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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  
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Quercetin for COVID-19
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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: nadasshaker@gmail.com.
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
doi:10.30476/ijms.2023.98947.3102
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.
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