Efficacy of Nanocurcumin as an Add-On Treatment for Patients Hospitalized with COVID-19: A Double-Blind, Randomized Clinical Trial
Sedigheh Ahmadi, Zeinab Mehrabi, Morteza Zare, Sara Ghadir, Seyed Jalil Masoumi
International Journal of Clinical Practice, doi:10.1155/2023/5734675
Background. Curcumin is a polyphenol derivative of the Curcuma longa rhizome, with potential antioxidant, anticancer, antidepressant, antiviral, and anti-infammatory efects. Tis compound can be prepared as biodegradable polymer nanoparticles, called nanocurcumin, to improve its solubility, stability, half-life, and bioavailability. Aim. We explored nanocurcumin's efect on the clinical manifestations of patients hospitalized with mild-to-moderate COVID-19. Methods. Tis double-blind, randomized clinical trial involved 76 COVID-19 patients admitted to Ali-Asghar Hospital from December 2021 to March 2022. All patients received standard coronavirus treatment as per national guidelines. In addition, four times a day for two weeks, the curcumin group received 40 mg of nanocurcumin, while the control group received a placebo. Clinical manifestations were examined and recorded by the associate doctors working in the department. Statistical analysis was done using SPSS v. 21. Results. Tirty-nine people from the control group and 29 from the curcumin group completed the study. At baseline, the groups were comparable in age, gender, body mass index, hospitalization duration, and background diseases. Te mean age of patients in the control and treatment groups was 53.9 ± 11.9 and 54.6 ± 13.4, respectively. Compared with the placebo, nanocurcumin minimized coughs (P � 0.036), fatigue (P � 0.0001), myalgia (P � 0.027), oxygen demand (P � 0.036), oxygen usage (P � 0.05), and respiratory rate (P < 0.0001). By discharge, the curcumin group had a signifcantly greater increase in SPO 2 than the control group (P � 0.006). Conclusions. Tis preliminary study suggests that nanocurcumin has a potentiating anti-infammatory efect when combined with standard COVID-19 treatment, helping the recovery from the acute infammatory phase of the disease in hospitalized patients with mild-to-moderate disease severity. Tis trial is registered with Iranian Registry of Clinical Trials: IRCT20211126053183N1 (registered while recruiting on 13/12/2021).
Ethical Approval Tis study was conducted in line with the ethical principles of Shiraz University of Medical Sciences (Ethics Committee approval code: IR.SUMS.SCHEANUT.REC.1400.031) and the Helsinki Declaration of 1964 and its later amendments.
Consent Informed consent was obtained from all subjects.
Disclosure Te present article was extracted from the dissertation written by Sedigheh Ahmadi.
Conflicts of Interest Te authors declare that they have no conficts of interest.
Authors' Contributions SA was responsible for study design, implementation, data interpretation, original draft preparation, and manuscript revision. ZM was responsible for study design, data collection, and manuscript revision. MZ was responsible for study design, data analysis, and manuscript revision. SG was responsible for study implementation, data interpretation, and original draft preparation. SJM was responsible for study concept, design, funding acquisition, implementation, supervision, and manuscript revision. All authors have read and approved the fnal version of the manuscript.
References
Adibian, Hodaei, Nikpayam, Sohrab, Hekmatdoost et al., Te efects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profle in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial, Phytotherapy Research
Allegra, Innao, Russo, Gerace, Alonci et al., Anticancer activity of curcumin and its analogues: preclinical and clinical studies, Cancer Investigation
Avasarala, Zhang, Liu, Wang, London et al., Curcumin modulates the infammatory response and inhibits subsequent fbrosis in a mouse model of viralinduced acute respiratory distress syndrome, PLoS One
Bhaskar, Sinha, Banach, Mittoo, Weissert et al., Cytokine storm in COVID-19-immunopathological mechanisms, clinical considerations, and therapeutic approaches: the REPROGRAM consortium position paper, Frontiers in Immunology
Boroumand, Samarghandian, Hashemy, Immunomodulatory, anti-infammatory, and antioxidant efects of curcumin, Journal of Herbmed Pharmacology
Canoglu, Çalıs ¸kan, COVID-19 and thrombosis: prophylaxis and management, Tuberkuloz Ve Toraks
Cohen, Veena, Srivatsan, Wang, Suppression of interleukin 6 and 8 production in head and neck cancer cells with curcumin via inhibition of Iκβ kinase
Conti, Ronconi, Carafa, Gallenga, Ross et al., Induction of pro-infammatory cytokines (IL-1 and IL-6) and lung infammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-infammatory strategies, Journal of Biological Regulators & Homeostatic Agents
Dai, Gu, Su, Wang, Zhao et al., Inhibition of curcumin on infuenza A virus infection and infuenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways, International Immunopharmacology
