Conv. Plasma
Nigella Sativa

All quercetin studies
Meta analysis
study COVID-19 treatment researchQuercetinQuercetin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Anti-cytokine Storm Activity of Fraxin, Quercetin, and their Combination on Lipopolysaccharide-Induced Cytokine Storm in Mice: Implications in COVID-19

Shaker et al., Iranian Journal of Medical Sciences, doi:10.30476/ijms.2023.98947.3102
Sep 2023  
  Source   PDF   All Studies   Meta AnalysisMeta
Quercetin for COVID-19
22nd treatment shown to reduce risk in July 2021
*, now known with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Mouse study showing benefit with quercetin for COVID-19 treatment by reducing proinflammatory cytokines and protecting lung and kidney tissues against lipopolysaccharide-induced damage. Lipopolysaccharide is used to induce cytokine storm resembling the severe inflammation seen in advanced COVID-19. Quercetin reduced IL-1β, IL-6, and TNF-α levels in serum of lipopolysaccharide-treated mice. Histopathological lung and kidney tissue analysis showed quercetin protected against edema, infiltration, congestion and hemorrhage compared to lipopolysaccharide-only mice. Quercetin performed similarly to the positive control dexamethasone in reducing cytokine levels and tissue damage scores. When combined with fraxin, the quercetin and fraxin combination did not show greater efficacy than either compound individually.
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spike Note A, Alavi, Azmi (B), Chandran, Kandeil, Mandal, Moschovou, Nguyen, Pan, Thapa (B), Şimşek, Mpro Note B, Akinwumi, Alanzi, Ibeh, Kandeil, Mandal, Moschovou, Nguyen, Qin, Rehman, Sekiou (B), Singh, Thapa (B), Wang, Zhang, Shaik, Waqas, RNA-dependent RNA polymerase Note C, Corbo, PLpro Note D, Ibeh, Zhang, ACE2 Note E, Chandran, Ibeh, Qin, Thapa (B), Şimşek, Alkafaas, TMPRSS2 Note F, Chandran, helicase Note G, Alanzi, Singh (B), endoribonuclease Note H, Alavi, cathepsin L Note I, Ahmed, Wnt-3 Note J, Chandran, FZD Note K, Chandran, LRP6 Note L, Chandran, ezrin Note M, Chellasamy, ADRP Note N, Nguyen, NRP1 Note O, Şimşek, EP300 Note P, Hasanah, PTGS2 Note Q, Qin, HSP90AA1 Note R, Qin, Hasanah, matrix metalloproteinase 9 Note S, Sai Ramesh, IL-6 Note T, Yang, Yang (B), IL-10 Note U, Yang, VEGFA Note V, Yang (B), and RELA Note W, Yang (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note X, DiGuilio, A549 Note Y, Yang, HEK293-ACE2+ Note Z, Singh (C), Huh-7 Note AA, Pan, Caco-2 Note AB, Roy, Vero E6 Note AC, Kandeil, El-Megharbel, Roy, mTEC Note AD, Wu, and RAW264.7 Note AE, Wu cells. Animal studies demonstrate efficacy in K18-hACE2 mice Note AF, Aguado, db/db mice Note AG, Wu, Wu (B), BALB/c mice Note AH, Shaker, and rats El-Megharbel (B). Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice Shaker.
Shaker et al., 1 Sep 2023, peer-reviewed, 3 authors. Contact:
This PaperQuercetinAll
Anti-cytokine Storm Activity of Fraxin, Quercetin, and their Combination on Lipopolysaccharide-Induced Cytokine Storm in Mice: Implications in COVID-19
Nada Sahib, PhD Nibras J Tahseen, PhD Nada Shaker
Background: Cytokine release syndrome (CRS) is the leading cause of mortality in advanced stages of coronavirus patients. This study examined the prophylactic effects of fraxin, quercetin, and a combination of fraxin+quercetin (FQ) on lipopolysaccharide-induced mice. Methods: Sixty mice were divided into six groups (n=10) as follows: control, LPS only, fraxin (120 mg/Kg), quercetin (100 mg/Kg), dexamethasone (5 mg/Kg), and FQ. All treatments were administered intraperitoneally (IP) one hour before induction by LPS (5 mg/Kg) IP injection. Twenty-four hours later, the mice were euthanized. Interleukin one beta (IL1-β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA), and lung and kidney tissues were examined for histopathological alterations. This study was conducted at Al-Nahrain University, Baghdad, Iraq, in 2022. Results: FQ reduced IL-1β (P<0.001). All treatments significantly suppressed IL-6, fraxin, quercetin, dexamethasone, and FQ, all with P<0.001. The TNF-α level was reduced more with dexamethasone (P<0.001) and quercetin (P<0.001). Histopathological scores were significantly reduced mainly by quercetin and FQ in the lungs with scores of 12.30±0.20 (P=0.093), and 15.70±0.20 (P=0.531), respectively. The scores were 13±0.26 (P=0.074) and 15±0.26 (P=0.222) for quercetin and FQ in the kidneys, respectively. Conclusion: All used treatments reduced proinflammatory cytokine levels and protected against LPS-induced tissue damage.
