key: cord-0919497-ajuvt31b
authors: Al-kuraishy, Hayder M.; Al-Gareeb, Ali I.; El-Saber Batiha, Gaber
title: The possible role of Ursolic acid in Covid-19: A real game changer
date: 2022-01-04
journal: Clin Nutr ESPEN
DOI: 10.1016/j.clnesp.2021.12.030
sha: b46f38f601523d168fda9dc08a6b2424f963287e
doc_id: 919497
cord_uid: ajuvt31b

Ursolic acid (UA) is a pentacyclic terpenoid is usually found in the fruit peels and stem bark as secondary metabolites. UA has antiviral, antibacterial, and antiparasitic properties. UA has a wide spectrum of pharmacological activities against different infections. Because of the greatest antiviral and anti-inflammatory properties of UA, so it could be a plausible therapeutic herbal medicine in Covid-19 treatment. Covid-19 is a recent worldwide virulent disease pandemic due to severe acute respiratory coronavirus disease 2 (SARS-CoV-2). The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and exaggerated immune response by which acute lung injury (ALI) and/or acute respiratory distress syndrome might be developed in critical cases. UA may inhibit main protease of SARS-CoV-2, and inhibits the interface flanked by SARS-CoV-2 viral proteins and its entry point commonly recognized as angiotensin converting enzyme 2 (ACE2). In addition, UA attenuates SARS-CoV-2-induced inflammatory reactions and oxidative stress. Therefore, UA could avert SARS-CoV-2 infection from causing ALI. This opinion proposed that UA might be a potential candidate therapy against Covid-19 and can mitigate post-Covid-19 complications such as lung fibrosis. In this regards, forthcoming studies are reasonable to substantiate the therapeutic role of UA in Covid-19. However, taken into account that Covid-19 is yet to be investigating for further evaluations, therefore, clinical trials are recommended regarding use and dose of UA in Covid-19 treatment, as well as secondary effects.

for treatment of different cardiovascular complications including heart failure, hypertension, and tachycardia by cardioprotective effects (7). UA restore enzyme activity and prevents DNA damage of cardiomyocytes (7). UA improves peripheral insulin sensitivity, inhibits development of insulin resistance with regulation of insulin secretion from pancreatic β-cells (16) . Therefore. UA is efficient in attenuation of diabetic nephropathy through mitigation of hyperglycemia-induced oxidative stress and inflammatory reaction in the kidneys (13). In addition, UA has imperative action on the bone; it reduces the activity of osteoclasts and improves osteoblastic activity, thereby reducing risk for development of osteoporosis (42) .

Despite of these potential benefits from use of UA, it may have some adverse effects including nausea, vomiting, abdominal pain, mild hematuria, skin rash and hypernatremia (45) . The most dangerous adverse effects from using of UA are dose-dependent hepatotoxicity (46) and promote vascular plaque formation and may increase risk of cardiovascular complications (47) . However, UA should not be an alternative for approved medical remedies. The most important pharmacological effects of UA on the clinicpathological disorders are revised and summarized [ Table 1 ].

The main mechanism of UA is related to the different pathways, one key mechanism is the ability of UA to inhibit mitogen activated protein kinase (MAPK) and mammalian target of rapemycin (mTOR), which involved in cell replications, and growths as well as different inflammatory pathways (43). Besides, UA blocks cyclooxgenase-2 (COX-2) enzyme, which is important for development of inflammation (39) and nuclear factor kappa B (NF-κB), a signaling pathway vital in the regulation of immune response (34) . Likewise, UA attenuates oxidative stress through inhibition generation of reactive oxygen species (ROS) and also efficient against chronic hepatitis C (HCV) through inhibition of NS5B RNAdependent polymerase and can be used alone or in combination with other anti-HCV drugs (19) . Furthermore, UA has anti-herpes activity by blocking early stages of herpes simplex virus adsorption and replication (20 (23) . Additionally, UA limits proliferation and spreads of enterovirus 71(EV71) (24) . In vitro study revealed that UA reduces expression of human papilloma virus -18 (HPV-18) E6/E7 genes in HeLa cells; however expression of p53 did not change (25) . Similarly, a recent study by Chen et al., revealed that UA derivatives are effective against porcine reproductive and respiratory syndrome virus through direct inactivation of viral virion and replication (26) .

From these findings, UA has broad-spectrum anti-viral activities, by which it reduces viral load and viral proliferation through interruption of viral replication cycle (27) .

Because of the greatest antiviral and anti-inflammatory properties of UA, so it might be a plausible therapeutic herbal medicine in treating Covid-19, a recent worldwide virulent disease pandemic due to severe acute respiratory coronavirus disease 2 (SARS-CoV-2) (28) . The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and exaggerated immune response by which acute lung injury (ALI) and/or acute respiratory distress syndrome might be developed in the critical cases (28) . Contemporary 

The authors had no conflicts of interest to declare. Funding

This opinion paper had no funding. 

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