curcumin and Cytokine-Release-Syndrome

Selected traditional medicinal plants exhibit therapeutic effects in coronavirus disease (Covid-19) patients. This review aims to identify the phytochemicals from five traditional medicinal plants (Glycyrrhiza glabra, Nigella sativa, Curcuma longa, Tinospora cordifolia and Withania somnifera) with high potential in modulating the main protease (Mpro) activity and cytokine storm in Covid-19 infection. The Mpro binding affinity of 13 plant phytochemicals were in the following order: Withanoside II>withanoside IV>withaferin A>α-hederin>withanoside V>sitoindoside IX>glabridin>liquiritigenin, nigellidine>curcumin>glycyrrhizin>tinocordiside>berberine. Among these phytochemicals, glycyrrhizin, withaferin A, curcumin, nigellidine and cordifolioside A suppressed SARS-CoV-2 replication and showed stronger anti-inflammatory activities than standard Covid-19 drugs. Both preclinical and clinical evidences supported the development of plant bioactive compounds as Mpro inhibitors.

Topics: COVID-19 Drug Treatment; Curcumin; Cytokine Release Syndrome; Glycyrrhizic Acid; Humans; Molecular Docking Simulation; Peptide Hydrolases; Phytochemicals; Plants, Medicinal; Protease Inhibitors; SARS-CoV-2

Due to lack of approved drugs and vaccines, the medical world has resorted to older drugs, produced for viral infections and other diseases, as a remedy to combat COVID-19. The accumulating evidence from in vitro and in vivo studies for SARS-CoV and MERS-CoV have demonstrated that several polyphenols found in plants and zinc- polyphenol clusters have been in use as herbal medicines have antiviral activities against viruses with various mechanisms.. Curcumin, zinc and zinc-ionophores have been considered as nutraceuticals and nutrients showing great antiviral activities with their medicinal like activities.. In this work, we discussed the potential prophylactic and/or therapeutic effects of curcumin, zinc and zinc-ionophores in treatment of viral infections including COVID-19.. Curcuminoids and Zinc classified as nutraceuticals under GRAS (Generally Recognized As Safe) by FDA can provide complementary treatment for COVID 19 patients with their immunity-boosting and antiviral properties.

Topics: Antiviral Agents; COVID-19; Curcumin; Cytokine Release Syndrome; Dietary Supplements; Food; Humans; Inflammation; Ionophores; Pandemics; Plant Extracts; Plant Preparations; Polyphenols; Trace Elements; Virus Replication; Zinc

We aimed to design RGD-anchored liposomes encapsulating an antipyroptosis drug that could efficiently target macrophages and relieve the rate of cytokine release syndrome, providing a new strategy for sepsis treatment, especially sepsis-induced acute renal injury.. Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by host response disorders due to infection. Sepsis has a high incidence and remains one of the leading causes of death worldwide.. Macrophage-mediated pyroptosis plays an important role in the occurrence and development of cytokine release syndrome and organ injury caused by sepsis. Curcumin can inhibit inflammasome assembly and slow the progression of pyroptosis by scavenging intracellular reactive oxygen species, but it has poor water solubility and low bioavailability. The emergence of drug-delivery nanosystems has overcome this problem, but there is still a lack of research on how to accurately deliver antipyroptotic drugs to innate immune cells and subsequently hinder pyroptosis.. We constructed a curcumin-loaded RGD-modified liposome (RGD-lipo/Cur) and demonstrated that RGD-lipo/Cur could effectively target macrophages.. In vitro, RGD-lipo/Cur reduced the upregulation of caspase-1, caspase-3, NLRP3, IL-1β and GSDMD, inhibiting pyroptosis, reducing oxidative stress, and attenuating the proinflammatory cytokine cascade.. RGD-lipo/Cur was considered to have great potential for sepsis treatment.

