Update on Uses and Properties of Citrus Flavonoids: New Findings in Anticancer, Cardiovascular, and Anti-inflammatory Activity

Abstract

Significantly, much of the activity of Citrus flavonoids appears to impact blood and microvascular endothelial cells, and it is not surprising that the two main areas of research on the biological actions of Citrus flavonoids have been inflammation and cancer. Epidemiological and animal studies point to a possible protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely known. Many of the pharmacological properties of Citrus flavonoids can be linked to the abilities of these compounds to inhibit enzymes involved in cell activation. Attempts to control cancer involve a variety of means, including the use of suppressing, blocking, and transforming agents. Suppressing agents prevent the formation of new cancers from procarcinogens, and blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions. Flavonoids can act as all three types of agent. Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of cardiovascular diseases. In coronary heart disease, the protective effects of flavonoids include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. The anti-inflammatory properties of the Citrus flavonoids have also been studied. Several key studies have shown that the anti-inflammatory properties of Citrus flavonoids are due to its inhibition of the synthesis and biological activities of different pro-inflammatory mediators, mainly the arachidonic acid derivatives, prostaglandins E 2, F 2, and thromboxane A 2. The anti-oxidant and anti-inflammatory properties of Citrus flavonoids can play a key role in their activity against several degenerative diseases and particularly brain diseases. The most abundant Citrus flavonoids are flavanones, such as hesperidin, naringin, or neohesperidin. However, generally, the flavones, such as diosmin, apigenin, or luteolin, exhibit higher biological activity, even though they occur in much lower concentrations. Diosmin and rutin have a demonstrated activity as a venotonic agent and are present in several pharmaceutical products. Apigenin and their glucosides have been shown a good anti-inflammatory activity without the side effects of other anti-inflammatory products. In this paper, we discuss the relation between each structural factor of Citrus flavonoids and the anticancer, anti-inflammatory, and cardiovascular protection activity of Citrus flavonoids and their role in degenerative diseases.

The pleiotropic effects of fisetin and hesperetin on human acute promyelocytic leukemia cells are mediated through apoptosis, cell cycle arrest, and alterations in signaling networks

“…Thus, flavonoids (both natural and synthetic analogs) are being investigated for their potentials in cancer therapy. Fisetin and hesperetin, plant-derived flavonoids, have been shown to produce a wide range of pharmacological effects including antioxidant, anti-inflammatory, and anticancer effects and found to induce apoptosis in various tumor cells by causing alterations in various cellular processes [7,13]. The potential anticarcinogenic effects of fisetin and hesperetin, naturally occurring flavonoids, have been considered in various cancer types especially solid tumors including lung, colon, and breast cancers through several different mechanisms [11,12,16,17].…”

“…Hesperidin and hesperetin are the most important examples of these flavonones found in citrus fruits such as lemon and orange with a wide range of pharmacological properties including antioxidant, anti-inflammatory, and anticancer effects [13]. Hesperidin could be considered as a pro-drug, since it is metabolized to hesperetin before absorption [14].…”

The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer cells via abrogating the function of the AHA1/Hsp90 complex

“…The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer cells via abrogating the function of the AHA1/Hsp90 complex Hui-juan LIU 1 , Xiao-xiao JIANG 1 , Yi-zhen GUO 1 , Fang-hui SUN 1 , Xin-hui KOU 1 , Yong BAO 1 , Zhu-qing ZHANG 1 , Zhao-hu LIN 2 , Ting-bo DING 1 , Lan JIANG 3 , Xin-sheng LEI 4 , Yong-hua YANG 1, * important in cancer development owing to its simultaneous regulation of various oncogenic proteins [10] . A number of proteins in oncogenic pathways are Hsp90 client proteins, and many of these proteins are involved in cell proliferation, cell cycle progression and cell survival, which are crucial for tumor progression [10,11] .…”

“…Flavonoids have been exploited for their effectiveness and beneficial effects against various human cancers, as they have good antineoplastic activity and low toxicity [1] . Quercetin, one of the most common flavonoids in the diet, is well known for its anti-carcinogenic potential.…”

Naringenin stimulates cholecystokinin secretion in STC-1 cells

“…Naringenin has been reported to have antioxidant [7], anticancer [8], and antiatherogenic [9] activity, and to have effects on lipid metabolism [10,11], plasma glucose levels [11][12][13], and metabolic syndrome [14]. Naringin has also been reported to have anticancer, anti-inflammatory, and cardioprotective activity [15], and to have effects on plasma glucose levels [16], lipid metabolism [17], and metabolic syndrome [18]. Based on this information, we hypothesized that naringenin and naringin have a wide spectrum of biological activities and might stimulate CCK secretion and contribute to inhibition of food intake.…”