Browsing by Author "Choudhary Harsha"

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Chronic diseases, inflammation, and spices: How are they linked?
(BioMed Central Ltd., 2018) Ajaikumar B. Kunnumakkara; Bethsebie L. Sailo; Kishore Banik; Choudhary Harsha; Sahdeo Prasad; Subash Chandra Gupta; Alok Chandra Bharti; Bharat B. Aggarwal
Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either acute or chronic. Acute inflammation persists for a short duration and is the host defense against infections and allergens, whereas the chronic inflammation persists for a long time and leads to many chronic diseases including cancer, cardiovascular diseases, neurodegenerative diseases, respiratory diseases, etc. Numerous lines of evidence suggest that the aforementioned risk factors induced cancer through chronic inflammation. First, transcription factors NF-ΚB and STAT3 that regulate expression of inflammatory gene products, have been found to be constitutively active in most cancers; second, chronic inflammation such as pancreatitis, prostatitis, hepatitis etc. leads to cancers; third, activation of NF-ΚB and STAT3 leads to cancer cell proliferation, survival, invasion, angiogenesis and metastasis; fourth, activation of NF-ΚB and STAT3 leads to resistance to chemotherapy and radiation, and hypoxia and acidic conditions activate these transcription factors. Therefore, targeting these pathways may provide opportunities for both prevention and treatment of cancer and other chronic diseases. We will discuss in this review the potential of various dietary agents such as spices and its components in the suppression of inflammatory pathways and their roles in the prevention and therapy of cancer and other chronic diseases. In fact, epidemiological studies do indicate that cancer incidence in countries such as India where spices are consumed daily is much lower (94/100,000) than those where spices are not consumed such as United States (318/100,000), suggesting the potential role of spices in cancer prevention. © 2018 The Author(s).
Curcumin mediates anticancer effects by modulating multiple cell signaling pathways
(Portland Press Ltd, 2017) Ajaikumar B. Kunnumakkara; Devivasha Bordoloi; Choudhary Harsha; Kishore Banik; Subash C. Gupta; Bharat B. Aggarwal
Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170].Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s).
Googling the guggul (Commiphora and Boswellia) for prevention of chronic diseases
(Frontiers Media S.A., 2018) Ajaikumar B. Kunnumakkara; Kishore Banik; Devivasha Bordoloi; Choudhary Harsha; Bethsebie L. Sailo; Ganesan Padmavathi; Nand K. Roy; Subash C. Gupta; Bharat B. Aggarwal
Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug discovery which is based on thinking that most chronic diseases are caused by alteration of a single gene and thus most therapies are single gene-targeted therapies. However, extensive research has revealed that most chronic diseases are caused by multiple gene products. Although most drugs designed by man are mono-targeted therapies, however, those designed by "mother nature" and have been used for thousands of years, are "multi-targeted" therapies. In this review, we examine two agents that have been around for thousands of years, namely "guggul" from Commiphora and Boswellia. Although we are all familiar with the search engine "google," this is another type of "guggul" that has been used for centuries and being explored for its various biological activities. The current review summarizes the traditional uses, chemistry, in vitro and in vivo biological activities, molecular targets, and clinical trials performed with these agents. © 2018 Kunnumakkara, Banik, Bordoloi, Harsha, Sailo, Padmavathi, Roy, Gupta and Aggarwal.
Inflammation, nf-κb, and chronic diseases: How are they linked?
