Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver.

Abeer H Elmaidomy,Hani A Alhadrami,Hossam M Hassan,Usama Ramadan Abdelmohsen,Hanan F Aly,Elham Amin,Mona H Hetta,Mostafa E Rateb,Asmaa M Othman

doi:10.3390/molecules25143116

Abstract

Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant native to different tropical regions. Although some reports addressed their anti-inflammatory, cytotoxic, and antituberculotic effects, their hepatoprotective potential is yet to be discovered. Accordingly, this study investigated the crude extract and different fractions of the plant leaves; metabolic profiling using liquid chromatography/high-resolution electrospray ionization mass spectroscopy (LC–HRESIMS) analysis, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties for the dereplicated metabolite via online PreADMET program, ROS scavenger activity on the Hep G2 human liver cancer cell line, and the possible hepatic cellular treatment effects in alcohol-inflamed liver female Wistar albino rats. Metabolic profiling dereplicated a total of 28 metabolites from the crude extract and its various fractions. In silico ADMET and ROS scavenger activity screening suggested plant metabolites are of potential bioactivity. In vivo hepatic treatment with crude, defatted crude, and n-hexane leave extracts suggested all extracts significantly improved liver damage, which was indicated by the reduction of elevated serum levels of bilirubin, AST, ALT, ALP, CRP, TNF-α, ICAM-1, VCAM-1, and MDA. The reduced levels of GSH and TAC were normalized during the study. Histological examinations of liver tissue showed collagen fiber distribution nearly back to its normal pattern. The anti-inflammatory and antioxidant potentials of Premna odorata extracts could be partly related to the combined effects of these phytochemicals or their synergistic interactions.

Highlights

The liver is primarily responsible for alcohol metabolism in the human body and as this is the case, it is vulnerable to alcohol-related injuries [1]
The ion at mass-to-charge ratio (m/z) 433.1361 corresponding to the suggested molecular formula C21 H20 O10 was dereplicated as vitexin (1) [9,17], which was formerly reported in Premna odorata
C30 H38 O17 were characterized as premnoside A (2) and 6-O-α-L-(2”-O-trans-caffoyl) rhamnopyranosyl catalpol (3) from the ions at m/z 833.2746 and 671.1910, respectively, which were previously reported in Premna odorata [11,12]

Summary

Introduction

The liver is primarily responsible for alcohol metabolism in the human body and as this is the case, it is vulnerable to alcohol-related injuries [1]. Chronic alcohol consumption causes liver cell inflammation which triggers an immune response through recognition of damage-associated molecular patterns (DAMPs). DAMPs signal damage or necrosis through transmembrane toll-like receptors (TLRs), a class of proteins that play a key role in the innate immune system [2]. TLRs activate common signaling pathways that activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a key regulator of inflammatory gene expression. This results in the activation of numerous physiological responses: cytokine tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interlukin-1 (IL-l), IL-6, IL-12, cell adhesion molecules, such as vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1

Methods

Results

Discussion

Conclusion