curcumin and Respiratory-Distress-Syndrome

Curcumin is a safe, non-toxic, readily available and naturally occurring compound, an active constituent of Curcuma longa (turmeric). Curcumin could potentially treat diseases, but faces poor physicochemical and pharmacological characteristics. To overcome these limitations, we developed a stable, water-soluble formulation of curcumin called cyclodextrin-complexed curcumin (CDC). We have previously shown that direct delivery of CDC to the lung following lipopolysaccharides exposure reduces acute lung injury (ALI) and effectively reduces lung injury, inflammation and mortality in mice following Klebsiella pneumoniae. Recently, we found that administration of CDC led to a significant reduction in angiotensin-converting enzyme 2 and signal transducer and activator of transcription 3 expression in gene and protein levels following pneumonia, indicating its potential in treating coronavirus disease 2019 (COVID-19). In this review, we consider the clinical features of ALI and acute respiratory distress syndrome (ARDS) and the role of curcumin in modulating the pathogenesis of bacterial/viral-induced ARDS and COVID-19.

Topics: Acute Lung Injury; Animals; COVID-19; Curcumin; Lung; Mice; Respiratory Distress Syndrome

We are being confronted with the most consequential pandemic since the Spanish flu of 1918‑1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS‑CoV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso‑pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried‑and‑true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID‑19; acute respiratory distress syndrome (ARDS); known treatments; ii) Structure and functions of SARS‑CoV2 and proposed antiviral drugs; iii) The combination of arginine‑ascorbate.

Topics: Amiodarone; Animals; COVID-19; Curcumin; Humans; Pioglitazone; Respiratory Distress Syndrome; SARS-CoV-2; Simvastatin

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), characterized by uncontrolled lung inflammation, is one of the most devastating diseases with high morbidity and mortality. As the first line of defense system, macrophages play a crucial role in the pathogenesis of ALI/ARDS. Therefore, it has great potential to selectively target M1 macrophages to improve the therapeutic effect of anti-inflammatory drugs. l-arginine plays a key role in regulating the immune function of macrophages. The receptors mediating l-arginine uptake are highly expressed on the surface of M1-type macrophages. In this study, we designed an l-arginine-modified liposome for aerosol inhalation to target M1 macrophages in the lung, and the anti-inflammatory drug curcumin was encapsulated in liposomes as model drug. Compared with unmodified curcumin liposome (Cur-Lip), l-arginine functionalized Cur-Lip (Arg-Cur-Lip) exhibited higher uptake by M1 macrophages in vitro and higher accumulation in inflamed lungs in vivo. Furthermore, Arg-Cur-Lip showed more potent therapeutic effects in LPS-induced RAW 264.7 cells and the rat model of ALI. Overall, these findings indicate that l-arginine-modified liposomes have great potential to enhance curcumin treatment of ALI/ARDS by targeting M1 macrophages, which may provide an option for the treatment of acute lung inflammatory diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome and middle east respiratory syndrome.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; COVID-19; Curcumin; Liposomes; Macrophages; Rats; Respiratory Distress Syndrome

Epidemic modeling has been a key tool for understanding the impact of global viral outbreaks for over two decades. Recent developments of the COVID-19 pandemic have accelerated research using compartmental models, like SI, SIR, SEIR, with their appropriate modifications. However, there is a large body of recent research consolidated on homogeneous population mixing models, which are known to offer reduced tractability, and render conclusions hard to quantify. As such, based on our recent work, introducing the heterogeneous geo-spatial mobility population model (GPM), we adapt a modified SIR-V (susceptible-infected-recovered-vaccinated) epidemic model which embodies the idea of patient relapse from R back to S, vaccination of R and S patients (reducing their infectiousness), thus altering the infectiousness of V patients (from

Topics: Acute Lung Injury; Adherens Junctions; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antigens, CD; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; beta Catenin; Brain Ischemia; Cadherins; Carcinogenesis; Catalysis; Cell Line; Cells, Cultured; Curcuma; Curcumin; Dioxoles; Disease Models, Animal; Endothelial Cells; Epithelial Cells; Heme Oxygenase (Decyclizing); Humans; Inflammasomes; Intestinal Diseases; Intestinal Mucosa; Ischemic Stroke; Kidney Neoplasms; Lignans; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; NAD(P)H Dehydrogenase (Quinone); Nanostructures; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phytotherapy; Plant Extracts; Pneumonia; PPAR gamma; Proto-Oncogene Proteins c-akt; Pyroptosis; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reperfusion Injury; Respiratory Distress Syndrome; Sepsis; Sesamum; Signal Transduction; Silybin; Silybum marianum; Silymarin; Sirtuin 3; Titanium; Transfection; Treatment Outcome; White Matter

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS.. A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested.. Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10.. Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Cell Differentiation; Curcumin; Cytokines; Disease Models, Animal; Female; Inflammation; Interleukin-10; Macrophages; Male; Mice; Mice, Inbred C57BL; Respiratory Distress Syndrome; T-Lymphocytes, Regulatory

