Comparative protein profiling reveals the inhibitory role of curcumin on IL-17A mediated minichromosome maintenance (MCM) proteins as novel putative markers for acute lung injury in vivo.

The Pro-inflammatory cytokine, Interleukin 17A (IL-17A) plays a vital role in the pathogenesis of inflammatory-induced acute lung injury (ALI). But, the mechanisms of this pro-inflammatory cytokine in response to activation after replication stress are not yet known. Control on DNA replication (DR) is vital for maintaining genome stability. Minichromosome maintenance (MCM) proteins play essential roles in various cancers, but their involvement during ALI is not yet been discussed. The present study was carried out to assess the participation of IL-17A during replication stress and to evaluate the contribution of curcumin on this. Mass spectrometry-based proteomic approach has been used on mice lung tissues treated with IL-17A, as a prime mediator to cause injury and curcumin a natural polyphenol as an intervention. Several trends were identified from the proteomic subset which revealed that IL-17A induces expressions of proteins like MCM2, MCM3, and MCM6 along with other proteins involved in DR. Interestingly, curcumin was found in suppressing the expression levels of these proteins. This was also confirmed via validating LC-MS/MS data using appropriate molecular techniques. Pathway and gene ontology analysis were performed with DAVID GO databases. Apart from this, the present study also reports the unique contribution of curcumin in suppressing the mRNA levels of other MCMs like MCM4, MCM5, and MCM7 as well as of ORC1 and ORC2. Hence, the present study revolves around linking the replication stress by pro-inflammatory effects, highlighting the implications for ALI and therapies. This study, therefore, enhances our capacity to therapeutically target DR-specific proteins.

Therapeutic properties of Punica granatum L (pomegranate) and its applications in lung-based diseases: A detailed review.

Respiratory diseases are the prime cause of death and disability worldwide. The majority of lung-based diseases are resistant to treatment. Hence, research on unique drugs/compounds with a more efficient and minimum side effect for treating lung diseases is urgent. Punica granatum L (pomegranate) fruit has been used in the prevention and treatment of various respiratory disorders in recent times. In vivo and in vitro studies have demonstrated that pomegranate fruit, as well as its juice, extract, peel powder, and oil, exert anti-proliferative, anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-tumorigenic properties by attenuating various respiratory conditions such as asthma, lung fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and alveolar inflammation via modulating various signaling pathways. The current review summarizes the potential properties and medical benefits of pomegranate against different lung-based diseases, also highlighting its possible role in the lung fibrinolytic system. The available data suggest that pomegranate is effective in controlling the disease progressions and could be a potential therapeutic target benefiting human health status. Furthermore, this review also outlines the preclinical and clinical studies highlighting the role of pomegranate in lung diseases further evoking future studies to investigate the effect of intake of this anti-oxidant fruit in larger and well-defined human clinical trials. PRACTICAL APPLICATIONS: This review outlines the putative pharmacologic benefits of P. granatum L (pomegranate) in treating various chronic lung-based diseases such as lung cancer, COPD, ARDS, asthma, lung fibrosis, and cystic fibrosis. This review also highlights the possible inhibitory role of P. granatum L (pomegranate) in the lung fibrinolytic system triggering the fibrinolytic markers. This review summarizes the preclinical and clinical studies using in vitro, in vivo, and human models highlighting the potential role of P. granatum L (pomegranate) in lung diseases. This review evokes future research to investigate the effect of intake of pomegranate fruit in well-defined human clinical trials.

Curcumin Targets p53-Fibrinolytic System in TGF-ß1 Mediated Alveolar Epithelial Mesenchymal Transition in Alveolar Epithelial Cells.

AIMS: We aim to investigate curcumin interaction with p53-fibrinolytic system, smad dependent and independent pathways underlying their prime role during lung injury and fibrosis. BACKGROUND: Curcumin, an active component of Curcuma longa plant, substantially modulates respiratory conditions. TGF-ß1 plays a central role in lung remodeling by balancing extracellular matrix (ECM) production and degradation, which is a hallmark for alveolar EMT. However, the crosstalk of curcumin is not known yet with TGF- ß1 mediated p53-Fibrinolytic system regulating alveolar EMT leading to IPF. In the present study, the potential molecular mechanism of curcumin in TGF-ß1 mediated p53-fibrinolytic system in basal alveolar epithelial cells was explored. OBJECTIVES: To understand the potential molecular mechanism of curcumin in TGF-ß1 mediated p53-fibrinolytic system in basal alveolar epithelial cells. METHODS: Basal alveolar epithelial cells were treated with TGF- ß1 to induce alveolar EMT and after 24 hrs curcumin was administered to study its anti-fibrotic effects. Molecular techniques like immunoblot, RT-PCR and immunofluorescence were performed to assess the anti-fibrotic role of curcumin on EMT markers, IL-17A, p53-smad interaction to investigate the anti-fibrotic role of curcumin. RESULTS: The results indicated that TGF-ß1-induced EMT in A549 cells exhibited altered expression of the IL-17A, p53-fibrinolytic markers and EMT markers at the mRNA and protein level. Intervention with curcumin attenuated alveolar EMT and inactivated TGF-ß1 induced Smad/non Smad signaling pathways via blocking p53-fibrinolytic system. CONCLUSION: This study provides the first evidence of the dynamic response of curcumin on TGF- ß1 mediated p53-fibrinolytic system during alveolar injury in vitro.

Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.

Curcumin Suppresses Epithelial Growth Factor Receptor (EGFR) and Proliferative Protein (Ki 67) in Acute Lung Injury and Lung Fibrosis In vitro and In vivo.

BACKGROUND: Acute lung injury is one of the common conditions caused due to bleomycin therapy which leads to pulmonary fibrosis, which is one of the severe interstitial lung diseases most commonly affecting the elderly individuals. EGFR and Ki67 can be marked as beneficial markers for detecting pulmonary fibrosis based on which clinicians can guide the therapy. OBJECTIVE: The aim of the study was to evaluate the effect of curcumin as an intervention on two prognostic markers EGFR and Ki67 in bleomycin-induced basal alveolar epithelial cells and C57BL/6 mice. Protein expressions and pathological expressions of EGFR and Ki67 were evaluated to analyze the effect of curcumin via both in vitro and in vivo approaches. METHODS: The effect of curcumin was investigated both on cell lines (A549) and animal model (both normal and bleomycin-induced mice, n=6) via techniques like western blotting for protein expression. Techniques like immunofluorescence and immunohistochemistry were carried out and examined under confocal microscopy and phase contrast microscopy to analyze the expressions of the said biomarkers. Bleomycin was used as a causative agent to induce inflammation. RESULTS: The natural polyphenol curcumin could downregulate the expressions levels of Ki67 and EGFR both in vitro and in vivo. Immunofluorescence analysis of proliferative marker Ki67 showed a reduced expression on curcumin treatment in vitro. The pathological sections from treated lungs showed a significant decrease in EGFR and Ki67 levels when exposed to curcumin. CONCLUSION: We conclude that curcumin, a well-known natural bioactive compound holds strong antiproliferative effects on Ki67 and EGFR expressions.We observed that a clinical outcome in the diagnosis of pulmonary fibrosis remains to be unconvincing so far. Curcumin can be considered as a potential therapeutic.