PMID: 

Oncol Lett. 2017 Nov ;14(5):5989-5993. Epub 2017 Sep 14. PMID: 29113236

Abstract Title: 

Biochanin A induces anticancer effects in SK-Mel-28 human malignant melanoma cells via induction of apoptosis, inhibition of cell invasion and modulation of NF-κB and MAPK signaling pathways.

Abstract: 

The present study aimed to investigate the antitumor activity of Biochanin A in SK-Mel-28 human malignant melanoma cells. An MTT assay was used to study the cytotoxic effects of Biochanin A.wound healing and invasion assays were used to investigate the effects on cell migration and invasion. Fluorescence microscopy using acridine orange/propidium iodide was used to study effects on cell morphology and apoptosis. Nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) protein expression levels were determined by western blot analysis. The results indicated that Biochanin A significantly inhibited the growth of SK-Mel-28 cells in a dose and time dependent manner. Treatment of the cells with Biochanin A induced apoptosis in a dose dependent manner. Additionally, Biochanin A led to inhibition of cell migration and invasion in a dose-dependent manner and upregulated the expression of key proteins in the NF-κB and MAPK signaling pathways.

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PMID: 

Exp Ther Med. 2018 Mar ;15(3):2830-2836. Epub 2018 Jan 10. PMID: 29456686

Abstract Title: 

Biochanin A extirpates the epithelial-mesenchymal transition in a human lung cancer.

Abstract: 

The natural iso-flavonoid, biochanin A, is categorized as a phytoestrogen and has been demonstrated to exhibit various pharmacological properties. However, no effects of biochanin A on lung cancer cell lines have been reported. Therefore, the present study aimed to demonstrate whether biochanin A has the ability to reduce lung cancer triggered pro-inflammatory effects from leukemic monocytes. We studied the release of cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, from the cocultured cells of A427:AML-193. In addition to this, epithelial-mesenchymal transition was also monitored. In the cocultured A427 and AML-193, AML-193 was stimulated by A427 cells assisting the release of TNF-α and IL-6 cytokines, but the addition of A427 withbiochanin A reduced A427-triggered generation of cytokines by AML-193. Moreover, this non-functional A427:AML-193 coculture reduced the metastasis effects of A427 cells, as determined by wound healing assays and migration/invasion assays. These results were further confirmed by a reduction in Snailand E-cadherin expression levels, which are indicators of the epithelial-mesenchymal transition. These findings suggest the therapeutic effect of biochanin A against lung cancer evoked inflammation and pro-inflammatory functions from monocytic cells.

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PMID: 

Int Immunopharmacol. 2018 Aug ;61:8-19. Epub 2018 May 21. PMID: 29793166

Abstract Title: 

Renoprotective effect of the isoflavonoid biochanin A against cisplatin induced acute kidney injury in mice: Effect on inflammatory burden and p53 apoptosis.

Abstract: 

Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40 mg/kg) in mice treated with a single injection of cisplatin (10 mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen. Further, renal homogenates showed increased level of inflammatory cytokines and upregulation of the expressionof p53 up-regulated modulator of apoptosis (PUMA), p53 and caspase 3 but downregulation in Nrf2 expression. Furthermore, cisplatin group showed marked necrosis and degenerated tubular lining epithelial cells with frequently detected apoptotic bodies. Mice treated with biochanin A (10, 20 or 40 mg/kg) for 14 days prior to cisplatin abrogated cisplatin-mediated damage. Furthermore, the elevated serum creatinine and urea levels were lessened by some doses of biochanin A, indicating protection against renal injury. Similarly, the changes in apoptosis and inflammatory markers have amelioratedto significant levels (P 

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PMID: 

Pharmazie. 2018 06 1 ;73(6):335-341. PMID: 29880086

Abstract Title: 

The effect of biochanin A on cell growth, apoptosis, and migration in osteosarcoma cells.

Abstract: 

Biochanin A has been reported to be associated to tumour cell proliferation, apoptosis and drug resistance in hepatocellular carcinoma, prostate cancer, and colorectal cancer, etc, while the relation of biochanin A on osteosarcoma is not clear. Hence, in this study, we examined the effects of biochanin A treatment on osteosarcoma cell lines MG63 and U2OS on proliferation, apoptosis, invasion and migration. We then investigated the involved molecular mechanism and found a time- and dose-dependent inhibition of cell viability in MG63 and U2OS cells with biochanin A treatment. Under the same circumstances, an increased ratio of cells in G0/G1 phase but a decreased ratio of cells in G2/M phase was observed. In addition, after biochanin A treatment, apoptotic rates clearly increased and decreased migration and invasion ability were observed in MG63 and O2OS cells. Meanwhile, relevant genes involved in cell proliferation, apoptosis, invation and migration demonstrated altered expressions in MG63 and U2OS cells. The present study supports the assumption that biochanin A has suppressive effects on osteosarcoma through regulating cell proliferation, apoptosis, invasion, and migration.

