Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All metformin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19early.org COVID-19 treatment researchMetforminMetformin (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‑inflammatory effect of metformin against an experimental model of LPS‑induced cytokine storm

Taher et al., Experimental and Therapeutic Medicine, doi:10.3892/etm.2023.12114
Jul 2023  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 84 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments. c19early.org
Mouse study showing that metformin attenuated LPS-induced increases in inflammatory cytokines, demonstrating an anti-inflammatory effect that may be useful against cytokine storm.
60 female mice were pretreated with oral or intraperitoneal (IP) metformin daily for 30 days. Lipopolysaccharide (LPS) was then injected to induce a cytokine storm and trigger inflammation. Metformin pretreatment, both oral and IP, significantly reduced the LPS-induced increase in serum levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. IP metformin was more effective than oral metformin at reducing IL-6 levels. Neither oral nor IP metformin had a significant effect on IL-17 levels.
The results suggest metformin may have potential to suppress damaging inflammatory cytokine storms, suggesting benefit for treating cytokine storm-related diseases like COVID-19.
6 preclinical studies support the efficacy of metformin for COVID-19:
A systematic review and meta-analysis of 15 non-COVID-19 preclinical studies showed that metformin inhibits pulmonary inflammation and oxidative stress, minimizes lung injury, and improves survival in animal models of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) Wang. Metformin inhibits SARS-CoV-2 in vitro Parthasarathy, Ventura-López, minimizes LPS-induced cytokine storm in a mouse model Taher, minimizes lung damage and fibrosis in a mouse model of LPS-induced ARDS Miguel, may protect against SARS-CoV-2-induced neurological disorders Yang, may be beneficial via inhibitory effects on ORF3a-mediated inflammasome activation Zhang, reduces UUO and FAN-induced kidney fibrosis Miguel, increases mitochondrial function and decreases TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells Miguel, and may improve outcomes via modulation of immune responses with increased anti-inflammatory T lymphocyte gene expression and via enhanced gut microbiota diversity Petakh.
Taher et al., 13 Jul 2023, peer-reviewed, 4 authors. Contact: itaher@ju.edu.sa.
This PaperMetforminAll
Anti‑inflammatory effect of metformin against an experimental model of LPS‑induced cytokine storm
Dr Ibrahim Taher, Eman El‑masry, Mohamed Abouelkheir, Ahmed E Taha
Experimental and Therapeutic Medicine, doi:10.3892/etm.2023.12114
Cytokine storm is one of the leading causes of death in patients with COVID-19. Metformin has been shown to inhibit the action of a wide range of proinflammatory cytokines such as IL-6, and TNF-α which may ultimately affect cytokine storm due to Covid-19. The present study analyzed the anti-inflammatory effect of oral and intraperitoneal (IP) metformin administration routes in a mouse model of lipopolysaccharide (LPS)-induced cytokine storm. A total of 60 female BALB/c mice were randomly assigned to one of six groups: i) Control; ii) LPS model; iii) oral saline + LPS; iv) oral metformin + LPS; v) IP saline + LPS; and vi) IP metformin + LPS. Metformin or saline were administered to the mice for 30 days, after which an IP injection of 0.5 mg/kg LPS induced a cytokine storm in the five treatment groups. Mice were sacrificed and serum cytokine levels were measured. Pretreatment of mice with either oral or IP metformin significantly reduced the increase in IL-1, IL-6 and TNF-α following LPS injection. Both metformin administration routes significantly reduced IL-1 and TNF-α levels, although IP metformin appeared to be significantly more effective at reducing IL-6 levels compared with oral metformin. Neither the oral or IP route of administration of metformin demonstrated a significant effect on IL-17 levels. Based on its ability to suppress the proinflammatory LPS-induced cytokine storm, metformin may have future potential benefits in ameliorating human diseases caused by elevated cytokine levels.
