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Nutrients Jan 2023Phytoestrogens are literally estrogenic substances of plant origin. Although these substances are useful for plants in many aspects, their estrogenic properties are... (Review)
Review
Phytoestrogens are literally estrogenic substances of plant origin. Although these substances are useful for plants in many aspects, their estrogenic properties are essentially relevant to their predators. As such, phytoestrogens can be considered to be substances potentially dedicated to plant-predator interaction. Therefore, it is not surprising to note that the word phytoestrogen comes from the early discovery of estrogenic effects in grazing animals and humans. Here, several compounds whose activities have been discovered at nutritional concentrations in animals and humans are examined. The substances analyzed belong to several chemical families, i.e., the flavanones, the coumestans, the resorcylic acid lactones, the isoflavones, and the enterolignans. Following their definition and the evocation of their role in plants, their metabolic transformations and bioavailabilities are discussed. A point is then made regarding their health effects, which can either be beneficial or adverse depending on the subject studied, the sex, the age, and the physiological status. Toxicological information is given based on official data. The effects are first presented in humans. Animal models are evoked when no data are available in humans. The effects are presented with a constant reference to doses and plausible exposure.
Topics: Humans; Animals; Phytoestrogens; Isoflavones; Plants; Estrogens; Models, Animal
PubMed: 36678189
DOI: 10.3390/nu15020317 -
Antioxidants (Basel, Switzerland) Apr 2022Pterocarpans and related polyphenolics are known as promising neuroprotective agents. We used models of rotenone-, paraquat-, and 6-hydroxydopamine-induced neurotoxicity...
Pterocarpans and related polyphenolics are known as promising neuroprotective agents. We used models of rotenone-, paraquat-, and 6-hydroxydopamine-induced neurotoxicity to study the neuroprotective activity of polyphenolic compounds from and their effects on mitochondrial membrane potential. We isolated 11 polyphenolic compounds: a novel coumestan lespebicoumestan A () and a novel stilbenoid 5'-isoprenylbicoloketon () as well as three previously known pterocarpans, two pterocarpens, one coumestan, one stilbenoid, and a dimeric flavonoid. Pterocarpans and , stilbenoid , and dimeric flavonoid significantly increased the percentage of living cells after treatment with paraquat (PQ), but only pterocarpan slightly decreased the ROS level in PQ-treated cells. Pterocarpan and stilbenoid were shown to effectively increase mitochondrial membrane potential in PQ-treated cells. We showed that pterocarpans and , containing a 3'-methyl-3'-isohexenylpyran ring; pterocarpens and , with a double bond between C-6a and C-11a; and coumestan significantly increased the percentage of living cells by decreasing ROS levels in 6-OHDA-treated cells, which is in accordance with their rather high activity in DPPH and FRAP tests. Compounds and effectively increased the percentage of living cells after treatment with rotenone but did not significantly decrease ROS levels.
PubMed: 35453394
DOI: 10.3390/antiox11040709 -
Frontiers in Bioengineering and... 2023The isoflavonoid derivatives, pterocarpans and coumestans, are explored for multiple clinical applications as osteo-regenerative, neuroprotective and anti-cancer agents.... (Review)
Review
The isoflavonoid derivatives, pterocarpans and coumestans, are explored for multiple clinical applications as osteo-regenerative, neuroprotective and anti-cancer agents. The use of plant-based systems to produce isoflavonoid derivatives is limited due to cost, scalability, and sustainability constraints. Microbial cell factories overcome these limitations in which model organisms such as offer an efficient platform to produce isoflavonoids. Bioprospecting microbes and enzymes can provide an array of tools to enhance the production of these molecules. Other microbes that naturally produce isoflavonoids present a novel alternative as production chassis and as a source of novel enzymes. Enzyme bioprospecting allows the complete identification of the pterocarpans and coumestans biosynthetic pathway, and the selection of the best enzymes based on activity and docking parameters. These enzymes consolidate an improved biosynthetic pathway for microbial-based production systems. In this review, we report the state-of-the-art for the production of key pterocarpans and coumestans, describing the enzymes already identified and the current gaps. We report available databases and tools for microbial bioprospecting to select the best production chassis. We propose the use of a holistic and multidisciplinary bioprospecting approach as the first step to identify the biosynthetic gaps, select the best microbial chassis, and increase productivity. We propose the use of microalgal species as microbial cell factories to produce pterocarpans and coumestans. The application of bioprospecting tools provides an exciting field to produce plant compounds such as isoflavonoid derivatives, efficiently and sustainably.
