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The Science of the Total Environment Jun 2020Natural products (NPs) will continue to serve humans as matchless source of novel drug leads and an inspiration for the synthesis of non-natural drugs. As our scientific... (Review)
Review
Natural products (NPs) will continue to serve humans as matchless source of novel drug leads and an inspiration for the synthesis of non-natural drugs. As our scientific understanding of 'nature' is rapidly expanding, it would be worthwhile to illuminate the pharmacological distinctions of NPs to the scientific community and the public. Flavonoids have long fascinated scientists with their remarkable structural diversity as well as biological functions. Consequently, this review aims to shed light on the sources and pharmacological significance of a dietary isoflavone, biochanin A, which has been recently emerged as a multitargeted and multifunctional guardian of human health. Biochanin A possesses anti-inflammatory, anticancer, neuroprotective, antioxidant, anti-microbial, and hepatoprotective properties. It combats cancer development by inducing apoptosis, inhibition of metastasis and arresting cell cycle via targeting several deregulated signaling pathways of cancer. It fights inflammation by blocking the expression and activity of pro-inflammatory cytokines via modulation of NF-κB and MAPKs. Biochanin A acts as a neuroprotective agent by inhibiting microglial activation and apoptosis of neurons. As biochanin A has potential to modulate several biological networks, thus, it can be anticipated that this therapeutically potent compound might serve as a novel lead for drug development in the near future.
Topics: Anti-Inflammatory Agents; Apoptosis; Genistein; Humans; NF-kappa B
PubMed: 32208265
DOI: 10.1016/j.scitotenv.2020.137907 -
Pharmacological Research Jun 2022Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic... (Review)
Review
Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.
Topics: Genistein; Humans; Inflammation; Isoflavones; Phytochemicals; Phytotherapy
PubMed: 35562014
DOI: 10.1016/j.phrs.2022.106246 -
Frontiers in Pharmacology 2019Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption that is known to have various effects, including... (Review)
Review
Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption that is known to have various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects. BCA is already commercially available and is among the main ingredients in many types of supplements used to alleviate postmenopausal symptoms in women. The activity of BCA has not been adequately evaluated in humans. However, the results of many and studies investigating the potential health benefits of BCA are available, and the complex mechanisms by which BCA modulates transcription, apoptosis, metabolism, and immune responses have been revealed. Many efforts have been exerted to improve the poor bioavailability of BCA, and very promising results have been reported. This review focuses on the major effects of BCA and its possible molecular targets, potential uses, and limitations in health maintenance and treatment.
PubMed: 31354500
DOI: 10.3389/fphar.2019.00793 -
The American Journal of Chinese Medicine 2021Biochanin A (BCA) is a dietary isoflavone, isolated from the leaves and stems of L and many other herbs of Chinese medicine. Recent findings indicated BCA as a... (Review)
Review
Biochanin A (BCA) is a dietary isoflavone, isolated from the leaves and stems of L and many other herbs of Chinese medicine. Recent findings indicated BCA as a promising drug candidate with diverse bioactive effects. On the purpose of evaluating the possibility of BCA in clinical application, this review is trying to provide a comprehensive summary of the pharmacological actions of BCA. The publications collected from PubMed, ScienceDirect, and Wiley databases were summarized for the last 10 years. Then, the potential therapeutic use of BCA on the treatment of various diseases was discussed according to its pharmacological properties, namely, anticancer, anti-inflammatory, anti-bacterial, anti-diabetic, and anti-obesity effects as well as neuroprotective, hepatoprotective, cardioprotective, and osteoprotective effects. BCA might mainly regulate the MAPK, PI3K, NRF2, and NF-kB pathways, respectively, to exert its bioactive effects. However, the limited definitive targets, poor biological availability, and insufficient safety evaluation might block the clinical application of BCA. This review may provide new insights for the development of BCA in the application of related diseases.
