-
Animals : An Open Access Journal From... Feb 2020Biochanin A is a naturally occurring flavonoid compound that is found in plant species such as red clover () and alfalfa (). Flavonoids have been reported to regulate...
Biochanin A is a naturally occurring flavonoid compound that is found in plant species such as red clover () and alfalfa (). Flavonoids have been reported to regulate ruminal fermentation, and the objective of this study was to evaluate the effects of biochanin A on ruminal microbial composition and nitrogen metabolism. The experiment was performed by in vitro batch culturing of a control (without biochanin A) and a biochanin A treatment. Following a 24-h incubation, gas production and the amounts of ammonia-nitrogen (NH-N), volatile fatty acid (VFA), and amino acids were measured. Microbial population using 16S rRNA gene sequence. We found that the addition of biochanin A significantly increased microbial gas production; but had no effect on VFA production. Biochanin A supplementation also resulted in reduced microbial urease activity with half the maximal inhibitory concentration of 320 nM and also inhibited the degradation rates of total amino acids, valine, lysine, methionine and leucine by 18%, 56%, 37%, 13%, and 12%, respectively. This inhibition of urease activity and amino acid decomposition resulted in a significant reduction in the NH-N concentration. High-throughput sequencing of the 16S rRNA sequence to monitor microbial composition showed that biochanin A significantly reduced the abundance of the proteolytic bacteria and ureolytic bacteria , but increased the abundance of the lactic acid metabolizing bacteria and . In conclusion, biochanin A reduced the production of ammonia by inhibiting proteolytic bacteria and their decomposition of urea and amino acids.
PubMed: 32106487
DOI: 10.3390/ani10030368 -
International Journal of Molecular... Sep 2022Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine.... (Review)
Review
Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine. Isoflavones are often divided into three subgroups: simple O-substituted derivatives, prenylated derivatives, and glycosides. Simple O-substituted isoflavones and their glycosides, such as daidzein (daidzin), genistein (genistin), glycitein (glycitin), biochanin A (astroside), and formononetin (ononin), are the most common ingredients in legumes and are considered as phytoestrogens for daily dietary hormone replacement therapy due to their structural similarity to 17-β-estradiol. On the basis of the known estrogen-like potency, these above isoflavones possess multiple pharmacological activities such as antioxidant, anti-inflammatory, anticancer, anti-angiogenetic, hepatoprotective, antidiabetic, antilipidemic, anti-osteoporotic, and neuroprotective activities. However, there are very few review studies on the protective effects of these novel isoflavones and their related compounds in cerebral ischemia reperfusion. This review primarily focuses on the biosynthesis, metabolism, and neuroprotective mechanism of these aforementioned novel isoflavones in cerebral ischemia reperfusion. From these published works in in vitro and in vivo studies, simple O-substituted isoflavones could serve as promising therapeutic compounds for the prevention and treatment of cerebral ischemia reperfusion via their estrogenic receptor properties and neuron-modulatory, antioxidant, anti-inflammatory, and anti-apoptotic effects. The detailed mechanism of the protective effects of simple O-substituted isoflavones against cerebral ischemia reperfusion might be related to the PI3K/AKT/ERK/mTOR or GSK-3β pathway, eNOS/Keap1/Nrf-2/HO-1 pathway, TLRs/TIRAP/MyD88/NFκ-B pathway, and Bcl-2-regulated anti-apoptotic pathway. However, clinical trials are needed to verify their potential on cerebral ischemia reperfusion because past studies were conducted with rodents and prophylactic administration.
Topics: Anti-Inflammatory Agents; Antioxidants; Brain Ischemia; Estradiol; Estrogens; Genistein; Glycogen Synthase Kinase 3 beta; Humans; Hypoglycemic Agents; Isoflavones; Kelch-Like ECH-Associated Protein 1; Myeloid Differentiation Factor 88; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Phytoestrogens; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Reperfusion; TOR Serine-Threonine Kinases
PubMed: 36142301
DOI: 10.3390/ijms231810394 -
Molecules (Basel, Switzerland) Jul 2022Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of...
Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting K1.1 and Ca1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba currents through Ca1.2 channels (I) were blocked in a concentration-dependent manner by sativanone, 3'--methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7--[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside], ambocin, butin, and biochanin A increased I. In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs.
Topics: Animals; Asian People; Dalbergia; Humans; Hypertension; Plant Extracts; Rats; Vasodilator Agents
PubMed: 35889386
DOI: 10.3390/molecules27144505 -
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 -
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 Plant Science 2022Mercury (Hg) contamination is increasing worldwide in both wild ecosystems and agricultural soils due to natural processes, but mostly to anthropic activities. The...
