INTRODUCTION:

Hesperidin is chemical that is mainly extracted from citrus fruits [1]. The plant’s chemical extract can be used alone, or combined with other plant chemicals for medicinal purposes. The drug is classified under the flavonoid group and may have antimicrobial or antioxidant properties. Because of these, it may have some effects on the human immune system. Apart from the effects on the immune system, when combined with other ingredients, hesperidin has been found to have medical benefits to the blood circulatory system [2-5].

Hesperidin:

Hesperidin is made up of anti-oxidants. Hesperidin has been known to treat various conditions including lymphedema, hemorrhoids, venous stasis, and varicose veins. It is also used in treatment of cardiovascular and celebralvascular diseases as well as some abortion cases [6-12]. Hesperidin is mainly applied during cancer surgeries. This implies that it can be effective at any stage of cancer treatment. Although toleration of hesperidin supplements is quite high, there are possible side effects. The adverse effects mainly involve gastrointestinal reactions. These include diarrhea and nausea among others [13-17].

The typical hesperidin is in the form of nutritional supplements like Vitamin C. However, they often contain other bioflavonoids. Hesperidin is also presented in other forms such as hesperidin-complex supplements, combinations with diosmin, different formulations with hesperidin, and orange juice with pulp [4]. Because of its forms, hesperidin is often considered as a non-prescription drug. Instead, it is considered as a supplement [13].

Clinical study tested the effect of the drug in treating various types of cancer including colon cancer, skin cancer esophageal cancer, and urinary bladder cancer among others. This research showed that hesperidin was more potent than other bioflavonoids and flavonoids. However, there is need for more clinical trials to ascertain the effects of hesperidin [14].

The drug is mainly used in the treatment of breast cancer. [7].

Other Names:

Hesperidin has other names that include Bioflavonoïdes d’Agrumes, Bioflavonoide, bioflavonoid Concentrate, Citrus Bioflavonoid, Bioflavonoid, Bioflavonoid Extract, Citrus Bioflavones, Bioflavonoid Complex, Bioflavonoïde d’Agrume, and Citrus Bioflavonoid Extract among others [7] [18-20].

Author	Year of Publication	Title	Fact(s)
Balakrishnan, A., and Menon, V.	2007	Antioxidant properties of hesperidin in nicotine-induced lung toxicity	Talks about hesperidin and its actions
Fathiazad, F., and Afshar, J.	2004	An investigation on methylation methods of hesperidin	Hesperidin has low solubility in water
Kar, A.	2003	Pharmacognosy and pharmacobiotechnology	Discusses the pharmacology and pharmacokinetics of hesperidin
Kingherbs	2007	Hesperidin	Drug monograph of hesperidin
Lee et al.,	2004	Antiallergic activity of hesperidin is activated by intestinal microflora	Presents a clinical test of hesperidin using animals
Natural Standard	2011	Hesperidin	Presents the drug monograph of hesperidin
Rizza et al.,	2011	Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome	Talks about hesperidin and its properties
Shi et al.,	2012	Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced diabetic rats	Presents a clinical test of hesperidin using animals
WebMD	2013	Hesperidin	Discusses other names of hesperidin, properties and medical use
Westerink, B., and Cremers, T.	2007	Handbook of microdialysis: Methods, applications and perspectives	Hesperidin anti-oxidant properties among others
Yanez et al.,	2008	Pharmacokinetics of selected chiral flavonoids: Hesperetin, naringenin and eriodictyol in rats and their content in fruit juices	Hesperidin has a short half-life
Sahelian, R.	n.d.	Hesperidin found in oranges and lemons	Hesperidin is a flavonoid found in citrus fruits
Wong, C.	2013	Hesperidin	Hesperidin is extracted from citrus fruits
Health Grades Inc.	2011	Hesperidin	Hesperidin has medical uses
WebMD.	2013	Hesperidin	Hesperidin has medical uses
Focus Technology Co., Ltd.	2013	Hesperidin	Hesperidin has medical uses
Dahl, D.	2010	What is hesperidin (Vitamin P)?	Hesperidin has medical uses
MedMelon	2010	Hesperidin	Hesperidin has medical uses
Plant Extract	n.d.	Hesperidin	Hesperidin has medical uses
Natural Standard	2011	Hesperidin	Hesperidin has medical uses
Milenkovic et al.,	n.d.	Hesperidin displays relevant role in the nutrigenomic effect of orange juice on blood leukocytes in human volunteers: A randomized controlled cross-over study.	Hesperidin has medical benefits and side effects
Truven Health Analytics	2013	Hesperidin	Hesperidin has side effects
Wood-Moen, R.	2010	Side effects of hesperidin	Hesperidin has side effects
RxList Inc.	2013	Hesperidin	Hesperidin has other names
Drugs.com	2013	Hesperidin	Hesperidin has other names
Hesperidin REACH	n.d.	Hesperidin substance description	Hesperidin has other names
MIMs	2013	Diosmin + hesperidin	Overdose is rare

