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F1000Research 2023This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported... (Review)
Review
This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A needs to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions.
Topics: Male; Female; Humans; Isoflavones; Glycine max; Neoplasms
PubMed: 38106650
DOI: 10.12688/f1000research.126059.3 -
Behavioral Sciences (Basel, Switzerland) Mar 2022Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by the demyelination of nerves, neural...
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by the demyelination of nerves, neural degeneration, and axonal loss. Cognitive impairment, including memory decline, is a significant feature in MS affecting up to 70% of patients. Thereby, it substantially impacts patients' quality of life. Biochanin A (BCA) is an o-methylated isoflavone with a wide variety of pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective activities. Thus, this study aimed to investigate the possible protective effects of BCA on memory decline in the cuprizone (CPZ) model of MS. Thirty Swiss albino male mice (SWR/J) were randomly divided into three groups (n = 10): control (normal chow + i.p. 1:9 mixture of DMSO and PBS), CPZ (0.2% / of CPZ mixed into chow + i.p. 1:9 mixture of DMSO and PBS), and CPZ + BCA (0.2% / of CPZ mixed into chow + i.p. 40 mg/kg of BCA). At the last week of the study (week 5), a series of behavioral tasks were performed. A grip strength test was performed to assess muscle weakness while Y-maze, novel object recognition task (NORT), and novel arm discrimination task (NADT) were performed to assess memory. Additionally, histological examination of the hippocampus and the prefrontal cortex (PFC) were conducted. BCA administration caused a significant increase in the grip strength compared with the CPZ group. Additionally, BCA significantly improved the mice's spatial memory in the Y-maze and recognition memory in the NORT and the NADT compared with the CPZ group. Moreover, BCA mitigated neuronal damage in the PFC and the hippocampus after five weeks of administration. In conclusion, our data demonstrates the possible protective effect of BCA against memory deterioration in mice fed with CPZ for five weeks.
PubMed: 35323389
DOI: 10.3390/bs12030070 -
Journal of Oncology 2022To investigate the regulatory effect of ZEB1 on PD-L1 expression and the pharmacodynamic effects of Biochanin A on the malignant biological behaviors of colorectal...
OBJECTIVE
To investigate the regulatory effect of ZEB1 on PD-L1 expression and the pharmacodynamic effects of Biochanin A on the malignant biological behaviors of colorectal cancer (CRC).
METHODS
The correlation between epithelial-mesenchymal transition (EMT) score and features of the tumor microenvironment (TME) was investigated using the Cancer Genome Atlas (TCGA) dataset. The correlation between ZEB1 and PD-L1 expression was validated using immunohistochemistry (IHC) staining, and the regulatory effect of ZEB1 on PD-L1 expression was explored by in vitro assays. Moreover, the pharmacodynamic effects of Biochanin A on ZEB1 and PD-L1 expression, as well as malignant biological behaviors of CRC cells, were evaluated by in vitro and in vivo assays.
RESULTS
EMT score was positively correlated with a majority of immunostimulators, immune checkpoints, activities of antitumor immunity cycles, and infiltration levels of most immune cells in the TCGA dataset. In addition, ZEB1 was correlated with and positively regulated PD-L1 expression in CRC. Besides, Biochanin A, an inhibitor for the ZEB1/PD-L1 axis, notably inhibited ZEB1-mediated aggressiveness and PD-L1 expression of CRC cells. Moreover, Biochanin A also exerted a tumor-inhibitory role in vivo in the CRC mouse model.
CONCLUSION
Overall, we found that ZEB1 is a main regulator of PD-L1 expression in CRC. In addition, we also identified Biochanin A as a novel inhibitor for the ZEB1/PD-L1 axis, which could inhibit tumor progression and immune escape.
PubMed: 35242187
DOI: 10.1155/2022/3224373 -
Pharmaceuticals (Basel, Switzerland) Jan 2024The aim of this study was to investigate the antifungal activity of biochanin A (BCA) against planktonic growth and biofilms of six species, including , , , , , and ....
The aim of this study was to investigate the antifungal activity of biochanin A (BCA) against planktonic growth and biofilms of six species, including , , , , , and . We applied various assays that determined (a) the antimicrobial effect on growth of species, (b) the effect on formation of hyphae and biofilm, (c) the effect on the expression of genes related to hyphal growth and biofilm formation, (d) the influence on cell wall structure, and (e) the effect on cell membrane integrity and permeability. Moreover, disk diffusion tests were used to investigate the effect of a combination of BCA with fluconazole to assess their possible synergistic effect on drug-resistant , , and Our results showed that the BCA MIC values against species ranged between 125 µg/mL and 500 µg/mL, and the MIC values were in a concentration range from 250 µg/mL to 1000 µg/mL. The treatment with BCA inhibited adhesion of cells, cell surface hydrophobicity (CSH), and biofilm formation and reduced hyphal growth in all the analyzed species. Real-time qRT-PCR revealed that BCA down-regulated the expression of biofilm-specific genes in . Furthermore, physical destruction of cell membranes and cell walls as a result of the treatment with BCA was observed. The combination of BCA and fluconazole did not exert synergistic effects against fluconazole-resistant .
