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Cancer Cell International 2020Hepatocellular carcinoma (HCC) is the most aggressive and frequently diagnosed malignancy of the liver. Despite aggressive therapy, life expectancy of many patients in...
BACKGROUND
Hepatocellular carcinoma (HCC) is the most aggressive and frequently diagnosed malignancy of the liver. Despite aggressive therapy, life expectancy of many patients in these cases is extended by only a few months. Hepatocellular carcinoma (HCC) has a particularly poor prognosis and would greatly benefit from more effective therapies.
METHODS
The CCK-8 assay and colony formation assays were used to test the cell proliferation and viability. The effects of combination Biochanin A and SB590885 on apoptosis and cell cycle arrest of HCC cells were analysed by flow cytometry. The expression of ERK MAPK and PI3K/AKT/mTOR signalling as well as apoptosis and cell cycle-related proteins in HCC cells were tested by western blotting. The HCC cell xenograft model was established to test the tumor proliferation. Serum and plasma were tested for liver and kidney safety markers (ALP, ALT, AST, total bilirubin, creatinine, urea nitrogen) by using SpectraMax i3X.
RESULTS
The combination of natural product Biochanin A with the BRAF inhibitor SB590885 synergistically suppressed proliferation, and promoted cell cycle arrest and apoptosis in vitro. Furthermore, we demonstrated that the combination of Biochanin A and SB590885 led to increased impairment of proliferation and HCC tumour inhibition through disrupting of the ERK MAPK and the PI3K/AKT pathways in vitro. The volumes tumors and the weights of tumours were significantly reduced by the combination treatment compared to the control or single treatments in vivo. In addition, we found that there was no significant hepatorenal toxicity with the drug combination, as indicated by the hepatorenal toxicity test.
CONCLUSION
The results identify an effective combination therapy for the most aggressive form of HCC and provide the possibility of therapeutic improvement for patients with advanced HCC.
PubMed: 32774165
DOI: 10.1186/s12935-020-01463-w -
Experimental and Therapeutic Medicine Dec 2020Biochanin A (BA) is an organic compound produced by and with anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of...
Biochanin A (BA) is an organic compound produced by and with anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis. Experimental rats (n=25) were distributed equally into five groups: i) Healthy control (control) group; ii) experimental periodontitis (ligation) group; and iii) and ligation plus low, medium and high dose of BA (12.5, 25 and 50 mg/kg/day, respectively) groups. A nylon ligature was inserted around rats' maxillary molars for 14 days to trigger the experimental periodontitis. BA was intravenous injected once daily for 4 weeks. After that, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and osteocalcin (OCN) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR. Alveolar bone volume was assessed via hematoxylin and eosin staining and micro-computed tomography. Osteoclasts were identified by tartrate-resistant acid phosphatase staining, and the level of the nuclear factor erythroid-2 related factor 2 (Nrf2) was also detected by immunohistochemical staining. BA treatment groups showed alleviated alveolar bone resorption compared with the ligation group. Moreover, BA treatment significantly inhibited IL-1β, TNF-α, ROS levels, and reduced leukocyte acid phosphatase-positive cells, as well as increased OCN and Nrf2 levels compared with the ligation group. BA had beneficial effects on experimental periodontitis of rats. BA treatment inhibited inflammation, regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss.
PubMed: 33178349
DOI: 10.3892/etm.2020.9381 -
Life (Basel, Switzerland) Dec 2022Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such as , ,...
Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such as , , and . These enzymes are among the most efficient degraders of collagen, playing a crucial role in host colonization. Thus, they are an important target for developing new anti-infective agents because of their pivotal roles in the infection process. A primary screening using a fluorescence resonance energy-transfer assay was used to experimentally evaluate the inhibitory activity of 77 compounds on collagenase A. Based on their inhibitory activity and chemical diversity, a small number of compounds was selected to determine the corresponding half maximal inhibitory con-centration (IC50). Additionally, we used molecular docking to get a better understanding of the enzyme-compound interaction. Several natural compounds (capsaicin, 4',5-dihydroxyflavone, curcumin, dihydrorobinetin, palmatine chloride, biochanin A, 2'-hydroxychalcone, and juglone) were identified as promising candidates for further development into useful anti-infective agents against infections caused by multi-drug-resistant bacterial pathogens which include collagenase A in their enzymatic set.
