BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

INTRODUCTION: Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. MATERIALS AND METHODS: Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. RESULTS: In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. CONCLUSIONS: BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems.

Attenuation of chromium (VI) and arsenic (III)-induced oxidative stress and hepatic apoptosis by phloretin, biochanin-A, and coenzyme Q10 via activation of SIRT1/Nrf2/HO-1/NQO1 signaling.

Heavy metal contamination is an alarming concern on a global scale, as drinking tainted water significantly increases human susceptibility to heavy metals. In a realistic scenario, humans are often exposed to a combination of harmful chemicals rather than a single toxicant. Phloretin (PHL), biochanin-A (BCA), and coenzyme Q10 (CoQ10) are bioactive compounds owning plentiful pharmacological properties. Henceforth, the current research explored the putative energizing effects of selected nutraceuticals in combined chromium (Cr) and arsenic (As) intoxicated Swiss albino mice. Potassium dichromate (75 ppm) and sodium meta-arsenite (100 ppm) were given in the drinking water to induce hepatotoxicity, conjugated with PHL and BCA (50 mg/kg each), and CoQ10 (10 mg/kg) intraperitoneally for 2 weeks. After the statistical evaluation, it was observed that the hepato-somatic index, metal load, and antioxidant activity (lipid peroxidation and protein carbonyl content) increased along with the concomitant decrease in the antioxidants (catalase, glutathione-S-transferase, superoxide dismutase, reduced glutathione, and total thiol) in the Cr and As intoxicated mice. Additionally, light microscopy observations, DNA breakages, decreased silent information regulator 1 (SIRT1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) gene expressions, together with stimulated apoptotic cell death manifested by the increased expressions of caspase 8 and caspase 3, thus, proved consistency with the aforementioned outcomes. Importantly, the treatment with nutraceuticals not only restored the antioxidant activity but also favorably altered the expressions of SIRT1, Nrf2, HO-1, and NQO1 signaling and apoptosis markers. These findings highlight the crucial role of the PHL, BCA, and CoQ10 combination in reducing Cr and As-induced hepatotoxicity in mice. By averting the triggered apoptosis in conjunction with oxidative stress, this combination increases the SIRT1, Nrf2, HO-1, and NQO1 signaling, thereby reassuringly maintaining the cellular equilibrium.

O-Methylated Isoflavones Induce nod Genes of Mesorhizobium ciceri and Pratensein Promotes Nodulation in Chickpea.

Legume plants form symbiotic relationships with rhizobia, which allow plants to utilize atmospheric nitrogen as a nutrient. This symbiosis is initiated by secretion of specific signaling metabolites from the roots, which induce the expression of nod genes in rhizobia. These metabolites are called nod gene inducers (NGIs), and various flavonoids have been found to act as NGIs. However, NGIs of chickpea, the second major pulse crop, remain elusive. We conducted untargeted metabolome analysis of chickpea root exudates to explore metabolites with increased secretion under nitrogen deficiency. Principal component (PC) analysis showed a clear difference between nitrogen deficiency and control, with PC1 alone accounting for 37.5% of the variance. The intensity of two features with the highest PC1 loading values significantly increased under nitrogen deficiency; two prominent peaks were identified as O-methylated isoflavones, pratensein and biochanin A. RNA-seq analysis showed that they induce nodABC gene expression in the Mesorhizobium ciceri symbiont, suggesting that pratensein and biochanin A are chickpea NGIs. Pratensein applied concurrently with M. ciceri at sowing promoted chickpea nodulation. These results demonstrate that pratensein and biochanin A are chickpea NGIs, and pratensein can be useful for increasing nodulation efficiency in chickpea production.

Genistein transfersome-embedded topical delivery system for skin melanoma treatment: in vitro and ex vivo evaluations.

