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1.
Article in Chinese | WPRIM | ID: wpr-1028753

ABSTRACT

AIM To explore the effects of genistein on reducing myocardial fibrosis in diabetic rats and the possible mechanism.METHODS The rat models of type 2 diabetes mellitus(T2DM)established by high-fat diet feeding and intraperitoneal streptozotocin(STZ)injection were randomly divided into the model group,the metformin group(100 mg/kg)and the low-dose and high-dose genistein groups(50,100 mg/kg),in contrast to those of the normal group given normal diet,with 10 rats in each group.After 8 weeks gavage of the corresponding drugs,the rats had detections of their weight of the body and the heart,the heart function,levels of the cardiac indices,the biomarkers of serum creatine kinase isoenzyme(CK-MB),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)activities,the extent of myocardial fibrosis,myocardial mRNA and protein expressions of transforming growth factor-β1(TGF-β1)and Smad homologue 3(Smad 3),and the myocardial distribution and expressions of Collagen Ⅰ and Collagen Ⅲ.RESULTS Compared with the model group,the genistein groups shared increased body weight,stroke output(SV)and ejection fraction(EF)(P<0.01);decreased levels of cardiac indices,left ventricular internal diameter end systole(LVIDs),CK-MB,AST and LDH activities(P<0.05,P<0.01);decreased relative area and myocardial expressions of CollagenⅠand CollagenⅢ(P<0.05,P<0.01);and decreased myocardial expressions of TGF-β1 and Smad3 mRNA and protein(P<0.05,P<0.01).Additionally,the high-dose genistein group was observed with decreased level of left ventricular internal diameter end-diastole(LVIDd)(P<0.05).CONCLUSION Genistein can protect the hearts of T2DM rat models by reducing their myocardial fibrosis via TGF-β1/Smad3 signaling pathway.

2.
Journal of Clinical Hepatology ; (12): 706-711, 2024.
Article in Chinese | WPRIM | ID: wpr-1016513

ABSTRACT

ObjectiveTo investigate the protective effect of Genistein against nonalcoholic fatty liver disease (NAFLD) in ovariectomized (OVX) mice and its mechanism. MethodsA total of 40 female C57BL/6 mice, aged 6 weeks, were used to establish an OVX mouse model, and then they were randomly divided into blank group, 4-week model group, 6-week model group, 8-week model group, and 10-week model group, with 8 mice in each group. Under the same environmental conditions, the mice were given high-fat diet for modeling, and pathological examination showed that NAFLD was successfully induced by 10-week high-fat diet. Another 40 female C57BL/6 mice, aged 6 weeks, were randomly divided into blank group, sham operation group (Sham group), OVX group, OVX+L-Genistein (4 mg/kg body weight) group, and OVX+H-Genistein (8 mg/kg body weight) group. The mice in the Sham group were given the same procedure of OVX, without the ligation of the ovarian artery and the resection of the ovary. The mice in the blank group were given normal diet, and those in the other groups were given high-fat diet. Genistein was dissolved in DMSO, and the mice in the Sham group and the OVX group were treated with solvent solution alone by gavage, once a day for 10 consecutive weeks. Body weight and visceral index were recorded, and the mice were sacrificed to collect serum and liver tissue. Kits were used to measure the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the serum levels of triglyceride (TG) and total cholesterol (TC), and HE staining and oil red O staining were used to observe liver histopathology; Western blot was used to measure the protein expression levels of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor alpha (PPARα) associated with lipid metabolism in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett-t test was used for further comparison between two groups. ResultsAfter 10 weeks of high-fat diet, the OVX+L-Genistein group and the OVX+H-Genistein group had significantly lower body weight, liver index, and liver tissue weight (all P<0.05). In addition, Genistein significantly downregulated the serum levels of TC and TG (P<0.05) and reduced the activities of serum AST and ALT (P<0.05). HE and oil red O staining showed that compared with the OVX group, the OVX+L-Genistein group and the OVX+H-Genistein group had a significant reduction in the accumulation of lipid droplets. Western blot showed that after Genistein intervention, there was a significant reduction in the protein expression level of SREBP-1c and a significant increase in the protein expression level of PPARα (P<0.05). ConclusionGenistein exerts a protective effect against NAFLD in OVX mice possibly by regulating the expression of SREBP-1c and PPARα, thereby promoting fatty acid oxidation and inhibiting liver lipid synthesis.

3.
Article in Chinese | WPRIM | ID: wpr-1025614

ABSTRACT

Objective:To explore the effects of genistein-3'-sodium sulfonate (GSS) on on motor function and brain autophagy levels in Parkinson disease (PD) model mice.Methods:Forty C57BL/6J mice were randomly divided into control group, model group, low-dose GSS group (0.15 mg/kg), medium-dose GSS group (0.50 mg/kg) and high-dose GSS group (1.50 mg/kg), with 8 mice in each group.Mice in the model group and the high, medium, and low-dose GSS groups were injected intraperitoneally with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine to establish the PD mouse model, then mice in high, medium and low-close GSS group were intraperitoneally injected with corresponding doses of GSS (once a day for 21 days). The mice in model group were injected with equal volume 0.9% sodium chloride solution(once a day for 21 days), while the control group mice were fed normally.After 21 days, the motor and cognitive abilities of mice were evaluated by gait analysis, open field test, rotarod test, and modified Y maze test.Western blot was used to detect the expression levels of LC3-Ⅱ and Beclin-1 proteins in the cerebral cortex and striatum tissues of mice.SPSS 26.0 software was used for data analysis.One-way ANOVA was used for normal distribution data comparison among multiple groups, and LSD test was used for further pairwise comparisons, while Kruskal-Wails H test was used for non normal distribution data comparison. Results:(1) Gait analysis showed that there were statistically significant differences in the stride length of left forelimb, left hindlimb, right hindlimb( F=5.93, 6.21, 3.78, all P<0.01) and regularity index( H=14.409, P<0.01). The regularity index of the model group mice was lower than that of the control group ( P<0.05), and the regularity indexes of the low, medium, and high-dose GSS groups were all higher than that of the model group (all P<0.05). (2)In the open field test, there were statistically significant differences in the total distance and speed of movement among the 5 groups ( F=5.49, 5.49, both P<0.01). The total distance and speed of movement in the model group were both lower than those in the control group (both P<0.05). The total distance and speed of movement in the medium-dose GSS group( (2 395.57±319.35) cm, (7.98±1.06) cm/s) and high-dose GSS group ((2 386.51±396.00) cm, (7.95±1.32) cm/s) were higher than those of the model group ((1 863.31±278.96) cm, (6.21±0.93) cm/s) and the low-dose GSS group ((1 956.90±297.15) cm, (6.52±0.99) cm/s) (all P<0.05). (3) In the rotarod test and modified Y maze test, there were significant differences in latency to fall and residence time among the 5 groups ( F=58.41, 9.90, both P<0.01). The latency to fall and residence time of model group were lower than those of control group (both P<0.05), while those in the medium-dose and high-dose GSS groups were higher than those in the model group and low-dose GSS group (all P<0.05). (4) Western blot results showed that there were significant differences in the expression levels of LC3-Ⅱ/LC3-Ⅰ ratio ( F=8.17, 15.47, both P<0.01)and Beclin-1 protein( F=29.07, 20.54, both P<0.01) in cerebral cortex and striatum among the five groups.The LC3-Ⅱ/LC3-Ⅰ ratio and Beclin-1 protein levels in the cerebral cortex ((0.51±0.14), (0.46±0.06)) and striatum ((0.58±0.09), (0.55±0.10)) of the model group were lower than those in the control group (cerebral cortex: (1.00±0.10), (1.00±0.05), striatumm: (1.00±0.06), (1.00±0.25), all P<0.01). The LC3-Ⅱ/LC3-Ⅰratio and Beclin-1 protein in the medium-dose GSS group were higher than those in the model group, low-dose and high-dose GSS groups in both cerebral cortex and striatum (all P<0.05). The level of Beclin-1 of cerebral cortex in model group was lower than those in various doses of GSS group(all P<0.05). There were no statistically significant differences of Beclin-1 protein levels between the model group mice and various doses of GSS groups in striatum (all P>0.05). Conclusion:GSS can improve the motor and cognitive functions of PD model mice, and the mechanism may be related to the upregulation of autophagic activity in the cerebral cortex and striatum of mice.

4.
Braz. J. Pharm. Sci. (Online) ; 60: e22542, 2024. tab, graf
Article in English | LILACS | ID: biblio-1533990

ABSTRACT

We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studie


Subject(s)
Genistein/pharmacology , Nanoparticles/analysis , Melanoma/drug therapy , Particle Size , Spectrum Analysis/classification , Calorimetry, Differential Scanning/methods , Chromatography, High Pressure Liquid/methods
5.
Rev. Bras. Ortop. (Online) ; 59(2): 228-234, 2024. graf
Article in English | LILACS | ID: biblio-1565381

ABSTRACT

Abstract Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1, KISS1R, AR and INSR, by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R, INSR and AR showed higher expression in the G3 group (p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.


Resumo Objetivo Avaliar os efeitos do estrogênio, raloxifeno e genisteína na expressão de KISS1 (kisspeptina), KISS1R (receptor da kisspeptina), AR (receptor de androgênio) e INSR (receptor de insulina) nos ossos de ratas ovariectomizadas. Métodos Quarenta e oito ratas adultas foram divididas aleatoriamente em 6 grupos, contendo 8 animais cada: G1-controle não ovariectomizado); G2-ovariectomizado e tratado com estrogênios conjugados equinos (50 µg/Kg/dia); G3-ovariectomizado e tratado com raloxifeno (0,75 mg/kg/dia); G4-ovariectomizado que recebeu extrato de soja com genisteína (300 mg/kg/dia); G5-ovariectomizado que recebeu estrogênio e genisteína; e G6-ovariectomizado que recebeu estrogênio e raloxifeno. Após 3 meses da cirurgia, os animais castrados receberam os fármacos diariamente por via oral, durante 120 dias. Todos os animais foram sacrificados após esse período, por aprofundamento da anestesia. A tíbia esquerda foi removida para extração de RNA total e análise da expressão gênica de KISS1, KISS1R, AR e INSR, por reação de cadeia de polimerase quantitativa em tempo real (quantitative real-time polymerase chain reaction, qRT-PCR, em inglês). Resultados KISS1 não foi detectado em nenhum dos grupos tratados. KISS1R, INSR e AR mostraram maior expressão no grupo G3 (p < 0,001), enquanto menores níveis de transcritos para esses genes foram observados em G4 e G5. Os animais de G2 apresentaram hipoexpressão dos genes avaliados. Conclusão Os resultados indicam que o raloxifeno, isolado ou combinado com estrogênio, foi capaz de induzir a expressão de genes associados à recuperação da homeostase do tecido ósseo em ratas ovariectomizadas.


Subject(s)
Animals , Rats , Osteoporosis , Genistein , Raloxifene Hydrochloride/therapeutic use , Estrogens , Kisspeptins
6.
Rev. bras. cir. plást ; 38(2): 1-6, abr.jun.2023. ilus
Article in English, Portuguese | LILACS-Express | LILACS | ID: biblio-1443466

ABSTRACT

Skin quality deteriorates with age for various reasons, including hormone deficiencies. In women, the decline in estrogen levels during menopause plays an important role in skin degeneration, with consequent atrophy, collagen reduction, loss of elasticity, and impaired wound healing. Research has demonstrated the beneficial effects of topical phytoestrogen in preventing and repairing skin aging, with localized action and without side effects. The objective of this study was to review the relevant literature, demonstrating that this can be a safe and effective alternative for treating the skin of perimenopausal women.


A qualidade da pele deteriora-se com a idade por vários motivos, incluindo as deficiências hormonais. Nas mulheres, o declínio dos níveis de estrógeno, durante a menopausa, tem papel importante na degeneração cutânea, com consequente atrofia, redução do colágeno, perda de elasticidade e deficiência da cicatrização de feridas. Pesquisas têm demonstrado efeitos benéficos do fitoestrogênio tópico na prevenção e reparação do envelhecimento cutâneo, com ação localizada e sem efeitos colaterais. O objetivo deste estudo foi revisar a literatura pertinente ao assunto, demonstrando que esta pode ser uma alternativa segura e eficaz para o tratamento da pele de mulheres na perimenopausa.

7.
Yao Xue Xue Bao ; (12): 439-446, 2023.
Article in Chinese | WPRIM | ID: wpr-965710

ABSTRACT

Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.

8.
Article in Chinese | WPRIM | ID: wpr-971113

ABSTRACT

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX)drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.


Subject(s)
Mice , Female , Animals , Genistein , Lymphoma , Cyclophosphamide , Thrombophilia , Inflammation , Lectins, C-Type
9.
Article in Chinese | WPRIM | ID: wpr-976529

ABSTRACT

Objective To compare the contents variation of six flavonoids includingdaidzin,glycitin, genistin, daidzein, glycitein and genisteinin black beans, semifinished and finished Sojae Semen Praeparatum.Methods The contents of flavonoids were determined by HPLC,the condition were Diamonsil C18 column (4.6×250 mm, 5 μm) , column temperature 30 ℃, detection wavelength 260 nm, mobile phase 0.2% acetic acid water (A) - methanol (B), gradient elution, flow rate 1.0 ml/min.Results The linearity of this method to determine 6 isoflavones was good (r≥0.9993) within the determination range, and the recovery rate met the requirements. The RSD of precision, repeatability and stability experiment was less than 4%, 3%and 3%. The results of HPLC showed that the contents of six flavonoidsin Sojae Semen Praeparatum increased significantly compared with black beans. And, the contents of six flavonoids in finished Sojae Semen Praeparatum were slightly more than those in semifinished Sojae Semen Praeparatum. Conclusion The HPLC method established in this study could accurately determine the content of 6 isoflavones in Sojae Semen Praeparatum. The content of six isoflavones in black beans could be increased by the fermentation, and the combined isoflavones were transformed into free isoflavones during the fermentation process.

10.
Tianjin Medical Journal ; (12): 1288-1292, 2023.
Article in Chinese | WPRIM | ID: wpr-1020941

ABSTRACT

Objective To investigate the effect of genistein on the proliferation,migration and invasion of prostate cancer cells and its molecular mechanism.Methods Prostate cancer LNCaP and CWR22RV1 cells were divided into the control group(conventional culture)and the experimental group(50μmol/L genistein treatment).The effect of genistein on the proliferation of prostate cancer cells were analyzed by MTT assay.The effect of genistein on the migration and invasion of prostate cancer cells were analyzed by cell scratch assay and Transwell assay.The protein levels of epithelial interstital transformation(EMT)intermediate markers E-Cadherin,N-Cadherin,Vimentin,and tumor stem cell markers CD44 and Oct-4 were detected by Western blot assay.Results MTT assay showed that genistein could inhibit the proliferation of prostate cancer cells.The scratch closure rates of LNCaP and CWR22RV1 cells were significantly reduced in the experimental group compared with those in the control group,and the number of cells passing through the Transwell membrane was significantly reduced(P<0.05).Western blot assay showed that genistein could down-regulate the expression levels of N-Cadherin,Vimentin,CD44 and Oct4 in prostate cancer cells,and up-regulate the expression of E-Cadherin in epithelial cells(P<0.01).Conclusion Genistein reduces the dryness of prostate cancer cells by inhibiting the EMT process,thus reducing the proliferation,migration and invasion of prostate cancer cells.

11.
Clinics ; Clinics;78: 100141, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1430229

ABSTRACT

ABSTRACT Objective: The tyrosine-protein kinase inhibitor, genistein, can inhibit cell malignant transformation and has an antitumor effect on various types of cancer. It has been shown that both genistein and KNCK9 can inhibit colon cancer. This research aimed to investigate the suppressive effects of genistein on colon cancer cells and the association between the application of genistein and KCNK9 expression level. Methods: The Cancer Genome Atlas (TCGA) database was used to study the correlation between the KCNK9 expression level and the prognosis of colon cancer patients. HT29 and SW480 colon cancer cell lines were cultured to examine the inhibitory effects of KCNK9 and genistein on colon cancer in vitro, and a mouse model of colon cancer with liver metastasis was established to verify the inhibitory effect of genistein in vivo. Results: KCNK9 was overexpressed in colon cancer cells and was associated with a shorter Overall Survival (OS), a shorter Disease-Specific Survival (DFS), and a shorter Progression-Free Interval (PFI) of colon cancer patients. In vitro experiments showed that downregulation of KCNK9 or genistein application could suppress cell proliferation, migration, and invasion abilities, induce cell cycle quiescence, promote cell apoptosis, and reduce epithelialmesenchymal transition of the colon cancer cell line. In vivo experiments revealed that silencing of KCNK9 or application of genistein could inhibit hepatic metastasis from colon cancer. Additionally, genistein could inhibit KCNK9 expression, thereby attenuating Wnt/β-catenin signaling pathway. Conclusion: Genistein inhibited the occurrence and progression of colon cancer through Wnt/β-catenin signaling pathway that could be mediated by KCNK9.

12.
Braz. j. otorhinolaryngol. (Impr.) ; Braz. j. otorhinolaryngol. (Impr.);88(1): 105-111, Jan.-Feb. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364573

ABSTRACT

Abstract Highlights Cisplatin is an antineoplastic agent used malignant diseases. Cisplatin ototoxicity is generally bilateral, irreversible, and progressive. Genistein is a phytoestrogen. Genistein functions as antioxidant and cell cycle inhibitor by inhibiting DNA topoisomerase. Genistein showed positive effects on ototoxicity with its antioxidant. Objective Cisplatin is an antineoplastic agent used in adults and children for the treatment of various malignant diseases. It can cause irreversible ototoxicity. Genistein is a phytoestrogen. Genistein functions as an antioxidant and cell cycle inhibitor by inhibiting the DNA topoisomerase and tyrosine protein kinase enzymes. The protective effect of genistein in preventing cisplatin-induced ototoxicity and levels of the oxidative stress was investigated. Methods 32 Sprague Dawley rats were used in 4 groups (control, cisplatin, cisplatin + genistein, genistein). Otoacoustic emission measurements of the distortion product were performed on the 1st, 2nd and 5th days of the test protocol. Serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, total antioxidant status, total oxidant status and oxidative stress index measurements were made. Results The hearing of the cisplatin + genistein group was found to be better than that of the cisplatin group. While the malondialdehyde, total oxidant status and oxidative stress index parameters decreased significantly in the cisplatin + genistein group compared to the cisplatin group, superoxide dismutase increased significantly (p < 0.05). Conclusion Genistein showed positive effects against ototoxicity with its antioxidant effect. Level of evidence Level 3.


Resumo DESTAQUES A cisplatina é um agente antineoplásico usado em lesões malignas. A ototoxicidade da cisplatina é geralmente bilateral, irreversível e progressiva. A genisteína é um fitoestrógeno. A genisteína funciona como antioxidante e inibidor do ciclo celular ao inibir a topoisomerase do DNA. A genisteína apresentou efeitos positivos sobre a ototoxicidade com seu efeito antioxidante. Objetivo A cisplatina é um agente antineoplásico usado em adultos e crianças para o tratamento de diversas lesões malignas. Pode causar ototoxicidade irreversível. A genisteína é um fitoestrógeno que funciona como antioxidante e inibidor do ciclo celular ao inibir as enzimas DNA topoisomerase e tirosina-quinase. O efeito protetor da genisteína na prevenção da ototoxicidade induzida pela cisplatina e os níveis de estresse oxidativo foram investigados. Método Trinta e dois ratos Sprague Dawley foram usados em 4 grupos (controle, cisplatina, cisplatina + genisteína, genisteína). As medidas das emissões otoacústicas por produto de distorção foram tomadas nos dias 1, 2 e 5 do protocolo do teste. Foram medidos os níveis séricos de malondialdeído, superóxido dismutase, catalase, glutationa peroxidase, estado antioxidante total, estado oxidante total e índice de estresse oxidativo. Resultados A audição do grupo cisplatina + genisteína foi melhor do que a do grupo cisplatina. Enquanto os parâmetros malondialdeído, estado oxidante total e índice de estresse oxidativo diminuíram significantemente no grupo cisplatina + genisteína em comparação com o grupo cisplatina, o superóxido dismutase mostrou aumento significantemente (p < 0,05). Conclusão A genisteína apresentou efeitos positivos contra a ototoxicidade com seu efeito antioxidante. Nível de evidência Nível 3.

13.
Chinese Journal of Biotechnology ; (12): 749-759, 2022.
Article in Chinese | WPRIM | ID: wpr-927741

ABSTRACT

Genistein and its monoglucoside derivatives play important roles in food and pharmaceuticals fields, whereas their applications are limited by the low water solubility. Glycosylation is regarded as one of the effective approaches to improve water solubility. In this paper, the glycosylation of sophoricoside (genistein monoglucoside) was investigated using a cyclodextrin glucosyltransferase from Penibacillus macerans (PmCGTase). Saturation mutagenesis of D182 from PmCGTase was carried out. Compared with the wild-type (WT), the variant D182C showed a 13.42% higher conversion ratio. Moreover, the main products sophoricoside monoglucoside, sophoricoside diglucoside, and sophoricoside triglucoside of the variant D182C increased by 39.35%, 56.05% and 64.81% compared with that of the WT, respectively. Enzymatic characterization showed that the enzyme activities (cyclization, hydrolysis, disproportionation) of the variant D182C were higher than that of the WT, and the optimal pH and temperature of the variant D182C were 6 and 40℃, respectively. Kinetics analysis showed the variant D182C has a lower Km value and a higher kcat/Km value than that of the WT, indicating the variant D182C has enhanced affinity to substrate. Structure modeling and docking analysis demonstrated that the improved glycosylation efficiency of the variant D182C may be attributed to the increased interactions between residues and substrate.


Subject(s)
Cyclodextrins , Genistein , Glucosyltransferases/metabolism , Glycosylation , Kinetics
14.
Zhongnan Daxue xuebao. Yixue ban ; (12): 707-716, 2022.
Article in English | WPRIM | ID: wpr-939803

ABSTRACT

OBJECTIVES@#Neuropathic pain (NP) is a chronic pain caused by somatosensory neuropathy or disease, and genistein (Gen) might be a potential drug for the treatment of NP. Therefore, this study aims to investigate the effect of Gen on lipopolysaccharide (LPS)-induced inflammatory injury of dorsal root ganglion neuron (DRGn) in rats and the possible molecular mechanism.@*METHODS@#The DRGn of 1-day-old juvenile rats were taken for isolation and culture. The DRGn in logarithmic growth phase were divided into a control group, a LPS group, a tubastatin hydrochloride (TSA)+LPS group, a Gen1+LPS group, a Gen2+LPS group, a Gen2+LPS+TSA group, a Gen2+pcDNA-histone deacetylase 6 (HDAC6)+LPS group, and a Gen2+pcDNA3.1+LPS group. The LPS group was treated with 1 μg/mL LPS for 24 h; the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group were treated with 5 μmol/L TSA, 5 μmol/L Gen, 10 μmol/L Gen respectively for 0.5 h, and then added 1 μg/mL LPS for 24 h; the Gen2+TSA+LPS group was treated with 10 μmol/L Gen and 5 μmol/L TSA for 0.5 h and then added 1 μg/mL LPS for 24 h; the Gen2+pcDNA-HDAC6+LPS group and the Gen2+pcDNA3.1+LPS group received 100 nmol/L pcDNA-HDAC6 and pcDNA3.1 plasmids respectively, and 24 h after transfection, 10 μmol/L Gen was pretreated for 0.5 h, and then added 1 μg/mL LPS for 24 h. Real-time RT-PCR was used to detect the HDAC6 mRNA expression in DRGn; CCK-8 method was used to detect cell viability of DRGn; flow cytometry was used to detect cell apoptosis of DRGn; ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in DRGn culture supernatant; Western blotting was used to detect the protein expression of HDAC6, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κB p65 in DRGn.@*RESULTS@#Compared with the control group, the expression levels of HDAC6 mRNA and protein, the expression levels of TLR4 and MyD88 protein in DRGn of LPS group rats were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, and the activity of DRGn was significantly decreased, the apoptosis rate was significantly increased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05). Compared with the LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the TSA+LPS group, the Gen1+LPS group, the Gen2+LPS group and the Gen2+TSA+LPS group were significantly down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly decreased, the activity of DRGn was significantly increased, the apoptosis rate was significantly decreased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly decreased (all P<0.05), and the above changes were most obvious in the Gen2+TSA+LPS group. Compared with the Gen2+LPS group, the expression levels of HDAC6 mRNA and protein, TLR4 and MyD88 protein expression levels in DRGn of the Gen2+pcDNA-HDAC6+LPS group were significantly up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was significantly increased, the activity of DRGn was significantly decreased, and the apoptosis rate was significantly increased, and the levels of IL-1β, IL-6 and TNF-α in the DRGn culture supernatant were significantly increased (all P<0.05).@*CONCLUSIONS@#Gen can alleviate LPS-induced DRGn inflammatory injury in rats, which might be related to down-regulating the expression of HDAC6 and further inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.


Subject(s)
Animals , Rats , Ganglia, Spinal , Genistein/pharmacology , Histone Deacetylase 6/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Myeloid Differentiation Factor 88 , NF-kappa B/metabolism , Neurons/metabolism , RNA, Messenger , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
15.
Article in English | WPRIM | ID: wpr-950199

ABSTRACT

@# Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

16.
China Pharmacy ; (12): 1196-1204, 2021.
Article in Chinese | WPRIM | ID: wpr-876886

ABSTRACT

OBJECTIVE:To study the inhibi tory effects of genistein on the growth of human nasopharyngeal carcinoma. CNE 1 cells and predict its potential target. METHODS :CCK-8 method was used to test the effects of 0(blank control ),12.5,25,50, 100,150 µmol/L genistein on the proliferation of CNE 1 cells after treated for 24,48,72 h. Flow cytometry was carried out to detect the effects of 0(blank control ),15,30,60 µmol/L genistein on the cell cycle and ap optosis of CNE 1 cells after treated for 24 h. Scratch test was used to investigate the effects of 0(blank control ), 10, 20, 30 µmol/L genistein on themigration ability of CNE 1 cells after treated for 24 h. High (No.18210156) throughput sequencing was conducted to discover the differential genes in CNE 1 cells after treated with 0(blankcontrol),30 µmol/L genistein for 24 h. RT-qPCR assay was adopted to verify the mRNA expression of related differential genes in above trials. RESULTS : Compared with blank control,12.5,25,50,100,150 µmol/L genistein sho wed significant inhibitory effect on the proliferation of CNE 1 cells(P< 0.01),in a concentration- time-effect manner ;15,30 µmol/L genistein could arrest CNE 1 cell cycle at G 0/G1 stage(P<0.05 or P< 0.01);30,60 µmol/L could arrest CNE 1 cell cycle at G 2/M stage and promoted cell apoptosis (P<0.05 or P<0.01). 10,20,30 µmol/L genistein could significantly inhibit the migration ability of CNE 1 cells(padj<0.01). High throughput sequencing revealed a total of 2 271 differentialgenes(P<0.05),1 154 of which were up-regulated while 1 117 of which were down-regulated ;8 potential target genes ,including p53,p21,STC2,FGF2,CDK6,CYCLIN D ,PI3K,AKT,were screened by cell experiment. After validated by RT-qPCR assay ,mRNA expression of p53,p21,STC2,FGF2,CDK6,CYCLIN D and AKT were significantly down-regulated(P<0.05),which consistent with the sequencing results. CONCLUSIONS :Genistein can effectively inhibit the growth of human nasopharyngeal carcinoma CNE 1 cells,the mechanism of which may associated with inhibiting the expression of mutant gene p53,restoring the function of wild-type P 53 protein and inhibiting the activity of PI 3K/Akt pathway.

17.
Article in English | WPRIM | ID: wpr-962186

ABSTRACT

ABSTRACT@#The goal of this study was to investigate differences in alkaline phosphatase (ALP) levels in young and old rabbits after administering the soybean isoflavone genistein during orthodontic tooth movement. Twelve rabbits were used and assigned to four groups (n = 3); OG (old rabbits), OGS (old rabbits + soybean), YG (young rabbits), and YGS (young rabbits + soybean). The rabbit mandibulary incisors were distalised using a nickel-titanium open coil spring (50 g force). Genistein was administered from the initial orthodontic force delivery until day 21, at a dose of 1.2 mg/kg BW once a day. ALP levels (U/mg) were measured on days 1, 7, 14, 21 after orthodontic force delivery using a UV-Vis 6300 spectrophotometer at a 405 nm wavelength. The results were analysed by one-way analysis of variance followed by Tukey’s Honest Significant Difference (HSD) test (p < 0.05). The ALP levels between the young and old age groups were significantly different. ALP levels were highest in the YGS group, and significantly lowest in the OG group (p < 0.05). Moreover, the ALP level of the OGS group was significantly higher than that in the OG group (p < 0.05). In conclusion, daily consumption of soybean isoflavone genistein could enhance ALP levels during orthodontic tooth movement, particularly in older rabbits.


Subject(s)
Rabbits , Alkaline Phosphatase , Tooth Movement Techniques
18.
Article in Chinese | WPRIM | ID: wpr-1006771

ABSTRACT

【Objective】 To explore the effect of Genistein on the proliferation and cell cycle regulation of ovarian cancer cells. 【Methods】 Ovarian cancer OVCAR-5 cells were treated with Genistein. Cell counting and MTS assays were performed to determine the alterations of cell proliferation. Real-time PCR and Western blotting were conducted to examine the expression changes of key cell cycle regulators. 【Results】 Genistein significantly promoted the proliferation and viability of OVCAR-5 cells. After Genistein treatment, cellular mRNA and protein expression levels of cell cycle activators such as PCNA, Cyclin D1 and CDK4 were increased, but those of cell cycle inhibitors such as p21 and p27 were decreased. 【Conclusion】 Genistein can upregulate the proliferation and G1-S transition of ovarian cancer OVCAR-5 cells. The discrepancy may be caused by diverged experimental conditions and/or different ER expression patterns of cell lines. The findings may provide basic information for in-depth analysis of the role(s) and mechanisms by which genistein confers its effect on ovarian cancer cells.

19.
Araçatuba; s.n; 2021. 66 p. graf, ilus.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1434346

ABSTRACT

O objetivo deste estudo foi investigar a ação sinérgica do risedronato de sódio sistêmico e da genisteína administrada localmente, através da funcionalização de implantes, de ratas submetidas a ovariectomia e com hábitos de mimetizam a síndrome metabólica. A parte in vitro deste estudo foi executado em 2 etapas. Na primeira etapa, foi realizada a funcionalização da superfície de discos/implantes com genistína na concentração de 100 µM pela técnica layer by layer (lbl). Na segunda etapa foram feitos testes biológicos em culturas de células, para avaliar as propriedades da superfície funcionalizada, quanto às respostas osteogênicas. Para a cultura de células foram utilizadas células mesenquimais diferenciadas em osteoblastos, isoladas de fêmures de ratos. Após a validação pelos testes executados nas superfícies funcionalizadas, foi realizado estudo in vivo (3ª etapa). Para tanto, no dia 0, as ratas Wistar adultas jovens, fêmeas (n=64) foram divididas em 4 grupos: 1- SHAM (n= 16), animais foram submetidos à ovariectomia (OVX) fictícia e dieta balanceada. 2- SHAM Síndrome Metabólica (SM) (n=16), animais foram submetidos à ovariectomia fictícia e dieta de cafeteria. 3- OVX SM (n=16), animais foram submetidos à ovariectomia bilateral e dieta de cafeteria. 4- OVX SM Risedronato (RIS) (n=16), animais foram submetidos à ovariectomia bilateral, dieta de cafeteria e tratadas com risedronato de sódio. Em cada grupo há 2 subgrupos: A- implantes convencionais e B- implantes funcionalizados com genisteína. No dia 30, foi iniciado o tratamento medicamentoso com risedronato de sódio, na concentração de 0,35mg/kg, ou apenas solução salina, via gavagem, 1 vez por semana. Passados 60 dias da medicação (dia 90), todos os animais foram submetidos à cirurgia para exodontia dos 1os molares superiores bilateralmente e, imediatamente, no alvéolo da raiz mesial, foi instalado os implantes com superfície convencional ou funcionalizada. Os animais foram eutanasiados aos 28 dias (dia 118) após a instalação dos implantes para mensuração do torque de falha na interface osso implante em N/cm. Os dados foram submetidos ao teste de homocedasticidade (Shapiro Wilk). Houve a confirmação de distribuição normal dos dados amostrais e na sequência, foi realizado o teste paramétrico ANOVA One Way or Two Way, seguido do pós teste de Tukey, com o nível de significância de 5% (p< 0,05). Concluiu-se que, a concentração de 100 µM da genisteína manteve a viabilidade celular e resultados favoráveis quanto a genotoxicidade. A dieta de cafeteria e a ovariectomia bilateral mimetizam a síndrome metabólica e a predisposição para osteoporose por deficiência de esteroides gonadais. E, a ação sinérgica entre fármaco sistêmico (risedronato de sódio) e genisteína local foi promissora para a melhora no processo de reparo periimplantar, principalmente no grupo SHAM e OVX SM RIS(AU)