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PMID: 

Behav Neurol. 2018 ;2018:1960106. Epub 2018 Jun 3. PMID: 29971136

Abstract Title: 

Biochanin A Reduces Inflammatory Injury and Neuronal Apoptosis following Subarachnoid Hemorrhage via Suppression of the TLRs/TIRAP/MyD88/NF-B Pathway.

Abstract: 

Inflammatory injury and neuronal apoptosis participate in the period of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Suppression of inflammation has recently been shown to reduce neuronal death and neurobehavioral dysfunction post SAH. Biochanin A (BCA), a natural bioactive isoflavonoid, has been confirmed to emerge the anti-inflammatory pharmacological function. This original study was aimed at evaluating and identifying the neuroprotective role of BCA and the underlying molecular mechanism in an experimental Sprague-Dawley rat SAH model. Neurobehavioral function was evaluated via the modified water maze test and modified Garcia neurologic score system. Thus, we confirmed that BCA markedly decreased the activated level of TLRs/TIRAP/MyD88/NF-B pathway and the production of cytokines. BCA also significantly ameliorated neuronal apoptosis which correlated with the improvement of neurobehavioral dysfunction post SAH. These results indicated that BCA may provide neuroprotection against EBI through the inhibition of inflammatory injury and neuronal apoptosis partially via the TLRs/TIRAP/MyD88/NF-B signal pathway.

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PMID: 

Oncol Res. 2018 Jul 23. Epub 2018 Jul 23. PMID: 30037363

Abstract Title: 

Biochanin A regulates the growth and migration of NSCLC through suppressing the VEGF/VEGFR2 signaling pathway.

Abstract: 

Non-small cell lung cancer (NSCLC) is the most common lung cancer with 15.9% of predicted 5-year survival rate which represents extremely poor prognosis. In this study, we aimed to investigate the effects of Biochanin A (BIO-A) on NSCLC both in vitro and in vivo and to explore its underlying mechanism. We found that BIO-A could effectively inhibit the proliferation of NSCLC cell line A549 in a dose-dependent manner through down-regulating Ki-67 and VEGF, induce apoptosis by activation of cleaved-Caspase-3 and cleaved-Caspase-9, and suppress cell migration by downregulating of MMP-2 and VEGF. Mechanistically, the results of western blot indicated that BIO-A exerted its anti-growth ability through blocking VEGF/VEGFR2 signaling pathway. Moreover, BIOA significantly inhibited the growth of tumor in NSCLC xenograft model. Taken together, our investigation has suggested that BIO-A exhibits potent antitumor activities against NSCLC both in vitro and in vivo and provided a molecular basis for BIO-A potential applications in the treatment of NSCLC and other VEGF-induced diseases.

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PMID: 

Biomed Pharmacother. 2018 Nov ;107:1119-1127. Epub 2018 Aug 27. PMID: 30257324

Abstract Title: 

Biochanin A improves insulin sensitivity and controls hyperglycemia in type 2 diabetes.

Abstract: 

Biochanin A (5,7-Dihydroxy-4'-methoxyisoflavone) is an O-methylated isoflavone known for its anti-inflammatory, lipid lowering and anti-cancer activity. The current study was designed to find out antidiabetic efficacy of Biochanin A in type 2 diabetes in rats. Induction of type 2 diabetes mellitus in experimental animals was carried out by manipulation of diet using high fat diet for fourteen days and then administration of streptozotocin at low dose of 35 mg/kg, i.p. The diabetic animals were treated with 10, 20 and 40 mg/kg of Biochanin A for 28 days. The effect of Biochanin A treatment in diabetic animals was evaluated by measuring changes in body weight, biochemical parameters, insulin sensitivity index, Homeostatic model assessment-Insulin resistance (HOMA-IR), oral glucose tolerance test, glycohaemoglobin and hepatic glycogen level. Changes in histopathological characteristics of pancreatic tissue were also evaluated after treatment with Biochanin A. Immunohistochemical analysis of pancreatic tissue was carried out for the expressionof SIRT1. The results showed that the selected doses of (10, 20 and 40 mg/kg) Biochanin A significantly decreased blood glucose (p 

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PMID: 

J Environ Sci Health A Tox Hazard Subst Environ Eng. 2019 ;54(9):865-873. Epub 2019 Apr 20. PMID: 31007129

Abstract Title: 

Biochanin A prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced adipocyte dysfunction in cultured 3T3-L1 cells.

