Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study

Francesco Di Pierro, Giuseppe Derosa, Pamela Maffioli, Alexander Bertuccioli, Stefano Togni, Antonella Riva, Pietro Allegrini, Amjad Khan, Saeed Khan, Bilal Ahmad Khan, Naireen Altaf, Maria Zahid, Ikram Din Ujjan, Roohi Nigar, Mehwish Imam Khushk, Maryam Phulpoto, Amanullah Lail, Bikha Ram Devrajani, Sagheer Ahmed, Francesco Di Pierro, Giuseppe Derosa, Pamela Maffioli, Alexander Bertuccioli, Stefano Togni, Antonella Riva, Pietro Allegrini, Amjad Khan, Saeed Khan, Bilal Ahmad Khan, Naireen Altaf, Maria Zahid, Ikram Din Ujjan, Roohi Nigar, Mehwish Imam Khushk, Maryam Phulpoto, Amanullah Lail, Bikha Ram Devrajani, Sagheer Ahmed

Abstract

Background: Quercetin, a well-known naturally occurring polyphenol, has recently been shown by molecular docking, in vitro and in vivo studies to be a possible anti-COVID-19 candidate. Quercetin has strong antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties, and it is characterized by a very high safety profile, exerted in animals and in humans. Like most other polyphenols, quercetin shows a very low rate of oral absorption and its clinical use is considered by most of modest utility. Quercetin in a delivery-food grade system with sunflower phospholipids (Quercetin Phytosome®, QP) increases its oral absorption up to 20-fold.

Methods: In the present prospective, randomized, controlled, and open-label study, a daily dose of 1000 mg of QP was investigated for 30 days in 152 COVID-19 outpatients to disclose its adjuvant effect in treating the early symptoms and in preventing the severe outcomes of the disease.

Results: The results revealed a reduction in frequency and length of hospitalization, in need of non-invasive oxygen therapy, in progression to intensive care units and in number of deaths. The results also confirmed the very high safety profile of quercetin and suggested possible anti-fatigue and pro-appetite properties.

Conclusion: QP is a safe agent and in combination with standard care, when used in early stage of viral infection, could aid in improving the early symptoms and help in preventing the severity of COVID-19 disease. It is suggested that a double-blind, placebo-controlled study should be urgently carried out to confirm the results of our study.

Keywords: Phytosome®; SARS-CoV-2; botanicals; coronavirus; infectious diseases; pneumonia.

Conflict of interest statement

FDP is a member of the Scientific Board of Pharmextracta. AB provided scientific advice to Pharmextracta S.p.A. PA, ST and AR are employees of and belong to the Scientific Board of Indena. AR reports a pending patent WO2019016146A1 for quercetin phytosome. The authors report no other conflicts of interest in this work.

© 2021 Di Pierro et al.