Authors' Contribution N.Sh and H.S: Study concept, study design, drafting, and critical reviewing; N.T: Study concept, study design, data acquisition, interpretation, and reviewing the manuscript; All authors read and approved the final manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved. Conflict of Interest: None declared.
An, Sun, Hou, Yang, Chen et al., Protective effect of oxytocin on LPSinduced acute lung injury in mice, Sci Rep, doi:10.1038/s41598-019-39349-1
Baranova, Souza, Bocharov, Vishnyakova, Hu et al., Human SR-BI and SR-BII Potentiate Lipopolysaccharide-Induced Inflammation and Acute Liver and Kidney Injury in Mice, J Immunol, doi:10.4049/jimmu-nol.1501709
Beekmann, Rubio, De Haan, Actis-Goretta, Van Der Burg et al., The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-gamma), Iran J Med Sci, doi:10.1039/c5fo00076a
Bhaskar, Quercetin modulates toll-like receptor-mediated protein kinase signaling pathways in oxLDL-challenged human PBMCs and regulates TLR-activated atherosclerotic inflammation in hypercholesterolemic rats, Mol Cell Biochem, doi:10.1007/s11010-016-2824-9
Chang, Jung, Yoon, Oh, Hong et al., Fraxin Prevents Chemically Induced Hepatotoxicity by Reducing Oxidative Stress, Molecules, doi:10.3390/molecules22040587
Cron, Goyal, Chatham, Cytokine Storm Syndrome, Annu Rev Med, doi:10.1146/annurev-med-042921-112837
Cui, Hu, Peng, Mu, Liu et al., Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression, Med Sci Monit, doi:10.12659/MSM.916044
Dibal, Garba, Jacks, Acute toxicity of quercetin from onion skin in mice, Pharmaceutical and Biomedical Research, doi:10.18502/pbr.v6i4.5113
Diniz, Souza, Duarte, Sousa, Mechanistic Aspects and Therapeutic Potential of Quercetin against COVID-19-Associated Acute Kidney Injury, Molecules, doi:10.3390/molecules25235772
Ekinci-Akdemi, Ngol, Yildirim, Kandemi, Kucukler et al., The investigation of the effect of fraxin on hepatotoxicity induced by cisplatin in rats, Iran J Basic Med Sci, doi:10.22038/ijbms.2020.38773.9200
Kim, Lee, Yang, Lee, Effenberger et al., Immunopathogenesis and treatment of cytokine storm Iran, Theranostics, doi:10.7150/thno.49713
Lei, Chai, Lin, Chen, Zhao et al., Dihydroquercetin Activates AMPK/Nrf2/ HO-1 Signaling in Macrophages and Attenuates Inflammation in LPS-Induced Endotoxemic Mice, Front Pharmacol, doi:10.3389/fphar.2020.00662
Li, Li, Liu, Liu, Li, Synergistic antiinflammatory effects of quercetin and catechin via inhibiting activation of TLR4-MyD88mediated NF-kappaB and MAPK signaling pathways, Phytother Res, doi:10.1002/ptr.6268
Li, Li, Zang, Liu, Yao et al., Fraxin ameliorates lipopolysaccharideinduced acute lung injury in mice by inhibiting the NF-kappaB and NLRP3 signalling pathways, Int Immunopharmacol, doi:10.1016/j.intimp.2018.12.003
Lopez-Carreras, Fernandez-Vallinas, Miguel, Aleixandre, Long-Term Effect of an Aqueous Fraxinus excelsior L. Seed Extract in Spontaneously Hypertensive Rats, Int J Hypertens, doi:10.1155/2014/565212
Lucida, Primadini, A study on the acute toxicity of quercetin solid dispersion as a potential nephron protector, Rasayan Journal of Chemistry, doi:10.31788/RJC.2019.1224068
Ma, Liu, Feng, Zhang, Huang et al., Fraxin Alleviates LPS-Induced ARDS by Downregulating Inflammatory Responses and Oxidative Damages and Reducing Pulmonary Vascular Permeability, Inflammation, doi:10.1007/s10753-019-01052-8
