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1.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2721-2728, 2022 May.
Article in Chinese | MEDLINE | ID: mdl-35718492

ABSTRACT

This study aims to unveil the effect of ophiopogonin D(OPD) on isoproterenol(ISO)-induced apoptosis of rat cardiomyocytes and the possible targets, which is expected to provide clues for further research on the myocardial protection of ophiopogonins. Cell count kit-8(CCK-8) assay was used to detect viability of cells treated with OPD and ISO, Western blot to examine the effect of OPD and ISO on the expression of endoplasmic reticulum stress-related Bip, Bax, Perk, ATF4, caspase-12, and CHOP, flow cytometry to determine cell apoptosis rate, and Hoechst 33258 and Tunel staining to observe cell apoptosis and morphological changes. In addition, the probe for calcium ion-specific detection was employed to investigate calcium ion release from the endoplasmic reticulum, and OPD-bond epoxy-activated agarose solid-phase microspheres were prepared and used as affinity matrix to capture OPD-binding target proteins in H9 c2 cell lysate. For the target proteins of OPD identified by high-resolution mass spectrometry, the related signal pathways were enriched and the potential targets of OPD against cardiomyocyte injury were discussed. The experimental result showed that 10 µmol·L~(-1) ISO can significantly induce the expression of endoplasmic reticulum stress-related proteins and promote cell apoptosis. Different concentration of OPD can prevent the damage of myocardial cells caused by ISO. According to mass spectrometry results, 19 proteins, including Fam129 a and Pdia6, were involved in multiple signaling pathways such as the unfolded protein reaction bound by the ERN1 sensor, tricarboxylic acid cycle, and Nrf2 signal transduction pathway. The above results indicate that OPD protects cardiomyocytes by regulating multiple signaling pathways of target proteins and affecting cell cycle progression.


Subject(s)
Myocytes, Cardiac , Spirostans , Animals , Apoptosis , Calcium/pharmacology , Endoplasmic Reticulum Stress , Isoproterenol/toxicity , Rats , Saponins , Spirostans/pharmacology
2.
J Pharm Sci ; 104(8): 2489-500, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26052932

ABSTRACT

The aim of the current investigation is to explore graphene oxide (GO) special electric and electrochemical properties in modulating and tuning drug delivery in tumor special environment of electrophysiology. The electric-sensitive drug release and redox behavior of GO-bearing berberine (Ber) was studied. Drug release in cell potential was applied in a designed electrode system: tumor environment was simulated at pH 6.2 with 0.1 V pulse voltage, whereas the normal was at pH 7.4 with 0.2 V. Quite different from the pH-depended profile, the electricity-triggered behavior indicated a high correlation with the carriers' structure: GO-based nanocomposite showed a burst release on its special "skin effect," whereas the PEGylated ones released slowly owing to the electroviscous effect of polymer. Cyclic voltammetry was used to investigate the redox behaviors of colloid PEGylated GO toward absorbed Ber in pH 5.8 and 7.2 solutions. After drug loading, the oxidation of Ber was enhanced in a neutral environment, whereas the enhancement of PEG-GO was in an acidic one, which means a possible increased susceptibility of their biotransformation in vivo. The studies designed in this work may help to establish a kind of carrier system for the sensitive delivery and metabolic regulation of drugs according to the different electrophysiological environment in tumor therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Berberine/chemistry , Graphite/chemistry , Nanocomposites/chemistry , Nanoparticles/chemistry , Absorption, Physicochemical , Antineoplastic Agents, Phytogenic/administration & dosage , Berberine/administration & dosage , Colloids , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Drug Compounding , Electrochemical Techniques , Hydrogen-Ion Concentration , Kinetics , Microscopy, Electron, Transmission , Molecular Structure , Nanocomposites/ultrastructure , Nanoparticles/ultrastructure , Oxidation-Reduction , Oxides/chemistry , Polyethylene Glycols/chemistry , Solubility , Surface Properties , Viscosity
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