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Cellular and Molecular Mechanisms of Repurposed Antidiabetic Drug as an Adjunctive Treatment for Tuberculosis

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Targeting Cellular Signalling Pathways in Lung Diseases

Abstract

Apart from the accessibility of antitubercular therapy (ATT), tuberculosis (TB) emerged to be a chief cause of mortality around the world. The present ATT had a disadvantage of lengthy period that creates a problem of noncompliance in patients and growth of resistance. The greater price and delayed temperament of TB medication development coupled with low advantages lead to repurposing of complementary drugs which may contribute as an innovative pharmaceutical approach. Metformin has currently engrossed a major consideration as a host-directed adjunctive therapy (HDT) and has several complementary roles on cellular and molecular metabolism, immunity of host, and transcription of genes engaged in innate host responses to M. tuberculosis. It has an inhibitory effect on mitochondrial complex I and has been found to increase AMP/ATP ratio, with the help of a series of several pathways, and causes bacterial killing. This chapter would discuss in detail about the cellular and molecular mode of action of metformin including its impact on T helper cell 1 (TH1) along with trends which metformin demonstrates in reference to CD4+ and CD8+ cells. The necessity for adjunctive host-targeted therapy and the synergistic role of metformin with other antitubercular medications have been thoroughly debated. Novel strategy to fight drug-resistant TB in concurrence with future perspectives has been discussed in this chapter.

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Authors and Affiliations

  1. Department of Pharmacology, MM School of Pharmacy, Maharishi Markandeshwar University, Sadopur-Ambala, Haryana, India

    Rupesh K. Gautam

  2. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

    Ritu Mishra & Manju Sharma

  3. Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India

    Kanika Sharma

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  1. Rupesh K. Gautam
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  2. Ritu Mishra
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  3. Kanika Sharma
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  4. Manju Sharma
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Editors and Affiliations

  1. Graduate School of Health, Discipline of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia

    Kamal Dua

  2. Drug Development and Innovation Centre, University of Alberta, Edmonton, AB, Canada

    Raimar Löbenberg

  3. Haematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil

    Ângela Cristina Malheiros Luzo

  4. Graduate School of Health, Discipline of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia

    Shakti Shukla

  5. School of Pharmaceutical Sciences & Division of Research & Development, Lovely Professional University, Phagwara, Punjab, India

    Saurabh Satija

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Gautam, R.K., Mishra, R., Sharma, K., Sharma, M. (2021). Cellular and Molecular Mechanisms of Repurposed Antidiabetic Drug as an Adjunctive Treatment for Tuberculosis. In: Dua, K., Löbenberg, R., Malheiros Luzo, Â.C., Shukla, S., Satija, S. (eds) Targeting Cellular Signalling Pathways in Lung Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-33-6827-9_15

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