Pharmacology/Pharmacokinetics:

Hesperidin has low solubility in water [21]. Despite this, it is has higher solubility in water than aglycone hesperidin. It also has a low solubility in alcohol, and is insoluble in chloroform, benzene, and ether [6]. Hesperidin may contain either of several actions that include vasoprotective, anti-allergic, anticarcinogenic, anti-inflammatory, hypolipemic, or of antioxidant actions [22]. With regard to its potential anti-inflammatory action, aglycone hesperidin may be responsible. This is because hesperidin has been linked to the interference in the process of arachidonic acid. Additionally, hesperidin has been associated with inhibiting the release of histamine from the mast cells. This is possibly the reason for hesperidin’s anti-allergic activity. Regarding the hypolipidemic action of hesperidin, it is probably the effect of hesperidin in reducing levels of plasma cholesterol through deterring enzymes that perform that opposite task [14]. Moreover, hesperidin reduces microvascular permeability, which is a possible explanation for its vasoprotective action. Other actions of hesperidin do not have clear explanations [23].

With regard to pharmacokinetics of hesperidin, it remains unclear whether the drug is absorbed from the intestines as glycoside. However, it is assumed that hesperidin’s glucuronidation could take place in the intestine wall and in the liver. Aglycone hesperidin is detected in urine after about three hours from the time of ingesting hesperidin [14]. Moreover, following ingestion of hesperidin, it is detected in serum. However, it remains unclear whether the hesperidin is formed before or after absorption [23]. Hesperidin has a relatively short half-life of about 3-7 hours [24].

Dosage:

The dosage of hesperidin varies depending on its different forms. The dosages may be 20mg for nutritional supplements, 500mg to 2g for hesperidin-complex supplements, and 1-3g for combination product. These are daily dosages. Reports of over-dosage are rare [23] [25].

CONCLUSION:

Hesperidin is mainly used as a supplement. Although the drug has been found to have some medical benefits, there is need for more clinical tests to ascertain its effects. Currently, there are gaps or grey areas regarding the clinical efficacy of hesperidin. Although the drug is considered to treat certain diseases including breast cancer, cardiovascular diseases, and celebralvasuclar diseases among others, the actions of the drug are still not fully understood. Therefore, the pharmacokinetics and pharmacology of the drug is filled with some assumptions to fill the grey areas. However, hesperidin continues to be used as a supplement drug because it has limited adverse affects [9].

REFERENCES:

1. Sahelian, R. (n.d.). Hesperidin found in oranges and lemons. Retrieved from http://www.raysahelian.com/hesperidin.html

2. Westerink, B., and Cremers, T. (2007). Handbook of microdialysis: Methods, applications and perspectives. Academic Press.

3. Rizza, S., Muniyappam R., Iantorno, M., Kim, J., Chen, H., and …Quon, M. (2011). Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial functions and reducing inflammatory markers in patients with metabolic syndrome. JCEM, 96(5), E782-E792.

