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Molecules (Basel, Switzerland) Jan 2017Biotransformation of daidzein, genistein and biochanin A by three selected filamentous fungi was investigated. As a result of biotransformations, six glycosylation...
Biotransformation of daidzein, genistein and biochanin A by three selected filamentous fungi was investigated. As a result of biotransformations, six glycosylation products were obtained. Fungus converted all tested isoflavones to 4″--methyl-7--glucosyl derivatives, whereas and were able to transform genistein and biochanin A to genistin and sissotrin, respectively. In the culture of , in addition to the sissotrin, the product of glucosylation at position 5 was formed. Two of the obtained compounds have not been published so far: 4″--methyl-7--glucosyl biochanin A and 5-glucosyl biochanin A (isosissotrin). Biotransformation products were obtained with 22%-40% isolated yield.
Topics: Absidia; Beauveria; Bioreactors; Biotransformation; Fermentation; Genistein; Glycosylation; Isoflavones
PubMed: 28054950
DOI: 10.3390/molecules22010081 -
Pharmaceuticals (Basel, Switzerland) Sep 2023Herpes simplex keratitis (HSK) is a blinding eye disease that is initiated by the herpes simplex virus type 1 (HSV-1). Resistance to acyclovir (ACV) and the side effects...
Herpes simplex keratitis (HSK) is a blinding eye disease that is initiated by the herpes simplex virus type 1 (HSV-1). Resistance to acyclovir (ACV) and the side effects of corticosteroid drugs have become concerning issues, so it is crucial to develop new antivirals for treating HSK. In this study, we report that biochanin A (BCA), a naturally occurring flavonoid compound, provides multifaceted protective effects with anti-viral, anti-inflammatory, anti-oxidative stress and anti-apoptotic activities to alleviate HSK. The results show that BCA significantly inhibited HSV-1 replication in vitro and further proved that BCA principally influenced the early stage of virus infection. We reveal that BCA downregulated the expression of pro-inflammatory factors triggered by HSV-1, including TNF-α, RANTES, IL-1β and IL-6. Furthermore, BCA treatment alleviated oxidative stress and apoptotic arising from HSV-1 infection. Lastly, we induced HSK in male C57BL/6 mice and treated them with either BCA or phosphate buffer solution (PBS) eye drops. We observed the ocular surface lesions; determined the virus load in the tear fluid, corneas as well as trigeminal ganglions (TGs); and detected the levels of inflammation and apoptosis in the corneas simultaneously. These results show that BCA inhibits HSV-1 and alleviates the corneal lesion degree. Our study illustrates that BCA is a promising therapeutic approach for application in treating HSK.
PubMed: 37765049
DOI: 10.3390/ph16091240 -
Bioengineered Dec 2021Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a...
Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (, and ) and cell proliferation (, and ) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.
Topics: Anticarcinogenic Agents; Antiviral Agents; Atlases as Topic; COVID-19; Colorectal Neoplasms; Cyclin D1; ErbB Receptors; Gene Expression Regulation, Neoplastic; Genistein; Humans; Interleukin-1alpha; Interleukin-2; Janus Kinases; Metabolic Networks and Pathways; Molecular Targeted Therapy; Multigene Family; Network Pharmacology; PPAR gamma; Pharmacogenetics; Phosphatidylinositol 3-Kinases; Phytoestrogens; Proto-Oncogene Proteins c-akt; Receptors, Interleukin-6; SARS-CoV-2; STAT Transcription Factors; Signal Transduction; COVID-19 Drug Treatment
PubMed: 34931923
DOI: 10.1080/21655979.2021.2005876 -
Frontiers in Endocrinology 2021We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for...
We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both and , whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.
Topics: Animals; Apoptosis; Brain; Brain Ischemia; Cell Proliferation; Cell Survival; Endoplasmic Reticulum Stress; Female; Genistein; Glucose; Humans; In Vitro Techniques; Infarction, Middle Cerebral Artery; Male; Oxygen; Phosphorylation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 34322090
DOI: 10.3389/fendo.2021.646720 -
Molecules (Basel, Switzerland) Nov 2023The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was...
The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was investigated. There was a significant reduction in liver weight and hepatocyte propagation, with much lower cell injury in rat groups treated with BCA (25 mg/kg and 50 mg/kg) following a TAA induction. These groups had significantly lower levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA). The liver homogenates showed increased antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as decreased malondialdehyde (MDA) levels. The serum biomarkers associated with liver function, namely alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transaminase (GGT), returned to normal levels, comparable to those observed in both the normal control group and the reference control group. Taken together, the normal microanatomy of hepatocytes, the inhibition of PCNA and α-SMA, improved antioxidant enzymes (SOD, CAT, and GPx), and condensed MDA with repairs of liver biomarkers validated BCA's hepatoprotective effect.
