Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

Abstract

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 107 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.

Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease

“…In addition, curcumin has been shown to induce antioxidant activity not only by scavenging reactive oxygen and nitrogen species, but also by induction of antioxidant enzymes expression [3]. Together with its innocuous, inexpensive and easily available properties, the therapeutic effect of curcumin has been widely studied in numerous diseases such as acute lung injury [15], acute respiratory distress syndrome [4] and allergic asthma [6]. As chronic inflammation and oxidative stress in the lung are thought to be key components of the pathogenesis of COPD, curcumin may play a protective role in the development of COPD.…”

Curcumin Treatment Suppresses CCR7 Expression and the Differentiation and Migration of Human Circulating Fibrocytes

“…Increasing evidence suggests that curcumin has antifibrotic effects on cardiac fibrosis in spontaneously hypertensive rats via PPAR-γ activation[15]; on liver fibrosis in carbon tetrachloride treated rats via inhibition of transforming growth factor 1 and connective tissue growth factor expression[16], suppressing cannabinoid receptor type-1 [17], as well as ameliorating intrahepatic angiogenesis [18]; on renal fibrosis in unilateral ureteral obstruction (UUO) rat via inhibiting of nuclear factor kappa-B and activator protein-1[19] and in 5/6 nephrectomized rat via modulating Nrf2-Keap1 pathway [20]; on pulmonary fibrosis in viral-induced acute respiratory distress syndrome mice through the alteration of inflammation and myofibroblast differentiation [21] and in bleomycin treated mice via overexpression of cathepsins K and L [22]. …”

Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

“…-SD rats (BLM, 7.5 U/kg) Tang et al (2016) Astragalin Diospyros kaki L.f. -Wistar rats (BLM, 2.5 mg/kg), ICR mice (LPS, 5 mg/kg) - Akgedik et al (2012) and Zhang et al (2015) Curcumin Curcuma longa L. PMVEC, primary FB (IR, 2 Gy) C57BL/6 mice (0.5 μg LPS or 13.5 Gy IR), CBA/J mice (reovirus 1/L, 10 7 PFU) FB (TGF-β, 6 ng/ml), PF patients Lee et al (2010), Smith et al (2010), Avasarala et al (2013) and Jiang and Zhang (2015a) EGCG Camellia sinensis (L.) Kuntze FB WI−38 (TGF-β1, 10 ng/ml) Wistar rats (BLM, 6.5 U/kg), SD rats (IR, 22 Gy) - Sriram et al (2009aSriram et al ( , 2009bSriram et al ( , 2015 and You et al (2014) Corilagin Caesalpinia coriaria (Jacq. )…”

“…Moreover, 1% curcumin significantly decreased TNF-α level in BALF from LPS-challenged mice; the decrease was more pronounced when curcumin was given at a dose of 5% (Lee et al, 2010). Using the model of reovirus 1/L-induced acute viral pneumonia which displays many characteristics of human acute respiratory distress syndrome (ARDS)/ALI, 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 (Avasarala et al, 2013). The study showed that curcumin treatment in vivo effected both inflammatory (diffuse alveolar damage) and fibrotic lesion development leading to a significant reduction in the development of ALI/ARDS in reovirus 1/Linfected mice, potentially via the modulation of cytokine/chemokine expression through the NF-κB pathway as well as the host fibrotic response during the regeneration phase of the disease through modulation of the TGF-β pathway (Avasarala et al, 2013).…”