Singla, E, Dharwal, V & Naura, AS 2020, 'Gallic acid protects against the COPD-linked lung inflammation and emphysema in mice', INFLAMMATION RESEARCH, vol. 69, no. 4, pp. 423-434.View/Download from: Publisher's site
Dharwal, V, Sandhir, R & Naura, AS 2019, 'PARP-1 inhibition provides protection against elastase-induced emphysema by mitigating the expression of matrix metalloproteinases.', Molecular and cellular biochemistry, vol. 457, no. 1-2, pp. 41-49.View/Download from: Publisher's site
In our previous study, we have shown that PARP-1 inhibition (genetic or pharmacological) ameliorates elastase-induced inflammation and emphysema. Since matrix metalloproteinases (MMPs) particularly MMP-2 and MMP-9 are known to play a critical role in emphysema development, the present work was designed to evaluate the effects of PARP-1 inhibition on their expression utilizing elastase-induced mouse model of emphysema. Our data show that olaparib administration at a dose of 5 mg/kg b.wt. (daily) significantly prevented the elastase-induced inflammation as indicated by decreased inflammatory cells particularly macrophages in BALF at 1 week post-injury. In addition, the drug restored the altered redox balance in the lungs of elastase-treated mice toward normal. Further, PCR data show that olaparib administration ameliorates the elastase-induced expression of MMP-2 and MMP-9 without having much effect on the expressions of their inhibitors TIMP-1 and TIMP-2. Next, our data on immunoblot, gelatin zymography, and immunohistochemical analysis indeed confirm that olaparib reduced the elastase-induced expression of MMP-2 and MMP-9. Reduction in the expression of metalloproteinases correlate well with the PARP activity as olaparib treatment suppressed the elastase-induced expression of PAR modified proteins markedly. Overall, our data strongly suggest that PARP-1 inhibition blunts elastase-induced MMP-2 and MMP-9 expression, which may be partly responsible for prevention of emphysema.
Chaudhary, M, Sharma, P, Mittal, M, Kaur, R, Dharwal, V, Kumar, A & Naura, AS 2018, 'Beneficial effects of Caesalpinia digyna extract against acid aspiration-Induced acute lung injury in mice', Pharmacognosy Research, vol. 10, no. 3, pp. 243-249.View/Download from: Publisher's site
© 2018 Pharmacognosy Research | Published by Wolters Kluwer-Medknow. Objective: Caesalpinia digyna belongs to the genus Caesalpinia, which is known since ancient times for its medicinal properties. The present work was designed to evaluate the beneficial potential of hydroalcoholic extract of the roots of C. dignea against hydrochloric acid (HCl)-induced acute lung injury in mice. Materials and Methods: Ethanolic extract of C. dignea roots at a dose of 50, 100, or 200 mg/kg boy weight was given once orally 90 min before HCl administration. Mice were then analyzed for infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF) and oxidative stress markers in the lung tissue. Further, the effects of the extract were compared with bergenin isolated from the extract. Results: Our results showed that an oral administration of the extract 90 min before HCl instillation reduced the infiltration of neutrophils in the lungs in a dose-dependent manner. Reduction in lung inflammation was associated with decline in pulmonary edema as the total protein content in the BALF was found to be decreased substantially. The drug also restored the redox balance in the lungs toward normal on HCl treatment as assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and catalase activity. Bergenin, isolated from the plant, was able to suppress the neutrophils but increased the macrophage number in BALF when administered before HCl instillation, suggesting immunoregulatory properties of the key constituent of the extract. Conclusion: Our data suggest that hydroalcoholic extract of Caesalpinia digyna roots constitute the phytochemicals that can protect against HCl-induced acute lung injury in mice..
Dharwal, V & Naura, AS 2018, 'PARP-1 inhibition ameliorates elastase induced lung inflammation and emphysema in mice', BIOCHEMICAL PHARMACOLOGY, vol. 150, pp. 24-34.View/Download from: Publisher's site
Kaur, G, Jaswal, P, Banga, R, Dharwal, V, Kumar, A & Naura, AS 2018, 'Hydroalcoholic Extract of Argyreia speciosa Roots Ameliorates HCl-mediated Acute Lung Injury in Mice', PHARMACOGNOSY MAGAZINE, vol. 14, no. 55, pp. S8-S13.View/Download from: Publisher's site
Naura, A, Chaudhary, M, Sharma, P, Mittal, M, Kaur, R, Dharwal, V & Kumar, A 2018, 'Beneficial effects of Caesalpinia digyna extract against acid aspiration-Induced acute lung injury in mice', Pharmacognosy Research, vol. 10, no. 3, pp. 243-243.View/Download from: Publisher's site
Sethi, G, Dharwal, V & Amarjit Singh, N 2019, 'Immunological Basis of Oxidative Stress-Induced Lung Inflammation in Asthma and COPD' in Oxidative Stress in Lung Diseases, Springer Nature, Switzerland, pp. 196-223.View/Download from: Publisher's site
Oxidative stress is an outcome of imbalance in production vis-à-vis removal of reactive oxygen species (ROS). The critical role of oxidative stress in several chronic inflammatory diseases has been reported. In this chapter, we have discussed the participation of oxidative stress in the pathogenesis of chronic inflammatory disease of lungs: asthma and chronic obstructive pulmonary disease (COPD). Despite the differences in etiology, immunology, pathogenesis, and clinical symptoms, the involvement of oxidative stress in the manifestation of chronic airway inflammation is the most common feature of both respiratory disorders. First, we have discussed the role of various types of immune cell in the orchestration of oxidative stress-mediated lung inflammation in both asthma and COPD. Next, the contribution of cellular sources of ROS (mitochondria and NADPH oxidase) in activation of cellular signaling pathways, particularly nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear erythroid 2-related factor 2 (Nrf2), is elaborated. Finally, we have highlighted the involvement of oxidative stress in the manifestation of steroid-stable conditions in patients with severe asthma and COPD. Unraveling the participation of ROS at cellular as well as intracellular events may enhance our understanding of the pathogenesis of both asthma and COPD for the development of effective treatment strategies in the area.
Naura, AS & Dharwal, V 2018, 'Pharmacological Inhibition of Poly ADP-Ribose Polymerase Ameliorates Elastase Induced Inflammation and Emphysema in Mice', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, International Conference of the American-Thoracic-Society, AMER THORACIC SOC, San Diego, CA.