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Biomedicine & Pharmacotherapy =... Jan 2024The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast...
The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis.
Topics: Rats; Mice; Animals; Cardiomegaly; Myocardium; Myocytes, Cardiac; Fibrosis; Mice, Inbred C57BL; Angiotensin II; Ventricular Remodeling
PubMed: 38091641
DOI: 10.1016/j.biopha.2023.116002 -
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 -
Pharmaceuticals (Basel, Switzerland) Jan 2024The aim of this study was to investigate the antifungal activity of biochanin A (BCA) against planktonic growth and biofilms of six species, including , , , , , and ....
The aim of this study was to investigate the antifungal activity of biochanin A (BCA) against planktonic growth and biofilms of six species, including , , , , , and . We applied various assays that determined (a) the antimicrobial effect on growth of species, (b) the effect on formation of hyphae and biofilm, (c) the effect on the expression of genes related to hyphal growth and biofilm formation, (d) the influence on cell wall structure, and (e) the effect on cell membrane integrity and permeability. Moreover, disk diffusion tests were used to investigate the effect of a combination of BCA with fluconazole to assess their possible synergistic effect on drug-resistant , , and Our results showed that the BCA MIC values against species ranged between 125 µg/mL and 500 µg/mL, and the MIC values were in a concentration range from 250 µg/mL to 1000 µg/mL. The treatment with BCA inhibited adhesion of cells, cell surface hydrophobicity (CSH), and biofilm formation and reduced hyphal growth in all the analyzed species. Real-time qRT-PCR revealed that BCA down-regulated the expression of biofilm-specific genes in . Furthermore, physical destruction of cell membranes and cell walls as a result of the treatment with BCA was observed. The combination of BCA and fluconazole did not exert synergistic effects against fluconazole-resistant .
PubMed: 38256922
DOI: 10.3390/ph17010089 -
Neural Regeneration Research Sep 2024JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic...
JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic effects, can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury; however, its effect on spinal cord injury is still unclear. In this study, a rat model of spinal cord injury was established using the heavy object impact method, and the rats were then treated with Biochanin A (40 mg/kg) via intraperitoneal injection for 14 consecutive days. The results showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal cord tissue injury, reduced inflammation and oxidative stress in spinal cord neurons, and reduced apoptosis and pyroptosis. In addition, Biochanin A inhibited the expression of inflammasome-related proteins (ASC, NLRP3, and GSDMD) and the Toll-like receptor 4/nuclear factor-κB pathway, activated the Nrf2/heme oxygenase 1 signaling pathway, and increased the expression of the autophagy markers LC3 II, Beclin-1, and P62. Moreover, the therapeutic effects of Biochanin A on early post-spinal cord injury were similar to those of methylprednisolone. These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways. These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.
PubMed: 38227535
DOI: 10.4103/1673-5374.390953 -
Journal of Orthopaedic Surgery and... Dec 2023With the development of society, the number of patients with osteoporosis is increasing. The prevention and control of osteoporosis has become a serious and urgent... (Review)
Review
CONTEXT
With the development of society, the number of patients with osteoporosis is increasing. The prevention and control of osteoporosis has become a serious and urgent issue. With the continuous progress of biomedical research, ferroptosis has attracted increased attention. However, the pathophysiology and mechanisms of ferroptosis and osteoporosis still need further study. Natural products are widely used in East Asian countries for osteoporosis prevention and treatment.
OBJECTIVE
In this paper, we will discuss the basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, and in vitro and in vivo studies of natural products to prevent osteoporosis by interfering with ferroptosis.
METHODS
This article takes ferroptosis, natural products, osteoporosis, osteoblasts and osteoclast as key words. Retrieve literature from 2012 to 2023 indexed in databases such as PubMed Central, PubMed, Web of Science, Scopus and ISI.
RESULTS
Ferroptosis has many regulatory mechanisms, including the system XC -/GSH/GPX4, p62/Keap1/Nrf2, FSP1/NAD (P) H/CoQ10, P53/SAT1/ALOX15 axes etc. Interestingly, we found that natural products, such as Artemisinin, Biochanin A and Quercetin, can play a role in treating osteoporosis by promoting ferroptosis of osteoclast and inhibiting ferroptosis of osteoblasts.
