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Applied and Environmental Microbiology Jul 2020Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation...
Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation by Cyclodextrins (CDs) are generally believed to be carriers for phytosterol delivery and can improve the production of AD and ADD due to their effects on steroid solubilization and alteration in cell wall permeability for steroids. To better understand the mechanisms of CD promotion, we performed proteomic quantification of the effects of hydroxypropyl-β-CD (HP-β-CD) on phytosterol metabolism in TCCC 11978 C2. Perturbations are observed in steroid catabolism and glucose metabolism by adding HP-β-CD in a phytosterol bioconversion system. AD and ADD, as metabolic products of phytosterol, are toxic to cells, with inhibited cell growth and biocatalytic activity. Treatment of mycobacteria with HP-β-CD relieves the inhibitory effect of AD(D) on the electron transfer chain and cell growth. These results demonstrate the positive relationship between HP-β-CD and phytosterol metabolism and give insight into the complex functions of CDs as mediators of the regulation of sterol metabolism. Phytosterols from soybean are low-cost by-products of soybean oil production and, owing to their good bioavailability in mycobacteria, are preferred as the substrates for steroid drug production via biotransformation by However, the low level of production of steroid hormone drugs due to the low aqueous solubility (below 0.1 mmol/liter) of phytosterols limits the commercial use of sterol-transformed strains. To improve the bioconversion of steroids, cyclodextrins (CDs) are generally used as an effective carrier for the delivery of hydrophobic steroids to the bacterium. CDs improve the biotransformation of steroids due to their effects on steroid solubilization and alterations in cell wall permeability for steroids. However, studies have rarely reported the effects of CDs on cell metabolic pathways related to sterols. In this study, the effects of hydroxypropyl-β-CD (HP-β-CD) on the expression of enzymes related to steroid catabolic pathways in were systematically investigated. These findings will improve our understanding of the complex functions of CDs in the regulation of sterol metabolism and guide the application of CDs to sterol production.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Bacterial Proteins; Excipients; Mycobacteriaceae; Phytosterols; Proteomics
PubMed: 32414803
DOI: 10.1128/AEM.00441-20 -
International Journal of Molecular... Oct 2022Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events... (Review)
Review
Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as β-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.
Topics: Oxysterols; Cholesterol, LDL; Soybean Proteins; Polyphenols; Cholesterol, Dietary; Cholesterol; Phytosterols; Immune System; beta-Glucans
PubMed: 36293093
DOI: 10.3390/ijms232012236 -
Combinatorial Chemistry & High... 2021Genus Erythrina belongs to family Fabaceae, which is widely distributed in tropical and subtropical areas. It has been used in both traditional herbal medicines and... (Review)
Review
BACKGROUND
Genus Erythrina belongs to family Fabaceae, which is widely distributed in tropical and subtropical areas. It has been used in both traditional herbal medicines and pharmacological applications. Original research articles and publications on the overview of alkaloids related to this genus are available, but a supportive systematic review account which highlighted phytochemical aspects of other types of secondary metabolites is currently insufficient.
OBJECTIVE
With the utilization of data and information from SCI-Finder, Google Scholar, the Web of Science, Scopus, Science Direct, PubMed, Chemical Abstracts, ACS journals, Springer, Taylor Francis, Bentham Science and IOP Science, the reliable material sources of this systematic review paper were obtained from the literature published from the 1980s to now.
CONCLUSION
A vast amount of data showed that the non-alkaloidal secondary metabolites were obtained from genus Erythrina with various classes of chemical structures. Herein, approximately five hundred constituents were isolated, comprising flavonoids, terpenoids, saponins, phytosterols, phenols, arylbenzofurans, coumarins, alcohols, ceramides, mono-sugars and fatty acid derivatives. In agreement with the previous phytochemical reports on the plants of the family Fabaceae, flavonoids reached a high amount in the plants of genus Erythrina. Numerous biological activity investigations such as anti-bacteria, anti-cancer, anti-virus using isolated compounds from Erythrina species suggested that secondary metabolites of Erythrina plants are now becoming the promising agents for drug developments.
Topics: Erythrina; Fatty Acids; Flavonoids; Humans; Molecular Structure; Phytochemicals; Phytosterols; Phytotherapy; Plant Extracts; Plants, Medicinal; Saponins; Secondary Metabolism; Terpenes
PubMed: 32516097
DOI: 10.2174/1386207323666200609141517 -
Molecules (Basel, Switzerland) Feb 2022Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse... (Review)
Review
Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body's healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.
Topics: Diabetes Mellitus, Type 2; Diet; Humans; Insulin Resistance; Phytosterols; Sterols
PubMed: 35268696
DOI: 10.3390/molecules27051595 -
Nature Communications May 2023Eukaryotes produce highly modified sterols, including cholesterol, essential to eukaryotic physiology. Although few bacterial species are known to produce sterols, de...
