SARS-CoV-2 cytokine storm inhibited by curcumin nanoparticles

In a latest research printed within the journal ACS Utilized Bio Supplies, researchers demonstrated the inhibitory potential of curcumin-encapsulated polysaccharide nanoparticles (CUR−PS-NPs) in opposition to extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (CoV2-SP)-stimulated cytokine storm in lung and liver epithelial cells.

The multi-organ failure, lung harm, and poor prognosis of extreme illness in coronavirus illness 2019 (COVID-19) sufferers are immediately related to the interleukin (IL)-induced profound cytokine storm developed in response to SARS-CoV-2 an infection in these sufferers. The interplay between SARS-CoV-2 and human angiotensin-converting enzyme 2 (hACE2) receptors triggers the cytokine storm adopted by life-threatening systemic inflammatory responses. The deadly inflammatory syndrome is characterised by increased circulating cytokine ranges and immune cell hyperactivation, resulting in secondary organ dysfunction, particularly hepatic, pulmonary, or renal.

A dietary polyphenolic antioxidant compound named CUR obtained from turmeric plant Curcuma longa L. is legendary for its sturdy anti-inflammatory exercise. Nonetheless, in vivo efficacy of CUR is constrained due to its insufficient bioavailability.

Research: Nanocurcumin Potently Inhibits SARS-CoV-2 Spike Protein-Induced Cytokine Storm by Deactivation of MAPK/NF-κB Signaling in Epithelial Cells​​​​​​​. Picture Credit score: COLOA Studio / Shutterstock

Concerning the research

Within the current research, the authors in contrast the anti-inflammatory impact of CUR−PS-NPs directed in direction of CoV2-SP-stimulated cytokine storm with bulk-CUR (B-CUR) and PS-NPs in lung and liver epithelial cells. Additional, the researchers interpreted the mechanism related to the inhibition of nuclear issue κB (NF-κB) signaling and mitogen-activated protein kinase (MAPK) deactivation by CUR that inhibited the CoV2-SP-mediated cytokine storms. The group additionally evaluated the operate of CUR in decreasing CoV2-SP-induced phosphorylation of p42/44 MAPK, p65/NF-κB, p38 MAPK, and nuclear p65/NF-κB expression, and launch of development elements, chemokines, and cytokines related to the lung and liver epithelial cell harm.

CUR (97% purity), purified biotinylated recombinant hACE2, and SARS-CoV-2 S recombinant glycoproteins have been used on this research. Additional, the liver Huh7.5 and lung A549 epithelial cells have been procured from the American Kind Tradition Assortment (ATCC)-recognized cell repository at Nationwide Centre for Cell Sciences, Pune, India.

The PS-rich fraction was remoted and characterised from the dried rhizomes of C. longa. An emulsion solvent evaporation method with minor modifications was used within the CUR−PS-NPs’ preparation. The epithelial cells have been seeded and incubated with CoV2-SP containing inventory answer.

The overall ribonucleic acid (RNA) was remoted from the CoV2-SP-exposed epithelial cell pallets utilizing an RNeasy mini package. Subsequently, reverse transcription-quantitative polymerase chain response (RT-qPCR) experiments have been carried out within the genes of CoV2-SP-exposed and unexposed epithelial cells. The interplay between CoV2-SP and hACE2 was assessed by enzyme-linked immunosorbent assay (ELISA). The cell viability was evaluated by the fluorescence-activated cell sorting (FACS) evaluation, fluorescence microscopy, and Alamar blue assay utilizing propidium iodide (PI) and Annexin V-FITC.

Research findings

The outcomes indicated that the dimensions of the CUR−PS-NPs was throughout the nanomaterial vary, and there was a steady CUR launch from the CUR–PS-NPs. 

CUR–PS-NPs confirmed a excessive potential to inhibit the discharge of chemokines equivalent to IP10, MCP-1, and CXCL8, development elements equivalent to vascular endothelial development issue (VEGF) and C-C chemokine ligand 3 (CCL3), and cytokines equivalent to IL-12, IL-6, and IL-1 related to the impairment of CoV2-SP-triggered lung A549 and liver Huh7.5 epithelial cells.

The inhibition of chemokines, cytokines, and development elements by CUR–PS-NPs in A549 and Huh7.5 cells was increased than PS-NPs and B-CUR-treated cells. Nonetheless, the inhibition of VEGF-A, CCL10, and CCL5 in PS-NPs and B-CUR-treated A549 cells have been increased than the CUR–PS-NPs-treated cells. No vital inhibitory results on the discharge of IL-8 and IL-6 in CoV2-SPs-triggered Huh7.5 and A549 cells have been demonstrated by the PS-NPs therapy alone.

Therapeutical methods using CUR–PS-NPs efficiently diminished the interplay between CoV2-SP and host ACE2. CUR−PS-NPs’ potential to inhibit the interplay of CoV2-SP and human ACE2 was increased than that of PS-NPs and B-CUR.

On the 10 μM dose, each B-CUR and nano-CUR triggered vital reductions in cell viability whereas, on the 5 μM dose, neither B-CUR nor nano-CUR triggered any lethality to the cells. Moreover, nano-CUR had superior bioavailability than B-CUR.

CUR-PS-NPs act by decreasing NF-κB/MAPK signaling, ensuing within the discount of CoV2-SP-induced phosphorylation of p65/NF-κB, p38 MAPK, p65/NF-κB, and p42/44 MAPK expression. The discount of CoV2-SP-induced phosphorylation of protein kinases brought on by CUR-PS-NPs was increased than B-CUR-induced reductions.

Conclusions

The research findings indicated that natural NPs of CUR obtained from a PS-affluent fraction of turmeric rhizome, CUR−PS-NPs, have a excessive inhibitory potential in direction of CoV2-SP-induced cytokine storm in human lung A549 and liver Huh7.5 epithelial cells. Moreover, the therapy of CUR−PS-NPs in CoV2-SP-triggered epithelial cells prevented the epithelial cell injury by inhibiting the discharge of chemokines, development elements, and cytokines via the deactivation of the NF-κB/MAPK signaling pathway.  

General, the research emphasised that the CUR−PS-NPs might need the potential to develop into a protected and efficient drug for COVID-19 therapy. Nonetheless, extra in vivo investigations are wanted to validate the CoV2-SP-induced cytokine storm inhibitory potential of CUR-PS-NPs in lung and liver epithelial cells.