title: Leptin inhibitors from fungal endophytes (LIFEs): Will be novel therapeutic drugs for obesity and its associated immune mediated diseases.
abstract: Treatment of obesity and its associated immune mediated diseases is challenging due to impaired function of leptin system. Thus leptin is providing an interesting target for therapeutic intervention. Leptin, an adipose tissue-derived adipokine, displays a variety of immune functions, and regulate both innate and adaptive immune responses. The increased secretion of leptin (hyperleptinemia) and production of proinflammatory cytokines has been implicated in the pathogenesis of obesity-related immune diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer, systemic lupus erythematosus, rheumatoid arthritis, crohn's disease and multiple sclerosis. These disorders are managed through antibiotics and by cytokines replacement. However, the effectiveness of cytokines coupled to the complexity of the cytokine network leads to severe side-effects, which can still occur after careful preclinical evaluation. In addition, synthetic immunotherapeutics carries a degree of risk, is time-consuming and expensive. Hence, the complexity of existing therapy and adverse effects emphasizes the need of an alternative approach for the management of immune dysfunction associated with obesity and its related diseases. For the aforementioned diseases that are related to leptin overabundance, new drugs blocking leptin signaling need to be generated. The research on the discovery of clinically important novel compounds from natural source is expanding due to their safety and no side effect. The fungal endophytes are the microbes that colonize internal tissue of plants without causing negative effects to the host. They produce plethora of substances of potential use to modern medicinal and pharmaceutical industry. The increasing body of evidence associated with application of bioactive metabolites derived from fungal endophytes in diverse disease states merits its use as therapeutic drugs. In particular, the saponins have been extensively proved to modulate the immune system, which has raised a significant interest in their potential as immunomodulators. Thus, our hypothesis is that the saponins derived from fungal endophytes can be explored as clinical applicable leptin inhibitors for treating immune mediated diseases.
authors.affiliation: Department of Biotechnology, Vikrama Simhapuri University, Nellore, Andhra Pradesh, India. Electronic address: bennypaulmouli@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Chandra Mouli
authors.affiliation: Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: D
authors.initials: D
authors.lastname: Pragathi
authors.affiliation: Department of Botany, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: U
authors.initials: U
authors.lastname: Naga Jyothi
authors.affiliation: Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: V
authors.initials: V
authors.lastname: Shanmuga Kumar
authors.affiliation: Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: M
authors.initials: M
authors.lastname: Himalaya Naik
authors.affiliation: Department of Physiology, GIMSR, GITAM University, Visakhapatnam, Andhra Pradesh, India.
authors.forename: P
authors.initials: P
authors.lastname: Balananda
authors.affiliation: Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: B
authors.initials: B
authors.lastname: Suman
authors.affiliation: Department of Biochemistry, BPS Govt Medical College for Women, Sonepat, Haryana, India.
authors.forename: V
authors.initials: V
authors.lastname: Seshadri Reddy
authors.affiliation: Department of Botany, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.
authors.forename: T
authors.initials: T
authors.lastname: Vijaya
mesh_terms: D017667:Adipocytes / Q000166:cytology; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D060026:Endophytes / Q000737:chemistry*; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D007107:Immune System; D007154:Immune System Diseases / Q000188:drug therapy*; D007155:Immunologic Factors / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000276:immunology; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D057170:Translational Research, Biomedical
chemical_list: D054392:Adipokines; D016207:Cytokines; D007155:Immunologic Factors; D020738:Leptin; D016328:NF-kappa B