Browsing by Author "Sahdeo Prasad"

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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).
Inflammation and ROS in arthritis: Management by Ayurvedic medicinal plants
(Royal Society of Chemistry, 2021) Sahdeo Prasad; Alok Kulshreshtha; Rajiv Lall; Subash C. Gupta
Chronic joint inflammatory disorders like osteoarthritis and rheumatoid arthritis, which are manifested by joint dysfunction, show an upsurge in inflammation and oxidative stress. Although conventional anti-arthritic drugs are being used to relieve pain from arthritic symptoms, they usually cause severe side effects. Traditionally used Ayurvedic medicinal plants are a promising alternative for the management of arthritic symptoms, as they are safe and effective. Ayurvedic medicinal plants improve arthritic symptoms by reducing joint tenderness, joint pain, swelling, bone and cartilage damage, and increasing knee flexion, walking distance and sports activities. These beneficial effects of Ayurvedic medicinal plants on arthritis are mediated through various cellular mechanisms including inhibition of the inflammatory markers NF-?B, cytokines, adipokines, PGE2, NO, iNOS, COX-2, and MMPs and induction of antioxidant status by decreasing free radicals, lipid peroxidation, and myeloperoxidase, and increasing antioxidant enzymes, Nrf2, and HO-1. Thus, a strategy requires using these Ayurvedic medicinal plants to treat arthritis. This article describes the status of inflammation and oxidative stress in arthritic conditions. We also provide evidence that Ayurvedic medicinal plants and their bioactive components are highly effective in improving arthritic symptoms. © 2021 The Royal Society of Chemistry.
Neem (Azadirachta indica): An indian traditional panacea with modern molecular basis
(Elsevier GmbH, 2017) Subash Chandra Gupta; Sahdeo Prasad; Amit K. Tyagi; Ajaikumar B. Kunnumakkara; Bharat B. Aggarwal
Background For centuries, agents derived from natural sources (mother nature), especially plants have been the primary source of medicine. Neem, also referred to as Azadirachta indica is one such plant that has been so named because it provides freedom from all diseases, and used for thousands of years in Indian and African continents. Different parts of the plant including flowers, leaves, seeds and bark have been used to treat both acute and chronic human diseases; and used as insecticide; antimicrobial, larvicidal, antimalarial, antibacterial, antiviral, and spermicidal. Purpose What is there in neem and how it manifests its wide variety of effects is the focus of this review. How neem and its constituents modulate various cellular pathways is discussed. The animal and human studies carried out with neem and its constituents is also discussed. Conclusion Over 1000 research articles published on neem has uncovered over 300 structurally diverse constituents, one third of which are limonoids including nimbolide, azadarachtin, and gedunin. These agents manifest their effects by modulating multiple cell signaling pathways. © 2017
Oxidative Stress and Cancer: Advances and Challenges
(Hindawi Limited, 2016) Sahdeo Prasad; Subash C. Gupta; Manoj K. Pandey; Amit K. Tyagi; Lokesh Deb
[No abstract available]
Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals
(Elsevier Ireland Ltd, 2017) Sahdeo Prasad; Subash C. Gupta; Amit K. Tyagi
Extensive research over the past half a century indicates that reactive oxygen species (ROS) play an important role in cancer. Although low levels of ROS can be beneficial, excessive accumulation can promote cancer. One characteristic of cancer cells that distinguishes them from normal cells is their ability to produce increased numbers of ROS and their increased dependence on an antioxidant defense system. ROS are produced as a byproduct intracellularly by mitochondria and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs, xenobiotics, and radiation. ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to cellular transformation, inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic changes in genes, which is helpful in diagnosing diseases. This review considers the role of ROS in the various stages of cancer development. Finally, we provide evidence that nutraceuticals derived from Mother Nature are highly effective in eliminating cancer cells. © 2016 Elsevier Ireland Ltd
Serendipity in Cancer Drug Discovery: Rational or Coincidence?
(Elsevier Ltd, 2016) Sahdeo Prasad; Subash C. Gupta; Bharat B. Aggarwal
Novel drug development leading to final approval by the US FDA can cost as much as two billion dollars. Why the cost of novel drug discovery is so expensive is unclear, but high failure rates at the preclinical and clinical stages are major reasons. Although therapies targeting a given cell signaling pathway or a protein have become prominent in drug discovery, such treatments have done little in preventing or treating any disease alone because most chronic diseases have been found to be multigenic. A review of the discovery of numerous drugs currently being used for various diseases including cancer, diabetes, cardiovascular, pulmonary, and autoimmune diseases indicates that serendipity has played a major role in the discovery. In this review we provide evidence that rational drug discovery and targeted therapies have minimal roles in drug discovery, and that serendipity and coincidence have played and continue to play major roles. The primary focus in this review is on cancer-related drug discovery. © 2016 Elsevier Ltd.
γ-Tocotrienol suppresses growth and sensitises human colorectal tumours to capecitabine in a nude mouse xenograft model by down-regulating multiple molecules
(Nature Publishing Group, 2016) Sahdeo Prasad; Subash C. Gupta; Amit K. Tyagi; Bharat B. Aggarwal
Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide and even develops resistance to chemotherapeutic agents over time. As a result survival for patients with CRC remains poor.Method:We investigated both in vitro and in vivo effects of γ-tocotrienol (γ-T3) alone and in combination with capecitabine. Apoptosis and cytotoxicity assays were performed by MTT and FACS analysis, whereas expression of proteins was investigated using western blotting and immunohistochemistry. Results: The γ-T3 inhibited the proliferation of CRC cells with wild-type or mutated KRAS. It also induced apoptosis, inhibited colony formation, and suppressed key regulators of cell survival, cell proliferation, invasion, angiogenesis, and metastasis. Furthermore, γ-T3 enhanced the anticancer effects of capecitabine in CRC cells. In a nude mouse xenograft model of human CRC, oral administration of γ-T3 inhibited tumour growth and enhanced the antitumour efficacy of capecitabine. Western blot and immunohistochemical analysis results indicated that expression of Ki-67, cyclin D1, MMP-9, CXCR4, NF-κB/p65, and VEGF was lower in tumour tissue from the combination treatment group. Combination treatment also downregulated NF-κB and NF-κB-regulated gene products. Conclusions: Our findings suggest that γ-T3 inhibited the growth of human CRC and sensitised CRC to capecitabine by regulating proteins linked to tumourigenesis. © 2016 Cancer Research UK.