4. Wong, C. (2013). Hesperidin. Retrieved from http://altmedicine.about.com/od/herbsupplementguide/a/Hesperidin.htm

5. Health Grades Inc. (2011). Hesperidin. Retrieved from http://www.rightdiagnosis.com/vitamin/hesperidin.htm

6. Kar, A. (2003). Pharmacognosy and pharmacobiotechnology. New Age International.

7. WebMD. (2013). Hesperidin. Retrieved from http://www.webmd.com/vitamins-supplements/ingredientmono-1033-HESPERIDIN.aspx?activeIngredientId=1033andactiveIngredientName=HESPERIDIN

8. Focus Technology Co., Ltd. (2013). Hesperidin. Retrieved from http://china-cac1.en.made-in-china.com/product/volmBLkPhaRX/China-Hesperidin.html

9. Dahl, D. (2010). What is hesperidin (Vitamin P)? Retrieved from http://www.livestrong.com/article/342775-what-is-hesperidin-vitamin-p/

10. MedMelon (2010). Hesperidin. Retrieved from http://www.medmelon.gr/frontend/new.php?aid=291andcid=111

11. Plant Extract (n.d.). Hesperidin. Retrieved from http://www.naturalplantextract.com/active-ingredients/hesperidin.html

12. Natural Standard (2011). Hesperidin. Retrieved from http://www.weiserx.com/ns/DisplayMonograph.asp?storeID=D5014D8206A24FA7A9B57A43F807BE7EandDocID=hesperidin

13. Milenkovic, D., Deval, C., Dubray, C., Mazur, A., and Morand, C. (n.d.). Hesperidin displays relevant role in the nutrigenomic effect of orange juice on blood leukocytes in human volunteers: A randomized controlled cross-over study. Retrieved from http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026669

14. Lee, N., Choi, S., Park, S., Park, E., and Kim, D. (2004). Antiallergic activity of hesperidin is activated by intestinal microflora. Pharmacology, 71(4), 174-80.

15. Shi, X., Liao, S., Mi, H., Guo, C., Qi, D., Li, F., and ... Yang, Z. (2012). Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Molecules (Basel, Switzerland), 17(11), 12868-12881. doi:10.3390/molecules171112868

16. Truven Health Analytics (2013). Hesperidin. Retrieved from http://loyolauniversity.adam.com/content.aspx?productId=48andpid=48andgid=10459

17. Wood-Moen, R. (2010). Side effects of hesperidin. Retrieved from http://www.livestrong.com/article/215299-side-effects-of-hesperidin/

18. RxList Inc. (2013). Hesperidin. Retrieved from http://www.rxlist.com/hesperidin/supplements.htm

19. Drugs.com (2013). Hesperidin. Retrieved from http://www.drugs.com/international/hesperidin.html

20. Hesperidin REACH (n.d.). Hesperidin substance description. Retrieved from http://www.hesperidin-sief.com/hespiridin-substance-description

21. Fathiazad, F., and Afshar, J. (2004). An investigation on methylation methods of hesperidin. Daru, 12(2), 67-70.

22. Balakrishnan, A., and Menon, V. (2007). Antioxidant properties of hesperidin in nicotine-induced lung toxicity. Fundamental and Clinical Pharmacology, 21(5), 535-546.

23. Kingherbs (2007). Hesperidin. Retrieved from http://www.kingherbs.com.cn/english.asp?id=40

24. Yanez, J. A., Remsberg, C. M., Miranda, N. D., Vega-Villa, K. R., Andrews, P. K., and Davies, N. M. (2008). Pharmacokinetics of selected chiral flavonoids: Hesperetin, naringenin and eriodictyol in rats and their content in fruit juices. Biopharmaceuticals and Drug Disposition, 29(2), 63-82

25. MIMS (2013). Diosmin + hesperidin. Retrieved from http://www.mims.com/USA/drug/info/diosmin%20+%20hesperidin/diosmin%20+%20hesperidin?type=full

Received on 30.07.2013 Modified on 05.09.2013

Research J. Pharm. and Tech. 7(1): Jan. 2014; Page 78-80