Lipopolysaccharide (LPS) is one of the most powerful proinflammatory factor and can induce acute pulmonary inflammation even lung injury after inhalation or systemic administration. LPS induces sepsis and multiple organ damage. Curcumin (diferuloylmethane), a major component of turmeric, exhibits protection against LPS-induced acute lung injury (ALI). We aimed to investigate effects of intranasal curcumin on LPS-induced ALI in mice where curcumin (10 mg/kg, intranasal (i.n.) was given an hour before LPS exposure. After 24 h of intranasal LPS instillation, a marked increase in neutrophil recruitment and myeloperoxidase (MPO) activity was noted which were significantly ameliorated in curcumin treatment group. Oxidative stress markers like nitric oxide (NO), malondialdehyde (MDA) level and evans blue capillary leakage assay also revealed suppression after curcumin treatment; interestingly, levels of anti-oxidative enzymes such as superoxide dismutase (SOD) and catalase were upregulated. Inflammatory cytokine, tumour necrosis factor alpha (TNF-α) level was significantly attenuated by curcumin. Hence, intranasal curcumin could be a novel therapeutic strategy for LPS-induced ALI by directly targeting the lungs and enhancing anti-oxidant levels.

Topics: Acute Lung Injury; Administration, Intranasal; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Capillary Permeability; Catalase; Curcumin; Disease Models, Animal; Lipopolysaccharides; Lung; Malondialdehyde; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitrites; Oxidative Stress; Random Allocation; Respiratory Distress Syndrome; Sepsis; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemokine CCL2; Curcumin; Disease Models, Animal; Female; Fibrosis; Gene Expression; Humans; Inflammation; Injections, Intraperitoneal; Interferon-gamma; Interleukin-10; Interleukin-6; Mice; Mice, Inbred CBA; Orthoreovirus, Mammalian; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Reoviridae Infections; Respiratory Distress Syndrome; Signal Transduction; Tenascin; Transcription Factor RelA; Transforming Growth Factor beta1

To investigate potential effects of curcumin or dexamethasone on lung transplantation-associated lung injury.. Prospective, randomized, controlled study.. Research laboratory.. Adult male Sprague-Dawley rats.. Sham-operated rats were used as time-matched controls. Experimental rats were subjected to unilateral orthotopic lung transplantation with 4 hrs of cold ischemia followed by 2 hrs (or 24 hrs) of reperfusion. Animals were randomly assigned to vehicle-, curcumin-, or dexamethasone-treated groups.. Transplantation-associated lung injury was characterized by an increased alveolar-capillary permeability and myeloperoxidase activity and decreased levels of arterial oxygen tension/inspired oxygen concentration ratio. Pretreatment with curcumin and dexamethasone significantly prevented barrier disruption, lung edema, tissue inflammation, and decreased PaO2 at the early stage of posttransplantation. Nuclear factor-kappaB in transplanted lungs was activated, accompanied by an increase in messenger RNA levels and protein content of tumor necrosis factor-alpha, interleukin-6, and matrix metalloproteinase-9 in lung graft. Those changes were prevented by pretreatment with curcumin and dexamethasone.. Curcumin can be an alternative therapy for protecting lung transplantation-associated injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capillary Permeability; Curcumin; Cytokines; Dexamethasone; Lung Transplantation; Male; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Curcumin; Enzyme Activation; Humans; Neutrophils; p38 Mitogen-Activated Protein Kinases; Respiratory Distress Syndrome; Sepsis

An early feature of paraquat (PQ) toxicity is the influx of inflammatory cells, releasing proteolytic enzymes and oxygen free radicals, which can destroy the lung epithelium and result in pulmonary fibrosis. Therefore, the ability to suppress early lung injury seems to be an appropriate therapy of pulmonary damage before the development of irreversible fibrosis. Here I show curcumin confers remarkable protection against PQ lung injury. A single intraperitoneal injection of PQ (50 mg/kg) resulted in a significant rise in the levels of protein, angiotensin converting enzyme (ACE), alkaline phosphatase (AKP), N-acetyl-beta-D-glucosaminidase (NAG) and thiobarbituric acid reactive substances (TBARS), and neutrophils in the bronchoalveolar lavage fluid (BALF), while a decrease in glutathione levels. In paraquat rats bronchoalveolar lavage (BAL) cell TBARS concentration was increased with a simultaneous decrease in glutathione content. In addition, the data also demonstrated that PQ caused a decrease in ACE and glutathione levels and an increase in levels of TBARS and myeloperoxidase (MPO) activity in the lung. Interestingly, curcumin prevented the general toxicity and mortality induced by PQ and blocked the rise in BALF protein, ACE, AKP, NAG TBARS and neutrophils. Similarly, curcumin prevented the rise in TBARS content in both BAL cell and lung tissue and MPO activity of the lung. In addition, PQ induced reduction in lung ACE and BAL cell and lung glutathione levels was abolished by curcumin treatment. These findings indicate that curcumin has important therapeutic implications in facilitating the early suppression of PQ lung injury.

Topics: Animals; Bronchoalveolar Lavage Fluid; Curcumin; Dose-Response Relationship, Drug; Drug Interactions; Herbicides; Male; Neutrophils; Paraquat; Protective Agents; Rats; Rats, Wistar; Respiratory Distress Syndrome