Abstract: 

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant. TCDD accumulates in the food chain, mainly in the fatty tissues of the human body where it causes various toxic effects. Biochanin A is a natural organic compound in the class of phytochemicals known as flavonoids. We investigated whether biochanin A suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. In the present study, biochanin A suppressed TCDD-induced loss of lipid accumulation. Pretreating the cells with biochanin A increased the levels of the adipogenesis-associated factors peroxisome proliferator-activated receptorγ and adiponectin, which were inhibited by TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with biochanin A. Biochanin A also inhibited the TCDD-driven decrease in production of insulin receptor substrate-1 and glucose transporter 4. These results suggest a preventive effect of biochanin A against TCDD in the development of insulin resistance and diabetes. TCDD increased production of intracellular calcium ([Ca]), prostaglandin E, cytosolic phospholipase A2, and cyclooxygenase-1, while reducing the level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha. However, biochanin A inhibited these TCDD-induced effects. We conclude that biochanin A is an attractive compound for preventing TCDD-induced wasting syndrome.

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PMID: 

Can J Diabetes. 2018 Dec ;42(6):639-644. Epub 2018 Apr 3. PMID: 30054234

Abstract Title: 

Effect of Biochanin A on Retina Levels of Vascular Endothelial Growth Factor, Tumor Necrosis Factor-Alpha and Interleukin-1Beta in Rats With Streptozotocin-Induced Diabetes.

Abstract: 

OBJECTIVES: Without proper medication for the treatment of diabetic retinopathy, retinal cells become malnourished and degenerate, which results in damage to vision cells and can lead to blindness. Flavonoids such as biochanin A (BCA) can directly target various facets of angiogenesis. We assessed the effect of administrating BCA on angiogenic and inflammatory markers in the retina of rats with diabetes.METHODS: We randomly selected 2 groups from 30 male Wistar rats. We used 6 rats in each group. We selected 1 control group, Group 1 (which received 0.5% dimethyl sulfoxide), and a second group, Group 2, which received 10 mg/kg body weight (bw) of BCA. Type 1 diabetes was induced in other rats by a single injection of streptozotocin (55 mg/kg bw). Rats with diabetes were randomly divided into 3 groups as follows: Group 3, the control group with diabetes, which received 0.5% dimethyl sulfoxide; and Groups 4 and 5, which received 10 and 15 mg/kg bw of BCA, respectively. The concentration of vascular endothelial growth factor, tumor necrosis factor-alpha and interleukin-1beta were quantified in the retina of rats with diabetes that received BCA for 6 weeks, and the levels were compared to those of control rats.RESULTS: Administration of BCA to rats with diabetes resulted in a significant restoration of fasting blood glucose levels. After administration of BCA, retina concentrations of vascular endothelial growth factor, tumor necrosis factor-alpha and interleukin-1beta decreased in the 2 groups of treated rats with diabetes compared to the control group with diabetes (p

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PMID: 

Life Sci. 2018 Nov 15 ;213:174-182. Epub 2018 Oct 13. PMID: 30326221

Abstract Title: 

Formononetin and biochanin A protects against ritonavir induced hepatotoxicity via modulation of NfκB/pAkt signaling molecules.

Abstract: 

AIMS: Ritonavir (RIT) is a human immune deficiency virus (HIV) protease inhibitor (PI) active against HIV-1 and HIV-2. Among various adverse effects of PIs, hepatotoxicity is a very common adverse reaction of RIT which is concentration dependent. Red clover isoflavones are found to possess anti-inflammatory, antioxidant and anti-apoptosis activity. Furthermore, recent studies have demonstrated that these isoflavones can be used to alleviate the side-effects of drugs. Hence, the present study was inquested to ascertain the effect of Formononetin (FMN) and Biochanin A (BCA) on RIT induced hepatotoxicity.MAIN METHODS: Five groups of animals were subjected to treatment as control, toxic control (RIT), third group (RIT + FMN), fourth group (RIT + BCA), the fifth group (RIT + FMN + BCA) and sixth group (FMN + BCA) for 14 days. The animals were evaluated for estimation of liver toxicity markers, inflammatory biomarkers, in-vivo biochemical antioxidant parameters. The liver tissues were furtherevaluated histopathologically and western blotting examination for localization of apoptotic gene expression that plays a pivotal role in hepatotoxicity.KEY FINDINGS: FMN and BCA ameliorated the increased levels of biochemical markers of liver, attenuated the RIT induced Bax, caspase-3, NFκB and eNOS activation and persuaded the Bcland pAkt level. Alteration in the levels of inflammatory markers was also observed in both hepatic tissue and serum.SIGNIFICANCE: FMN and BCA exerts hepatoprotective effect through modulating the oxidative stress, inflammation, apoptosis and reversing the tissue degeneration suggesting its therapeutic role in hepatotoxicity and other hepatocellular diseases.

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