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Kaempferol as a Dietary Anti-Inflammatory Agent: Current Therapeutic Standing
Inflammation is a physiological response to different pathological, cellular or vascular damages due to physical, chemical or mechanical trauma. It is characterized by pain, redness, heat and swelling. Current natural drugs are carefully chosen as a novel therapeutic strategy for the management of inflammatory diseases. Different phytochemical constituents are present in natural products. These phytochemicals have high efficacy both in vivo and in vitro. Among them, flavonoids occur in many foods, vegetables and herbal medicines and are considered as the most active constituent, having the ability to attenuate inflammation. Kaempferol is a polyphenol that is richly found in fruits, vegetables and herbal medicines. It is also found in plant-derived beverages. Kaempferol is used in the management of various ailments but there is no available review article that can summarize all the natural sources and biological activities specifically focusing on the anti-inflammatory effect of kaempferol. Therefore, this article is aimed at providing a brief updated review of the literature regarding the anti-inflammatory effect of kaempferol and its possible molecular mechanisms of action. Furthermore, the review provides the available updated literature regarding the natural sources, chemistry, biosynthesis, oral absorption, metabolism, bioavailability and therapeutic effect of kaempferol.
Journal Article
Natural products in drug discovery: advances and opportunities
Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.
Journal Article
Patient-focused network integration in biopharma : strategic imperatives for the years ahead
\"Preface This book started out as an interesting set of conversations with some very insightful and intelligent people. For twenty-five years, I've studied supply chains in almost every industry, including oil and gas, automotive, electronics, industrial production, and even financial services. And every time I met with executives, I met with the same statements: \"We're different-- you don't understand.\" But in the end, after spending enough time with these executives, it became clear that the same principles of supply chain management applied. Perhaps a different context, different terminology, but in the end, the same rules applied. When I started dabbling in healthcare, I originally encountered the same sets of objections. \"Healthcare is different,\" I would hear, \"After all, you have to consider the patient.\" But as I spent more and more time with healthcare executives, I only rarely heard the patient mentioned in the discussion. More often than not, the discussion focused on compliance, reimbursement, diagnosis-related groups (DRGs), and other terms that had very little to do with patient care. And as I studied the industry more, it became clear that organizations in the healthcare value chain, from the patient through hospitals, wholesalers, through insurance payers, manufacturers, and finally research and development (R&D), were not very well connected at all\"-- Provided by publisher.
Book
The re-emergence of natural products for drug discovery in the genomics era
Key Points
Natural products continue to be an important source of leads for new medicines, despite reduced interest from large pharmaceutical companies.
Screening collections of natural products can be assembled economically to provide excellent coverage of drug-like chemical space and in formats that are compatible with high-throughput bioassays.
Metabolomics enables the rapid identification of novel compounds in complex mixtures of natural products and also provides a means to monitor the production of target molecules during fermentation or other production processes.
Metagenomics and other genetic engineering techniques are enabling the production of target compounds in convenient systems, breaking away from the bottleneck otherwise created by microorganisms that are difficult to culture.
Examples of recent and current applications of natural products are described for the discovery of antimicrobials and for inhibitors of protein–protein interactions, particularly as anticancer agents.
The screening of natural products for lead molecules is an attractive strategy, as most natural products fall within biologically relevant chemical space. In this Review, Harvey, Edrada-Ebel and Quinn discuss how advanced screening, metabolomics and metagenomics approaches can be used in the identification, validation and production of naturally sourced compounds, and highlight examples of naturally derived antimicrobials and inhibitors of protein–protein interactions.
Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein–protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.
Journal Article
Marine Natural Products: A Source of Novel Anticancer Drugs
Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.
Journal Article
Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases
The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA) in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases.
Journal Article
Plant Secondary Metabolites Produced in Response to Abiotic Stresses Has Potential Application in Pharmaceutical Product Development
Plant secondary metabolites (PSMs) are vital for human health and constitute the skeletal framework of many pharmaceutical drugs. Indeed, more than 25% of the existing drugs belong to PSMs. One of the continuing challenges for drug discovery and pharmaceutical industries is gaining access to natural products, including medicinal plants. This bottleneck is heightened for endangered species prohibited for large sample collection, even if they show biological hits. While cultivating the pharmaceutically interesting plant species may be a solution, it is not always possible to grow the organism outside its natural habitat. Plants affected by abiotic stress present a potential alternative source for drug discovery. In order to overcome abiotic environmental stressors, plants may mount a defense response by producing a diversity of PSMs to avoid cells and tissue damage. Plants either synthesize new chemicals or increase the concentration (in most instances) of existing chemicals, including the prominent bioactive lead compounds morphine, camptothecin, catharanthine, epicatechin-3-gallate (EGCG), quercetin, resveratrol, and kaempferol. Most PSMs produced under various abiotic stress conditions are plant defense chemicals and are functionally anti-inflammatory and antioxidative. The major PSM groups are terpenoids, followed by alkaloids and phenolic compounds. We have searched the literature on plants affected by abiotic stress (primarily studied in the simulated growth conditions) and their PSMs (including pharmacological activities) from PubMed, Scopus, MEDLINE Ovid, Google Scholar, Databases, and journal websites. We used search keywords: “stress-affected plants,” “plant secondary metabolites, “abiotic stress,” “climatic influence,” “pharmacological activities,” “bioactive compounds,” “drug discovery,” and “medicinal plants” and retrieved published literature between 1973 to 2021. This review provides an overview of variation in bioactive phytochemical production in plants under various abiotic stress and their potential in the biodiscovery of therapeutic drugs. We excluded studies on the effects of biotic stress on PSMs.
Journal Article
Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities
Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article covers different indications, treatment settings, administration volumes, and injection devices. We focus on biotherapeutics in rheumatoid arthritis (RA), immunoglobulin-replacement therapy in primary immunodeficiency (PI), beta interferons in multiple sclerosis (MS), and monoclonal antibodies (mAbs) in oncology. While most subcutaneous biotherapeutics in RA, PI, and MS are self-administered at home, mAbs for oncology are still only approved for administration in a healthcare setting. Beside concerns around the safety of biotherapeutics in oncology, a key challenge for self-administration in this area is that doses and dosing volumes can be comparatively large; however, this difficulty has recently been overcome to some extent by the development of high-concentration solutions, the use of infusion pumps, and the coadministration of the dispersion enhancer hyaluronidase. Furthermore, given the increasing number of biotherapeutics being considered for combination therapy and the high dosing complexity associated with these, especially when administered intravenously, subcutaneous delivery of fixed-dose combinations might be an alternative that will diminish these burdens on healthcare systems.
Journal Article