In a recent study published in Scientific Reports, researchers investigated the effects of curcumin and curcuminoids on a human neuroblastoma cell line (SH-SY5Y) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2. Image Credit: Photoongraphy/Shutterstock.com

Background

SARS-CoV-2 has had a profound impact on global public health and the economy, with a significant burden of morbidity and mortality. Besides the acute phase of coronavirus disease 2019 (COVID-19), there are concerns of lingering effects, such as neurological dysfunction.

An estimated 10% to 15% of people infected by SARS-CoV-2 experience diverse symptoms beyond recovery, a condition termed long COVID.

People with severe COVID-19 manifestations have a higher risk of neurological symptoms. Nevertheless, the underlying neuropathogenesis remains unclear. Curcumin has drawn substantial attention for its potential to treat conditions characterized by inflammatory responses and immune system perturbations.

Likewise, curcuminoids can inhibit some enzymes linked with inflammatory processes and carcinogenic reactive oxygen species (ROS).

A systematic review reported that curcumin supplementation caused a significant reduction in COVID-19 symptoms, length of hospitalization, and mortality.

The study suggested that curcumin alleviates cytokine storms by activating anti-inflammatory pathways and reducing pro-inflammatory factors. Notwithstanding, the antiviral effects of curcumin in neuronal cells infected with SARS-CoV-2 remain unclear.

The study and findings

The present study investigated the antiviral, anti-inflammatory, and antioxidant effects of curcumin, curcuminoids, and turmeric extract in SH-SY5Y cells. First, cells were treated with varying concentrations of curcuminoids (Me08 and Me28), turmeric extract, and curcumin and tested for cell viability.

Curcumin showed cytotoxicity at 14 μg/ml, 18 μg/ml, 28 μg/ml, and 90 μg/ml, with cell viability being 40.1%, 40.8%, 33.4%, and 20.4%, respectively; however, cell viability was ≥ 95% at ≤ 7.2 μg/ml. Conversely, turmeric extract was not cytotoxic at any tested concentration. Further, no cytotoxicity was observed with curcuminoids at 60 μM or lower.

Next, the team examined their effects on the expression of angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), TMPRSS11D, and furin genes.

To this end, cells were treated with curcumin (7.2 μg/ml), curcuminoids (60 μM), and turmeric extract (3.6 μg/ml). No significant differences were observed in TMPRSS2, furin, or ACE2 expression after treatment with these compounds.

However, TMPRSS11D expression was reduced two-fold. Further, protein levels of TMPRSS2 were decreased by 30% with Me23 treatment, and those of TMPRSS11D declined by 50% with Me08 and 60% with Me23. Next, the team explored the effects of these compounds on ROS production post-SARS-CoV-2 infection.

They found significantly reduced ROS levels in infected cells treated with Me23. While SARS-CoV-2 infection did not affect the expression of the nuclear factor erythroid 2-related factor 2 (NRF2) gene, the Me23 treatment increased it 10-fold.

Besides, while infection reduced the levels of NAD(P)H quinone oxidoreductase 1 (NQO1) (which is upregulated by NRF2), the Me23 treatment restored its levels.

Further, the team established an ACE2-overexpression cell line, i.e., SH-ACE2. SH-SY5Y and SH-ACE2 cells were treated with the test compounds, followed by SARS-CoV-2 infection. The team observed ACE2 upregulation in the SH-ACE2 line, with an over 10,000 times increase compared to SH-SY5Y cells.

This overexpression corresponded with an elevated viral load at 24 hours post-infection. Notably, none of the compounds significantly affected viral replication in SH-SY5Y cells.

Finally, the researchers investigated the impact of inflammatory factors in SH-ACE2 cells following SARS-CoV-2 infection. Me08 significantly reduced interferon (INF)-γ levels by 10% compared to controls.

All compounds showed substantial reduction of interleukin (IL)-6, IL-17, and tumor necrosis factor (TNF)-α. Notably, Me08 mounted a more pronounced anti-inflammatory effect than others.

Conclusions

In sum, the researchers evaluated the effects of curcumin, curcuminoids, and turmeric extract on SH-SY5Y cells. They noted that the curcuminoid, Me23, had significantly reduced the expression of TMPRSS2 and TMPRSS11D and SARS-CoV-2-induced ROS levels.

It also increased the antioxidant pathway by modulating NRF2 and NQO1, inhibited viral replication, and exerted anti-inflammatory effects.

Overall, Me23 is a promising agent for mitigating the impact of COVID-19. Further research is required to elucidate the underlying mechanisms and determine effectiveness in clinical settings.