica in modulating Lipopolysaccharide and Cigarette smoke-induced acute lung injury; an in-vitro, in-vivo, and in-silico approach.

ETHNOPHARMACOLOGICAL RELEVANCE

ARDS (Acute Respiratory Distress Syndrome) and ALI (Acute Lung Injury) are severe pulmonary alterations manifested by amplified inflammatory and oxidative responses contributing to high mortality rates. ALI triggered by various provoking factors, including cigarette smoke (CS), or pathogens (Lipopolysaccharide or SARS-CoV-2), cause severe life-threatening morbidities. Salvadora persica has been used across various countries for cough and asthma, however; there is a paucity of data on its use in ALI.

AIM OF THE STUDY

This research explores signaling pathways and the potential of S-persica in treating ALI, emphasizing the feasibility of its compounds being advanced into therapeutic agents via pre-clinical trials and computational approaches.

MATERIALS AND METHODS

In-vitro, GC-MS, phytochemicals, antioxidants (Phosphomolybdenum, DPPH, ABTS, and FRAP), and enzyme inhibition (AChE & BChE) assays were performed. 60 rats were divided into 12 groups (n = 5 each), and assigned to SP-mx (100, 200, and 300 mg/kg), Dexa (1 mg/kg), Control (NS), LPS-challenged and CS-exposed groups, to establish in-vivo models. After 24 h (LPS-challenged) and day 10th (CS-exposure), oxygen saturation, inflammatory cells, lung weight, histopathology, MDA, TOS, TAC, and mRNA expression of IL-1β, TNF-α, IL-6, NF-κβ, COX-2, IL-4 and IL-10 were evaluated. Further, in-silico studies were conducted via Docking, Swiss ADME, Molinspiration, and ProTox-III.

RESULTS

In both models, SP-mx reduced edema, inflammatory cells infiltration, histopathological alterations, oxidative stress, expression of pro-inflammatory cytokines, COX-2 and NF-κB, while elevating TAC and anti-inflammatory cytokines. Its high phenolic contents along with antioxidant and anticholinesterase activities, endorsed SP-mx remarkable ability to combat oxidative stress. In-silico studies confirmed its interactions with AChE, BChE, COX-2, TNF-α, IL-1β, and NF-κB, as well as its favorable ADMET, and drug-likeness properties.

CONCLUSION

These findings highlight that SP-mx is a potential therapeutic candidate for treating ALI by possibly modulating COX-2/NF-κB signaling pathways, warranting further research for clinical translation.