PubMed: 38256922
DOI: 10.3390/ph17010089 -
Oxidative Medicine and Cellular... 2020Biochanin A (BCA), a dietary isoflavone extracted from red clover and cabbage, has been shown to antagonize hypertension and myocardial ischemia/reperfusion injury....
Biochanin A (BCA), a dietary isoflavone extracted from red clover and cabbage, has been shown to antagonize hypertension and myocardial ischemia/reperfusion injury. However, very little is known about its role in atherogenesis. The aim of this study was to observe the effects of BCA on atherosclerosis and explore the underlying mechanisms. Our results showed that administration of BCA promoted reverse cholesterol transport (RCT), improved plasma lipid profile, and decreased serum proinflammatory cytokine levels and atherosclerotic lesion area in apoE mice fed a Western diet. In THP-1 macrophage-derived foam cells, treatment with BCA upregulated ATP-binding cassette (ABC) transporter A1 (ABCA1) and ABCG1 expression and facilitated subsequent cholesterol efflux and diminished intracellular cholesterol contents by activating the peroxisome proliferator-activated receptor (PPAR)/liver X receptor (LXR) and PPAR/heme oxygenase 1 (HO-1) pathways. BCA also activated these two signaling pathways to inhibit the secretion of proinflammatory cytokines. Taken together, these findings suggest that BCA is protective against atherosclerosis by inhibiting lipid accumulation and inflammatory response through the PPAR/LXR and PPAR/HO-1 pathways. BCA may be an attractive drug for the prevention and treatment of atherosclerotic cardiovascular disease.
Topics: ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; Animals; Atherosclerosis; Brassica; Cholesterol; Cytokines; Diet, Western; Disease Models, Animal; Foam Cells; Genistein; Heme Oxygenase-1; Humans; Inflammation; Lipid Metabolism; Lipids; Liver X Receptors; Male; Mice; Mice, Knockout, ApoE; PPAR gamma; Phytotherapy; Plant Extracts; Protective Agents; Signal Transduction; THP-1 Cells; Trifolium
PubMed: 33959213
DOI: 10.1155/2020/8965047 -
Antioxidants (Basel, Switzerland) May 2023Nephropathy is the most prevalent microvascular disorder in diabetes mellitus. Oxidative stress and inflammatory cascade provoked by the persistent hyperglycemic milieu...
Nephropathy is the most prevalent microvascular disorder in diabetes mellitus. Oxidative stress and inflammatory cascade provoked by the persistent hyperglycemic milieu play integral roles in the aggravation of renal injury and fibrosis. We explored the impact of biochanin A (BCA), an isoflavonoid, on the inflammatory response, nod-like receptor protein 3 (NLRP3) inflammasome activation, oxidative stress, and fibrosis in diabetic kidneys. A high-fat-diet/streptozotocin (HFD/STZ)-induced experimental model of diabetic nephropathy (DN) was established in Sprague Dawley rats, and in vitro studies were performed in high-glucose-induced renal tubular epithelial (NRK-52E) cells. Persistent hyperglycemia in diabetic rats was manifested by perturbation of renal function, marked histological alterations, and oxidative and inflammatory renal damage. Therapeutic intervention of BCA mitigated histological changes, improved renal function and antioxidant capacity, and suppressed phosphorylation of nuclear factor-kappa B (NF-κB) and nuclear factor-kappa B inhibitor alpha (IκBα) proteins. Our in vitro data reveal excessive superoxide generation, apoptosis, and altered mitochondrial membrane potential in NRK-52E cells that were cultured in a high-glucose (HG) environment were subsided by BCA intervention. Meanwhile, the upregulated expressions of NLRP3 and its associated proteins, the pyroptosis-indicative protein gasdermin-D (GSDMD) in the kidneys, and HG-stimulated NRK-52E cells were significantly ameliorated by BCA treatment. Additionally, BCA blunted transforming growth factor (TGF)-β/Smad signaling and production of collagen I, collagen III, fibronectin, and alfa-smooth muscle actin (α-SMA) in diabetic kidneys. Our results indicate the plausible role of BCA in attenuating DN, presumably through modulation of the apoptotic cascade in renal tubular epithelial cells and the NF-κB/NLRP3 axis.
PubMed: 37237918
DOI: 10.3390/antiox12051052 -
Discover Oncology Dec 2022Lung adenocarcinoma is the major subtype of lung cancer, accounting for approximately 40% of lung cancers. During clinical treatment, the emergence of chemotherapy...