PubMed: 36556479
DOI: 10.3390/life12122114 -
Molecules (Basel, Switzerland) Sep 2022The novel biochanin A-chromium(III) complex was synthesized by chelating chromium with biochanin A (BCA). The structure of the complex was determined and the complex...
The novel biochanin A-chromium(III) complex was synthesized by chelating chromium with biochanin A (BCA). The structure of the complex was determined and the complex ([CrBCA]) was composed of chromium(III) and three ligands, and the chromium content was 55 μg/mg. The hypoglycemic activity of the complex was studied in db/db mice and C57 mice. The sub-acute toxicity test of the complex was carried out by the maximum limit method in KM mice. The hypoglycemic activity showed that the complex could reduce the weight of db/db mice and lower the fasting blood glucose and random blood glucose levels. The complex also improved the organ index, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results of db/db mice, and some of the indicators were similar to those of the positive control group after treatment with the complex. The histopathology study showed significant improvements in the liver, kidney, pancreas and skeletal muscle compared with the diabetes model group. The complex also showed a significant improvement in serum biochemical indices and antioxidant enzyme activities, as well as glycogen levels. The sub-acute toxicity study showed that the complex did not cause death or any dangerous symptoms during the study. In addition, the sub-acute toxicity study showed that the complex had no significant effect on the serum biochemical indices, antioxidant capacity and organs of normal mice. This study showed that [CrBCA] had good hypoglycemic activity in vivo and had no sub-acute toxicity. This work provides an important reference for the development of functional hypoglycemic foods or drugs.
Topics: Animals; Antioxidants; Blood Glucose; Chromium; Diabetes Mellitus, Experimental; Genistein; Glycogen; Hypoglycemic Agents; Insulin; Insulins; Mice
PubMed: 36144522
DOI: 10.3390/molecules27185786 -
Frontiers in Oncology 2021Abnormal metabolism serves a critical role in glioblastoma (GBM). Biochanin A (BCA), a flavonoid phenolic compound found in edible and herbal plants, has antioxidative...
Abnormal metabolism serves a critical role in glioblastoma (GBM). Biochanin A (BCA), a flavonoid phenolic compound found in edible and herbal plants, has antioxidative and antitumor activities. However, it remains unclear whether BCA has an effect on energy metabolism. The aim of the present study was to evaluate the anticancer effects and molecular mechanism of the effect of BCA on energy metabolism. We observed that BCA inhibited the growth of U251 cells by the mitochondria-mediated intrinsic apoptotic pathway. BCA treatment reduced metabolic function, repressed mitochondrial membrane potential, and increased the production of reactive oxygen species (ROS) in GBM. In addition, we found that BCA decreased aerobic glycolysis by inactivation of the AKT/mTOR pathway. Taken together, the results demonstrate that treatment with BCA inhibited the proliferation of GBM by regulating metabolic reprogramming.
PubMed: 34307130
DOI: 10.3389/fonc.2021.652008 -
BioMed Research International 2018Lung cancer is among the most common malignancies with a poor 5-year survival rate reaching only 16%. Thus, new effective treatment modalities and drugs are urgently...