Topics: Rats; Animals; Antioxidants; Thioacetamide; Proliferating Cell Nuclear Antigen; Oxidative Stress; Rats, Wistar; Liver; Liver Cirrhosis; Alanine Transaminase; Superoxide Dismutase; Chemical and Drug Induced Liver Injury; Aspartate Aminotransferases
PubMed: 38005330
DOI: 10.3390/molecules28227608 -
Frontiers in Pharmacology 2021Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher...
Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher prevalence of Alzheimer's disease in females. Biochanin A (BCA), a natural phytoestrogen, has been reported to protect neurons against ischemic brain injury. However, the neuroprotective effects of BCA in the postmenopausal-like model of ovariectomized (OVX) rats remain to be investigated. All the rats except for the sham group underwent the resection of bilateral ovaries. Seven days after the OVX surgery, rats were randomly divided into six groups: sham, OVX, OVX + BCA (5 mg/kg), OVX + BCA (20 mg/kg), OVX + BCA (60 mg/kg), and OVX + estradiol (E2; 0.35 mg/kg), which were administrated daily by gavage for 12 weeks. Learning and memory were examined using the Morris water-maze test before the end of the experiment. Morphological changes of the rat hippocampus were observed by HE staining and electron microscopy. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the hippocampus were measured. The effect of BCA on cell viability was measured in the presence of hydrogen peroxide (HO) using CCK8. Flow cytometry was used to measure neuronal apoptosis and reactive oxygen species (ROS) induced by HO. Expression of Bcl-2, Bax, and Caspase-3 was determined by Western blotting using hippocampal tissues and primary cultures of hippocampal neurons. Chronic treatment with BCA mimicked the ability of E2 to reverse the deficit of learning and memory in the Morris water-maze test in OVX rats. BCA normalized OVX-induced morphological changes as revealed by HE staining and electron microscopy. In addition, BCA significantly decreased the levels of MDA, the biomarker of oxidative damage, and increased the activity of the intracellular antioxidant enzymes SOD and GSH-Px in OVX rats. Further, in primary cultures of hippocampal neurons, BCA reversed HO-induced decreases in cell viability and accumulation of ROS. Finally, BCA reversed OVX- or HO-induced increases in Bax and Caspase-3 and decreases in Bcl-2 in the hippocampus and primary cultures of hippocampal neurons. These results suggest that BCA improves memory through its neuroprotective properties in the brain under the circumstance of estrogen deficiency and can be used for treatment of memory loss in postmenopausal women.
PubMed: 33815102
DOI: 10.3389/fphar.2021.603316 -
Biochemical and Biophysical Research... Aug 2017Interleukin (IL)-17-producing T cells play important roles in autoimmunity, chronic inflammation and host protection against extracellular bacteria and fungi. The...
Interleukin (IL)-17-producing T cells play important roles in autoimmunity, chronic inflammation and host protection against extracellular bacteria and fungi. The retinoic acid receptor-related orphan receptors (ROR) α and γ are key regulators of the IL-17-producing phenotype. We previously showed that the isoflavone biochanin A enhanced ROR-mediated transcriptional activity. Here, we investigated the possible mechanisms underlying this ROR activation. Biochanin A-treated murine thymoma EL4 and primary splenocytes demonstrated enhanced induction of IL-17. Biochanin A also induced tyrosine-phosphorylation of signal transducer and activator of transcription 3 (STAT3) in these cells. Stable knockdown of either RORγ or STAT3 in EL4 cells canceled biochanin A-induced upregulation of IL-17 expression. Importantly, biochanin A enhanced complex formation between RORγ and STAT3 or nuclear-receptor coactivator 1 (NCOA1). Furthermore, the biochanin A-induced RORγ-NCOA1 complex was disrupted by a dominant negative mutant of STAT3 or by the STAT3 specific inhibitor Stattic. These results suggest that biochanin A activates RORγ-dependent IL-17 transcription through the enhancement of STAT3 phosphorylation and STAT3-mediated recruitment of NCOA1 to RORγ.
Topics: Animals; Cells, Cultured; Dose-Response Relationship, Drug; Female; Genistein; Mice; Mice, Inbred C57BL; Nuclear Receptor Coactivator 1; Nuclear Receptor Subfamily 1, Group F, Member 3; STAT3 Transcription Factor; Structure-Activity Relationship
PubMed: 28579428
DOI: 10.1016/j.bbrc.2017.05.181 -
International Journal of Molecular... May 2021Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with bare metal stents. Conventional polymers and anti-proliferative drugs...
Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with bare metal stents. Conventional polymers and anti-proliferative drugs suffer from stent thrombosis due to the non-selective nature of the drugs and hypersensitivity to polymer degradation products. Alternatively, various herbal anti-proliferative agents are sought, of which biochanin A (an isoflavone phytoestrogen) was known to have anti-proliferative and vasculoprotective action. PLA-PEG diblock copolymer was tagged with heparin, whose degradation releases heparin locally and prevents thrombosis. To get a controlled drug release, biochanin A was loaded in layered double hydroxide nanoparticles (LDH), which are further encapsulated in a heparin-tagged PLA-PEG copolymer. LDH nanoparticles are synthesized by a co-precipitation process; in situ as well as ex situ loading of biochanin A were done. PLA-PEG-heparin copolymer was synthesized by esterification reaction, and the drug-loaded nanoparticles are coated. The formulation was characterized by FTIR, XRD, DSC, DLS, and TEM. In vitro drug release studies, protein adhesion, wettability, hemocompatibility, and degradation studies were performed. The drug release was modeled by mathematical models to further emphasize the mechanism of drug release. The developed drug-eluting stent coating is non-thrombogenic, and it offers close to zero-order release for 40 days, with complete polymer degradation in 14 weeks.
Topics: Drug Delivery Systems; Drug Liberation; Drug-Eluting Stents; Genistein; Heparin; Humans; Hydroxides; Lactates; Models, Theoretical; Nanoparticles; Polyethylene Glycols; Polymers; Thrombosis
PubMed: 34063962
DOI: 10.3390/ijms22115433 -
Frontiers in Microbiology 2023Biochanin A (BCA), an isoflavone phytoestrogen, is a secondary metabolite produced mainly in leguminous plants. The objective of this study was to evaluate the effect of...
Biochanin A (BCA), an isoflavone phytoestrogen, is a secondary metabolite produced mainly in leguminous plants. The objective of this study was to evaluate the effect of BCA on lactation performance, nitrogen metabolism, and the health of dairy goat. Thirty mid-lactation Saanen dairy goats were divided into three groups randomly: control, 2 g/d BCA group, and 6 g/d BCA group. After 36 days of feeding, 30 dairy goats were transferred to individual metabolic cages. Subsequently, milk yield, feed intake, total feces, and urine excretion were recorded and samples were collected continuously for 3 days. Blood and ruminal fluid samples were collected over the subsequent 4 days. Milk yield, milk protein, fat content, and the feed conversion ratio of dairy goat were significantly increased by the BCA treatment. The levels of serum 17β-estradiol, growth hormone, insulin-like growth factor 1, glutathione peroxidase activity, and total antioxidant capacity were also increased significantly by BCA, indicating that BCA enhanced the antioxidant capacity of dairy goat. Amino acid degradation was significantly inhibited, while the ammonia nitrogen content was reduced significantly by BCA. Total volatile fatty acids was significantly increased by BCA supplementation. In addition, the relative abundance of was decreased significantly. However, the growth of nitrogen metabolism and cellulolytic bacteria was significantly increased under BCA treatment, including ., , , and . In conclusion, supplementation with BCA improved the milk production performance, nitrogen metabolism, rumen fermentation and antioxidant capacity, and regulated the rumen microbiome of dairy goat.
PubMed: 36814572
DOI: 10.3389/fmicb.2023.1101849 -
Medicines (Basel, Switzerland) May 2020L. is an endemic species from the Iberian Peninsula used in Portuguese traditional medicine to treat inflammation-related diseases; this and other health-promoting... (Review)
Review
L. is an endemic species from the Iberian Peninsula used in Portuguese traditional medicine to treat inflammation-related diseases; this and other health-promoting effects are usually associated with the flavonoids produced by this species. In fact, anti-inflammatory properties were established for several of these flavonoid derivatives. A careful survey of the reported data, using mainly the Scopus database and and as keywords, was done. We have examined the papers involving the plant and those about the most relevant flavonoids anti-inflammatory activity. The literature survey demonstrates that species are used to treat several health problems such as antihyperglycemia, hypertension, and inflammatory episodes. It was also possible to establish its richness in flavonoid derivatives, from which several are potential anti-inflammatory agents. From our described and discussed analysis, it can be concluded that is an excellent source of bioactive flavonoids. Moreover, its traditional use to treat inflammation episodes may be due to its flavonoid content, from which genistein, biochanin A, rutin, and daidzein can be emphasized.
PubMed: 32486147
DOI: 10.3390/medicines7060031