Eukaryotes produce highly modified sterols, including cholesterol, essential to eukaryotic physiology. Although few bacterial species are known to produce sterols, de novo production of cholesterol or other complex sterols in bacteria has not been reported. Here, we show that the marine myxobacterium Enhygromyxa salina produces cholesterol and provide evidence for further downstream modifications. Through bioinformatic analysis we identify a putative cholesterol biosynthesis pathway in E. salina largely homologous to the eukaryotic pathway. However, experimental evidence indicates that complete demethylation at C-4 occurs through unique bacterial proteins, distinguishing bacterial and eukaryotic cholesterol biosynthesis. Additionally, proteins from the cyanobacterium Calothrix sp. NIES-4105 are also capable of fully demethylating sterols at the C-4 position, suggesting complex sterol biosynthesis may be found in other bacterial phyla. Our results reveal an unappreciated complexity in bacterial sterol production that rivals eukaryotes and highlight the complicated evolutionary relationship between sterol biosynthesis in the bacterial and eukaryotic domains.
Topics: Sterols; Bacteria; Cholesterol; Phytosterols; Eukaryota
PubMed: 37217541
DOI: 10.1038/s41467-023-38638-8 -
Scientific Reports Aug 2021Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is...
Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Blockade of phytosterol absorption either by therapeutic inhibition or by genetic inactivation of NPC1L1 prevented the induction of inflammation and arrhythmogenesis. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These comorbidities provide insight into the underlying pathophysiological mechanism for phytosterolemia-associated risk of sudden cardiac death.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Animals; Arrhythmias, Cardiac; Cytokines; Death, Sudden, Cardiac; Fibrosis; Heart Failure; Hypercholesterolemia; Inflammation; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols
PubMed: 34465831
DOI: 10.1038/s41598-021-96936-x -
Biotechnology Advances Dec 2021Steroid-based drugs have been developed as the second largest medical category in pharmaceutics. The well-established route of steroid industry includes two steps: the... (Review)
Review
Steroid-based drugs have been developed as the second largest medical category in pharmaceutics. The well-established route of steroid industry includes two steps: the conversion of natural products with a steroid framework to steroid-based drug intermediates and the synthesis of varied steroid-based drugs from steroid-based drug intermediates. The biosynthesis of steroid-based drug intermediates from phytosterols by Mycolicibacterium cell factories bypasses the potential undersupply of diosgenin in the traditional steroid chemical industry. Moreover, the biosynthesis route shows advantages on multiple steroid-based drug intermediate products, more ecofriendly processes, and consecutive reactions carried out in one operation step and in one pot. Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD) and 9-hydroxyandrostra-4-ene-3,17-dione (9-OH-AD) are the representative steroid-based drug intermediates synthesized by mycolicibacteria. Other steroid metabolites of mycolicibacteria, like 4-androstene-17β-ol-3-one (TS), 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), 22-hydroxy-23,24-bisnorchol-1,4-diene-3-one (1,4-HBC), 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one (9-OH-HBC), 3aα-H-4α-(3'-propionic acid)-7aβ-methylhexahydro-1,5-indanedione (HIP) and 3aα-H-4α-(3'-propionic acid)-5α-hydroxy-7aβ-methylhexahydro-1-indanone-δ-lactone (HIL), also show values as steroid-based drug intermediates. To improve the bio-production efficiency of the steroid-based drug intermediates, mycolicibacterial strains and biotransformation processes have been continuously studied in the past decades. Many mycolicibacteria that accumulate steroid drug intermediates have been isolated, and subsequently optimized by conventional mutagenesis and genetic engineering. Especially, with the clarification of the mycolicibacterial steroid metabolic pathway and the developments on gene editing technologies, rational design is becoming an important measure for the construction and optimization of engineered mycolicibacteria strains that produce steroid-based drug intermediates. Hence, by reviewing researches in the past two decades, this article updates the overall process of steroid metabolism in mycolicibacteria and provides comprehensive schemes for the rational construction of mycolicibacterial strains that accumulate steroid-based drug intermediates. In addition, the special strategies for the bioconversion of highly hydrophobic steroid in aqueous media are discussed as well.
Topics: Biotransformation; Metabolic Networks and Pathways; Pharmaceutical Preparations; Phytosterols; Steroids
PubMed: 34710554
DOI: 10.1016/j.biotechadv.2021.107860 -
Journal of Atherosclerosis and... Oct 2023
Topics: Humans; Cholesterol; Biomarkers; Sitosterols; Intestinal Absorption; Phytosterols
PubMed: 36709995
DOI: 10.5551/jat.ED225 -
Pakistan Journal of Biological Sciences... Jan 2022<b>Background and Objective:</b> Lemongrass (<i>Cymbopogon citratus</i>) and turmeric (<i>Curcuma longa</i>) are widely used by the...
<b>Background and Objective:</b> Lemongrass (<i>Cymbopogon citratus</i>) and turmeric (<i>Curcuma longa</i>) are widely used by the community for traditional medicinal spices and cooking spices. In the era of the COVID-19 pandemic, people use lemongrass and turmeric to increase immunity and protect the body from infection with the SARS-CoV-2 virus. However, the antiviral mechanisms have not been studied much. This study aims to predict the bioactivity of the phytosterol compounds of lemongrass and turmeric for COVID-19 therapy through inhibition of 3C-like protease (3CLPro) <i>in silico</i>. <b>Materials and Methods:</b> The 3CLPro protein 3D structure was downloaded from the PDB database with the access code 2ZU2 and the phytosterol compounds of lemongrass and turmeric were taken from PubChem. A total of 59 total phytosterol compounds from turmeric and lemongrass were screened for their bioactivity as an antiviral by using online PASS. Compounds with a high activating potential (Pa) were interacted with 3CLPro protein with the PyRx program and analyzed by Discovery Studio version 19.0 and LigPlus. <b>Results:</b> A total of 22 total phytosterol compounds were identified as potential antiviral agents. Based on the Pa value, 15 phytosterol compounds have the potential to act as inhibitor agents for 3CLPro SARS-CoV-2. The phytosterol compounds of lemongrass and turmeric bind to the 3CLPro protein in the N-finger domain region and the A and B domain inhibitors connect residues of the 3CLPro protein. The phytosterols of lemongrass and turmeric show a low binding affinity with 3CLPro SARS-CoV-2, indicating a strong interaction between ligand and protein. The inhibition of phytosterols against 3CLPro protein can be used as a basis for determining candidates for COVID-19 therapeutic agents. <b>Conclusion:</b> The phytosterol compounds contained in lemongrass and turmeric have the potential to act as 3CLPro inhibitors. Further studies both <i>in vitro</i> and <i>in vivo</i> need to be done to prove the inhibitory potential of phytosterol compounds.
Topics: Antiviral Agents; Curcuma; Cymbopogon; Humans; Pandemics; Peptide Hydrolases; Phytosterols; SARS-CoV-2; Viral Proteins; COVID-19 Drug Treatment
PubMed: 36098090
DOI: 10.3923/pjbs.2022.867.874 -
Advances in Experimental Medicine and... 2024The characteristic steroid skeleton, with its 4-ringed 17-carbon structure, is one of the most recognizable organic compounds in biochemistry. In the presence of a... (Review)
Review
The characteristic steroid skeleton, with its 4-ringed 17-carbon structure, is one of the most recognizable organic compounds in biochemistry. In the presence of a hydroxyl ion bound to the third carbon, this structure is defined as a "sterol" (chemical formula: CHO). The hydroxyl group provides a hydrophilic site for the otherwise hydrophobic molecule, yielding an amphipathic lipid, which is a vital property for cellular function. It is crucial to remark that the term "steroid" describes a larger group of compounds that often retain the hydroxyl group but are primarily characterized by methyl groups, double bonds in the rings, and an aliphatic side-chain extending from the 17th carbon. In addition to serving various structural roles in the cellular membrane, sterols and steroids contribute to cellular and systemic functions as messengers, hormones, and regulators of several critical metabolic pathways.Sterol nomenclature is often confusing, partly due to structural complexity and partly due to the sheer number of different compounds that fall under the definition. Fortunately, the foremost sterols of interest in biochemistry are much fewer, and therefore, these lipids have been defined and studied vigorously. With the renaissance of lipid research during the 1990s and 2000s, many different metabolites of sterols, and more specifically phytosterols, were found to be associated with various diseases and conditions, including cardiovascular disease, hypercholesterolemia, cancer, obesity, inflammation, diabetes, and inborn errors of metabolism; thus, it is evident that the ever-evolving research in this field has been, and will continue to be, exceedingly productive.With respect to inflammation and inflammatory diseases, plant-based sterols (i.e., phytosterols) have gained considerable fame due to their anti-inflammatory and cholesterol-lowering effects demonstrated by experimental and clinical research. Besides, the exceptional pharmacological benefits of these sterols, which operate as antioxidant, antidiabetic, and anti-atherosclerotic agents, have been the subject of various investigations. While the underlying mechanisms necessitate further research, the possible function of phytosterols in improving health outcomes is an important topic to explore.In this regard, the current review aims to offer comprehensive information on the therapeutic potential of plant-based sterols in the context of human health, with a focus on preclinical effects, bioavailability, and clinical use.
Topics: Humans; Sterols; Phytosterols; Cholesterol; Inflammation; Carbon
PubMed: 38036884
DOI: 10.1007/978-3-031-43883-7_13