Inoyat Zhumaev
@ibb-nuu.uz
Cell Biophysics
INSTITUTE OF BIOPHYSICS AND BIOCHEMISTRY AT THE NATIONAL UNIVERSITY OF UZBEKISTAN
RESEARCH, TEACHING, or OTHER INTERESTS
Biophysics, Physiology, Pharmacology, General Pharmacology, Toxicology and Pharmaceutics
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Yulduzkhon T. Mirzayeva, Abdisalim A. Zaripov, Inoyat Z. Zhumaev, Pulat B. Usmanov, Shavkat Yu. Rustamov, Sadriddin N. Boboev, Shakhnoza B. Qurbonova, Eldor B. Ibragimov, Madina K. Musaeva, Sardor B. Sobirov,et al.
Oriental Scientific Publishing Company
Introduction: Using conventional organ bath procedures, the current study sought to determine how vincanine hydrochloride affected vasorelaxation brought on by hypoxia in rat aortic rings. Methods: To induce hypoxia, we used a glucose-free Krebs solution that was infused with 95% N2 and 5% CO2. After 60 minutes of hypoxia, the effect of vincanine was evaluated on aortic rings that were precontracted with either 50 mM KCl or 1 µM phenylephrine (PE). The effect of vincanine was more noticeable in aortic rings that had been precontracted by PE as opposed to KCl. Additionally, when verapamil, a blocker of L-type VDCCs, was preincubated with endothelium-intact aortic rings and KCI was used for precontraction, the effect of vincanine on hypoxia-induced vasorelaxation was significantly reduced. Results: Vincanine inhibited hypoxia-induced vasorelaxation in aortic rings precontracted with PE in a calcium-free buffer. Furthermore, the presence of glibenclamide, a specific inhibitor of ATP-sensitive K+-channels (KATP), and tetraethylammonium chloride (TEA), a nonspecific inhibitor of calcium-activated large conductance K+-channels (BKca), significantly reduced the effect of vincanine on hypoxia-induced vasorelaxation. The removal of the endothelium also had a significant impact on the effect of vincanine on hypoxia-induced vasorelaxation. Conclusion: The present findings showed that alkaloid vincanine isolated from the leaves of Vinca minor H. significantly abolished the hypoxia-induced vasorelaxation in rat aorta. The obtained results suggest that vincanine may protect the rat aorta against hypoxic injuries in the vasculature.
Юлия Игоревна Ощепкова, В. В. Узбеков, И. З. Жумаев, Ш. Ю. Рустамов, П. Б. Усманов, and Ш. И. Салихов
Folium Publishing Company
Определена антиаритмическая и инотропная активность комплексов амиодарона гидрохлорида (амиодарон ГХ) с глицирризиновой кислотой (ГК) и моноаммониевой солью глицирризиновой кислоты (МАСГК) на моделях CaCl2-индуцированной аритмии в сравнении с амиодароном ГХ. Показано, что амиодарон ГХ, ГК+амиодарон ГХ (8:1) и МАСГК + амиодарон ГХ (8:1) в разной степени вызывают отрицательный инотропный эффект и дозазависимо подавляют сократительную активность сердечной мышцы на 90,7 – 97,3 % (p ≤ 0,01). Амиодарон ГХ и комплексы амиодарона ГХ с ГК и МАСГК эффективно угнетают развитие спонтанных сокращений папиллярной мышцы сердца крысы, вызванные CaCl2, на 30 – 70 % (p ≤ 0,01). При этом эффект комплекса МАСГК + амиодарон ГХ (8:1) на 70 – 40 % (p ≤ 0,01) больше, по сравнению с эффектами амиодарона ГХ и комплекса ГК + амиодарон ГХ (8:1). Усиление отрицательной инотропной и антиаритмической активности комплекса МАСГК + амиодарон ГХ (8:1) может быть обусловлено повышением его липофильности.
V. V. Uzbekov, B. F. Abdullaev, I. Z. Jumayev, Yu. I. Oshchepkova, P. B. Usmanov, and Sh. I. Salikhov
Springer Science and Business Media LLC
Inoyat Z. Zhumaev, Sadriddin N. Boboev, Pulat B. Usmanov, Shakhnoza B. Qurbonova, Shavkat Yu. Rustamov, Adilbay T. Esimbetov, Gulnaz S. Begdullaeva, Abdisalim A. Zaripov, and Shahobiddin M. Adizov
Oriental Scientific Publishing Company
In the present study, the dose-dependent effect of the alkaloid vincanine on the contractile activity of rat heart papillary muscle was investigated and it was found to increase the force of muscle contraction at all concentrations. The half-maximal inotropic effect concentration (ED50) of vincanine was 21.8 μM, respectively. Studies of the effect of this alkaloid on the cardiomyocyte Na+-channel in the presence of its blocker lidocaine showed that the positive inotropic effect of vincanine does not involve the Na+-channel. When studying the effect of vincanine on Сa2+L-channels in the presence of nifedipine (IC50=0.01 μM), the positive inotropic effect of vincanine (50 μM) alkaloid was partially reduced. In general, it was found that the positive inotropic effect of vincanine on the force of papillary muscle contraction is partially mediated by Сa2+L-channels and mainly Na+/Сa2+ exchange.
