The anti-inflammatory and antioxidant effects of curcumin are well-established. Though complex, these effects are broadly attributed to its inhibitory effects on nuclear factor kappa B (NF-κB) activation, which is increased in response to inflammatory stimuli including disease-causing viruses.^1,2

Curcumin Inhibits Respiratory Syncytial Virus (RSV) and Influenza A Virus (IAV), Helping Prevent Lung Injury and Pneumonia

There is no shortage of evidence supporting the efficacy of curcumin against viral pathogens and associated pathology. Curcumin has been shown to inhibit respiratory syncytial virus (RSV) by directly inactivating the virus and blocking attachment to host cells, preventing viral replication in human laryngeal epithelial cells in vitro. These findings indicates that curcumin possesses prophylactic and therapeutic effects against RSV.³

Similarly, curcumin interferes with influenza A virus (IAV) entry via interaction with the receptor binding region of viral haemagglutination (HA) protein.⁴ IAV is not only a highly contagious respiratory virus, but one that usually causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) with substantial morbidity and mortality in severe cases. Further evidence shows that curcumin can directly inactivate IAV, blocking its adsorption and inhibiting its proliferation. As for the underlying mechanisms, curcumin could significantly inhibit IAV-induced oxidative stress, increase several anti-inflammatory pathways (e.g., antioxidant nuclear factor erythroid 2-related factor 2 [Nrf2]/heme oxygenase-1 [HO-1] and antiviral interferon beta [IFN-β]), while suppressing IAV-induced activation of several pro-inflammatory pathways (e.g., NF-κB). As indicated by improved IAV-induced lung histopathological changes, curcumin can improve IAV-induced ALI/ARDS in mice.⁵ Another mouse model derived similar conclusions from investigations into the effects of curcumin against severe IAV-induced pneumonia. Curcumin again attenuated lung injury and regulated macrophage cytokines production (including inhibiting NF-κB signalling).⁶

Curcumin Mediates Respiratory Inflammation and May Prevent Cytokine Storms

The unchecked release of cytokines that characterise cytokine storms can cause ARDS. ARDS is induced by the overactivation of immune responses rather than the viral load.⁷ The excessive immune responses are characterised by overproduction and prolonged high levels of numerous cytokines, such as proinflammatory cytokines (e.g., interleukin [IL]-1β, IL-6, IL-8, and tumour necrosis factor-alpha [TNF-α]) and insufficient control of anti-inflammatory cytokines (e.g., IL-10). The pro-inflammatory cytokines are responsible for initiating an inflammatory response against pathogenic infection, while the anti-inflammatory cytokines are crucial for ‘turning off’ the inflammatory reaction and preservation of organ function.^8-10

Preclinical and clinical evidence also suggests that curcumin could help avert a cytokine storm and subsequently ARDS. In contrast to the negative effect on pro-inflammatory mediators, anti-inflammatory IL-10 reduces the release of TNF-α, IL-6 and reactive oxygen species (ROS) from monocytes, thereby reducing tissue damage.¹⁰ Importantly, curcumin has been shown to promote

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regulatory T cell (Treg) differentiation and upregulate IL-10 expression in the serum and lungs of mice. Along with other immune modulating effects, the activity of curcumin was shown to reduce the severity of ALI and associated inflammation.¹¹

Six human clinical trials showed that curcumin supplementation led to a significant decrease in common symptoms (e.g., cough, fever, chills, dyspnoea, myalgia, taste and smell disturbances, and increased lymphocyte counts), duration of hospitalisation and deaths in mild to severe viral respiratory infection. Five of the six studies used the same type of highly bioavailable curcumin, taken in divided doses that equated to 160 or 180 mg/day of curcuminoids. The duration of four of the trials were 14 days, while the other two lasted for 21 days. In addition, all six trials showed that the intervention ameliorated cytokine storm effects, seen as a significant reduction in proinflammatory cytokines such as IL-1β and IL-6, with a concomitant significant increase in anti-inflammatory cytokines, including IL-10 and transforming growth factor alpha (TGF-α). Taken together, these findings suggested that curcumin helps restore the pro-inflammatory/anti-inflammatory balance. Further to this, curcumin may prevent progression to life-threatening ARDS,12 considering that significant elevations in IL-6 have been statistically significantly correlated with death in viral pneumonia patients who developed ARDS.¹³

Using Curcumin for Respiratory Infections and Inflammation

Curcumin has the dual benefit of downregulating pro-inflammatory signalling pathways (e.g., NF-κB) and cytokines (notably IL-1β and IL-6), while upregulating anti-inflammatory mediators (especially IL-10). To maximise delivery to target tissues via circulation, it is important to utilise bioavailable forms of curcumin. This optimises the preventative and therapeutic properties of curcumin, capable of lessening the severity of inflammation and lung damage in the event of viral respiratory infections (i.e., RSV, IAV and pneumonia), ALI/ARDS and potentially cytokine storms.

References

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2. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 1995 Oct;270(42):24995-5000. DOI: 10.1074/jbc.270.42.24995

3. Yang XX, Li CM, Li YF, Wang J, Huang CZ. Synergistic antiviral effect of curcumin functionalized graphene oxide against respiratory syncytial virus infection. Nanoscale. 2017 Oct;9(41):16086-92. DOI: 10.1039/c7nr06520e

4. Ou JL, Mizushina Y, Wang SY, Chuang DY, Nadar M, Hsu WL. Structure-activity relationship analysis of curcumin analogues on anti-influenza virus activity. FEBS J. 2013 Nov;280(22):5829-5840. DOI: 10.1111/febs.12503

5. Dai J, Gu L, Su Y, Wang Q, Zhao Y, Chen X, et al. Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways. Int Immunopharmacol. 2018 Jan;54:177-187. DOI: 10.1016/j.intimp.2017.11.009

6. Han S, Xu J, Guo X, Huang M. Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production. Clin Exp Pharmacol Physiol. 2018 Jan;45(1):84-93. DOI: 10.1111/1440-1681.12848

7. Montazersaheb S, Hosseiniyan Khatibi SM, Hejazi MS, Tarhriz V, Farjami A, Ghasemian Sorbeni F, et al. COVID-19 infection: an overview on cytokine storm and related interventions. Virol J. 2022 May;19(1):92. DOI: 10.1186/s12985-022-01814-1

8. Gu Y, Zuo X, Zhang S, Ouyang Z, Jiang S, Wang F, et al. The mechanism behind influenza virus cytokine storm. Viruses. 2021 Jul;13(7):1362. DOI: 10.3390/v13071362

9. Wang J, Yang X, Li Y, Huang JA, Jiang J, Su N. Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction. Virol J. 2021 Jun;18(1):117. DOI: 10.1186/s12985-021-01588-y

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10. Liu Z, Ying Y. The inhibitory effect of curcumin on virus-induced cytokine storm and its potential use in the associated severe pneumonia. Front Cell Dev Biol. 2020;8:479. DOI: 10.3389/fcell.2020.00479

11. Chai YS, Chen YQ, Lin SH, Xie K, Wang CJ, Yang YZ, et al. Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice. Biomed Pharmacother. 2020 May;125:109946. DOI: 10.1016/j.biopha.2020.109946

12. Vahedian-Azimi A, Abbasifard M, Rahimi-Bashar F, Guest PC, Majeed M, Mohammadi A, et al. Effectiveness of curcumin on outcomes of hospitalized COVID-19 patients: a systematic review of clinical trials. Nutrients. 2022 Jan;14(2):256. DOI: 10.3390/nu14020256

13. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul;180(7):934-943. DOI: 10.1001/jamainternmed.2020.0994