Dei Cas, Ghidoni, Dietary curcumin: correlation between bioavailability and health potential, Nutrients
Dolati, Ahmadi, Rikhtegar, Babaloo, Ayromlou et al., Changes in T17 cells function after nanocurcumin use to treat multiple sclerosis, International Immunopharmacology
Garg, Ahuja, Sankar, Kumar, Moss, Curcumin for maintenance of remission in ulcerative colitis, Cochrane Database of Systematic Reviews
Gera, Sharma, Ghosh, Lee, Min et al., Nanoformulations of curcumin: an emerging paradigm for improved remedial application, Oncotarget
Goel, Kunnumakkara, Aggarwal, Curcumin as "Curecumin": from kitchen to clinic, Biochemical Pharmacology
Haftcheshmeh, Khosrojerdi, Aliabadi, Lotf, Mohammadi et al., Immunomodulatory efects of curcumin in rheumatoid arthritis: evidence from molecular mechanisms to clinical outcomes, Biochemistry & Pharmacology
Han, Xu, Guo, Huang, Curcumin ameliorates severe infuenza pneumonia via attenuating lung injury and regulating macrophage cytokines production, Clinical and Experimental Pharmacology and Physiology
Hassaniazad, Eftekhar, Inchehsablagh, Kamali, Tousi et al., A triple-blind, placebo-controlled, randomized clinical trial to evaluate the efect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients, Phytotherapy Research
He, Yue, Zheng, Zhang, Chen et al., Curcumin, infammation, and chronic diseases: how are they linked?, Molecules
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Te Lancet
Hurley, Akinfresoye, Nwulia, Kamiya, Kulkarni et al., Antidepressant-like efects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF, Behavioural Brain Research
Jennings, Parks, Curcumin as an antiviral agent, Viruses
Jobin, Bradham, Russo, Juma, Narula et al., Curcumin blocks cytokine-mediated NF-κB activation and proinfammatory gene expression by inhibiting inhibitory factor I-κB kinase activity, Te Journal of Immunology
Kannan, Kolandaivel, Antiviral potential of natural compounds against infuenza virus hemagglutinin, Computational Biology and Chemistry
Karimi, Mahmoodpoor, Kooshki, Niazkar, Shoorei et al., Efects of nanocurcumin on infammatory factors and clinical outcomes in critically ill patients with sepsis: a pilot randomized clinical trial, European Journal of Integrative Medicine
Khan, Khan, Nano-gold displayed antiinfammatory property via NF-kB pathways by suppressing COX-2 activity, Nanomedicine, and Biotechnology
Kocaadam, ¸anlier, Curcumin, an active component of turmeric (Curcuma longa), and its efects on health, Critical Reviews in Food Science and Nutrition
Mollazadeh, Cicero, Blesso, Pirro, Majeed et al., Immune modulation by curcumin: the role of interleukin-10, Critical Reviews in Food Science and Nutrition
Rahmanzade, Rahmanzadeh, Hashemian, Tabarsi, Iran's approach to COVID-19: evolving treatment protocols and ongoing clinical trials, Frontiers in Public Health
Rodriguez-Morales, Cardona-Ospina, Gutiérrez-Ocampo, Villamizar-Peña, Holguin-Rivera et al., Clinical, laboratory and imaging features of COVID-19: a systematic review and metaanalysis, Travel Medicine and Infectious Disease
Saadati, Sadeghi, Mansour, Yari, Poustchi et al., Curcumin and infammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial, BMC Gastroenterology
Saber-Moghaddam, Salari, Hejazi, Amini, Taherzadeh et al., Oral nano-curcumin formulation efcacy in management of mild to moderate hospitalized coronavirus disease-19 patients: an open label nonrandomized clinical trial, Phytotherapy Research
Safarzadeh Kozani, Safarzadeh, Kozani, Mirarefn, Sheikhi et al., COVID-19 Vaccines in Iran
Sordillo, Helson, Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections, Vivo
Tahmasebi, El-Esawi, Mahmoud, Timoshin, Valizadeh et al., Immunomodulatory efects of Nanocurcumin on T17 cell responses in mild and severe COVID-19 patients, Journal of Cellular Physiology
Tahmasebi, Saeed, Temirgalieva, Yumashev, El-Esawi et al., Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2, Life Sciences
Wen, Kuo, Jan, Liang, Wang et al., Specifc plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus, Journal of Medicinal Chemistry
Xu, Liu, Curcumin alleviates macrophage activation and lung infammation induced by infuenza virus infection through inhibiting the NF-κB signaling pathway, Infuenza and other respiratory viruses
Yang, Li, Li, Wang, Huang, Synergistic antiviral efect of curcumin functionalized graphene oxide against respiratory syncytial virus infection, Nanoscale
Yazdanpanah, Hamblin, Rezaei, Te immune system and COVID-19: friend or foe?, Life Sciences
Zahedipour, Hosseini, Sathyapalan, Majeed, Jamialahmadi et al., Potential efects of curcumin in the treatment of COVID-19 infection, Phytotherapy Research
Zhao, Liu, Yi, Wang, Qiao et al., Curcumin inhibiting T17 cell diferentiation by regulating the metabotropic glutamate receptor-4 expression on dendritic cells, International Immunopharmacology
