Multi-Therapeutic Potential of Naringenin (4′,5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms

Abstract

Extensive research has been carried out during the last few decades, providing a detailed account of thousands of discovered phytochemicals and their biological activities that have the potential to be exploited for a wide variety of medicinal purposes. These phytochemicals, which are pharmacologically important for clinical use, primarily consist of polyphenols, followed by terpenoids and alkaloids. There are numerous published reports indicating the primary role of phytochemicals proven to possess therapeutic potential against several diseases. However, not all phytochemicals possess significant medicinal properties, and only some of them exhibit viable biological effects. Naringenin, a flavanone found in citrus fruits, is known to improve immunity, repair DNA damage, and scavenge free radicals. Despite the very low bioavailability of naringenin, it is known to exhibit various promising biological properties of medicinal importance, including anti-inflammatory and antioxidant activities. This review focuses on the various aspects related to naringenin, particularly its physicochemical, pharmacokinetic, and pharmacodynamic properties. Furthermore, various pharmacological activities of naringenin, such as anticancer, antidiabetic, hepatoprotective, neuroprotective, cardioprotective, nephroprotective, and gastroprotective effects, have been discussed along with their mechanisms of action.

Lepidium sativum as candidate against excitotoxicity in retinal ganglion cells

“…This could be easily related to the ameliorative effects of L. sativum extract on glutamate-induced DNA damage, cell viability, and the antioxidant effects or scavenging activity. This is in good agreement with two recent studies which demonstrated that quercetin and nariginin were shown to induce mitochondrial activity, significant membrane stabilization, and prevention of lipid peroxidation of treated cells [ 40 , 41 ]. Table 2 demonstrates the richness of L. sativum with tannins, flavonoids, alkaloids, and anthraquinones as phytochemical with well-documented therapeutic potency.…”

“…The antioxidant effects of L. sativum are shown in Table 6 . This could be attributed to the multiple antioxidant compounds recorded in this plant ( Tables 1 and 2 ) which demonstrate high scavenging power of lipid peroxides and ROS [ 40 , 41 ].…”

Naringenin Nano-Delivery Systems and Their Therapeutic Applications

“…NRG inhibits cyclin, and cyclin-dependent kinase helping to control leukemia. NRG has also an angio-inhibitory effect as it decreases the vascular endothelial growth factor, that helps reduce metastasis [ 146 ]. A variety NRG nano-based drug delivery systems of different materials have been used in those studies, such as poly( d , l -lactide- co -glycolide) (PLGA) nanoparticles, multi-walled carbon nanotubes, silk fibroin nanoparticles, nanohybrid hydrogel, eudragit E-100 nanoparticles, polycaprolactone (PCL) nanoparticles, soluthin–maltodextrin nanocarriers, chitosan nanoparticles, and Eudragit E/PVA nanoparticles [ 77 , 135 , 136 , 137 , 142 , 147 , 148 , 149 ].…”

“…Neurological disorders, including brain diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent one of the most important non-communicable diseases affecting the worldwide population and are associated with significant disease burden and disability [ 153 ]. Oxidative stress is occurs naturally during the aging process, and might play an important role increasing the severity of neurodegenerative diseases such as Parkinson and Alzheimer, for which NRG has shown to be effective in reducing oxidative stress with a high permeation to the brain [ 146 ]. While the blood–brain barrier (BBB) constitutes an essential protective barrier for the central nervous system (CNS), it is often a biological barrier to successful drug delivery to the CNS because drug penetration across the BBB is dramatically restricted, rendering ineffective therapeutics.…”

“…NRG has demonstrated anti-hyperglycemic activity by preventing glucose absorption from the intestine. The mechanism of NRG anti-diabetic effects are attributed to increasing insulin sensitivity, decreasing glucose blood levels, suppressing the macrophages migration into adipose tissue, inhibiting monocyte chemoattractant protein-1 (MCP-1), decreasing insulin receptor substrate-2 (IRS-2) levels, increasing phosphoinositide 3-kinase (PI3K) activity [ 146 ]. However, as explained above, its extreme water insolubility, rapid biodegradation, and low bioavailability restrict its oral administration.…”