Inhibition of Lipopolysaccharide E. coli-induced acute lung injury by extracted Antidesma bunius (L.) Spreng fruits as compared to Fluticasone Propionate, a corticosteroid

Munoz, M. N.; Lucero, J.; Benzon, K. S. H.; Reyes, J. I. L.; de Silva, C.; Delicana, R. C.; Tejada, U. A.; Chatterjee, S.; Watanabe, K.

doi:10.1101/2021.04.08.438930

bioRxiv · 10.1101/2021.04.08.438930

Inhibition of Lipopolysaccharide E. coli-induced acute lung injury by extracted Antidesma bunius (L.) Spreng fruits as compared to Fluticasone Propionate, a corticosteroid

Munoz, M. N.·Lucero, J.·Benzon, K. S. H.·Reyes, J. I. L.·de Silva, C.·Delicana, R. C.·Tejada, U. A.·Chatterjee, S.·Watanabe, K.

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Abstract

The hallmark of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is inflammation-induced alveolar-vascular barrier destruction and neutrophilic infiltration that leads to the formation of cytokines and oxygen radicals. The objective of the study is to investigate the protective and toxicological effects of Antidesma bunius (L.) Spreng [Bignay] in murine model of Lipopolysaccharide E. coli (LPS)-induced ALI and compared with Fluticasone Propionate (FP), a synthetic corticosteroid. We showed that extracted Bignay fruits have high amount of phenols, steroids and flavonoids but insignificant amount of heavy metals and aflatoxins. BALB/c mice of either sex were divided into 4 groups in the ALI mouse model; Group 1: vehicle control; Group 2: LPS alone; Group 3: Bignay + LPS; and Group 4: FP + LPS. Bignay and FP were administered via intraperitoneal injection while LPS was given intra-tracheally. Biomarkers of ALI such as total lung inflammatory cell count, total lung protein content, lung edema and interleukin-6 (IL-6) secretion were measured 24 hrs after vehicle control or LPS treatment. Compared to vehicle controls, LPS caused significant increased in all measured biomarkers of ALI in samples collected from bronchoalveolar lavage fluid and were significantly attenuated by Bignay fruit extract or FP. Pulmonary vascular leakage caused by LPS was also evaluated after injection with Evans blue dye, an indication of lung injury. Extracted Bignay fruits or FP when given to mice 2 hrs after LPS administration substantially decreased the pulmonary vascular leak. Our findings are the first evidence demonstrating the preventive and non-toxic effects of extracted Bignay fruits in a murine model of LPS-induced ALI. The results could be attributed to the presence of active secondary metabolites such as flavonoids, phenols and steroids. It is also evident that extracted Bignay fruits are as effective as FP, well-established steroid, in blocking the biomarkers of ALI caused by LPS.

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Munoz, M. N., Lucero, J., Benzon, K. S. H., Reyes, J. I. L., de Silva, C., Delicana, R. C., Tejada, U. A., Chatterjee, S., Watanabe, K.. 2021-04-08. Inhibition of Lipopolysaccharide E. coli-induced acute lung injury by extracted Antidesma bunius (L.) Spreng fruits as compared to Fluticasone Propionate, a corticosteroid. https://doi.org/10.1101/2021.04.08.438930

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