Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, has traditionally been used to treat hypertension. In the present study, the effect of tetrandrine on vascular smooth muscle was investigated by using the rat tail artery as a model of a resistance vessel. Tetrandrine relaxes the tension in tail artery helical strips produced by depolarization with 60 mM KCl. Further studies show that tetrandrine inhibits the KCl-induced intracellular Ca++ increase and L-type voltage-dependent Ca++ channel currents, suggesting that tetrandrine relaxes the vessel via inhibition of Ca++ influx through Ca++ channels. Tetrandrine also inhibits norepinephrine (NE)-induced vasocontraction in the presence of extracellular Ca++. It does not, however, inhibit NE-induced vasocontraction in the absence of extracellular Ca++. Tetrandrine also inhibits the NE-induced intracellular Ca++ increase in the presence of extracellular Ca++ and has no effect on the NE-induced intracellular Ca++ increase in the absence of extracellular Ca++. This suggests that tetrandrine also blocks NE-induced Ca++ influx but not NE-induced Ca++ release from the intracellular Ca++ stores. Furthermore, tetrandrine inhibits thapsigargin-induced intracellular Ca++ concentration increase, suggesting that, in addition to blocking Ca++ influx, tetrandrine also may interfere with the interaction between thapsigargin and Ca++ adenosine triphosphatase.
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PMID:Tetrandrine, a Ca++ antagonist: effects and mechanisms of action in vascular smooth muscle cells. 771 83

Extensive pharmacological investigations on tetrandrine, one of the traditional medicinal alkaloids, are reviewed. Tetrandrine has been used clinically in China for centuries in the treatment of many diseases. A recent series of studies has revealed major mechanisms underlying its multiple pharmacological and therapeutic actions. One of the most interesting discoveries is that tetrandrine is a new kind blocker of the voltage-activated, L-type Ca2+ channel in a variety of excitable cells, such as cardiac, GH3 anterior pituitary and neuroblastoma cells, as well as in rat neurohypophysial nerve terminals. Although tetrandrine does not belong to any of the three classical Ca2+ channel blocker groups, electrophysiological and radioligand binding studies show that tetrandrine is an L-type Ca2+ channel blocker with its binding site located at the benzothiazepine receptor on the alpha 1-subunit of the channel. In addition, tetrandrine is a blocker of the voltage-dependent T-type Ca2+ channel. It is clear that tetrandrine's actions in the treatment of cardiovascular diseases, including hypertension and supraventricular arrhythmia, are due primarily to its blocking of voltage-activated L-type and T-type Ca2+ channels. Furthermore, this alkaloid is a potent blocker of the Ca(2+)-activated K+ (K(Ca)) channels of neurohypophysial nerve terminals. The blocking kinetics of tetrandrine on the K(Ca) channel is quite different from that of typical K(Ca) channel blockers such as tetraethylammonium and Ba2+. Although the clinical role of tetrandrine as a blocker of the K(Ca) channels is unclear, it is a promising ligand for the study of K(Ca) channel function.
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PMID:Tetrandrine: a new ligand to block voltage-dependent Ca2+ and Ca(+)-activated K+ channels. 783 29

Tetrandrine, an alkaloid extracted from a Chinese medicinal herb traditionally used in hypertension treatment, inhibited aldosterone production induced in bovine adrenal glomerulosa cells by either potassium ion, angiotensin II, or ACTH in a concentration-dependent manner (IC50 = 10 microM). The inhibition of the response to potassium by tetrandrine had a pattern very similar to that of nickel, a blocker of T-type calcium channels. In addition, tetrandrine prevented calcium influx induced by potassium or angiotensin II without affecting the calcium release phase stimulated by the hormone. The effect of tetrandrine on voltage-activated barium currents was investigated using the whole cell configuration of the patch clamp technique. T-type currents were isolated by recording the slowly deactivating currents elicited during repolarization of the cell to -65 mV after various depolarizing pulses. These currents were blocked by micromolar concentrations of the drug. The voltage sensitivity of channel activation was not affected by tetrandrine; nevertheless, the drug significantly slowed the deactivation of the current. The action of tetrandrine did not require the activation of the channel. Tetrandrine also affected L-type currents, as assessed after inactivating T channels for 100 msec, but at higher concentrations of the drug. Thus, tetrandrine affects with a similar potency aldosterone production, calcium influx, and T-type calcium channel activity. This finding strongly suggests a role for these channels in calcium signaling and control of steroidogenesis in adrenal glomerulosa cells.
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PMID:Blocking T-type calcium channels with tetrandrine inhibits steroidogenesis in bovine adrenal glomerulosa cells. 838 95

