Protective effects of flavonoids against microbes and toxins: The cases of hesperidin and hesperetin

doi:10.1016/j.lfs.2015.07.014

Life Sciences

Volume 137, 15 September 2015, Pages 125-132

https://doi.org/10.1016/j.lfs.2015.07.014 Get rights and content

Abstract

Many plants produce flavonoids as secondary metabolites. These organic compounds may be involved in the defense against plant-threatening factors, such as microbes and toxins. Certain flavonoids protect their origin source against plant pathogens, but they also exhibit potential healthy properties in human organisms. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from the Citrus species that exhibit various biological properties, including antioxidant, antiinflammatory and anticancer effects. Recent studies indicated that Hst and Hsd possess antimicrobial activity. Although the exact mechanisms behind their antimicrobial properties are not fully understood, several mechanisms such as the activation of the host immune system, bacterial membrane disruption, and interference with microbial enzymes, have been proposed.

Hsd and Hst may also have protective effects against toxicity induced by various agents. These natural substances may contribute to the protection of cells and tissues through their antioxidant and radical scavenging activities.

This review discusses the protective activities of Hsd and Hst against microbes and several toxicities induced by oxidants, chemicals, toxins, chemotherapy and radiotherapy agents, which were reported in vitro and in vivo. Furthermore, the probable mechanisms behind these activities are discussed.

Graphical abstract

A schematic view of the protective effects of hesperidin and hesperetin against microbes and toxins.

Introduction

Polyphenols, a large class of biologically active substances, are distributed in plants as secondary metabolites. These substances provide color and flavor to different plant parts and they also play an important role in resistance against various microbial pathogens and protect against radiations and toxins. Many recent studies have mainly focused on polyphenols and their diverse biological effects [13], [49].

Flavonoids are one of the most common polyphenols, and they exhibit interesting and beneficial medicinal effects on human health. The various biological properties of flavonoids, such as antioxidant, antiinflammatory, anticancer, antibacterial, immune-stimulating and antiviral activities, have been reported extensively [22].

Hesperidin (Hsd) is the major flavonoid in citrus fruits, and it was isolated for the first time from citrus peel by Lebreton in 1827. The Hsd molecule is composed of an aglycone unit, namely hesperetin (Hst), and a disaccharide, rutinose (Fig. 1).

Hsd and Hst possess different activities, such as antioxidant, antiinflammatory, antimicrobial, anticarcinogenic and antiallergic effects. Hsd and Hst substances are also called bioflavonoids because of this wide range of effects. A descriptive review of the different biological activities and physicochemical properties of Hsd was published by Garg et al. in 2001 [21]. In addition, neuropharmacological, antioxidant, and antiinflammatory properties and the pharmacokinetics of Hsd and Hst were published in our recent review papers [42], [51]. The protective effects of Hsd and Hst against toxicities induced by certain chemotherapy drugs have been widely investigated [1], [58]. However, there has not been a comprehensive report on the protective effects of Hsd and Hst against invading pathogens and various toxicities induced by environmental toxins, occupational hazards, radiotherapy and chemotherapeutic agents.

Accordingly, this review provides a detailed overview of the current state of knowledge of the protective effects of the bioflavonoids, Hsd and Hst, against the aforementioned toxicities. The probable mechanisms governing these particular activities are also discussed.

Section snippets

Protective effects of Hsd and Hst against invading pathogens

Plant flavonoids play an important role in the protection against pathogenic microorganisms, such as bacteria, fungi and viruses. However, the high rate of microbial resistance to conventional antibiotics suggested flavonoids as suitable alternatives to antibiotics. Furthermore, flavonoids can be considered natural food preservatives because of their antimicrobial activities [50]. Generally, flavonoids are found in glycosylated forms in plants, and the presence of a sugar moiety is an important

Protective effects of Hsd and Hst against toxicities induced by various factors

Human health is threatened by pathogenic microorganisms, parasites and exposure to toxic materials, primarily occupational and environmental contaminations, such as heavy metals. Additionally, chemotherapy and radiotherapy have side effects and toxicities on the human body. These factors damage tissues and cells through different mechanisms, such as the induction of reactive oxygen species (ROS) production and oxidative stress (Fig. 2). Therefore, natural compounds that possess antioxidant

Conclusion

Hst and Hsd are citrus flavonoids that exhibit various biological activities. Numerous papers have been published on certain beneficial effects of Hsd, Hst and their derivatives. These substances play an important role in plant defense systems to combat different pathogens. Therefore, they may be useful polyphenolic substances that possess antibacterial, antiviral and antifungal activities in humans.

The exact mechanisms of antimicrobial activity are not fully understood. However, different

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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Review articleProtective effects of flavonoids against microbes and toxins: The cases of hesperidin and hesperetin

Abstract

Graphical abstract

Introduction

Section snippets

Protective effects of Hsd and Hst against invading pathogens

Protective effects of Hsd and Hst against toxicities induced by various factors

Conclusion

Conflict of interest statement

Res. Vet. Sci.

Int. J. Antimicrob. Agents

Curr. Opin. Biotechnol.

Bioorg. Med. Chem. Lett.

Phytochemistry

Pharmacol. Ther.

Mutat. Res.

Eur. J. Pharmacol.

Acta Trop.

Food Chem.

Trends Pharmacol. Sci.

Am. J. Clin. Nutr.

Microbiol. Res.

Exp. Toxicol. Pathol.

Food Chem.

Int. J. Food Microbiol.

J. Photochem. Photobiol. B

Eur. J. Pharmacol.

Life Sci.

Phytomedicine

Food Chem.

Food Res. Int.

Ecotoxicol. Environ. Saf.

Food Chem. Toxicol.

Food Chem.

LWT-Food Sci. Technol.

FEBS Lett.

Hesperidin alleviates doxorubicin-induced cardiotoxicity in rats

J. Egypt. Natl. Canc. Inst.

The protective effect of hesperidin on methotrexate-induced intestinal epithelial damage in rats: an experimental study

Med. Princ. Pract.

In vitro and in vivo effects of hesperidin treatment on adult worms of Schistosoma mansoni

J. Helminthol.

Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats

Redox Rep.

In vitro inhibitory effect of some flavonoids on rotavirus infectivity

Biol. Pharm. Bull.

Review article
Protective effects of flavonoids against microbes and toxins: The cases of hesperidin and hesperetin