Mercury (Hg) contamination is increasing worldwide in both wild ecosystems and agricultural soils due to natural processes, but mostly to anthropic activities. The molecular mechanisms involved in Hg toxicity and tolerance in plants have been extensively studied; however, the role of flavonoids in response to Hg stress remains to be investigated. We conducted a metabolomic study to analyze the changes induced at the secondary metabolite level in three Hg-tolerant and one Hg-sensitive cultivars. A total of 46 flavonoid compounds, classified into five different flavonoid families: anthocyanidins, flavones, isoflavones, pterocarpan flavonoids, and flavanones, along with their respective glycoconjugate derivatives, were identified in leaf and root tissues. The synthesis of free isoflavones, followed by monoglycosylation and further malonylation was shown to be characteristic of root samples, whereas higher glycosylation, followed by further acylation with coumaric and ferulic acid was characteristic of leaf tissues. While minor changes were observed in leaves, significant quantitative changes could be observed in roots upon Hg treatment. Some flavonoids were strongly upregulated in roots, including malonylglucosides of biochanin A, formononetin and medicarpin, and aglycones biochanin, daidzein, and irisolidone. Hg tolerance appeared to be mainly associated to the accumulation of formononetin MalGlc, tricin GlcAGlcA, and afrormosin Glc II in leaves, whereas aglycone accumulation was associated with tolerance to Hg stress in roots. The results evidence the alteration of the flavonoid metabolic profile and their glycosylation processes in response to Hg stress. However, notable differences existed between varieties, both in the basal metabolic profile and in the response to treatment with Hg. Overall, we observed an increase in flavonoid production in response to Hg stress, and Hg tolerance appeared to be associated to a characteristic glycosylation pattern in roots, associated with the accumulation of aglycones and monoglycosylated flavonoids. The findings are discussed in the context of the flavonoid biosynthetic pathway to provide a better understanding of the role of these secondary metabolites in the response and tolerance to Hg stress in .
PubMed: 35874019
DOI: 10.3389/fpls.2022.933209 -
Pharmaceutics Feb 2022The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers...
The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers were prepared with different contents of biochanin A by using an electrospinning method at specific process parameters. The obtained electrospun polylactide fibers, as carriers of biochanin A, were characterized by means of different methods. The presented results showed that the mechanical properties of PLA have not changed significantly in the presence of biochanin A. Scanning electron microscopy showed that the fine fiber structure is retained without visible deformations and biochanin A crystals on the surface of the fibres. The analysis by infrared spectroscopy showed that there are no strong interactions between polylactide and biochanin A molecules, which is a good prerequisite for the diffusion release of biochanin A from PLA fibers.The release of biochanin A from PLA fibers in buffer solution pH 7.4 at 37 °C was monitored by applying the HPLC method. The rate and time of the release of biochanin A from PLA fibers is in correlation with the amount of the active ingredient in the matrix of the carrier and follows zero-order kinetics. PLA fibers with biochanin A exhibit concentration-dependent activity on proliferation and migration of L929 fibroblasts in direct culture system in vitro, and proved to be suitable for a potential formulation for use in wound healing.
PubMed: 35335904
DOI: 10.3390/pharmaceutics14030528 -
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 -
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 -
Nutrients Feb 2023High-grade adult-type diffuse gliomas are the most common and deadliest malignant adult tumors of the central nervous system. Despite the advancements in the... (Review)
Review
High-grade adult-type diffuse gliomas are the most common and deadliest malignant adult tumors of the central nervous system. Despite the advancements in the multimodality treatment of high-grade adult-type diffuse gliomas, the five-year survival rates still remain poor. The biggest challenge in treating high-grade adult-type diffuse gliomas is the intra-tumor heterogeneity feature of the glioma tumors. Introducing dietary flavonoids to the current high-grade adult-type diffuse glioma treatment strategies is crucial to overcome this challenge, as flavonoids can target several molecular targets. This review discusses the anticancer mechanism of flavonoids (quercetin, rutin, chrysin, apigenin, naringenin, silibinin, EGCG, genistein, biochanin A and C3G) through targeting molecules associated with high-grade adult-type diffuse glioma cell proliferation, apoptosis, oxidative stress, cell cycle arrest, migration, invasion, autophagy and DNA repair. In addition, the common molecules targeted by the flavonoids such as Bax, Bcl-2, MMP-2, MMP-9, caspase-8, caspase-3, p53, p38, Erk, JNK, p38, beclin-1 and LC3B were also discussed. Moreover, the clinical relevance of flavonoid molecular targets in high-grade adult-type diffuse gliomas is discussed with comparison to small molecules inhibitors: ralimetinib, AMG232, marimastat, hydroxychloroquine and chloroquine. Despite the positive pre-clinical results, further investigations in clinical studies are warranted to substantiate the efficacy and safety of the use of flavonoids on high-grade adult-type diffuse glioma patients.
Topics: Humans; Adult; Brain Neoplasms; Glioma; Flavonoids; Quercetin; Rutin
PubMed: 36839156
DOI: 10.3390/nu15040797