Topics: Genistein; Humans; Isoflavones; Medicine, Chinese Traditional; Molecular Structure; Trifolium
PubMed: 34530697
DOI: 10.1142/S0192415X21500750 -
Molecular Biology Reports Jun 2023Biochanin-A is a naturally occurring plant phytoestrogen, which mimics specific the agonistic activity of estrogens. Biochanin-A is known to possess numerous activities,... (Review)
Review
Biochanin-A is a naturally occurring plant phytoestrogen, which mimics specific the agonistic activity of estrogens. Biochanin-A is known to possess numerous activities, including neuroprotective, anti-diabetic, hepatoprotective, anti-inflammatory, antioxidant, and antimicrobial activities, along with the anticancer activity. Neuroinflammation is thought to play a pivotal pathological role in neurodegenerative disease. Sustained neuroinflammatory processes lead to progressive neuronal damage in Parkinson's and Alzheimer's disease. Activation of PI3K/Akt cascade and inhibition of MAPK signaling cascade have been observed to be responsible for conferring protection against neuroinflammation in neurodegenerative diseases. An increased oxidative stress promotes neuronal apoptosis via potentiating the TLR-4/NF-κB and inhibiting PI3K/Akt signaling mediated increase in pro-apoptotic and decreases in antiapoptotic proteins. Various authors have explored biochanin-A's neuroprotective effect by using various cell lines and animal models. Biochanin-A has been reported to mediate its neuroprotective via reducing the level of oxidants, inflammatory mediators, MAPK, TLR-4, NF-κB, NADPH oxidase, AchE, COX-2 and iNOS. Whereas, it has been observed to increase the level of anti-oxidants, along with phosphorylation of PI3K and Akt proteins. The current review has been designed to provide insights into the neuroprotective effect of biochanin-A and possible signaling pathways leading to protection against neuroinflammation and apoptosis in the central nervous system. This review will be helpful in guiding future researchers to further explore biochanin A at a mechanistic level to obtain useful lead molecules.
Topics: Animals; NF-kappa B; Neuroprotective Agents; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Neuroinflammatory Diseases; Neurodegenerative Diseases; Toll-Like Receptor 4; Anti-Inflammatory Agents; Antioxidants
PubMed: 37039995
DOI: 10.1007/s11033-023-08397-2 -
Current Drug Research Reviews 2022Biochanin-A (5,7 dihydroxy 4 methoxy isoflavone) is a phytochemical phytoestrogen that is highly effective against various diseases. Biochanin-A is a nutritional and...
BACKGROUND
Biochanin-A (5,7 dihydroxy 4 methoxy isoflavone) is a phytochemical phytoestrogen that is highly effective against various diseases. Biochanin-A is a nutritional and dietary isoflavonoid naturally present in red clover, chickpea, soybeans and other herbs. Biochanin- A possesses numerous biological activities.
OBJECTIVE
The study focused on collective data of therapeutic activities of Biochanin-A.
METHODS
According to the literature, biochanin-A revealed a range of activities starting from chemoprevention, by hindering cell growth, activation of tumor cell death, hampering metastasis, angiogenic action, cell cycle regulation, neuroprotection, by controlling microglial activation, balancing antioxidants, elevating the neurochemicals, suppressing BACE-1, NADPH oxidase hindrance to inflammation, by mitigating the MAPK and NF- κB, discharge of inflammatory markers, upregulating the PPAR-γ, improving the function of heme oxygenase-1, erythroid 2 nuclear factors, detoxifying the oxygen radicals and stimulating the superoxide dismutase action, and controlling its production of transcription factors. Against pathogens, biochanin-A acts by dephosphorylating tyrosine kinase proteins, obstructing gram-negative bacteria, suppressing the development of cytokines from viruses, and improving the action of a neuraminidase cleavage of caspase-3, and acts as an efflux pump inhibitor. In metabolic disorders, biochanin-A acts by encouraging transcriptional initiation and inhibition, activating estrogen receptors, and increasing the activity of differentiation, autophagy, inflammation, and blood glucose metabolism.
CONCLUSION
Therefore, biochanin-A could be used as a therapeutic drug for various pathological conditions and treatments in human beings.
Topics: Humans; Heme Oxygenase-1; Caspase 3; Antioxidants; Biological Products; Phytoestrogens; Reactive Oxygen Species; Receptors, Estrogen; Neuraminidase; NF-kappa B; Inflammation; Isoflavones; PPAR gamma; Cytokines; Protein-Tyrosine Kinases; NADPH Oxidases; Superoxide Dismutase; Glucose
PubMed: 35579127
DOI: 10.2174/2589977514666220509201804 -
Phytomedicine : International Journal... Nov 2020Idiopathic Pulmonary Fibrosis (IPF) is a progressive inflammatory disorder driven by a fibrotic cascade of events such as epithelial to mesenchymal transition,...
