Ameliorative Effects of Dietary Ellagic Acid Against Severe Malaria Pathogenesis by Reducing Cytokine Storms and Oxidative Stress.

Shilpa Mohanty,Karuna Shanker,Anirban Pal,Anil Kumar Maurya,Dnyaneshwar Umrao Bawankule,Amit Chand Gupta

doi:10.3389/fphar.2021.777400

Abstract

Ellagic acid (EA), a fruit- and vegetable-derived flavonoid, has been reported for multiple pharmacological activities, which encouraged us to examine its useful effect in severe malaria pathogenesis, especially malaria-induced cytokine storms and oxidative stress linked to damage in major organs. Malaria was induced by injecting Plasmodium berghei–infected RBCs intraperitoneally into the mice. EA was given orally (5, 10, and 20 mg/kg) following Peter’s 4-day suppression test. EA exhibited the suppression of parasitemia, production of inflammatory cytokine storms and oxidative stress marker level quantified from vital organs significantly and an increase in hemoglobin, blood glucose, and mean survival time compared to the vehicle-treated infected group. EA administration also restored the blood–brain barrier integrity evidenced through Evans blue staining. Furthermore, we demonstrated the protecting effect of EA in LPS-induced inflammatory cytokine storms and oxidative stress in glial cells. The present study conclude that ellagic acid is able to alleviate severe malaria pathogenesis by reducing cytokine storms and oxidative stress–induced by malarial parasites. It also attributed promising antimalarial activity and afforded to improve the blood glucose and hemoglobin levels in treated mice. These research findings suggested the suitability of ellagic acid as a useful bioflavonoid for further study for the management of severe malaria pathogenesis.

Highlights

According to the WHO, the incidence and death rates due to malaria have dropped down worldwide over the past 16 years; in 2018, there were 228 million new cases and 405,000 deaths from malaria
These research findings suggested the suitability of ellagic acid as a useful bioflavonoid for further study for the management of severe malaria pathogenesis
In an attempt to evaluate the novel pharmacological activity of ellagic acid, we have explored the beneficial effect of Ellagic acid (EA) on oxidative stress and inflammation-linked severe malaria pathogenesis in mice

Summary

Introduction

According to the WHO, the incidence and death rates due to malaria have dropped down worldwide over the past 16 years; in 2018, there were 228 million new cases and 405,000 deaths from malaria. Still malaria is an important public health problem in many developing countries of the tropical and subtropical regions of the world, with high mortality in children and pregnant women (World Health Organization, 2019). Current findings established that free radicals and its connection with oxidative stress in severe malaria can be responsible for several additional complications (Pabon et al, 2003; Becker et al, 2004). Clinical indications in severe malaria were found to be linked with the blood stage of infection with an excessive release of inflammatory cytokines (TNF-α, IL-6, and INFγ) which contribute to further severity of infection such as organ damage and severe anemia (Saxena et al, 2016). Treatment of malaria has been complicated by the development of resistance to combination therapies based on artemisinin (Kumar et al, 2015)

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