Lung cancer is among the most common malignancies with a poor 5-year survival rate reaching only 16%. Thus, new effective treatment modalities and drugs are urgently needed for the treatment of this malignancy. In this study, we conducted the first investigation of the effects of Biochanin A on lung cancer and revealed the mechanisms underlying its potential anticancer effects. Biochanin A decreased cell viability in a time-dependent and dose-dependent manner and suppressed colony formation in A549 and 95D cells. In addition, Biochanin A induced S phase arrest and apoptosis and decreased mitochondrial membrane potential (ΔΨm) in A549 and 95D cells in a dose-dependent manner. Our results of subcutaneous xenograft models showed that the growth of Biochanin A group was significantly inhibited compared with that of control groups. Finally, P21, Caspase-3, and Bcl-2 were activated in Biochanin A-treated cells and Biochanin A-treated xenografts which also demonstrated that Biochanin A induced cell cycle arrest and apoptosis in lung cancer cells by regulating expression of cell cycle-related proteins and apoptosis-related proteins. In conclusion, this study suggests that Biochanin A inhibits the proliferation of lung cancer cells and induces cell cycle arrest and apoptosis mainly by regulating cell cycle-related protein expression and activating the Bcl-2 and Caspase-3 pathways, thus suggesting that Biochanin A may be a promising drug to treat lung cancer.
Topics: A549 Cells; Animals; Apoptosis; Dose-Response Relationship, Drug; Genistein; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Mice; S Phase Cell Cycle Checkpoints; Xenograft Model Antitumor Assays
PubMed: 30402472
DOI: 10.1155/2018/3545376 -
BMC Complementary and Alternative... Jan 2017Monoamine oxidase-B (MAO-B) inhibitors are widely used in the treatment of Parkinson's disease. They increase vital monoamine neurotransmitters in the brain. However,...
BACKGROUND
Monoamine oxidase-B (MAO-B) inhibitors are widely used in the treatment of Parkinson's disease. They increase vital monoamine neurotransmitters in the brain. However, there is a need for safer natural reversible MAO inhibitors with MAO-B selectivity. Our previous studies showed that Psoralea corylifolia seeds (PCS) extract contains compounds that inhibit monoamine oxidase-B.
METHODS
In this study, six of PCS constituents sharing a benzopyrone structure were investigated. The compounds Biochanin-A (BIO-A), isopsoralen, 6-prenylnaringenin, neobavaisoflavone, psoralen, and psoralidin, were tested for their ability to inhibit recombinant human MAO-A and B (hMAO-A and hMAO-B) isozymes. The ability of these compounds to inhibit MAO-A and MAO-B were compared to that of PCS ethanolic extract (PCSEE) using spectrophotometric assays and confirmed by luminescence assays. The highly potent and selective MAO-B inhibitor, BIO-A, was further investigated for both isozymes reversibility and enzyme kinetics. Molecular docking studies were used to predict the bioactive conformation and molecular interactions of BIO-A with both isozymes.
RESULTS
The data obtained indicate that benzopyrones inhibited hMAO-A and hMAO-B with different degrees as confirmed with the luminescence assay. BIO-A inhibited hMAO-B with high potency and selectivity in the present study (IC = 0.003 μg/mL) and showing 38-fold more selectivity than PCSEE (hMAO-B IC = 3.03 μg/mL, 17-fold selectivity) without affecting hydrogen peroxide. Furthermore, BIO-A reversibly and competitively inhibited both hMAOs with significantly lower inhibitory constant (K) in hMAO-B (3.8 nM) than hMAO-A (99.3 nM). Our docking studies indicated that the H-bonds and hydrophobic interactions at the human MAO-A and MAO-B active sites contributed to the reversibility and selectivity of BIO-A.
CONCLUSIONS
The data obtained indicate that BIO-A is a potent, reversible and selective MAO-B inhibitor and may be recommended for further investigation in its possible use in the therapeutic management of Parkinson's and Alzheimer's diseases.