Meng, Lv, Yu, Xu, Yan, Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression, Genet Mol Res, doi:10.4238/gmr.15037265
Nam, Thong, Hoa, Quang, Hoang et al., Is natural fraxin an overlooked radical scavenger?, RSC Adv, doi:10.1039/d1ra01360b
Nguemfo, Mbock, Bogning, Fongang, Kedi et al., Acute and sub-acute toxicity assessment of aqueous leaves extract of Crassocephalum crepidioides (Asteraceae) in Wistar rats, J Complement Integr Med, doi:10.1515/jcim-2020-0018
Niu, Liu, Li, Zhi, Yao et al., Hepatoprotective effect of fraxin against carbon tetrachloride-induced hepatotoxicity in vitro and in vivo through regulating hepatic antioxidant, inflammation response and the MAPK-NF-kappaB signaling pathway, Biomed Pharmacother, doi:10.1016/j.biopha.2017.09.029
Peter, Sandeep, Rao, Kalpana, Calming the Storm: Natural Immunosuppressants as Adjuvants to Target the Cytokine Storm in COVID-19, Front Pharmacol, doi:10.3389/fphar.2020.583777
Prasad, Kumar, Singh, Singh, Crosstalk between phytochemicals and inflammatory signaling pathways, Inflammopharmacology, doi:10.1007/s10787-023-01206-z
Rizvi, De Moraes, New Decade, Old Debate: Blocking the Cytokine Pathways in Infection-Induced Cytokine Cascade, Crit Care Explor, doi:10.1097/CCE.0000000000000364
Sahib, Hamid, The Acute Toxicity of Rutin in Mice, Iraqi Journal of Pharmaceutical Sciences, doi:10.31351/vol30iss2
Sahib, Kathum, Alanee, Jawad, Am, The Anti-Cytokine Storm Activity of Quercetin Zinc and Vitamin C Complex, Adv Virol, doi:10.1155/2022/1575605
Sarfraz, Rasul, Jabeen, Younis, Zahoor et al., Fraxinus: A Plant with Versatile Pharmacological and Biological Activities, Evid Based Complement Alternat Med, doi:10.1155/2017/4269868
Tiwari, Siddiqui, Mahmood, Farooqui, Bagga et al., An exploratory analysis on the toxicity & safety profile of Polyherbal combination of curcumin, quercetin and rutin, Clinical Phytoscience, doi:10.1186/s40816-020-00228-2
Topdagi, Tanyeli, Akdemir, Eraslan, Guler et al., Preventive effects of fraxin on ischemia/reperfusion-induced acute kidney injury in rats, Life Sci, doi:10.1016/j.lfs.2019.117217
Yang, Wang, Long, Li, Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine, Oxid Med Cell Longev, doi:10.1155/2020/8825387
Yang, Yu, Wang, Yuan, Wang et al., The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappaB activition, J Ethnopharmacol, doi:10.1016/j.jep.2017.02.013
Yao, Zhao, Song, Protective effects of fraxin on cerebral ischemia-reperfusion injury by mediating neuroinflammation and oxidative stress through PPAR-gamma/NF-kap-paB pathway, Brain Res Bull, doi:10.1016/j.brainresbull.2022.06.010
Zhang, Virgous, Si, Synergistic antiinflammatory effects and mechanisms of combined phytochemicals, J Nutr Biochem, doi:10.1016/j.jnut-bio.2019.03.009
Zhao, Cen, Tian, Li, Zhang et al., Combination treatment with quercetin and resveratrol attenuates high fat dietinduced obesity and associated inflammation in rats via the AMPKalpha1/SIRT1 signaling pathway, Exp Ther Med, doi:10.3892/etm.2017.5331
Zhao, Wang, Deng, Liao, Zhou et al., Quercetin as a protective agent for liver diseases: A comprehensive descriptive review of the molecular mechanism, Phytother Res, doi:10.1002/ptr.7104
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop