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Introduction: NLRP3, ASC, and procaspase-1 form the multiprotein complex known as the NLRP3 inflammasome. Following the priming of NLRP3 by TLR4 ligand, the activation of the NLRP3 inflammasome causes caspase-1 maturation, which results in the release of IL-1ß. Calcium channel antagonists are commonly employed as antihypertensive medications and have anti-inflammatory properties through the inhibition of cytokine release, specifically IL-1ß. The impact of calcium channel antagonists on NLRP3 inflammasomes, however, has not been well studied. This study aimed to investigate the effect of the calcium channel blocker benidipine hydrochloride on LPS-induced NLRP3 inflammasome activation in THP-1 macrophages and its possible mechanism. Methods: Firstly, the cytotoxicity of benidipine hydrochloride was determined by MTT. The effect of benidipine hydrochloride on LPS-induced IL-1ß release was determined by ELISA. Then, the effect of benidipine hydrochloride on the expression of IL-1ß, NLRP3, ASC, and Caspase-1 induced by LPS was determined by QPCR, and the expression of IL-1ß, GSDMD, Caspase-1, and their active forms was determined by Western blot, and the activation of NF-κB was determined by Western blot and immunofluorescence. Finally, the production of ROS was determined by flow cytometry and fluorescence microscopy. Results: Benidipine hydrochloride was found to drastically lower the expression of NLRP3, ASC, and caspase 1, which in turn decreased the amount of IL-1ß secreted by THP-1 macrophages. Benidipine hydrochloride dramatically reduced the phosphorylation level of NF-κB p65 and its nuclear translocation in THP-1 macrophages. Furthermore, benidipine hydrochloride significantly decreased the generation of ROS. Discussion: Based on these results, we deduced that benidipine hydrochloride prevents ROS formation in THP-1 macrophages and LPS-induced NF-κB signaling, which in turn prevents the activation of NLRP3 inflammasomes and the release of IL-1ß.

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Benidipine hydrochloride (BH), a medication frequently used by the hypertension patients, acts as a calcium channel blocker. However, its effects on the macrophages have not been investigated thus far. Our goal was investigating the effect of the benidipine hydrochloride to modulate the J774.2 murine macrophage cells inflammatory activity. Our results suggest that in the absence of a standard stimulating agent (LPS) BH did not stimulate the macrophages to produce pro-inflammatory IL-12p40, TNF-α, GM-CSF and IL-6 cytokines. However, when BH was administrated to the cells in the presence of LPS as stimulating agent, it reduced the production of these pro-inflammatory cytokines. Therefore, it had anti-inflammatory activity. At the clinical setting this study suggests that BH can be utilized as hypertension drug that can suppress the inflammation associated with it.

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Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hantavirus infection, and they also indicate the need for further research in vivo.

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Arenaviruses are a large family of enveloped negative-strand RNA viruses that include several causative agents of severe hemorrhagic fevers. Currently, there are no FDA-licensed drugs to treat arenavirus infection except for the off-labeled use of ribavirin. Here, we performed antiviral drug screening against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) using an FDA-approved drug library. Five drug candidates were identified, including mycophenolic acid, benidipine hydrochloride, clofazimine, dabrafenib, and apatinib, for having strong anti-LCMV effects. Further analysis indicated that benidipine hydrochloride inhibited LCMV membrane fusion, and an adaptive mutation on the LCMV glycoprotein D414 site was found to antagonize the anti-LCMV activity of benidipine hydrochloride. Mycophenolic acid inhibited LCMV replication by depleting GTP production. We also found mycophenolic acid, clofazimine, dabrafenib, and apatinib can inhibit the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Owing to their FDA-approved status, these drug candidates can potentially be used rapidly in the clinical treatment of arenavirus and SARS-CoV-2 infection.

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Objective To investigate the curative effect of benidipine hydrochloride on patients with coronary slow flow angina pectoris(CSFA).Methods Sixty cases patients with CSFA were randomly divided into two groups of 30 patients each.In the control group patients were received aspirin(100 mg,1 times/d) and atorvastatin(20 mg,1 times/d) as basic treatment;in the treatment group patients were received basic treatment plus benidipine hydrochloride(4 mg,1 times/d).Follow up for 6 mouths,the effectiveness rate of treatment(relief of angina and electrocardiogram of myocardial ischemia),the correction of thrombolysis in myocardial infarction(TIMI) frame count(CTFC) before and after the different intervention,and the incidence of adverse cardiovascular events were compared between the treatment group and the control group.Results The effectiveness rate of treatment in the treatment group(86.7%,26/30) was significantly higher than that in the control group(63.3%(19/30);χ2=4.356,P=0.037).There were significant reductions of CTFC in both groups after the different intervention(treatment group:(28.43±3.95) frames vs.(18.40±3.73) frames,t=10.254,P=0.000;control group:(27.87±4.14) frames vs.(21.87±4.17) frames,t=5.580,P=0.000).There was more significant reductions of CTFC in the treatment group as compared to the control group(t=2.138,P=0.037).The incidence of adverse cardiovascular events in the treatment group(10.0%(3/30)) was significantly lower than that in the control group(33.3%(10/30),P=0.028).Conclusion Benidipine hydrochloride is effective in the treatment of CSFA.

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Hypertension is associated with oxidative stress. Amlodipine besylate (AB) and benidipine hydrochloride (BH), which are Ca(2+) antagonists, have been reported to reduce oxidative stress. In this study, we examined the neuroprotective effects of AB and BH on oxidative stress-injured neural stem cells (NSCs), with a focus on the phosphatidylinositol 3-kinase (PI3K) pathway and the extracellular signal-regulated kinase (ERK) pathway. After treatment with H2O2, the viability of NSCs decreased in a concentration-dependent manner; however, co-treatment with AB or BH restored the viability of H2O2-injured NSCs. H2O2 increased free radical production and apoptosis in NSCs, whereas co-treatment with AB or BH attenuated these effects. To evaluate the effects of AB or BH on the H2O2-inhibited proliferation of NSCs, we performed BrdU labeling and colony formation assays and found that NSC proliferation decreased upon H2O2 treatment but that combined treatment with AB or BH restored this proliferation. Western blot analysis showed that AB and BH increased the expression of cell survival-related proteins that were linked with the PI3K and ERK pathways but decreased the expression of cell death-related proteins. To investigate whether the PI3K and ERK pathways were directly involved in the neuroprotective effects of AB and BH on H2O2-treated NSCs, NSCs were pretreated with the PI3K inhibitor, LY294002, or the ERK inhibitor, FR180204, which significantly blocked the effects of AB and BH. Together, our results suggest that AB and BH restore the H2O2-inhibited viability and proliferation of NSCs by inhibiting oxidative stress and by activating the PI3K and ERK pathways.

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OBJECTIVE:To establish a method for the dissolution determination of Benidipine hydrochloride tablets.METHODS:According to Chinese Pharmacopeia(2005 edition),Benidipine hydrochloride tablets were added into hydrochloride acid 0.1 mo?lL-1 at rotation speed of 50 r?min-1,then samples were obtained after 30 min.The absorbance of samples was detected at detection wavelength of 359 nm and accumulative dissolution was calculated.RESULTS:The linear range of benidipine hydrochloride was 5～30?g?mL-1(r=0.999 9)with an average recovery of 99.76%(RSD=0.47%).The accumulative dissolutions of 3 batches of samples were all above 80%.CONCLUSIONS:Established method is simple and reliable for the dissolution determina-tion of Benidipine hydrochloride tablets.