PubMed: 37187887
DOI: 10.3389/fbioe.2023.1154779 -
The Journal of Nutritional Biochemistry Apr 2023Flavonoids are a major group of phytoestrogens associated with physiological effects, and ecological and social impacts. Although the estrogenic activity of flavonoids... (Review)
Review
Flavonoids are a major group of phytoestrogens associated with physiological effects, and ecological and social impacts. Although the estrogenic activity of flavonoids was reported by researchers in the fields of medical, environmental and food studies, their molecular mechanisms of action have not been comprehensively reviewed. The estrogenic activity of the respective classes of flavonoids, anthocyanidins/anthocyanins, 2-arylbenzofurans/3-arylcoumarins/α-methyldeoxybenzoins, aurones/chalcones/dihydrochalcones, coumaronochromones, coumestans, flavans/flavan-3-ols/flavan-4-ols, flavanones/dihydroflavonols, flavones/flavonols, homoisoflavonoids, isoflavans, isoflavanones, isoflavenes, isoflavones, neoflavonoids, oligoflavonoids, pterocarpans/pterocarpenes, and rotenone/rotenoids, was summarized through a comprehensive literature search, and their structure-activity relationship, biological activities, signaling pathways, and applications were discussed. Although the respective classes of flavonoids contained at least one chemical mimicking estrogen, the mechanisms varied, such as those with estrogenic, anti-estrogenic, non-estrogenic, and biphasic activities, and additional activities through crosstalk/bypassing, which exert biological activities through cell signaling pathways. Such mechanistic variations of estrogen action are not limited to flavonoids and are observed among other broad categories of chemicals, thus this group of chemicals can be termed as the "estrogenome". This review article focuses on the connection of estrogen action mainly between the outer and the inner environments, which represent variations of chemicals and biological activities/signaling pathways, respectively, and form the basis to understand their applications. The applications of chemicals will markedly progress due to emerging technologies, such as artificial intelligence for precision medicine, which is also true of the study of the estrogenome including estrogenic flavonoids.
Topics: Flavonoids; Anthocyanins; Artificial Intelligence; Estrogens; Isoflavones
PubMed: 36509337
DOI: 10.1016/j.jnutbio.2022.109250 -
Biomedicine & Pharmacotherapy =... Dec 2023Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of... (Review)
Review
Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.
Topics: Animals; Humans; Male; Breast Neoplasms; Estrogens; Mammals; Phytoestrogens; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Steroids; Phytosterols
PubMed: 37944439
DOI: 10.1016/j.biopha.2023.115783 -
Journal of the American College of... May 2000Coronary artery disease is the leading overall cause of mortality for women and increases dramatically after menopause. Estrogen has many beneficial cardiovascular... (Review)
Review
Coronary artery disease is the leading overall cause of mortality for women and increases dramatically after menopause. Estrogen has many beneficial cardiovascular actions although concerns have been raised about its effects on the progression of breast and uterine neoplasms and its tendency to increase coagulability. Selective estrogen agonists may be superior to conventional estrogens. A dietary source of a partial estrogen agonist is the plant-based group of phytoestrogens, which include isoflavones, lignans and coumestans. Phytoestrogens have a similar structure to estradiol and have weak affinity for the estrogen receptor. Epidemiologic data indicate that women ingesting high amounts of phytoestrogens, particularly as isoflavones in soy products, have less cardiovascular disease, breast and uterine cancer and menopausal symptoms than those eating Western diets. Preclinical and clinical studies have found that isoflavones have lipid-lowering effects as well as the ability to inhibit low-density lipoprotein oxidation. They have been shown to normalize vascular reactivity in estrogen-deprived primates. Furthermore, phytoestrogens have antineoplastic effects with inhibition of cellular proliferation as well as angiogenesis, properties that could be protective against cancer development. Finally, menopausal symptoms and bone density may be favorably influenced by phytoestrogens. In summary, phytoestrogens, in the form of dietary isoflavones, represent a new area to explore in pursuit of nutritional approaches to cardiovascular protection.
Topics: Aged; Coronary Disease; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Middle Aged; Phytoestrogens; Plant Preparations; Glycine max; Survival Rate; Treatment Outcome
PubMed: 10807439
DOI: 10.1016/s0735-1097(00)00590-8 -
Animals : An Open Access Journal From... Oct 2022Legume crops and pastures have a high economic value in Australia. However, legume species commonly used for grazing enterprises have been identified to produce high... (Review)
Review
Legume crops and pastures have a high economic value in Australia. However, legume species commonly used for grazing enterprises have been identified to produce high concentrations of phytoestrogens. These compounds are heterocyclic phenolic, and are similar in structure to the mammalian estrogen, 17β-estradiol. The biological activity of the various phytoestrogen types; isoflavones, lignans and coumestans, are species-specific, although at concentrations of 25 mg/kg of dry matter each of the phytoestrogen types affect reproductive functions in grazing livestock. The impacts upon fertility in grazing livestock such as cattle and sheep, vary greatly over length of exposure time, age and health of animal and the stress stimuli the plant is exposed to. More recently, research into the other effects that phytoestrogens may have upon metabolism, immune capacity and growth and performance of grazing livestock has been conducted. Potential new benefits for using these phytoestrogens, such as daidzein and genistein, have been identified by observing the stimulation of production in lymphocytes and other antibody cells. Numerous isoflavones have also been recognized to promote protein synthesis, increase the lean meat ratio, and increase weight gain in cattle and sheep. In Australia, the high economic value of legumes as pasture crops in sheep and cattle production enterprises requires proactive management strategies to mitigate risk associated with potential loss of fertility associated with inclusion of pasture legumes as forages for grazing livestock.
