The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, while no treatment has been proven effective. COVID-19 pathophysiology involves the activation of three main pathways: the inflammatory, the coagulation and the bradykinin cascades. Here, we highlight for the first time the joint potential therapeutic role of bromelain and curcumin, two well-known nutraceuticals, in the prevention of severe COVID-19. Bromelain (a cysteine protease isolated from the pineapple stem) and curcumin (a natural phenol found in turmeric) exert important immunomodulatory actions interfering in the crucial steps of COVID-19 pathophysiology. Their anti-inflammatory properties include inhibition of transcription factors and subsequent downregulation of proinflammatory mediators. They also present fibrinolytic and anticoagulant properties. Additionally, bromelain inhibits cyclooxygenase and modulates prostaglandins and thromboxane, affecting both inflammation and coagulation, and also hydrolyzes bradykinin. Interestingly, curcumin has been shown in silico studies to prevent entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells as well as viral replication, while a recent experimental study has demonstrated that bromelain may also inhibit viral entry into cells. Notably, bromelain substantially increases the absorption of curcumin after oral administration. To the best of our knowledge, this is the first report highlighting the significance of bromelain and, most importantly, the potential preventive value of the synergistic effects of bromelain and curcumin against severe COVID-19.

Keywords: ACE2, angiotensin-converting enzyme 2; Bromelain; COVID-19; COVID-19, coronavirus disease 2019; COX-2, cyclooxygenase-2; Curcumin; NF-κB, nuclear factor kappa B; Nutraceuticals; PG, prostaglandin; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2; STAT-3, signal transducer and activator of transcription 3; TMPRSS-2, trans-membrane serine protease 2; TXA2, thromboxane A2.

Fig. 1

Bromelain (B) and curcumin (C) exert multiple immunomodulatory actions interfering in the crucial steps of COVID-19 pathophysiology. ACE-2, angiotensin-converting enzyme 2 receptor; COVID-19, coronavirus disease 2019; NF-κB, nuclear factor kappa B; PG; prostaglandin; SARS-CoV-2; severe acute respiratory syndrome coronavirus 2; STAT-3, signal transducer and activator of transcription 3; TMPRSS-2, trans-membrane serine protease 2; TXA2, thromboxane A2.