Authors' contributions All of the authors have made substantial contributions towards the completion of the present study. MA and AET conceived the present study, performed the experiments, were project administrators and prepared the draft manuscript. IAT, EAEM, MA and AET collected the data, obtained resources, performed data analysis and critically reviewed and edited the manuscript. IAT and EAEM acquired funding. IAT, MA and AET supervised the project. IAT and AET confirm the authenticity of the raw data. All authors read and approved the final version of the manuscript. Ethics approval and consent to participate Ethical approval was obtained from the Local Committee of Bioethics of Jouf University (approval no. 07-08-42; Sakaka, Saudi Arabia). Patient consent for publication Not applicable. Competing interests The authors declare that they have no competing interests.
References
Adeshirlarijaney, Zou, Tran, Chassaing, Gewirtz, Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota, Am J Physiol Endocrinol Metab
Ba, Xu, Yin, Yang, Wang et al., Metformin inhibits pro-inflammatory responses via targeting nuclear factor-κB in HaCaT cells, Cell Biochem Funct
Berliner, Hemophagocytic lymphohistiocytosis, Annu Rev Pathol
Carvalho, Aitken, Kumar, Gewirtz, Toll-like receptor-gut microbiota interactions: Perturb at your own risk!, Annu Rev Physiol
Catanzaro, Fagiani, Racchi, Corsini, Govoni, Immune response in COVID-19: Addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2, Signal Transduct Target Ther
Cavalli, Larcher, Tomelleri, Campochiaro, Della-Torre et al., Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID19 and hyperinfammation: A cohort study, Lancet Rheumatol
Channappanavar, Perlman, Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology, Semin Immunopathol
Chao, Hui-Jie, Fang, Ni, Kub, Anti-inflammatory effect of metformin LPS-induced inflammation in mice, Basic Clin Med
Cho, Song, Choi, Im, Hh et al., The suppressive effects of metformin on inflammatory response of otitis media model in human middle ear epithelial cells, Int J Pediatr Otorhinolaryngol
Chung, Nicol, Cheng, Lin, Chen et al., Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs, Exp Cell Res
Crayne, Albeituni, Nichols, Cron, The immunology of macrophage activation syndrome, Front Immunol
Dehkordi, Sattari, Khoshdel, Kasiri, Effect of folic acid and metformin on insulin resistance and inflammatory factors of obese children and adolescents, J Res Med Sci
Dias, Soares, Ferreira, Sacramento, Igues et al., Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators, PLoS Pathog
El A A, E S P I N O S A -Ol Iva A M, Sa Nt I A Go, García-Quintanilla, Oliva-Martín, Herrera et al., Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system, Toxicol Apple Pharmacol
Elbere, Kalnina, Silamikelis, Konrade, Zaharenko et al., Association of metformin administration with gut microbiome dysbiosis in healthy volunteers, PLoS One
Furuya, Kono, Hara, Hirayama, Sun et al., Interleukin 17A plays a role in lipopolysaccharide/D-galactosamine-induced fulminant hepatic injury in mice, J surg Res
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, Lancet
Hyun, Shin, Lee, Lee, Song et al., Metformin Down-regulates TNF-α secretion via suppression of scavenger receptors in macrophages, Immune Netw
Jang, Lee, Hong, Kwok, Cho et al., Metformin enhances the immunomodulatory potential of adipose-derived mesenchymal stem cells through STAT1 in an animal model of lupus, Rheumatology (Oxford)
Jing, Wu, Li, Yang, Li, Metformin improves obesity-associated inflammation by altering macrophages polarization, Mol Cell Endocrinol
Kelly, Tannahill, Murphy, Neill, Metformin inhibits the production of reactive oxygen species from NADH: Ubiquinone oxidoreductase to limit induction of interleukin-1β (IL-1β) and boosts interleukin-10 (IL-10) in lipopolysaccharide (LPS)-activated macrophages, J Biol Chem
Kim, Kwak, Cha, Jeong, Rhee et al., Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction, J Biol Chem
Kim, Lee, Lee, Kim, Jhun et al., Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation, Exp Mol Med