PubMed: 36230450
DOI: 10.3390/ani12192709 -
Biomolecules Nov 2021(L.) L. (Syn.: (L.) Hassak, Family: Asteraceae) is an important medicinal plant in the tropical and subtropical regions. It is widely used in treating various diseases... (Review)
Review
(L.) L. (Syn.: (L.) Hassak, Family: Asteraceae) is an important medicinal plant in the tropical and subtropical regions. It is widely used in treating various diseases of skin, liver and stomach in India, Nepal, Bangladesh, and other countries. The main aim of this review was to collect and analyze the available information on traditional uses, phytoconstituents, and biological activities of . The scientific information was collected from the online bibliographic databases such as Scopus, MEDLINE/PubMed, Google Scholar, SciFinder, etc. and books and proceedings. The active phytochemicals were coumestan derivatives, phenolic acid derivatives, flavonoids, triterpenoid and steroid saponins, substituted thiophenes, etc. Various extracts and isolated compounds of showed a wide range of biological activities such as antimicrobial, anticancer, hepatoprotective, neuroprotective and hair growth promoting activities. Relatively a few studies have been performed to reveal the exact phytoconstituents responsible for their corresponding pharmacological activities. Future studies should focus on detailed mechanism based studies using animal models and clinical studies.
Topics: Asteraceae; Eclipta; Medicine, Traditional
PubMed: 34827736
DOI: 10.3390/biom11111738 -
Journal of the American Chemical Society Oct 2022With the large number of Pd(II)-catalyzed C-H activation reactions of native substrates developed in the past decade, the development of catalysts to enable the use of...
With the large number of Pd(II)-catalyzed C-H activation reactions of native substrates developed in the past decade, the development of catalysts to enable the use of green oxidants under safe and practical conditions has become an increasingly important challenge. Notably, the compatibility of Pd(II) catalysts with sustainable aqueous HO has been a long-standing challenge in catalysis including Wacker-type oxidations. We report herein a bifunctional bidentate carboxyl-pyridone (CarboxPyridone) ligand that enables room-temperature Pd-catalyzed C-H hydroxylation of a broad range of benzoic and phenylacetic acids with an industry-compatible oxidant, aqueous hydrogen peroxide (35% HO). The scalability of this methodology is demonstrated by a 1000 mmol scale reaction of ibuprofen (206 g) using only a 1 mol % Pd catalyst loading. The utility of this protocol is further illustrated through derivatization of the products and synthesis of polyfluorinated natural product coumestan and pterocarpene from phenol intermediates prepared using this methodology.
Topics: Biological Products; Catalysis; Hydrogen Peroxide; Hydroxylation; Ibuprofen; Ligands; Oxidants; Palladium; Phenols; Phenylacetates; Pyridones; Temperature; Water
PubMed: 36137252
DOI: 10.1021/jacs.2c08332 -
Antimicrobial Agents and Chemotherapy May 2023Polyketide synthase 13 (Pks13) is an important enzyme found in () that condenses two fatty acyl chains to produce α-alkyl β-ketoesters, which in turn serve as the...
Polyketide synthase 13 (Pks13) is an important enzyme found in () that condenses two fatty acyl chains to produce α-alkyl β-ketoesters, which in turn serve as the precursors for the synthesis of mycolic acids that are essential building blocks for maintaining the cell wall integrity of Coumestan derivatives have recently been identified in our group as a new chemotype that exert their antitubercular effects via targeting of Pks13. These compounds were active on both drug-susceptible and drug-resistant strains of as well as showing low cytotoxicity to healthy cells and a promising selectivity profile. No cross-resistance was found between the coumestan derivatives and first-line TB drugs. Here we report that treatment of bacilli with 15 times the MIC of compound , an optimized lead coumestan compound, resulted in a colony forming unit (CFU) reduction from 6.0 log units to below the limit of detection (1.0 log units) per mL culture, demonstrating a bactericidal mechanism of action. Single dose (10 mg/kg) pharmacokinetic studies revealed favorable parameters with a relative bioavailability of 19.4%. In a mouse infection and chemotherapy model, treatment with showed dose-dependent mono-therapeutic activity, whereas treatment with in combination with rifampin showed clear synergistic effects. Together these data suggest that coumestan derivatives are promising agents for further TB drug development.
PubMed: 33558290
DOI: 10.1128/AAC.02190-20