Chemopreventive and Therapeutic Potential of “Naringenin,” a Flavanone Present in Citrus Fruits

Abstract

Cancer is one of the major causes of deaths in developed countries and is emerging as a major public health burden in developing countries too. Changes in cancer prevalence patterns have been noticed due to rapid urbanization and changing lifestyles. One of the major concerns is an influence of dietary habits on cancer rates. Approaches to prevent cancer are many and chemoprevention or dietary cancer prevention is one of them. Therefore, nutritional practices are looked at as effective types of dietary cancer prevention strategies. Attention has been given to identifying plant-derived dietary agents, which could be developed as a promising chemotherapeutic with minimal toxic side effects. Naringenin, a phytochemical mainly present in citrus fruits and tomatoes, is a frequent component of the human diet and has gained increasing interest because of its positive health effects not only in cancer prevention but also in noncancer diseases. In the last few years, significant progress has been made in studying the biological effects of naringenin at cellular and molecular levels. This review examines the cancer chemopreventive/therapeutic effects of naringenin in an organ-specific format, evaluating its limitations, and its considerable potential for development as a cancer chemopreventive/therapeutic agent.

Naringenin Impairs Two-Pore Channel 2 Activity And Inhibits VEGF-Induced Angiogenesis

“…Epidemiological studies have demonstrated that the consumption of vegetables and fruit with a high Nar content, such as citruses and tomatoes or their food products, is associated with a reduced incidence of metabolic and chronic-degenerative diseases 1, 2 . Following this kind of evidence, several in vitro studies have shown that Nar interacts with various cellular pathways, highlighting its potential as an antioxidant, antinflammatory, chemopreventive and antidegenerative agent 3 ; moreover, Nar was shown to exert anti-angiogenic effects in the avian chorio-allantoid membrane model 4 while this manuscript was being prepared. Naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet 5 .…”

“…Naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet 5 . Pre-clinical studies have revealed the potential of Nar and of its precursor naringin in the treatment of metabolic and cardiovascular disorders, including hyperlipidemia, hypertension, cardiac toxicity, hyperglycemia and diabetes, hepatic steatosis and atherosclerosis 2 ; its therapeutic use to combat various kinds of cancer has also been envisaged 3 . Indeed, Nar exerts chemopreventive and anticancer activity by blocking the progression and the formation of metastasis in various experimental models of oral 6 , melanoma 7 , breast 8, 9 , colon 10 , lung 11 and liver 12 cancer.…”

Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus

“…Importantly, its lipophilic character favors a good blood-brain barrier (BBB)-permeability, which suggests that naringenin could play a significant role in important functions of the CNS especially under pathological conditions. For example, naringenin exerts protective effect against cerebral ischemic injury, attenuates bamyloid toxicity [17], induces the activation of MAP kinases, modulates glutamate uptake [18] and protects against neurodegeneration with cognitive impairment caused by the intracerebroventricular-streptozotocin in diabetic oxidative damage rat model [19]. However, the mechanisms underlying the neuroprotective effects of naringenin on cholinergic and purinergic neurotransmission in animal models of iron exposure remain unknown.…”

Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and −9

“…In addition, shikonin triggers necrosis and apoptosis in gastric cancer cells (8). Furthermore, a bioactive compound isolated from citrus called naringenin has been revealed to trigger apoptosis and inhibit migration in cancer cells (9). Treatment with naringenin resulted in apoptosis by activation of the p38 mitogen-activated protein kinase and caspase 3 pathway in cancer cells that expressed estrogen receptor a or b (10).…”