Topics: Aspartic Acid; Curcumin; Cytokine Release Syndrome; Humans; Inflammasomes; Oligopeptides; Pyroptosis; Sepsis

An excessive inflammatory response induced by cytokine storms is the primary reason for the deterioration of patients with acute lung injury (ALI). Though natural polyphenols such as curcumin (CUR) have anti-inflammation activity for ALI treatment, they often have limited efficacy due to their poor solubility in water and oxidising tendency. This study investigates a highly cross-linked polyphosphazene nano-drug (PHCH) developed by copolymerisation of CUR and acid-sensitive units (4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide, D-HBD) with hexachlorotripolyphosphonitrile (HCCP) for improved treatment of ALI. PHCH can prolong the blood circulation time and targeted delivery into lung inflammation sites by enhancing CUR's water dispersion and anti-oxidant properties. PHCH also demonstrates the inflammation-responsive release of CUR in an inflammation environment due to the acid-responsive degradation of hydrazine bonds and triphosphonitrile rings in PHCH. Therefore, PHCH has a substantial anti-inflammation activity for ALI treatment by synergistically improving CUR's water-solubility, bioavailability and biocompatibility. As expected, PHCH attenuates the cytokine storm syndrome and alleviates inflammation in the infected cells and tissues by down-regulating several critical inflammatory cytokines (TNF-α, IL-1β, and IL-8). PHCH also decreases the expression of p-p65 and C-Caspase-1, inhibiting NLRP3 inflammasomes and suppressing NF-κB signalling pathways. The administrated mice experiments confirmed that PHCH accumulation was enhanced in lung tissue and showed the efficient scavenging ability of reactive oxygen species (ROS), effectively blocking the cytokine storm and alleviating inflammatory damage in ALI. This smart polyphosphazene nano-drug with targeting delivery property and inflammation-responsive release of curcumin has excellent potential for the clinical treatment of various inflammatory diseases, including ALI.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Curcumin; Cytokine Release Syndrome; Inflammation; Lipopolysaccharides; Lung; Mice; Nanoparticles; NF-kappa B

Topics: Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Cell Survival; Chemokines; Curcumin; Cytokine Release Syndrome; Cytokines; Humans; Intercellular Signaling Peptides and Proteins; MAP Kinase Signaling System; Nanoparticles; NF-kappa B; Phosphorylation; Signal Transduction; Spike Glycoprotein, Coronavirus

Pneumonia can lead to high morbidity and mortality secondary to uncontrolled inflammation of the lung tissue. Blocking cytokine storm storms may be the key to saving the life of patients with severe pneumonia. According to the medicinal guide theory of Traditional Chinese Medicine (TCM) and the inherent affinity with macrophages for the site of inflammation, we constructed the drug delivery platform (MNPs) derived from macrophage-membrane encapsulated reaction oxygen species (ROS)-responsive Platycodon grandiflorum polysaccharides (PGP) nanoparticles (PNPs) to calm the cytokine storm and improve lung inflammation. By loading the anti-inflammatory agent Curcumin (Cur), we demonstrated that MNPs@Cur significantly attenuated inflammation and cytokine storm syndrome in acute lung injury (ALI) mice by suppressing pro-inflammatory factor production and inflammatory cell infiltration. Interestingly, we observed that the PNPs also have potent pulmonary targeting ability compared to other polysaccharide carriers, which is in line with the medicinal guide theory of TCM. Our study revealed the rational design of drug delivery platforms to improve the treatment of lung injury, which inherits and develops the important theories of TCM through the perfect combination of guide theory and biomimetic nanotechnology and provides the experimental scientific basis for the clinical application of channel ushering drugs.

Topics: Animals; Curcumin; Cytokine Release Syndrome; Humans; Mice; Platycodon; Pneumonia; Polysaccharides

SARS-CoV-2 can stimulate the expression of various inflammatory cytokines and induce the cytokine storm in COVID-19 patients leading to multiple organ failure and death. Curcumin as a polyphenolic compound has been shown to have anti-inflammatory properties and inhibit the release of numerous pro-inflammatory cytokines. We present multiplex analysis using the Evidence Investigator biochip system to determine the effect of curcumin on serum level of cytokines which are typically elevated in cytokine storm events, including tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-10.

Topics: COVID-19 Drug Treatment; Curcumin; Cytokine Release Syndrome; Cytokines; Humans; Protein Array Analysis; SARS-CoV-2