Skin melanoma is considered the most dangerous form of skin cancer due to its association with high risk of metastasis, high mortality rate and high resistance to different treatment options. Genistein is a natural isoflavonoid with known chemotherapeutic activity. Unfortunately, it has low bioavailability due to its poor aqueous solubility and excessive metabolism. In the current study, genistein was incorporated into transferosomal hydrogel to improve its bioavailability. The prepared transferosomal formulations were characterized regarding: particle size; polydispersity index; zeta potential; encapsulation efficiency; TEM; FTIR; DSC; XRD; in vitro drug release; viscosity; pH; ex vivo anti-tumor activity on 3D skin melanoma spheroids and 1-year stability study at different storage temperatures. The optimized formulation has high encapsulation efficiency with an excellent particle size that will facilitate its penetration through the skin. The transfersomes have a spherical shape with sustained drug release profile. The anti-tumor activity evaluation of genistein transfersome revealed that genistein is a potent chemotherapeutic agent with enhanced penetration ability through the melanoma spheroids when incorporated into transfersomes. Stability study results demonstrate the high physical and chemical stability of our formulations. All these outcomes provide evidence that our genistein transferosomal hydrogel is a promising treatment option for skin melanoma.

Mesoscale characterization of osseointegration around an additively manufactured genistein-coated implant.

Given the hierarchical nature of bone and bone interfaces, osseointegration, namely the formation of a direct bone-implant contact, is best evaluated using a multiscale approach. However, a trade-off exists between field of view and spatial resolution, making it challenging to image large volumes with high resolution. In this study, we combine established electron microscopy techniques to probe bone-implant interfaces at the microscale and nanoscale with plasma focused ion beam-scanning electron microscopy (PFIB-SEM) tomography to evaluate osseointegration at the mesoscale. This characterization workflow is demonstrated for bone response to an additively manufactured Ti-6Al-4V implant which combines engineered porosity to facilitate bone ingrowth and surface functionalization via genistein, a phytoestrogen, to counteract bone loss in osteoporosis. SEM demonstrated new bone formation at the implant site, including in the internal implant pores. At the nanoscale, scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the gradual nature of the bone-implant interface. By leveraging mesoscale analysis with PFIB-SEM tomography that captures large volumes of bone-implant interface with nearly nanoscale resolution, the presence of mineral ellipsoids varying in size and orientation was revealed. In addition, a well-developed lacuno-canalicular network and mineralization fronts directed both towards the implant and away from it were highlighted.

Biochanin A restored the blood-brain barrier in cerebral ischemia-reperfusion in rats.

OBJECTIVE: Blood-brain barrier is a protective layer that regulates the influx and efflux of biological materials for cerebral tissue. The aim of this study was to investigate the effects of Biochanin A on cerebral histopathology and blood-brain barrier immunohistochemically. METHODS: A total of 24 rats were assigned to three groups: sham, ischemia-reperfusion, and ischemia-reperfusion+Biochanin A. Ischemia-reperfusion was performed by occluding the left carotid artery for 2/24 h. Notably, 20 mg/kg Biochanin A was administered to rats for 7 days after ischemia-reperfusion. Blood was collected for malondialdehyde and total oxidant/antioxidant status analysis. Cerebral tissues were processed for histopathology and further for immunohistochemical analysis. RESULTS: Malondialdehyde content with total oxidant status value was significantly increased and total antioxidant status values were significantly decreased in the ischemia-reperfusion group compared with the sham group. Biochanin A treatment significantly improved scores in the ischemia-reperfusion+Biochanin A group. The normal histological appearance was recorded in the cerebral sections of the sham group. Degenerated neurons and vascular structures with disrupted integrity of the cerebral cortex were observed after ischemia-reperfusion. Biochanin A alleviated the histopathology in the cerebrum in the ischemia-reperfusion+Biochanin A group. Ischemia-reperfusion injury decreased the expression of blood-brain barrier in the ischemia-reperfusion group compared to the sham group. Administration of Biochanin A upregulated the blood-brain barrier immunoreactivity in the cerebrum by restoring blood-brain barrier. CONCLUSION: Cerebral ischemia-reperfusion caused an increase in oxidative stress and pathological lesions in the cerebrum. Biochanin A treatment restored the adverse effects of ischemia-reperfusion injury by restoring blood-brain barrier.

Pulmonary administration of cross-linked chitosan nanoparticles of genistein for regulating blood glucose.

The research study focused on the development and characterization of sustained release formulation of genistein (GEN)-loaded chitosan (CS) nanoparticles to deliver in the form of dry powder inhaler (DPI) via pulmonary route to offer higher stability and anti-diabetic activity. The GEN-loaded nanoparticles were prepared by cross-linking reaction of CS and sodium hexametaphosphate (SHMP). The optimized formulation displayed particle size (PS) of 684.2 ± 26.5 nm, zeta potential (ZP) of 19.6 ± 4.50 mV, % entrapment efficiency (% EE) of 87.33 ± 8.46 % and drug release profile of 85.48 ± 5.50 % for 48 h. The in-vivo studies exhibited a superior sustained release formulation of GEN in the regulation of blood glucose levels (BGLs). The powder showed the emitted fraction (EF) of 86.76 % and effective inhalation index (EI) of 85.41 %. The reduction of BGLs (85 %) was observed in the diabetic group. This might be due to the inhibition of proliferation of pancreatic ß-cells (growth factor inhibition targeting cAMP and ERK1/2 pathway), antioxidative activity, reducing insulin resistance, and the adipose tissue mass and alteration of the hepatic glucose metabolism. Hence, these results proved the delivery of GEN in the form of DPI system as a favorable route for treating type-1 diabetes mellitus with a longer duration of action.

Genistein-3'-sodium sulfonate promotes brain functional rehabilitation in ischemic stroke rats by regulating astrocytes polarization through NF-κB signaling pathway.

The activation and polarization of astrocytes are involved in neuroinflammation and brain functional rehabilitation after ischemic stroke. Our previous studies display the neuroprotective effect of genistein-3'-sodium sulfonate (GSS) in the acute phase of cerebral ischemia-reperfusion injury (CI/RI). This study aimed to investigate the brain function improvement of GSS during the recovery period after CI/RI in rats and to explore the potential mechanism from the perspective of astrocyte activation and polarization. The transient middle cerebral artery occlusion (tMCAO) rats were treated with GSS (1 mg/kg) continuously for 28 days. The behavior tests were measured to assess neurological function. The mRNA and protein expression in affected cerebral cortex were detected on day 29 after tMCAO. Our results demonstrated that GSS treatment significantly improved the spatial and temporal gait parameters in the Catwalk gait test, prolonged the time on the stick and increased the rotation speed in the rotarod test, and decreased the time to find the hidden platform and increased the time in the target quadrant in the Morris water maze test. In addition, GFAP, GBP2, C3, IL-1ß protein expressions and Nos2A mRNA level were decreased, while Nrf2, BDNF, IL-10 protein expressions and Sphk1 and Nef2l2 mRNA levels increased after GSS treatment. Interestingly, GSS presented a strong binding affinity to TLR4 and suppressed the activation of NF-κB signaling. In conclusion, GSS can promote brain function recovery by inhibiting astrocyte activation and polarization to A1 phenotype, and enhancing astrocyte polarization to A2 phenotype via inactivating TLR4/NF-κB signaling, which provide a candidate compound for clinical rehabilitation therapy in the recovery period after ischemic stroke.

Genistein Promotes M2 Macrophage Polarization via Aryl Hydrocarbon Receptor and Alleviates Intestinal Inflammation in Broilers with Necrotic Enteritis.

The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates the immune system through complicated transcriptional programs. Genistein, an AhR ligand, exhibits anti-inflammatory properties. However, its role in modulating immune responses via the AhR signaling pathway remains unclear. In this study, 360 male Arbor Acre broilers (1-day-old) were fed a basal diet supplemented with 40 or 80 mg/kg genistein and infected with or without Clostridium perfringens (Cp). Our results demonstrated that genistein ameliorated Cp-induced intestinal damage, as reflected by the reduced intestinal lesion scores and improved intestinal morphology and feed-to-gain ratio. Moreover, genistein increased intestinal sIgA, TGF-ß, and IL-10, along with elevated serum IgG, IgA, and lysozyme levels. Genistein improved intestinal AhR and cytochrome P450 family 1 subfamily A member 1 (CYP1A1) protein levels and AhR+ cell numbers in Cp-challenged broilers. The increased number of AhR+CD163+ cells in the jejunum suggested a potential association between genistein-induced AhR activation and anti-inflammatory effects mediated through M2 macrophage polarization. In IL-4-treated RAW264.7 cells, genistein increased the levels of AhR, CYP1A1, CD163, and arginase (Arg)-1 proteins, as well as IL-10 mRNA levels. This increase was attenuated by the AhR antagonist CH223191. In summary, genistein activated the AhR signaling pathway in M2 macrophages, which enhanced the secretion of anti-inflammatory cytokines and attenuated intestinal damage in Cp-infected broilers Cp.

In silico screening and in vivo experimental validation of 15-PGDH inhibitors from traditional Chinese medicine promoting liver regeneration.

The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which acts as a negative regulator of prostaglandin E2 (PGE2) levels and activity, represents a promising pharmacological target for promoting liver regeneration. In this study, we collected data on 15-PGDH homologous family proteins, their inhibitors, and traditional Chinese medicine (TCM) compounds. Leveraging machine learning and molecular docking techniques, we constructed a prediction model for virtual screening of 15-PGDH inhibitors from TCM compound library and successfully screened genistein as a potential 15-PGDH inhibitor. Through further validation, it was discovered that genistein considerably enhances liver regeneration by inhibiting 15-PGDH, resulting in a significant increase in the PGE2 level. Genistein's effectiveness suggests its potential as a novel therapeutic agent for liver diseases, highlighting this study's contribution to expanding the clinical applications of TCM.

Assessment of the Diuretic Properties of Rice Bean Accessions Using a Mouse Model and Identification of Active Polyphenolic Compounds.

Rice bean [Vigna umbellata (Thunb.) Ohwi and Ohashi], an annual legume in the genus Vigna, is a promising crop suitable for cultivation in a changing climate to ensure food security. It is also a medicinal plant widely used in traditional Chinese medicine; however, little is known about the medicinal compounds in rice bean. In this study, we assessed the diuretic effect of rice bean extracts on mice as well as its relationship with the contents of eight secondary metabolites in seeds. Mice gavaged with rice bean extracts from yellow and black seeds had higher urinary output (5.44-5.47 g) and water intake (5.8-6.3 g) values than mice gavaged with rice bean extracts from red seeds. Correlation analyses revealed significant negative correlations between urine output and gallic acid (R = -0.70) and genistein (R = -0.75) concentrations, suggesting that these two polyphenols negatively regulate diuresis. There were no obvious relationships between mice diuresis-related indices (urine output, water intake, and weight loss) and rutin or catechin contents, although the concentrations of both of these polyphenols in rice bean seeds were higher than the concentrations of the other six secondary metabolites. Our study findings may be useful for future research on the diuretic effects of rice bean, but they should be confirmed on the basis of systematic medical trials.

Articulating the Pharmacological and Nanotechnological Aspects of Genistein: Current and Future Prospectives.

Throughout the past several centuries, herbal constituents have been the subject of scientific interest and the latest research into their therapeutic potential is underway. Genistein is a soy-derived isoflavone found in huge amounts in soy, along with the plants of the Fabaceae family. Scientific studies have demonstrated the beneficial effects of genistein on various health conditions. Genistein presents a broad range of pharmacological activities, including anticancer, neuroprotective, cardioprotective, antiulcer, anti-diabetic, wound healing, anti-bacterial, antiviral, skin, and radioprotective effects. However, the hydrophobic nature of genistein results in constrained absorption and restricts its therapeutic potential. In this review, the number of nanocarriers for genistein delivery has been explored, such as polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles, liposomes, micelles, transferosomes, and nanoemulsions and nanofibers. These nano-formulations of genistein have been utilized as a potential strategy for various disorders, employing a variety of ex vivo, in vitro, and in vivo models and various administration routes. This review concluded that genistein is a potential therapeutic agent for treating various diseases, including cancer, neurodegenerative disorders, cardiovascular disorders, obesity, diabetes, ulcers, etc., when formulated in suitable nanocarriers.

Characterization and Biosynthetic Regulation of Isoflavone Genistein in Deep-Sea Actinomycetes Microbacterium sp. B1075.

Deep-sea environments, as relatively unexplored extremes within the Earth's biosphere, exhibit notable distinctions from terrestrial habitats. To thrive in these extreme conditions, deep-sea actinomycetes have evolved unique biochemical metabolisms and physiological capabilities to ensure their survival in this niche. In this study, five actinomycetes strains were isolated and identified from the Mariana Trench via the culture-dependent method and 16S rRNA sequencing approach. The antimicrobial activity of Microbacterium sp. B1075 was found to be the most potent, and therefore, it was selected as the target strain. Molecular networking analysis via the Global Natural Products Social Molecular Networking (GNPS) platform identified 25 flavonoid compounds as flavonoid secondary metabolites. Among these, genistein was purified and identified as a bioactive compound with significant antibacterial activity. The complete synthesis pathway for genistein was proposed within strain B1075 based on whole-genome sequencing data, with the key gene being CHS (encoding chalcone synthase). The expression of the gene CHS was significantly regulated by high hydrostatic pressure, with a consequent impact on the production of flavonoid compounds in strain B1075, revealing the relationship between actinomycetes' synthesis of flavonoid-like secondary metabolites and their adaptation to high-pressure environments at the molecular level. These results not only expand our understanding of deep-sea microorganisms but also hold promise for providing valuable insights into the development of novel pharmaceuticals in the field of biopharmaceuticals.

Genistein: A promising phytoconstituent with reference to its bioactivities.

Genistein, a potent phytoconstituent, has garnered significant attention for its diverse bioactivities, making it a subject of extensive research and exploration. This review delves into the multifaceted properties of genistein, encompassing its antioxidant and anticancer potential. Its ability to modulate various cellular pathways and interact with diverse molecular targets has positioned it as a promising candidate in the prevention and treatment of various diseases. This review provides a comprehensive examination of Genistein, covering its chemical properties, methods of isolation, synthesis, therapeutic attributes with regard to cancer management, and the proposed mechanisms of action as put forth by researchers.

Harnessing Therapeutic Potentials of Biochanin A in Neurological Disorders: Pharmacokinetic and Pharmacodynamic Overview.

Biochanin A, an isoflavone flavonoid with estrogenic activity, is naturally found in red clover and other legumes. It possesses a wide range of pharmacological properties, including antioxidant, anti-inflammatory, anti-apoptotic, neuroprotective, and anticancer effects. In recent years, a growing body of pre-clinical research has focused on exploring the therapeutic potential of biochanin A in various neurological disorders, such as Alzheimer's and Parkinson's disease, multiple sclerosis, epilepsy, ischemic brain injury, gliomas, and neurotoxicity. This comprehensive review aims to shed light on the underlying molecular mechanisms that contribute to the neuroprotective role of biochanin A based on previous pre-clinical studies. Furthermore, it provides a detailed overview of the protective effects of biochanin A in diverse neurological disorders. The review also addresses the limitations associated with biochanin A administration and discusses different approaches employed to overcome these challenges. Finally, it highlights the future opportunities for translating biochanin A from pre-clinical research to clinical studies while also considering its commercial viability as a dietary supplement or a potential treatment for various diseases.

Identifying the Multitarget Pharmacological Mechanism of Action of Genistein on Lung Cancer by Integrating Network Pharmacology and Molecular Dynamic Simulation.

Food supplements have become beneficial as adjuvant therapies for many chronic disorders, including cancer. Genistein, a natural isoflavone enriched in soybeans, has gained potential interest as an anticancer agent for various cancers, primarily by modulating apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. However, in lung cancer, the exact impact and mechanism of action of genistein still require clarification. To provide more insight into the mechanism of action of genistein, network pharmacology was employed to identify the key targets and their roles in lung cancer pathogenesis. Based on the degree score, the hub genes AKT1, CASP3, EGFR, STAT3, ESR1, SRC, PTGS2, MMP9, PRAG, and AR were significantly correlated with genistein treatment. AKT1, EGFR, and STAT3 were enriched in the non-small cell lung cancer (NSCLC) pathway according to Kyoto Encyclopedia of Genes and Genomes analysis, indicating a significant connection to lung cancer development. Moreover, the binding affinity of genistein to NSCLC target proteins was further verified by molecular docking and molecular dynamics simulations. Genistein exhibited potential binding to AKT1, which is involved in apoptosis, cell migration, and metastasis, thus holding promise for modulating AKT1 function. Therefore, this study aimed to investigate the mechanism of action of genistein and its therapeutic potential for the treatment of NSCLC.

Combination Treatment of Biochanin A and Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism and Inducing Cell Cycle Arrest in Pancreatic Cancer Cells.

BACKGROUND/AIM: Pancreatic cancer is an aggressive type of cancer, with a dismally low survival rate of <5%. FDA-approved drugs like gemcitabine have shown little therapeutic success, prolonging survival by a mere six months. Isoflavones, such as biochanin A and daidzein, are known to exhibit anti-cancer activity, whereas statins reportedly have anti-proliferative effects. This study investigated the effects of combination treatment of biochanin A and atorvastatin on pancreatic cancer cells. MATERIALS AND METHODS: Pancreatic cancer cells AsPC-1, PANC-1, and MIA PaCa-2 were procured from ATCC. The cell viability studies were carried out using MTT & cell count assays. Flow cytometry was used to study cell apoptosis whereas cell metabolism studies were carried out using the Seahorse Mito stress test and XF-PMP assay. The effects of treatment on cell signaling pathways & cell cycle associated proteins were investigated using western blot whereas invasiveness of cancer cells was evaluated using gelatin zymography. RESULTS: The combination treatment decreased the survival and enhanced pro-apoptotic responses compared to single treatments in the pancreatic cancer cells. In PANC-1 cells, the combination treatment decreased invasiveness, reduced expression of activated STAT3 and expression of critical mediators of cell cycle progression. Furthermore, the combination treatment induced a differential inhibition of respiratory complexes in the pancreatic cancer cells. CONCLUSION: The combination treatment of biochanin A and atorvastatin exerts enhanced anti-cancer effects, inducing apoptosis, down-regulating cell cycle associated proteins and invasiveness in pancreatic cancer cells and merits further investigation for new, improved treatments for pancreatic cancer.

Molecular Pathways of Genistein Activity in Breast Cancer Cells.

The most common malignancy in women is breast cancer. During the development of cancer, oncogenic transcription factors facilitate the overproduction of inflammatory cytokines and cell adhesion molecules. Antiapoptotic proteins are markedly upregulated in cancer cells, which promotes tumor development, metastasis, and cell survival. Promising findings have been found in studies on the cell cycle-mediated apoptosis pathway for medication development and treatment. Dietary phytoconstituents have been studied in great detail for their potential to prevent cancer by triggering the body's defense mechanisms. The underlying mechanisms of action may be clarified by considering the role of polyphenols in important cancer signaling pathways. Phenolic acids, flavonoids, tannins, coumarins, lignans, lignins, naphthoquinones, anthraquinones, xanthones, and stilbenes are examples of natural chemicals that are being studied for potential anticancer drugs. These substances are also vital for signaling pathways. This review focuses on innovations in the study of polyphenol genistein's effects on breast cancer cells and presents integrated chemical biology methods to harness mechanisms of action for important therapeutic advances.

Genistein mitigates nitroglycerine-induced migraine: modulation of nitric oxide-mediated vasodilation and oxidative stress.

Migraine is a widespread brain condition described by frequent, recurrent episodes of incapacitating, moderate-to-severe headaches with throbbing pain that are usually one-sided. It is the 2nd most debilitating state lived with disability in terms of years, with a prevalence rate of 15-20%. Significant drops in estrogen levels have been associated with triggering acute migraine attacks in certain cases. Phytoestrogens are plant-derived compounds that resemble estrogen in structure, enabling them to imitate estrogen's functions in the body by attaching to estrogen receptors. Thus, the study was aimed to explore the protective effect of genistein against migraine. Moreover, the role of nitric oxide was also studied in the observed effect of genistein. Nitric oxide (NO) is implicated in migraine pathophysiology due to its role in promoting cerebral vasodilation and modulation of pain perception. Exploring L-NAME, a nitric oxide synthase inhibitor in migraine research helps scientists better understand the role of NO in migraine. Nitroglycerine treatment significantly increased the facial-unilateral head pain and spontaneous pain, as evidenced by the increased number of head scratching and groomings. Nitroglycerine treatment also induced anxiogenic behavior in mice. A significant reduction in the number of entries in the light phase and open arm, respectively. Biochemical analysis indicated a significant increase in inflammatory and oxidative stress in the nitroglycerin group. A significant increase and decrease in brain TBARS and GSH were observed with nitroglycerine treatment, respectively. Moreover, nitroglycerine treatment has uplifted the serum TNF-α level. Genistein (20 mg/kg) significantly mitigated the facial-unilateral head pain, spontaneous pain, photophobia, and anxiety-like behavior induced by nitroglycerine. Biochemical analysis showed that genistein (20 mg/kg) significantly abrogated the nitroglycerine-induced lipid peroxidation and increased serum TNF-α level. Genistein treatment also upregulated the brain GSH level and downregulated the serum TNF-α level. The L-NAME-mediated alleviation of the protective effect of genistein might be attributed to the vasodilatory effect of L-NAME. Conclusively, it can be suggested that genistein might provide relief from migraine pain by inhibiting nitric oxide-mediated vasodilation and oxidative stress.