References

    1. Kim HH, Ryu J. Social distancing attitudes, national context, and health outcomes during the COVID-19 pandemic: findings from a global survey. Prev Med. 2021;148:106544. doi:10.1016/j.ypmed.2021.106544
    1. Lindinger-Sternart S, Kaur V, Widyaningsih Y, Patel AK. COVID-19 phobia across the world: impact of resilience on COVID-19 phobia in different nations. Couns Psychother Res. 2021;21(2):290–302. doi:10.1002/capr.12387
    1. Nayak J, Mishra M, Naik B, Swapnarekha H, Cengiz K, Shanmuganathan V. An impact study of COVID-19 on six different industries: automobile, energy and power, agriculture, education, travel and tourism and consumer electronics. Expert Syst. 2021. doi:10.1111/exsy.12677
    1. Aschwanden C. Five reasons why COVID herd immunity is probably impossible. Nature. 2021;591(7851):520–522. doi:10.1038/d41586-021-00728-2
    1. Mirtaleb MS, Mirtaleb AH, Nosrati H, Heshmatnia J, Falak R, Zolfaghari Emameh R. Potential therapeutic agents to COVID-19: an update review on antiviral therapy, immunotherapy, and cell therapy. Biomed Pharmacother. 2021;138:111518. doi:10.1016/j.biopha.2021.111518
    1. Karki N, Verma N, Trozzi F, Tao P, Kraka E, Zoltowski B. Predicting Potential SARS-COV-2 drugs-in depth drug database screening using deep neural network framework SSnet, classical virtual screening and docking. Int J Mol Sci. 2021;22(4):1573. doi:10.3390/ijms22041573
    1. McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res. 2020;157:104859. doi:10.1016/j.phrs.2020.104859
    1. Zhang DH, Wu KL, Zhang X, Deng SQ, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. J Integr Med. 2020;18(2):152–158. doi:10.1016/j.joim.2020.02.005
    1. Smith M, Smith JC. Repurposing therapeutics for COVID-19: supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface. ChemRxiv. 2020. doi:10.26434/chemrxiv.11871402.v3
    1. Williamson G, Kerimi A. Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) viral spike protein-angiotensin converting enzyme-2 (ACE2) interaction. Biochem Pharmacol. 2020;178:114123. doi:10.1016/j.bcp.2020.114123
    1. Pandey P, Rane JS, Chatterjee A, et al. Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in-silico study for drug development. J Biomol Struct Dyn. 2020:1–11. doi:10.1080/07391102.2020.1796811.
    1. Khaerunnisa S, Kurniawan H, Awaluddin R, Suhartati S, Soetjipto S. Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study. Preprints. 2020. doi:10.20944/preprints.202003.0226.v1
    1. Abian O, Ortega-Alarcon D, Jimenez-Alesanco A, et al. Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int J Biol Macromol. 2020;164:1693–1703. doi:10.1016/j.ijbiomac.2020.07.235
    1. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84–89. doi:10.4103/0973-7847.194044
    1. Gao L, Liu G, Wang X, Liu F, Xu Y, Ma J. Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int J Pharm. 2011;404(1–2):231–237. doi:10.1016/j.ijpharm.2010.11.009
    1. Wang W, Sun C, Mao L, et al. The biological activities, chemical stability, metabolism, and delivery systems of quercetin: a review. Trends Food Sci Technol. 2016;56:21–38. doi:10.1016/j.tifs.2016.07.004
    1. Riva A, Ronchi M, Petrangolini G, Bosisio S, Allegrini P. Improved oral absorption of quercetin from quercetin Phytosome®, a new delivery system based on food grade lecithin. Eur J Drug Metab Pharmacokinet. 2019;44(2):169–177. doi:10.1007/s13318-018-0517-3
    1. Derosa G, Maffioli P, D’Angelo A, Di Pierro F. A role for quercetin in coronavirus disease 2019 (COVID-19). Phytother Res. 2021;35(3):1230–1236. doi:10.1002/ptr.6887
    1. Di Pierro F, Khan A, Bertuccioli A, et al. Quercetin Phytosome® as a potential candidate for managing COVID-19. Minerva Gastroenterol Dietol. 2020. doi:10.23736/S1121-421X.20.02771-3
    1. Batiha GE, Beshbishy AM, Ikram M, et al. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: quercetin. Foods. 2020;9(3):374. doi:10.3390/foods9030374
    1. Gautam N, Madathil S, Tahani N, et al. Medium-term outcome of severe to critically ill patients with SARS-CoV-2 infection. Clin Infect Dis. 2021. doi:10.1093/cid/ciab341
    1. Almatroodi SA, Alsahli MA, Almatroudi A, et al. Potential therapeutic targets of quercetin, a plant flavonol, and its role in the therapy of various types of cancer through the modulation of various cell signaling pathways. Molecules. 2021;26(5):1315. doi:10.3390/molecules26051315
    1. Patel RV, Mistry BM, Shinde SK, Syed R, Singh V, Shin HS. Therapeutic potential of quercetin as a cardiovascular agent. Eur J Med Chem. 2018;155:889–904. doi:10.1016/j.ejmech.2018.06.053
    1. Iqbal M, Ho HL, Petropoulos S, Moisiadis VG, Gibb W, Matthews SG. Pro-inflammatory cytokine regulation of P-glycoprotein in the developing blood-brain barrier. PLoS One. 2012;7(8):e43022. doi:10.1371/journal.pone.0043022
    1. Pawar A, Pal A. Molecular and functional resemblance of dexamethasone and quercetin: a paradigm worth exploring in dexamethasone-nonresponsive COVID-19 patients. Phytother Res. 2020;34(12):3085–3088. doi:10.1002/ptr.6886
    1. Pal A, Squitti R, Picozza M, et al. Zinc and COVID-19: basis of current clinical Trials. Biol Trace Elem Res. 2020;1–11. doi:10.1007/s12011-020-02437-9
    1. Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019;24(6):1123. doi:10.3390/molecules24061123
    1. Heinz SA, Henson DA, Austin MD, Jin F, Nieman DC. Quercetin supplementation and upper respiratory tract infection: a randomized community clinical trial. Pharmacol Res. 2010;62(3):237–242. doi:10.1016/j.phrs.2010.05.001
    1. Luo E, Zhang D, Luo H, et al. Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China. Chin Med. 2020;15(1):34. doi:10.1186/s13020-020-00317-x
    1. Brito JCM, Lima WG, Cordeiro LPB, da Cruz Nizer WS. Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: systematic review and meta-analysis of preclinical studies. Phytother Res. 2021. doi:10.1002/ptr.7122

Source: PubMed

3
Subscribe