Zh. F. Ziyavitdinov, U. Zh. Ishimov, N. Sh. Berdiev, I. Z. Zhumaev, Yu. I. Oshchepkova, P. B. Usmanov, and Sh. I. Salikhov
Springer Science and Business Media LLC
Khilola A. Rakhmanova, Sherzod N. Zhurakulov, Firuza M. Tursunkhodjayeva, Azizbek A. Azamatov, and Dilfuza M. Saidkhodjayeva
Oriental Scientific Publishing Company
It is known that natural isoquinoline alkaloids are widely used in pharmacology and have a variety of biological activities1. At the same time, synthetic analogs of isoquinoline alkaloids are of great interest, among which compounds have been identified that are promising agents that modulate the activity of the dopamine and serotonergic systems2,3, showing cardiprotective4 effect, antiproliferative5 and analgesic6 activity. Currently, in practical medicine, aspirin and anlagen are widely used as non-narcotic analgesics7. However, the low intensity of the analgesic effect, the lack of an analgesic effect in certain types of pain (thermal, mechanical, and other acute pain) and the large number of side effects caused by long-term use limits the scope of their application. The properties of 1-(4’-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) have not been previously described in the scientific literature. The analgesic and anti-inflammatory activity of 1-(4'-dimethylaminophenyl)-6,7- dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) was studied under conditions of thermal (hot plate test) and chemical (vinegar writhing test) irritation, anti-inflammatory activity - on the model of acute inflammatory arthritis. As a result of the studies, it was found that the compound 1-(4'-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline in various doses has an analgesic and anti-inflammatory effect. 1-(4'-Dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) showed a pronounced anti-inflammatory effect at a dose of 0.5 mg/kg, 3.3 times greater than the effect of diclofenac sodium. It has been shown that 1-(4’-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3) has a pronounced analgesic and anti-inflammatory activity and can be used in medical practice as a non-narcotic analgesic.
Pulat B. Usmanov, Inoyat Z. Jumayev, Shavkat Yu. Rustamov, Abdisalim A. Zaripov, Adilbay T. Esimbetov, Sherzod N. Zhurakulov, and Valentina I. Vinogradova
Oriental Scientific Publishing Company
This study investigated the positive inotropic andvasorelaxant activity ofDHQ-11, aconjugate of flavonoid dihydroquercetin with isoquinoline alkaloid 1-aryl-6,7-dimethoxy-1,2.3,4-tetrahydroisoquinoline.A study was performed using anterior papillary muscle removed from the left ventricle and thoracic aorta dissected from rats. DHQ-11 produceda concentration-dependent positive inotropic effect which was more potent than their parent compounds alone. The positive inotropic effect of conjugate DHQ-11was significantly attenuated by the β-adrenoreceptor inhibitor propranolol and L-type Ca2+ channel blocker nifedipine. Also,conjugate DHQ-11 markedly potentiated first post-rest responses indicating that it can modulate Ca2+ loading/release processes in the sarcoplasmic reticulum.These results suggest that positive inotropic effect produced by conjugate DHQ-11may be mediated through activation oftheβ-AR/AC/cAMP/PKA pathway that leads to increased Ca2+ influx and rises in Ca2+ loading/release in the SR, resulting in increased [Ca2+]i and enhanced contraction force. DHQ-11 significantly relaxed both high KCl- and phenylephrine-induced contractions of rat aortic rings whichwere significantly inhibited by lowering extracellular Ca2+ concentration and in the presence of verapamil.DHQ-11 significantly inhibited phenylephrine-induced contractions in a Ca2+-free medium, in the presence of verapamil. The vasorelaxant effect of the DHQ-11 was significantly reduced by the removal of endothelium and in the presenceof L-NAME and methylene blue as well as glibenclamide and TEA.These results suggest that the vasorelaxation produced by conjugate DHQ-11may be mediatedbyan endothelium-independent mechanism involving activation of KATP and BKCa channels and inhibition of L-type VDCCs and Ca2+ release from the sarcoplasmic reticulum and endothelium-dependent mechanism through activation of the NO/sGC/cGMP/PKG signaling pathway resulting in a decrease of intracellular Ca2+levels. These observations reveal that the conjugate DHQ-11 due to its high positive inotropic and vasorelaxant activity could be a promising compound for the design and development of new drugs for the treatment of heart failure.
Sh. S. Khushmatov, I. Z. Zhumaev, Sh. N. Zhurakulov, A. Sh. Saidov, and V. I. Vinogradova
Springer Science and Business Media LLC
Inoyat Jumayev, Pulat Usmanov, Shavkat Rustamov, and Sherzod Zhurakulov
Oriental Scientific Publishing Company
In this study, mechanisms of inotropic action of some isoquinoline alkaloids 1-(4-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (F-24), 1-(2-chloro4,5-methylenedioxyphenyl)-2-hydroxyethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (N-14) and 1-(2-chloro-4,5-methylenedioxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (F-14) were studied. The F-24, F-14, and N-14 alkaloids have been shown to have a negative effect on papillary muscle contraction activity, IC50 value -16,8 μM, 14,03 μM and 12 μM. Ca2+L-channel blocker nifedipine, adenylate cyclase (AC) activator–forskolin, ß-adrenoreceptor (ß-AR) blocker – propranolol, protein kinase C (PKC) activator – phorbol 12-myristate 13-acetate and SR RyR2 activator caffeine were used. Inotropic effects of F-24, F-14 and N-14 isoquinoline alkaloids on cardiomyocytes were suggested, based on results obtained in experiments carried in cardiomyocytes ß-AR → [cAMP] → PKA → [Ca2+]in ↑ cascade, PKC, RyR2 and Na+/Ca2+ modulation.