Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial

Ali Asadirad; Roohangiz Nashibi; Ali Khodadadi; Ata A Ghadiri; Mahvash Sadeghi; Azam Aminian; Sajad Dehnavi

Antiinflammatory potential of nano‐curcumin as an alternative therapeutic agent for the treatment of mild‐to‐moderate hospitalized COVID‐19 patients in a placebo‐controlled clinical trial

Ali Asadirad, Roohangiz Nashibi, Ali Khodadadi, Ata A Ghadiri, Mahvash Sadeghi, Azam Aminian, Sajad Dehnavi

Phytotherapy Research, doi:10.1002/ptr.7375

The present study conducted a placebo-controlled clinical trial to evaluate the impact of nano-curcumin on the inflammatory cytokines in mild-to-moderate hospitalized COVID-19 patients. A total of 60 COVID-19 patients were randomly divided into nano-curcumin and control groups, and then they received 240 mg/day nano-curcumin for 7 days. The clinical manifestation and laboratory parameters in patients were recorded on days 0 and seven. Also, SYBR Green real-time PCR and ELISA techniques were implicated in assessing the mRNA expression of IFN-γ, IL-1β, IL-6, MCP-1, and TNF-α and the serum levels of IL-1β, IL-6, and TNF-α inflammatory mediators, respectively. Although the clinical manifestations and laboratory parameters improved via the nano-curcumin treatment, the mRNA expression of IFN-γ (p = 0.006) and TNF-α (p = 0.04) were significantly reduced. Besides, a considerable difference was observed between the nano-curcumin and control groups in the expression of IFN-γ (p = 0.001), IL-1β (p = 0.0002), and IL-6 (p = 0.008). In addition, there was a significant difference between the nano-curcumin and control groups in the serum levels of IL-1β (p = 0.042). The evidence demonstrated that nano-curcumin could be implicated as a complementary medication to act as an antiinflammatory agent and inhibit inflammatory complications.

CONFLICT OF INTEREST All authors declare no conflict of interest. AUTHOR CONTRIBUTIONS

References

Ahmadi, Salari, Sharifi, Reihani, Rostamiani et al., Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebocontrolled clinical trial, Food Science & Nutrition

Avasarala, Zhang, Liu, Wang, London et al., Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome, PLoS One

Babaei, Nassiri-Asl, Hosseinzadeh, Curcumin (a constituent of turmeric): New treatment option against COVID-19, Food Science & Nutrition

Bahrami, Kamalinejad, Latifi, Seif, Dadmehr, Cytokine storm in COVID-19 and parthenolide: Preclinical evidence, Phytotherapy Research

Barnard, Kumaki, Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy, Future Virology

Cao, COVID-19: Immunopathology and its implications for therapy, Nature Reviews Immunology

Derosa, Maffioli, Simental-Mendia, Bo, Sahebkar, Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials, Pharmacological Research

Fan, Yao, Li, Hu, Shao et al., Anti-inflammatory and antioxidant effects of curcumin on acute lung injury in a rodent model of intestinal ischemia reperfusion by inhibiting the pathway of NF-kb, International Journal of Clinical and Experimental Pathology

Henry, Oliveira, Santos, Benoit, Plebani et al., Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis, Clinical Chemistry and Laboratory Medicine (CCLM)

Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet

Karimian, Pirro, Majeed, Sahebkar, Curcumin as a natural regulator of monocyte chemoattractant protein-1, Cytokine & Growth Factor Reviews

Kunnumakkara, Bordoloi, Padmavathi, Monisha, Roy et al., Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases, British Journal of Pharmacology

Kunnumakkara, Harsha, Banik, Vikkurthi, Sailo et al., Is curcumin bioavailability a problem in humans: Lessons from clinical trials, Expert Opinion on Drug Metabolism & Toxicology

Li, Fan, Lai, Han, Li et al., Coronavirus infections and immune responses, Journal of Medical Virology

Li, Ma, Acute respiratory failure in COVID-19: Is it "typical, ARDS? Critical Care

Liu, Huang, Law, Tian, Leung et al., Preventive effect of curcumin against chemotherapy-induced side-effects, Frontiers in Pharmacology

Mani, Johnson, Steel, Broszczak, Neilsen et al., Natural product-derived phytochemicals as potential agents against coronaviruses: A review, Virus Research

Mckee, Sternberg, Stange, Laufer, Naujokat, Candidate drugs against SARS-CoV-2 and COVID-19, Pharmacological Research

Okabayashi, Kariwa, Yokota, Iki, Indoh et al., Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections, Journal of Medical Virology

Pawar, Mastud, Pawar, Pawar, Bhoite et al., Oral Curcumin with Piperine as adjuvant therapy for the treatment of COVID-19: A randomized clinical trial, Frontiers in Pharmacology

Roshanravan, Seif, Ostadrahimi, Pouraghaei, Ghaffari, Targeting cytokine storm to manage patients with COVID-19: A mini-review, Archives of Medical Research

Ruan, Yang, Wang, Jiang, Song, Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China, Intensive Care Medicine

Saber-Moghaddam, Salari, Hejazi, Amini, Taherzadeh et al., Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial, Phytotherapy Research

Sahebkar, Cicero, Simental-Mendía, Aggarwal, Gupta, Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials, Pharmacological Research

Seif, Aazami, Khoshmirsafa, Kamali, Mohsenzadegan et al., JAK inhibition as a new treatment strategy for patients with COVID-19, International Archives of Allergy and Immunology

Shanmugam, Rane, Kanchi, Arfuso, Chinnathambi et al., The multifaceted role of curcumin in cancer prevention and treatment, Molecules

Song, Ge, Cai, Zhang, Curcumin protects mice from coxsackievirus B3-induced myocarditis by inhibiting the phosphatidylinositol 3 kinase/Akt/nuclear factor-κB pathway, Journal of Cardiovascular Pharmacology and Therapeutics

Soni, Mehta, Ratre, Tiwari, Amit et al., Curcumin, a traditional spice component, can hold the promise against COVID-19?, European Journal of Pharmacology

Valizadeh, Abdolmohammadi-Vahid, Danshina, Gencer, Ammari et al., Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients, International Immunopharmacology

Vitali, Bagri, Wessels, Arora, Ganugula et al., Curcumin can decrease tissue inflammation and the severity of HSV-2 infection in the female reproductive mucosa, International Journal of Molecular Sciences

Wang, Yang, Li, Wen, Zhang, Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China, Clinical Infectious Diseases

Xu, Liu, Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-κB signaling pathway, Influenza and Other Respiratory Viruses

Xu, Shi, Wang, Zhang, Huang et al., Pathological findings of COVID-19 associated with acute respiratory distress syndrome, The Lancet Respiratory Medicine

Zahedipour, Hosseini, Sathyapalan, Majeed, Jamialahmadi et al., Potential effects of curcumin in the treatment of COVID-19 infection, Phytotherapy Research

Zhang, Swamy, Balijepalli, Panicker, Mooliyil et al., Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia, The FASEB Journal

Zhu, Yang, Chen, Jiang, Wang et al., Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial, Phytotherapy Research

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