The present study aimed to explore FSH receptor binding inhibitor (FRBI) effects on the levels of c-Myc, K-Ras and VEGF related to ovarian cancer, to evaluate the mRNA and protein levels of FSHR in the cumulus-oocyte complex (COCs). COCs were cultured for 24 h in the in vitro maturation (IVM) media replenished with 0, 10, 20, 30 and 40 μg/mL FRBI. Contents of c-Myc, K-Ras, VEGF, cAMP and IP3 in IVM media were detected with ELISA kits, respectively. The results indicated that the levels of FSHR protein and mRNA were determined with Western blotting. C-Myc contents of four FRBI + FSH-treated groups (COM groups) were reduced after IVM of COCs. C-Myc concentrations of COM-3 group was lower than the FSH group (p < .05). K-Ras and IP3 contents of COM-4 were decreased as compared to FSH group (p < .05). Expression levels of FSHR mRNAs and proteins in COM-4 group were smaller than that of FSH group. This study revealed that FRBI treatment could decrease c-Myc and K-Ras levels in the IVM medium fluids, and depress the FSHR levels of COCs. Expression levels of FSHR mRNAs and proteins of COM-4 group were significantly decreased. FRBI exerted its action via the signal pathway of IP3 and cAMP.

2020-05-01·Neuropharmacology2区 · 医学

A novel biscoumarin compound ameliorates cerebral ischemia reperfusion-induced mitochondrial oxidative injury via Nrf2/Keap1/ARE signaling

2区 · 医学

Article

作者: Lv, Chao ; Zhang, Wentong ; Fan, Zhaoyang ; Wang, Yangang ; Li, Mingkai ; Wang, Jun ; Ma, Bo ; Zhang, Haomeng ; Li, Xia

Some phytochemical-derived synthetic compounds have been shown to improve neurological disorders, especially in ischemic stroke. In this study, we identified a novel biscoumarin compound, known as COM 3, which had substantial antioxidant effects in neurons. Next, we found that COM 3 occupies a critical binding site between the Nrf2 and Keap1 dipolymer, impairing the inhibitory effects of Keap1 on Nrf2, both of which play central roles in increasing endogenous antioxidant activity. We verified that COM 3 could increase the survival of neurons experiencing oxygen and glucose deprivation (OGD) from 51.1% to 77.2% when exposure to 2.5 and 10 μg/mL of COM 3, respectively. In addition, the same concentrations of COM 3 could reduce brain infarct volumes by 33.8%to13.7%, respectively, while also reducing the neurobehavioral score from 3.3 to 1.4 on average in mice with a middle cerebral artery occlusion (MCAO). COM 3 reduced neuronal death from 36.5% to 13.9% and apoptosis from 35.1% to 18.2%. In addition, COM 3 could improve the neuronal mitochondrial energy metabolism after experiencing oxidative stress caused by OGD or MCAO. The present study suggests that COM 3 protects against OGD in neurons and MCAO in mice by interfering with the structure of Keap1 to activate the nuclear transcription of Nrf2, which balances endogenous redox activity and restores mitochondrial function. Hence, COM 3 might be a potential therapeutic agent for ischemic stroke in the clinic.

2019-12-16·Anti-Cancer Agents in Medicinal Chemistry4区 · 医学

Receptor Binding Inhibitor Suppresses Carcinogenesis of Cervical Cancer by Depressing Levels of FSHR and ERβ in Mice

4区 · 医学

Article

作者: Yang, Juan ; Gong, Zhuandi ; Shen, Xiaoyun ; Wei, Suocheng ; Lai, Luju

Background:FSH Receptor Binding Inhibitor (FRBI) blocked the binding of FSH to FSHR. Our initial study revealed FRBI reduced the maturation rate, enhanced the apoptosis of sheep Cumulus-Oocyte Complex (COCs). Little is known about whether FRBI modulates ERβ and FSHR levels in the normal uterine and cancerous tissues. The present study aimed to evaluate the FRBI effects on the expressions of Estrogen Receptor-beta (ERβ) and FSH receptor (FSHR) in the uteri.Methods:Methods: 150 mice were assigned to FRBI+FSH (COM), FSH and control groups (CG). Mice of COM-1, COM-2 and COM-3 groups were simultaneously intramuscularly injected with 500, 750 and 1000 µg FRBI with 10 IU FSH, respectively for five days. Western blotting and qPCR were utilized to determine the expression of ERβ and FSHR.Results:In comparison with FSH group, uterine lumen and glands of COM groups became narrow. The uterine wall and endometrial epithelium were thinned, and uterine lumen became narrow. Epithelial cells were decreased. Uterine wall thicknesses of COM-1, COM-2 and COM-3 groups were reduced by 6.49%, 14.89% and 15.69% on day 30 as compared with FSH group. Uterine perimetrium thicknesses of COM-1, COM-2 and COM-3 groups were reduced by 16.17%, 17.93% and 19.92% on day 20 in comparison with FSH group. Levels of FSHR mRNAs and proteins of COM-1, COM-2 and COM-3 groups were less than FSH group on days 20 and 30 (P<0.05). ERβ protein of COM-3 group was less than FSH group. Serum estradiol (E2) and FSH concentrations of COM-2 and COM-3 were lower than that of FSH group on day 30.Conclusion:FRBI could decrease UWT and UPT, also block the uterine development, decline expression levels of ERβ and FSHR protein. Additionally, FRBI reduced the secretion of secretion of FSH and E2. Downregulating expression of FSHR and ERβ may be a potential treatment regimen for cervical cancer patients.

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	J07AJ52	-

研发状态

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适应症	国家/地区	公司	日期
白喉	-	Bharat Biotech International Ltd.	2012-12-01
破伤风	-	Bharat Biotech International Ltd.	2012-12-01
百日咳	-	Bharat Biotech International Ltd.	2012-12-01