Topics: Benzoquinones; Binding, Competitive; Genistein; Humans; Kinetics; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Plant Extracts; Psoralea
PubMed: 28069007
DOI: 10.1186/s12906-016-1525-y -
Molecules (Basel, Switzerland) Nov 2020In recent years, there is emerging evidence that isoflavonoids, either dietary or obtained from traditional medicinal plants, could play an important role as a... (Review)
Review
In recent years, there is emerging evidence that isoflavonoids, either dietary or obtained from traditional medicinal plants, could play an important role as a supplementary drug in the management of type 2 diabetes mellitus (T2DM) due to their reported pronounced biological effects in relation to multiple metabolic factors associated with diabetes. Hence, in this regard, we have comprehensively reviewed the potential biological effects of isoflavonoids, particularly biochanin A, genistein, daidzein, glycitein, and formononetin on metabolic disorders and long-term complications induced by T2DM in order to understand whether they can be future candidates as a safe antidiabetic agent. Based on in-depth in vitro and in vivo studies evaluations, isoflavonoids have been found to activate gene expression through the stimulation of peroxisome proliferator-activated receptors (PPARs) (α, γ), modulate carbohydrate metabolism, regulate hyperglycemia, induce dyslipidemia, lessen insulin resistance, and modify adipocyte differentiation and tissue metabolism. Moreover, these natural compounds have also been found to attenuate oxidative stress through the oxidative signaling process and inflammatory mechanism. Hence, isoflavonoids have been envisioned to be able to prevent and slow down the progression of long-term diabetes complications including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Further thoroughgoing investigations in human clinical studies are strongly recommended to obtain the optimum and specific dose and regimen required for supplementation with isoflavonoids and derivatives in diabetic patients.
Topics: Animals; Biological Availability; Biomarkers; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Hypoglycemic Agents; Isoflavones; Metabolic Networks and Pathways; Molecular Targeted Therapy; Phytochemicals; Polyphenols; Structure-Activity Relationship
PubMed: 33255206
DOI: 10.3390/molecules25235491 -
3 Biotech May 2022Arsenic and chromium are the most common environmental toxicants prevailing in nature. Hence, the present study endeavors to investigate the salutary effects of Coenzyme...
Arsenic and chromium are the most common environmental toxicants prevailing in nature. Hence, the present study endeavors to investigate the salutary effects of Coenzyme Q10 (CoQ10), Biochanin A (BCA), and Phloretin (PHL) on the combined neurotoxic impact of arsenic and chromium in the mice (). Sodium meta-arsenite (100 ppm) and potassium dichromate (75 ppm) were given orally in conjugation with CoQ10 (10 mg/kg), BCA & PHL (50 mg/kg each) in accordance with body weight per day for the 2 weeks experimental duration. Weight reduction was figured out in the exposed toxic group of arsenic and chromium in contrast with the comparison group (control), and with the selected anti-oxidants treatment, it rose significantly to the basal status ( < 0.05). The concentration of arsenic and chromium was reduced significantly ( < 0.001) amidst all the natural compounds co-medicated groups. Anti-oxidant indicators, viz. lipid peroxidation (LPO) and protein carbonyl content (PCC), were found elevated, with reduction observed in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione -transferase (GST), and total thiols (TT) in the arsenic and chromium, co-exposed mice. The alterations in redox homeostasis were well corroborated with the estimations of cholinesterase's enzymes ( < 0.05) along with DNA fragmentation assay and altered Nrf2 signaling. The administration of CoQ10, BCA, and PHL ameliorated the effects of arsenic and chromium induced oxidative stress in the exposed mice. Our research unfolds the remedial outcome of these natural compounds contrary to the combined arsenic and chromium associated-neurotoxicity in the experimental model.
PubMed: 35547012
DOI: 10.1007/s13205-022-03171-w -
Experimental and Therapeutic Medicine Mar 2018The natural iso-flavonoid, biochanin A, is categorized as a phytoestrogen and has been demonstrated to exhibit various pharmacological properties. However, no effects of...
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 with biochanin 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 Snail and 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.
PubMed: 29456686
DOI: 10.3892/etm.2018.5731