(Begell House Inc., 2020) Ajaikumar B. Kunnumakkara; Bano Shabnam; Sosmitha Girisa; Choudhary Harsha; Kishore Banik; Th. Babita Devi; Ruplekha Choudhury; Henamayee Sahu; Dey Parama; Bethsebie L. Sailo; Krishan Kumar Thakur; Subash C. Gupta; Bharat B. Aggarwal
Most chronic diseases, caused by lifestyle factors, appear to be linked to inflammation. Inflammation is activated mechanistically, and nuclear factor–κB (NF-κB) is a significant mediator. NF-κB, one of the most studied transcription factors, was first identified in the nucleus of B lymphocytes almost three decades ago. This protein has a key function in regulating the human immune system, and its dysregulation has been linked to many chronic diseases including asthma, cancer, diabetes, rheumatoid arthritis, inflammation, and neurological disorders. Physiologically, many cytokines have been discovered that activate NF-κB. Pathologically, environmental carcinogens such as cigarette smoke, radiation, bacteria, and viruses can also activate this transcription factor. NF-κB activation controls expression of more than 500 genes, and most are deleterious to the human body when dysregulated. More than 70,000 articles have been published regarding NF-κB. This review emphasizes the upside and downside of NF-κB in normal and disease conditions and the ways in which we can control this critical transcription factor in patients. © 2020 by Begell House, Inc. www.begellhouse.com.
Is curcumin bioavailability a problem in humans: lessons from clinical trials
(Taylor and Francis Ltd, 2019) Ajaikumar B. Kunnumakkara; Choudhary Harsha; Kishore Banik; Rajesh Vikkurthi; Bethsebie L. Sailo; Devivasha Bordoloi; Subash C. Gupta; Bharat B. Aggarwal
Introduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principal component of turmeric is curcumin and its efficacy has been advocated in various in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem. Areas covered: This article discusses over 200 clinical studies with curcumin that have demonstrated the pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies. Expert opinion: The therapeutic potential of curcumin, as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailability in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin, in combination with other compounds or as formulations, has shown enhanced bioavailability. Hence, bioavailability is not a problem in the curcumin-mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
Long noncoding RNAs in triple-negative breast cancer: A new frontier in the regulation of tumorigenesis
(John Wiley and Sons Inc, 2021) Krishan K. Thakur; Aviral Kumar; Kishore Banik; Elika Verma; Elina Khatoon; Choudhary Harsha; Gautam Sethi; Subash C. Gupta; Ajaikumar B. Kunnumakkara
In recent years, triple-negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%–24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease-free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms. © 2021 Wiley Periodicals LLC
Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives
(Academic Press, 2022) Elina Khatoon; Kishore Banik; Choudhary Harsha; Bethsebie Lalduhsaki Sailo; Krishan Kumar Thakur; Amrita Devi Khwairakpam; Rajesh Vikkurthi; Thengujam Babita Devi; Subash C. Gupta; Ajaikumar B. Kunnumakkara
Despite significant advancements made in the treatment of cancer during the past several decades, it remains one of the leading causes of death worldwide killing approximately 9.6 million people annually. The major challenge for therapeutic success is the development of chemoresistance in cancer cells against conventional chemotherapeutic agents via modulation of numerous survival and oncogenic signaling pathways. Therefore, sensitization of cancer cells to conventional drugs using multitargeted agents that suppress the survival and oncogenic pathways, in single or in combination, is an emerging strategy to overcome drug-resistance. During the last couple of decades, phytochemicals such as curcumin, resveratrol, tocotrienol and quercetin have emerged as potential chemosensitizing agents in cancer cells due to their less toxic and multitargeted properties. Numerous preclinical and clinical studies enumerated their potential to prevent drug resistance and sensitize cancer cells to chemotherapeutic agents by modulating several genes/proteins or pathways that regulate the key factors during the growth and progression of tumors such as inhibition of anti-apoptotic proteins, activation of pro-apoptotic proteins, reduced expression of different transcription factors, chemokines, enzymes, cell adhesion molecules, protein tyrosine kinases and cell cycle regulators. Therefore, natural chemosensitizing agents will have a special place in cancer treatment in the near future. This comprehensive review summarizes data obtained from various in vitro, in vivo and clinical studies to provide a new perspective for the application of agents obtained from “Mother Nature” as potential chemosensitizers for further cancer drug research and development. © 2020 Elsevier Ltd