Kindler, Thiel, Weber, Interaction of SARS and MERS coronaviruses with the antiviral interferon response, Adv Virus Res
Koh, Kim, Kim, Ko, Kim, Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer, J Gastroenterol Hepatol
Lee, Menezes, Umesaki, Mazmanian, Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis, Proc Natl Acad Sci
Lee, Moon, Kim, Seo, Yang et al., Metformin suppresses systemic autoimmunity in roquin san/san mice through inhibiting B cell differentiation into plasma cells via regulation of AMPK/mTOR/STAT3, J Immunol
Li, Geng, Peng, Meng, Lu, Molecular immune pathogenesis and diagnosis of COVID-19, J Pharm Anal
Li, Gu, Tu, Wang, Gu et al., Blockade of Interleukin-17 restrains the development of acute lung injury, Scand J Immunol
Liang, Wang, Chien, Yarmishyn, Yang et al., Highlight of immune pathogenic response and hematopathologic effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection
Liu, Liao, Zhang, Sun, Luo et al., Metformin affects gut microbiota composition and diversity associated with amelioration of dextran sulfate sodium-induced colitis in mice, Front Pharmacol
Lukens, Gurung, Vogel, Johnson, Carter et al., Dietary modulation of the microbiome affects autoinflammatory disease, Nature
Mehta, Mcauley, Brown, Sanchez, Tattersall et al., COVID-19: Consider cytokine storm syndromes and immunosuppression, Lancet
Min, Cheon, Ha, Sohn, Kim et al., Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity, Sci Rep
Montazersaheb, Khatibi, Hejazi, Tarhriz, Farjami et al., COVID-19 infection: An overview on cytokine storm and related interventions, Virol J
Moon, Lee, Choi, Lee, Yoo et al., Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts, J Transl Med
Park, Bang, Kwon, Moon, Kim et al., Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase, Biochem Pharmacol
Petrakis, Margină, Tsarouhas, Tekos, Stan et al., Obesity a risk factor for increased COVID19 prevalence, severity and lethality (Review), Mol Med Rep
Pfortmueller, Spinetti, Urman, Luedi, Schefold, COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment-A narrative review, Best Pract Res Clin Anaesthesiol
Postler, Peng, Bhatt, Ghosh, Metformin selectively dampens the acute inflammatory response through an AMPK-dependent mechanism, Sci Rep
Rodriguez, Hiel, Delzenne, Metformin: Old friend, new ways of action-implication of the gut microbiome?, Curr Opin Clin Nutr Metab Care
Saisho, Metformin and inflammation: Its potential beyond glucose lowering effect, Endocr Metab Immune Disord Drug Targets
Sarzi-Puttini, Sirotti, Marotto, Ardizzone, Rizzardini et al., COVID-19, cytokines and immunosuppression: What can we learn from severe acute respiratory syndrome?, Clin Exp Rheumatol
Schuiveling, Vazirpanah, Radstake, Zimmermann, Broen, Metformin, a new era for an old drug in the treatment of immune mediated disease?, Curr Drug Targets
Sciannimanico, Grimaldi, Vescini, Pergola, Iacoviello et al., Metformin: Up to date, Endocr Metab Immune Disord Drug Targets
Sun, Zhang, Zhang, Zhang, Qian, IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation, J Neuroinflammation
Tang, Yang, Chen, Shi, Ge et al., Metformin ameliorates sepsis-induced brain injury by inhibiting apoptosis, oxidative stress and neuroinflammation via the PI3K/Akt signaling pathway, Oncotarget
Yao, Zheng, Wu, Junhua, Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2, Aging (Albany NY)
Yin, Choi, Xu, Perry, Seay et al., Normalization of CD4+ T cell metabolism reverses lupus, Sci Transl Med
Yuan, Jiao, Qu, Yang, Liu, The development of COVID-19 treatment, Front Immunol
Zhang, Hu, Effects of metformin on the gut microbiota in obesity and type 2 diabetes mellitus, Diabetes Metab Cinder Obes
Zhang, Xu, Chen, Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice, Biomed Pharmacother
Zhao, Cao, Liu, Li, Xu et al., Behavioral, inflammatory and neurochemical disturbances in LPS and UCMS-induced mouse models of depression, Behav Brain Res
Loading..
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. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, 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   
Submit