Hesperidin - A possible defense against COVID-19

Flavonoids consist of a large group of naturally occurring, low molecular weight, polyphenolic compounds with more than 4000 molecular structures discovered so far. They are widely distributed in the plant kingdom and practically found in all parts of plants including fruit, vegetables, nuts, seeds, leaves, flowers and bark (Middleton, 1984)(Garg et al., 2001a) Hesperidin, a significant member of the bioflavonoid group, can be extracted in high concentrations from the rinds of citrus fruits e.g., Citrus aurantium L. (bitter orange), Citrus sinensis L. (sweet orange), and Citrus unshiu Marcov. (satsuma mandarin). (Wilmsen et al., 2005). 

Hespiridine is best described by its potential to act as antioxidant, able to scavenge free radicals and reactive oxygen species which are associated with several forms of tissue damage and disease, including cancer and cardiovascular diseases, as well as with aging(Wilmsen et al., 2005). Supplemental hesperidin also helps in reducing oedema or excess swelling in the legs due to fluid accumulation(Agrawal et al., n.d.).

Pharmacological Significance of Hesperidin 

Hesperidin and its aglycone hesperetin, have been reported to exhibit a wide range of pharmacological properties including anticancer, antihypertensive, antioxidant, antidiabetic, hepato-protective, neuroprotective, wound healing, cardiovascular, anti-inflammatory, antiobesity, hypoglycemic, lipid-lowering and beneficial effects on bone and Alzheimer’s disease. (Agrawal et al., n.d.) These pharmacologic properties are attributed to the scavenging behavior of hesperidin against free radicles and reactive oxygen species. (Wilmsen et al., 2005)(Garg et al., 2001b) Experimental studies also prove efficacy of hespiridine in the prophylaxis and treatment of COVID-19(Meneguzzo et al., n.d.).

Hesperidin Co-relation With COVID-19 

SARS-CoV-2 exhibitedan alarmingly high rate of human-to-human transmission and has threatened global health with a high mortality rate(Cheng et al., 2021). Several review articles have probed into the anti-SARS-CoV-2 activity of the hesperidin. Kandeil et al. cleanly demonstrated that the hesperidin imposes inhibitory effects on the viral replication of COVID-19 pathogen at the early stage of virus infection(Cheng et al., 2021). Hesperidin and its aglycone metabolite hesperetin suppresses the protein expression of ACE2 and TMPRSS2 in lung cells, impeding the cell entry of the SARS-CoV-2 pseudo-virus(Cheng et al., 2021). 

In SARS-CoV-2, most of the damage in COVID-19 is caused by the immune system itself as a result of un-controlled inflammatory response resulting in Cytokine Storm Syndrome. The uncontrolled production of pro-inflammatory cytokines(and chemokines) causes acute respiratory distress syndrome(ARDS) and multiple organ failure.(Meneguzzo et al., n.d.) Hesperidin with its high anti-inflammatory activity inhibits the secretion of pro-inflammatory cytokines such as IFN-γ and IL-2. (Haggag et al., 2020) The mechanism probably involves inhibition of interaction of ACE2 receptors of cells with S-protein of SARS-CoV-2 thus blocking entry into the lung cells, making hespiridine a promising agent in the treatment of COVID-19 infection(Haggag et al., 2020).

Commercial Preparation- BIOTEX HESPIRIDINE, 500mg 

Hesperidin is recognized as a potent anti-inflammatory, anticancer, and antioxidant agent. The poor bio-availability and absorption issues have been resolved by formulating this bioflavonoid as supplement by the Biotex Pharma in capsule form. No signs of toxicity have been observed with normal intake of hesperidin so far(Agrawal et al., n.d.).

The commercial preparation of BIOTEX HESPIRIDINE, 500mg oral capsule exhibits high efficacy which is the best alternative to the raw citrus fruits having low concentration of hespiridine. Toxicity studies have confirmed the high safety profile of hesperidin after oral intake of more than 2 g/kg with no allergic reactions reported (Agrawal et al., n.d.; Wilmsen et al., 2005). Experiments on rats treated with orange juice and mandarin juice have presented a 22% reduction in colon cancer and a 29% decline in lung cancer, respectively(Wilmsen et al., 2005). Hesperidin also appears to be extremely safe and without any side effects during pregnancy(Garg et al., 2001a).

References 

  • Agrawal, P. K., Agrawal, C., & Blunden, G. (n.d.). Pharmacological Significance of Hesperidin and Hesperetin, Two Citrus Flavonoids, as Promising Antiviral Compounds for Prophylaxis Against and Combating COVID-19. https://doi.org/10.1177/1934578X211042540
  • Cheng, F.-J., Huynh, T.-K., Yang, C.-S., Hu, D.-W., Shen, Y.-C., Tu, C.-Y., Wu, Y.-C., Tang, C.-H., Huang, W.-C., Chen, Y., Ho, C.-Y., Cheng, F.-J. ;, Huynh, T.-K. ;, Yang, C.-S. ;, Hu, D.-W. ;, Shen, Y.-C. ;, Tu, C.-Y. ;, & Wu, Y. (2021). Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection. https://doi.org/10.3390/nu13082800
  • Garg, A., Garg, S., Zaneveld, L. J. D., & Singla, A. K. (2001a). Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. In Phytotherapy Research (Vol. 15, Issue 8, pp. 655– 669). https://doi.org/10.1002/ptr.1074
  • Garg, A., Garg, S., Zaneveld, L. J. D., & Singla, A. K. (2001b). Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytotherapy Research, 15(8), 655–669. https://doi.org/10.1002/ptr.1074
  • Haggag, Y. A., El-Ashmawy, N. E., & Okasha, K. M. (2020). Is hesperidin essential for prophylaxis and treatment of COVID-19 Infection? Medical Hypotheses, 144, 109957. https://doi.org/10.1016/j.mehy.2020.109957
  • Meneguzzo, F., Ciriminna, R., Zabini, F., & Pagliaro, M. (n.d.). processes Review of Evidence Available on Hesperidin-Rich Products as Potential Tools against COVID-19 and Hydrodynamic Cavitation-Based Extraction as a Method of Increasing Their Production. https://doi.org/10.3390/pr8050549
  • Wilmsen, P. K., Spada, D. S., & Salvador, M. (2005). Antioxidant activity of the flavonoid hesperidin in chemical and biological systems. Journal of Agricultural and Food Chemistry, 53(12), 4757–4761. https://doi.org/10.1021/jf0502000
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