Health Promoting Properties of Citrus Flavones

By Sandra Nomoto

Further Studies Could Pay the Way to Development of New Functional Foods and Health-Promoting Neutraceuticals

Several studies have focused on food products that have been available for centuries and are the backbone of traditional medicine. The efficacy of traditional herbal remedies derives from the bioactive compounds coming from the original plant or fruit. Among these ‘classical’ sources are Citrus fruits, juices, and related products. Worldwide production of oranges, mandarins/tangerines, grapefruits, and lemons/limes is estimated at about 94 million tonnes, with oranges alone totalling half of that figure. The genus Citrus (family: Rutaceae, subfamily: Aurantioideae) comprises many species, varieties, cultivars, and hybrids. The most ancient are Citrus medica (citron), Citrus reticulata (tangerine) and Citrus maxima (pummelo).

Citrus fruits and juices are one of the main sources of nutrients in a standard balanced diet. One of the major groups of compounds responsible for health-beneficial effects are (poly)phenolics, especially flavonoids.

Antioxidant and Anti-Inflammatory Activity of Citrus Flavones

Citrus flavones, among the secondary metabolites in the Citrus species (spp.) are the most useful and promising compounds with antioxidant and anti-inflammatory activity. The most common flavones are the glycosylated forms of luteolin, apigenin, diosmetin, acacetin, chrysoeriol, and isoscutellarein.

Inflammation is an important facet in several diseases (cardiovascular, cancer, asthma, diabetes). Citrus flavonoids introduced with diet have different effects on inflammation at different stages with influence on several inflammatory diseases. Citrus flavonoids and flavones inhibit regulatory enzymes or possess mediating factors involved in inflammation. They carry the potential to inhibit the onset and development of inflammatory diseases, in both in vitro and in animal models. The Kimata et al. luteolin study showed a significant decrease in the release of histamine, leukotrienes, and prostaglandin D2.

In 2015, Weng et al. described the influence of luteolin in the release of mediators implicated in asthma. The results obtained on human mast cells showed an inhibition of histamine, β-hexosaminidase, TNF, and CCL2 release in mast cells derived from human cord blood, elements implicated in the recruitment of inflammatory cells. Luteolin improved systolic/diastolic functions in a study of rat hearts after ischemia/reperfusion.

Funakoshi-Tago et al. analyzed the mechanisms in the anti-inflammatory activity of apigenin, luteolin, and fisetin, and found significant similarity and difference in the modulation of biological pathways and proteins. Administration of apigenin and luteolin resulted in a remarkable inhibition of acute carrageenan-induced paw edema in mice.

Photo: Jessica Lewis

Antimicrobial and Antiviral Effect of Citrus Flavones

The antimicrobial potential of flavonoid-rich Citrus spp. polyphenol extracts from bergamot peel (Citrus bergamia Risso) was evaluated against Gram-negative bacteria (Escherichia coli, Pseudomonas putida, Salmonella enterica), Gram-positive bacteria (Listeria innocua, Bacillus subtilis, Staphylococcus aureus, Lactococcus lactis), and the yeast Saccharomyces cerevisiae. The extracts were mostly active against the Gram-negative bacteria. Bergamot juice was tested against isolates of Helicobacter pylori. The results confirmed that bergamot juice inhibited the growth of 50 percent of clinical isolates.

The antibacterial potential of Citrus polymethoxyflavones was studied by Johann et al. against standard strains of the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus. The most potent compounds were both extracts from C. reticulata, and 6,7-dimethoxycoumarin (also known as escoparone, scoparone, or scoparin), extracted from Citrus limon. In an animal study, nobiletin, extracted from Citrus nobilis, also showed an anti-inflammatory and antioxidant potential against generation of free radicals, demonstrating a possible correlation between antioxidant and antimicrobial activity.

Peel and pulp extracts of Citrus samples from Aceh, Indonesia were recently evaluated. Sinensetin and tangeretin were the most abundant, demonstrating potency against Staphylococcus aureus vs. Klebsiella pneumoniae. The peel extracts exhibited slightly better activity than the pulp.

Several studies investigated the potential antiviral properties of Citrus flavones. Xu et al. described the in vitro antiviral potential of a fluid extract of “Guangchenpi”, the edible and medicinal pericarps of C. reticulata ‘Chachi’, against the respiratory syncytial virus (RSV). RSV is a common pathogen responsible for pneumonia and bronchiolitis, which mainly affect infants and young children. The two most abundant polymethoxylated flavones identified in the extract of Guangchenpi, tangeretin and nobiletin, determined a dose-dependent inhibition of the virus.

The same authors subsequently investigated the activity of tangeretin from C. reticulata in vivo using 3-week-old male BALB/c mice. The results confirmed an inhibition of the RSV replication exerted by tangeretin in the lung of the mice, which also correlated with an important anti-inflammatory effect.

Anticancer Activity of Citrus Flavones

Flavones present in Citrus spp. show promising anticancer activity, especially apigenin, luteolin, diosmetin, and chrysoeriol, due to antioxidant activity, capacity to decrease proliferative growth, activation or blocking of metabolic pathways and key enzymes, reversal of multidrug resistance, or a combination of mechanisms.

Citrus spp. flavones show promising biological properties with a wide range of physiological and pharmacological effects. The data obtained in in vitro and in vivo laboratory studies shows the potential properties of these secondary metabolites. Epidemiologic and well-designed human studies are necessary to clarify the extent of their effects to uncover the mechanisms of these polyphenolics from fruit to the human body and the ability of these compounds to activate and modulate complex processes in the body. Further studies will pave the way to the development of new functional foods and nutraceuticals with health-promoting properties.

The information in this article was obtained from a Special Issue of 2019 Feature Papers by Plants’ Editorial Board Members, published in February 2020 by Davide Barreca, Giuseppina Mandalari, Antonella Calderaro, Antonella Smeriglio, Domenico Trombetta, Maria Rosa Felice and Giuseppe Gattuso.

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