The aim of this study was to investigate the synergistic action of systemic risedronate sodium and locally administered genistein, through implant functionalization, of rats submitted to ovariectomy and with habits mimicking the metabolic syndrome. The in vitro part of this study was performed in 2 steps. In the first step, the surface functionalization of discs/implants was performed with genistein at a concentration of 100 µM by the layer by layer (lbl) technique. In the second step biological tests were performed in cell cultures to evaluate the properties of the functionalized surface for osteogenic responses. For the cell culture, mesenchymal cells differentiated into osteoblasts, isolated from rat femurs, were used. After validation by tests performed on the functionalized surfaces, the in vivo study (third test) was performed. For this purpose, on day 0, young adult female Wistar rats (n=64) were divided into 4 groups: 1- SHAM (n=16), animals were submitted to sham ovariectomy (OVX) and balanced diet. 2- SHAM Metabolic Syndrome (MS) (n=16), animals were submitted to sham ovariectomy and cafeteria diet. 3- OVX SM (n=16), animals underwent bilateral ovariectomy and cafeteria diet. 4- OVX SM Risedronate (RIS) (n=16), animals underwent bilateral ovariectomy, cafeteria diet and treated with risedronate sodium. In each group there are 2 subgroups: A- conventional implants and B- implants functionalized with genistein. On day 30, drug treatment was started with risedronate sodium, at a concentration of 0.35 mg/kg, or just saline solution, via gavage, once a week. After 60 days of medication (day 90), all animals underwent surgery to extract the 1st upper molars bilaterally, and implants with conventional or functionalized surfaces were immediately installed in the mesial root alveolus. The animals were euthanized at 28 days (day 118) after implant installation to measure the failure torque at the implant-bone interface in N/cm. The data were submitted to the homoscedasticity test (Shapiro Wilk). The normal distribution of the sample data was confirmed and then the parametric One Way or Two Way ANOVA test was performed, followed by Tukey's post-test, with a significance level of 5% (p< 0.05). It was concluded that, the concentration of 100 µM of genistein maintained cell viability and favorable results regarding genotoxicity. The cafeteria diet and bilateral ovariectomy mimic the metabolic syndrome and predisposition to osteoporosis by gonadal steroid deficiency. And, the synergistic action between systemic drug (risedronate sodium) and local genistein was promising for the improvement in the periimplant repair process, especially in the SHAM and OVX SM RIS groups(AU)


Subject(s)
Rats , Gonadal Steroid Hormones , Dental Implants , Osseointegration , Genistein , Metabolic Syndrome , Risedronic Acid , Osteoporosis , Surgery, Oral , Bone and Bones , Ovariectomy , Cell Survival , Rats, Wistar , Genotoxicity
20.
Investig. andin ; 22(41)dic. 2020.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1550436

ABSTRACT

La genisteína es una isoflavona presente en la soya, de alto consumo en la población infantil por su uso como sucedáneo de la leche materna, sin embargo, poco se conoce acerca de los efectos a nivel endocrino. En este trabajo, Caenorhabditis elegans se utilizó como modelo para evaluar el efecto de disrupción endocrina de la genisteína a través de letalidad, crecimiento, reproducción, almacenamiento de lípidos y cambios en la expresión de genes de respuesta al estrés (hsp-3, sod-4 y gpx-4). Los resultados indicaron que, aunque la genisteína no indujo letalidad, sí promovió la reproducción, el aumento de la longitud del cuerpo, el incremento en la expresión de genes relacionados con estrés celular y estrés oxidativo y la acumulación lipídica. En conclusión, la genisteína generó efectos relacionados con el efecto de disrupción endocrina en C. elegans, muy probablemente a través de mecanismos de estrés oxidativo.


Genistein is an isoflavone present in soy, which children highly consume as a substitute for breast milk; however, little is known about its effects at the endocrine level. This paper used Caenorhabditis elegans as a model to evaluate the endocrine disrupting effect of genistein through lethality, growth, reproduction, lipid storage, and changes in the expression of stress response genes (hsp-3, sod- 4, and gpx-4). The results indicated that, although genistein did not induce lethality, it did promote reproduction and increased body length, expression of genes related to cellular stress and oxidative stress, and lipid accumulation. In conclusion, genistein produced effects related to endocrine disruption on C. elegans, most likely through oxidative stress mechanisms.

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