Lung adenocarcinoma is the major subtype of lung cancer, accounting for approximately 40% of lung cancers. During clinical treatment, the emergence of chemotherapy resistance seriously affects the effectiveness of treatment. Thus, finding new chemotherapeutic sensitizers is considered to be one of the effective solutions. Biochanin A, as a naturally occurring isoflavone, has been demonstrated to exhibit anticancer effects in various tumors. However, the potential mechanisms of Biochanin A to inhibit tumor development have not been clarified. In the present study, we found that the combinational treatment of cisplatin and Biochanin A exhibited strong synergistic repression on lung adenocarcinoma growth and progression in vitro and in vivo. Considering that epithelial-mesenchymal transition (EMT) is recognized to be associated with both chemoresistance and metastasis, we examined the EMT-related markers and found that Biochanin A could specifically inhibit the expression of ZEB1. Importantly, Biochanin A chemosensitizes lung adenocarcinoma and inhibits cancer cell metastasis by suppressing ZEB1. At the molecular level, Biochanin A affects the stability of ZEB1 protein through the deubiquitination pathway and thereby influences the progression of lung adenocarcinoma. In conclusion, our finding elucidates the potential efficacy of Bichanin A as a chemosensitizer and provides new strategy for the chemotherapy of advanced lung adenocarcinoma.
PubMed: 36512117
DOI: 10.1007/s12672-022-00601-2 -
Foods (Basel, Switzerland) Jun 2022This review covers a comprehensive overview of the phytoconstituents and bioactivities reported to date for clover honeys produced from various spp. against the... (Review)
Review
This review covers a comprehensive overview of the phytoconstituents and bioactivities reported to date for clover honeys produced from various spp. against the backdrop of a more general discussion of the chemistry and bioactivity of these important agricultural species. While research into the phytochemical composition of various honeys and their associated bioactivities is growing, this review demonstrates that the literature to date has seen only a limited number of studies on clover honeys. Surprisingly, there appear to be no comparative data on the concentration of flavonoids in general or isoflavonoids specifically in different clover honeys, although the latter have been identified as a main group of bioactive compounds in red clover plants. Based on the findings of this review, the presence of phytoestrogenic isoflavonoids (e.g., formononetin, biochanin A, genistein, daidzein, glycitein) in clover plants and, by extension, in clover honeys should be further investigated, specifically of clover species outside the three popular perennial clovers (red, white and alsike clovers) to exploit new opportunities of potential benefit to both the pharmaceutical and apiculture industries.
PubMed: 35804717
DOI: 10.3390/foods11131901 -
Neural Regeneration Research Sep 2024JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic...
JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic effects, can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury; however, its effect on spinal cord injury is still unclear. In this study, a rat model of spinal cord injury was established using the heavy object impact method, and the rats were then treated with Biochanin A (40 mg/kg) via intraperitoneal injection for 14 consecutive days. The results showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal cord tissue injury, reduced inflammation and oxidative stress in spinal cord neurons, and reduced apoptosis and pyroptosis. In addition, Biochanin A inhibited the expression of inflammasome-related proteins (ASC, NLRP3, and GSDMD) and the Toll-like receptor 4/nuclear factor-κB pathway, activated the Nrf2/heme oxygenase 1 signaling pathway, and increased the expression of the autophagy markers LC3 II, Beclin-1, and P62. Moreover, the therapeutic effects of Biochanin A on early post-spinal cord injury were similar to those of methylprednisolone. These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways. These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.
PubMed: 38227535
DOI: 10.4103/1673-5374.390953 -
Frontiers in Pharmacology 2020(Roxb. ex Willd.) DC. (Fabaceae), also known as Indian Kudzu (vidari kand), is a perennial herb distributed throughout India and other Asian countries. Traditionally,... (Review)
Review
(Roxb. ex Willd.) DC. (Fabaceae), also known as Indian Kudzu (vidari kand), is a perennial herb distributed throughout India and other Asian countries. Traditionally, tuber and leaves of this plant have extensively been reported for nutritional and medicinal properties in Ayurveda as well as in Chinese traditional practices. The objective of the present review is to compile and update the published data on traditional uses, pharmacological potential, and phytochemistry of compounds isolated from the plant . extracts and its purified compounds possess multiple activities such as anticancer, anticonvulsant, antidiabetic, antifertility, anti-inflammatory, antioxidant, anti-stress, antiulcerogenic, cardioprotective, hypolipidemic, hepatoprotective, immunomodulatory, nephroprotective, nootropic, neuroprotective, and wound healing. Tuber and leaf extracts of contain several bioactive constituents such as puerarin, daidzein, genistein, quercetin, irisolidone, biochanin A, biochanin B, isoorientin, and mangiferin, which possess an extensive range of pharmacological activities. The extensive range of pharmacological properties of provides opportunities for further investigation and presents a new approach for the treatment of ailments. Many phytochemicals have been identified and characterized from ; however, some of them are still unexplored, and there is no supporting data for their activities and exact mechanisms of action. Therefore, further investigations are warranted to unravel the mechanisms of action of individual constituents of this plant.
PubMed: 33708108
DOI: 10.3389/fphar.2020.582506