Isolation & identification of anti-inflammatory constituents of Randia dumetorum lamk. fruit: Potential beneficial effects against acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Randia dumetorum Lamk. is an Indian traditional medicinal plant that has been used for the treatment of various disorders including respiratory ailments. AIM OF THE STUDY: In continuation of our recent report that the Ethanol soluble fraction (ESF) of Randia dumetorum fruit had potent anti-inflammatory activity against acute lung injury (ALI) in mice, the present work was undertaken to unveil the key bioactive constituents possessing anti-inflammatory action against ALI by employing bioactivity-guided fractionation of ESF. MATERIAL AND METHODS: Different fractions/sub-fractions obtained by column chromatography of ESF were subjected to bioactivity studies by analyzing total and differential count, and protein content in broncho-alveolar lavage fluid (BALF) procured from mice. The most bioactive sub-fraction F3.2 was analyzed for the assessment of various inflammatory mediators using molecular techniques like ELISA, PCR, and western blotting. Further, an attempt was made to separate the key compounds in F3.2 using solvents of differential polarities; and isolated compounds were validated for their anti-inflammatory activity followed by their characterization using spectral techniques like 1HNMR, 13CNMR, FT-IR, and ESIMS Mass Spectrometry. RESULTS: The column chromatography of ESF yielded four fractions (F1, F2, F3, and F4) and data revealed that maximum activity resides in F3. Further fractionation of F3 yielded sub-fractions F3.1, F3.2, F3.3, and F3.4 which when tested for anti-inflammatory potential, showed F3.2 as the most active one. Moreover, the effect of F3.2 on oxidative stress parameters and inflammatory mediators analyzed via biochemical assays, PCR, and ELISA revealed the proficiency of this fraction in amelioration of ALI. F3.2 was then subjected to recrystallization using different solvents and two pure compounds were isolated which were characterized as D-Mannitol and Oleanolic acid (OA). D-Mannitol did not display any bioactivity, but OA showed potent anti-inflammatory activity. CONCLUSION: Considering the ethnopharmacological role of R. dumetorum in respiratory ailments, OA as an aglycone moiety seems to be the main active principle possessing anti-inflammatory potential against ALI.

COVID-19 and ARDS: Update on Preventive and Therapeutic Venues.

A novel coronavirus SARS-CoV-2, which initially originated in China, has outstretched to all nations and turned out to be an intense global concern for both the governments and the public. In addition to the health concerns, the COVID-19 pandemic has caused a tremendous impact on the economic and political conditions of every nation. Ever since the start of the pandemic, the physicians were constrained to rely on the management strategies due to a lack of clear understanding of the disease pathogenesis caused by SARS-CoV-2 infection. Scientists are working tirelessly to gather maximum information about the deadly virus and come up with various strategies, which can be used against COVID-19 infection in terms of therapeutics and vaccine development. It is quite evident that the virus infection leads to acute respiratory distress syndrome (ARDS), and most of the deaths occur due to respiratory failure. As the virus spreads through respiratory droplets, the strenuous exercise of preventive measures and diagnosis at a large scale has been in practice across the globe to prevent transmission. This review amalgamates the various updates and acts as an umbrella to provide insights on SARS-CoV-2 mediated ARDS pathogenesis, the impact of co-morbidities, diagnostics, current progress in vaccine development, and promising therapeutics and immuno-modulatory strategies, highlighting various concerns and gaps that need to be addressed to fight current and future pandemics effectively.

Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib, prevents acute lung injury associated cognitive deficits potentially through suppression of inflammatory response.

Acute lung injury (ALI) has been reported to be associated with high mortality rate. Moreover, ALI survivors, frequently present chronic cognitive deterioration. We have previously shown that 'two hit' (hydrochloric acid + lipopolysaccharide) induced ALI resulted in cognitive dysfunction through the induction of systemic inflammation. The present study was designed to explore the potential anti-inflammatory effects of olaparib (Poly ADP-ribose polymerase-1 inhibitor), on ALI mediated cognitive impairment. Olaparib was administered at dose of 5 mg/kg body weight (i.p.) 30 min before each hit. Data show that olaparib pre-treatment markedly reduced the neutrophil infiltration, alveolar capillary damage, inflammatory cytokines level (TNF-α/IL-1ß/IL-6) and oxidative stress in the lungs at 24 h after ALI induction. Also, olaparib pre-treatment ameliorated the ALI associated cognitive impairment as assessed by Morris water maze test on weekly basis for 2 consecutive weeks. Further, restoration of cognitive function was associated with normalization of serum levels of TNF-α/IL-1ß and improved the blood brain barrier (BBB) function, as reflected by data on expression of occludin/claudin-5 and extravasation of Evans-blue/FITC dextran in hippocampus at 1 week post injury. Finally, increased mRNA expression of VCAM-1, TNF-α and IL-1ß and NF-κB activation in hippocampus indicate induction of neuro-inflammation, which was downregulated upon olaparib administration. Further, olaparib treatment 1 week after ALI induction blunted the systemic inflammation which was associated with improved BBB and cognitive function. Altogether, our results showed that olaparib protects against ALI and associated cognitive deficits in mice, and thus may offer a new treatment avenue in the area.