BACKGROUND
Idiopathic Pulmonary Fibrosis (IPF) is a progressive inflammatory disorder driven by a fibrotic cascade of events such as epithelial to mesenchymal transition, extracellular matrix production and collagen formation in the lungs in a sequential manner. IPF incidences were raising rapidly across the world. FDA approved pirfenidone and nintedanib (tyrosine kinase inhibitors) are being used as a first-line treatment drugs for IPF, however, neither the quality of life nor survival rates have been improved because of patient noncompliance due to multiple side effects. Thus, the development of novel therapeutic approaches targeting TGF-β mediated cascade of fibrotic events is urgently needed to improve the survival of the patients suffering from devastating disease.
PURPOSE
The aim of this study was to investigate and validate the anti-fibrotic properties of Biochanin-A (isoflavone) against TGF-β mediated fibrosis in in vitro, ex vivo, in vivo models and to determine the molecular mechanisms that mediate these anti-fibrotic effects.
METHODS
The therapeutic activity of BCA was determined in in vitro/ex vivo models. Cells were pre-treated with BCA and incubated in presence or absence of recombinant-TGF-β to stimulate the fibrotic cascade of events. Pulmonary fibrosis was developed by intratracheal administration of bleomycin in rats. BCA treatment was given for 14 days from post bleomycin instillation and then various investigations (collagen content, fibrosis gene/protein expression and histopathological changes) were performed to assess the anti-fibrotic activity of BCA.
RESULTS
In vitro/ex vivo (Primary normal, IPF cell line and primary IPF cells/ Precision cut mouse lung slices) experiments revealed that, BCA treatment significantly (p < 0.001) reduced the expression of TGF-β modulated fibrotic genes/protein expressions (including their functions) which are involved in the cascade of fibrotic events. BCA treatment significantly (p < 0.01) reduced the bleomycin-induced inflammatory cell-infiltration, inflammatory markers expression, collagen deposition and expression of fibrotic markers in lung tissues equivalent or better than pirfenidone treatment. In addition, BCA treatment significantly (p < 0.001) attenuated the TGF-β1/BLM-mediated increase of TGF-β/Smad2/3 phosphorylation and resulted in the reduction of pathological abnormalities in lung tissues determined by histopathology observations.
CONCLUSION
Collectively, BCA treatment demonstrated the remarkable therapeutic effects on TGF-β/BLM mediated pulmonary fibrosis using IPF cells and rodent models. This current study may offer a novel treatment approach to halt and may be even rescue the devastating lung scarring of IPF.
Topics: Animals; Bleomycin; Cell Differentiation; Collagen; Epithelial-Mesenchymal Transition; Extracellular Matrix; Female; Genistein; Humans; Mice, Inbred C57BL; Myofibroblasts; Pulmonary Fibrosis; Rats, Wistar; Reproducibility of Results; Smad Proteins; Transforming Growth Factor beta
PubMed: 32781391
DOI: 10.1016/j.phymed.2020.153298 -
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 -
Pharmaceutics Mar 2023Biochanin A (BCA), an isoflavone derived from various plants such as chickpea, red clover and soybean, is attracting increasing attention and is considered to have... (Review)
Review
Biochanin A (BCA), an isoflavone derived from various plants such as chickpea, red clover and soybean, is attracting increasing attention and is considered to have applications in the development of pharmaceuticals and nutraceuticals due to its anti-inflammatory, anti-oxidant, anti-cancer and neuroprotective properties. To design optimised and targeted BCA formulations, on one hand there is a need for more in-depth studies on the biological functions of BCA. On the other hand, further studies on the chemical conformation, metabolic composition and bioavailability of BCA need to be conducted. This review highlights the various biological functions, extraction methods, metabolism, bioavailability, and application prospects of BCA. It is hoped that this review will provide a basis for understanding the mechanism, safety and toxicity of BCA and implementing the development of BCA formulations.
PubMed: 37111591
DOI: 10.3390/pharmaceutics15041105 -
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