CONCLUSIONS
Natural products have great potential to regulate OBs and OCs by mediating ferroptosis to prevent and treat osteoporosis, and it is worthwhile to explore and discover more natural products that can prevent and treat osteoporosis.
Topics: Humans; Ferroptosis; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Biological Products; Osteoporosis
PubMed: 38082321
DOI: 10.1186/s13018-023-04448-3 -
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 -
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 -
BMC Complementary Medicine and Therapies Jan 2024There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has...
Biochanin A abrogates osteoclastogenesis in type 2 diabetic osteoporosis via regulating ROS/MAPK signaling pathway based on integrating molecular docking and experimental validation.
BACKGROUND
There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied.
PURPOSE
To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism.
METHODS
Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway.
RESULTS
Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn't toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway.
CONCLUSION
BCA can prevent type 2 diabetic osteoporosis by restricting osteoclast differentiation via ROS/MAPK signaling pathway.
Topics: Animals; Mice; Humans; Osteogenesis; Molecular Docking Simulation; Reactive Oxygen Species; Diabetes Mellitus, Type 2; Signal Transduction
PubMed: 38191438
DOI: 10.1186/s12906-023-04332-x -
Membranes Jul 2023The macrolide polyene antibiotic amphotericin B (AmB), remains a valuable drug to treat systemic mycoses due to its wide antifungal activity and low probability of...
The macrolide polyene antibiotic amphotericin B (AmB), remains a valuable drug to treat systemic mycoses due to its wide antifungal activity and low probability of developing resistance. The high toxicity of AmB, expressed in nephropathy and hemolysis, could be partially resolved by lowering therapeutic AmB concentration while maintaining efficacy. This work discusses the possibility of using plant polyphenols and alkaloids to enhance the pore-forming and consequently antifungal activity of AmB. We demonstrated that phloretin, phlorizin, naringenin, taxifolin, quercetin, biochanin A, genistein, resveratrol, and quinine led to an increase in the integral AmB-induced transmembrane current in the bilayers composed of palmitoyloleoylphosphocholine and ergosterol, while catechin, colchicine, and dihydrocapsaicin did not practically change the AmB activity. Cardamonin, 4'-hydroxychalcone, licochalcone A, butein, curcumin, and piperine inhibited AmB-induced transmembrane current. Absorbance spectroscopy revealed no changes in AmB membrane concentration with phloretin addition. A possible explanation of the potentiation is related to the phytochemical-produced changes in the elastic membrane properties and the decrease in the energy of formation of the lipid mouth of AmB pores, which is partially confirmed by differential scanning microcalorimetry. The possibility of AmB interaction with cholesterol in the mammalian cell membranes instead of ergosterol in fungal membranes, determines its high toxicity. The replacement of ergosterol with cholesterol in the membrane lipid composition led to a complete loss or a significant decrease in the potentiating effects of tested phytochemicals, indicating low potential toxicity of these compounds and high therapeutic potential of their combinations with the antibiotic. The discovered combinations of AmB with plant molecules that enhance its pore-forming ability in ergosterol-enriched membranes, seem to be promising for further drug development in terms of the toxicity decrease and efficacy improvement.
PubMed: 37505036
DOI: 10.3390/membranes13070670 -
Natural Products and Bioprospecting Apr 2024Although non-alcoholic fatty liver disease (NAFLD) presents as an intricate condition characterized by a growing prevalence, the often-recommended lifestyle... (Review)
Review
Although non-alcoholic fatty liver disease (NAFLD) presents as an intricate condition characterized by a growing prevalence, the often-recommended lifestyle interventions mostly lack high-level evidence of efficacy and there are currently no effective drugs proposed for this indication. The present review delves into NAFLD pathology, its diverse underlying physiopathological mechanisms and the available in vitro, in vivo, and clinical evidence regarding the use of natural compounds for its management, through three pivotal targets (oxidative stress, cellular inflammation, and insulin resistance). The promising perspectives that natural compounds offer for NAFLD management underscore the need for additional clinical and lifestyle intervention trials. Encouraging further research will contribute to establishing more robust evidence and practical recommendations tailored to patients with varying NAFLD grades.
PubMed: 38556609
DOI: 10.1007/s13659-024-00445-z