Exploring Curcuminoids: A Natural Defense Against COVID-19

As the world continues to grapple with the long-term effects of COVID-19, researchers are increasingly focused on understanding the virus's impact on the nervous system and exploring potential therapeutic agents. In a recent study published in Scientific Reports, researchers examined 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).

The Neurological Impact of COVID-19

COVID-19, caused by SARS-CoV-2 virus, is primarily known for its respiratory symptoms. However, it has also been associated with a wide range of neurological complications. Patients have reported headaches, dizziness, loss of taste and smell, and more severe outcomes such as encephalitis, strokes, and long-term cognitive impairments.

SARS-CoV-2 has had a profound impact on global health and the economy, causing significant morbidity and mortality. Beyond the acute phase of COVID-19, there are concerns about lingering effects, such as neurological dysfunction.

An estimated 10% to 15% of individuals infected with SARS-CoV-2 experience diverse symptoms beyond the initial recovery, a condition known as long COVID.

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

Curcuminoids can also inhibit enzymes linked to inflammatory processes and carcinogenic reactive oxygen species (ROS).

A systematic review reported that curcumin supplementation significantly reduced 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. Nonetheless, the antiviral effects of curcumin in neuronal cells infected with SARS-CoV-2 remain unclear.

The Study and Findings:

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

Curcumin exhibited cytotoxicity at concentrations of 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 concentrations ≤ 7.2 μg/ml. In contrast, turmeric extract was not cytotoxic at any tested concentration, and curcuminoids showed no cytotoxicity at concentrations of 60 μM or lower.

The study then examined the effects of these compounds on the expression of genes related to viral entry: angiotensin-converting enzyme (ACE2), transmembrane protease serine 2 (TMPRSS2), TMPRSS11D, and Furin.

Cells were treated with curcumin (7.2 μg/ml), curcuminoids (60 μM), and turmeric extract (3.6 μg/ml). There were no significant differences in the expression of TMPRSS2, Furin, or ACE2 following treatment with these compounds. However, TMPRSS11D expression was reduced two-fold. Protein levels of TMPRSS2 decreased by 30% with Me23 treatment, and TMPRSS11D protein levels declined by 50% with Me08 and 60% with Me23.

The researchers also explored the effects of these compounds on reactive oxygen species (ROS) production post SARS-CoV-2 infection did not affect the expression of the nuclear factor erythroid 2-related factor 2 (NRF2) gene, Me23 treatment increased NRF2 expression ten-fold. Additionally, Me23 treatment restored the levels of NAD(P)H quinone oxidoreductase 1 (NQO1), which are typically upregulated by NRF2 but were reduced following infection.

Furthermore, the team established as ACE2-overexpression cell line (SH-ACE2). Both SH-SY5Y and SH-ACE2 cells were treated with the test compounds and then infected with SARS-CoV-2. The SH-ACE2 line showed an over 10,000-fold increase in ACE2 expression compared to SH-SY5Y cells, corresponding with an elevated viral load at 24 hours post-infection. Notably, none of the compounds significantly affected viral replication in SH-SY5Y cells.

Lastly, the study investigated the impact of these compounds on 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 substantially reduced interleukin (IL)-6, IL-17, and tumor necrosis factor (TNF)-α levels, with Me08 demonstrating a more pronounced anti-inflammatory effect than the others.

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

Me23 also enhanced the antioxidant pathway by modulating NRF2 and NQO1, inhibited viral replication, and exhibited anti-inflammatory effects.

Overall, Me23 shows promise as an agent for mitigating the impact of COVID-19. Further research is needed to elucidate the underlying mechanisms and determine its effectiveness in clinical settings.