Tetrandrine is an alkaloid from a Chinese herb which has been used to treat hypertension in humans. The mechanism(s) of its antihypertensive action is not clear. The goal of this study was to examine the direct effects of a derivative of tetrandrine, 7-O-ethyl tetrandrine (TD), on vascular smooth muscle. In particular, the goals were to study (1) the involvement of the endothelium in the responses of isolated aortic rings to TD, and (2) the effects of TD at intracellular sites involved in muscle contraction in skinned aortic strips treated with saponin. TD (1-100 mumol/l) decreased noradrenaline (NA) and K(+)-evoked contraction of isolated aortic rings with or without endothelium in a concentration-dependent manner although to a lesser degree with the K(+)-evoked contraction. In NA-contracted rings, the IC50 for TD was approximately 28-30 mumol/l, at which a 20% decrease in K(+)-force development of aortic rings was observed. The slope of the concentration-relaxation curve was steeper in aortic rings with endothelium than without endothelium (1.09 vs. 0.88) in NA-contracted rings. TD increased tone in acetylcholine (ACh)-relaxed rings but did not change the force in aortic rings relaxed by sodium nitroprusside (NaNP) or ATP. In TD pretreated rings, TD blocked ACh-induced relaxation, but not NaNP or ATP-induced relaxation. In skinned aortic strips, TD decreased Ca2+ uptake by the SR (IC50 approximately 77.4 mumol/l, slope = 0.88), did not affect Ca2+ release from the SR, and decreased Ca2+-activation of the contractile proteins at 300 mumol/l TD.
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PMID:Mechanisms of action of 7-O-ethyl tetrandrine in isolated vascular smooth muscle of the rabbit aorta. 851 Jul 72

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.
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PMID:Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells. 1007 15

Tetrandrine (Tet) is an alkaloid isolated from the Chinese herb Radix of Stephaniae tetrandrae S Moore. Cardiac and vascular remodeling confers a very definite risk of increased cardiovascular morbidity and mortality. Remodeling reversal has been achieved in human and experimental animals treated with some antihypertensive drugs but not all. This review will focus on cardiovascular remodeling and therapeutic effects of Tet. Three models, SHR, RHR (high renin), and DOCA-Salt HR (low renin) were used. Left ventricular and vascular remodeling had been developed in rats with 8-week untreated hypertension. Tet was administrated by ig 50 mg/kg/d for 9 weeks. Tet lowered SBP, left ventricular weight to body weight ratio, vascular media thickness, media to lumen ratio, cardiac and vascular wet weight, and collagen content. Tet decreased markedly the density and total number of dihydropyridine binding sites and also decreased Ca2+ overload in myocardium and vessels. Tet improved haemodynamic changes during remodeling special diastolic function such as LV compliance and stiffness, increased cardiac myosin ATPase activity and Na+-K+, Ca2+ ATPase activity, and normalized vascular reactivity. Tet inhibited proliferation of vascular smooth muscle cells, induced and sensitized VSMCs to pro-apoptosis stimulation, improved the endothelial function, and increased NO production. These results suggest that Tet was not only an anti-hypertensive drug but also an excellent drug to reverse cardiac and vascular remodeling.
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PMID:Effects of tetrandrine on cardiac and vascular remodeling. 1246 44

Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Such a combination treatment strategy not only provides synergistic effects but also reduces side effects from individual drug. Tetrandrine (Tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoimmune disorders, and hypertension in Mainland China for decades. The accumulated studies both in vitro and in vivo reveal that Tet preserves a wide variety of immunosuppressive effects. Importantly, the Tet-mediated immunosuppressive mechanisms are evidently different from some known DMARDs. The synergistic effects have also been demonstrated between Tet and other DMARDs like FK506 and cyclosporin. These results highlight Tet a very potential candidate to be considered as one of DMARDs in the treatment of autoimmune diseases, especially rheumatoid arthritis. This review summarizes evidence-based in vivo and in vitro studies on this potential Chinese immunosuppressive herb.
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PMID:Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases. 1246 46

Tetrandrine (TET) is a well known naturally occurred nonspecific Ca(2+) channel blocker. It has long been used for the treatment of arrhythmia, hypertension, and occlusive cardiovascular disorders. The objective of the present study was to investigate the effect of TET on the proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). TET significantly inhibited both 10% fetal bovine serum (FBS) and 50 ng/ml platelet-derived growth factor (PDGF)-BB-induced proliferation, [(3) H] ]thymidine incorporation into DNA, and p42/p44 mitogen-activated protein kinase (ERK1/2) phosphorylation at the concentration of 1.0 and 5.0 microM. Flow cytometry analysis of DNA content in synchronized cells revealed blocking of the FBS-inducible cell cycle progression by TET. In accordance with these findings, TET 5 microM caused a 48% decrease in the early elevation of c-fos expression induced after 10% FBS addition. Furthermore, in contrast to its distinguishable higher potency of Ca(2+) antagonistic activity, verapamil showed lower potent antiproliferative activities than TET. These results suggest that TET can exert antiproliferative effects against mitogenic stimuli for RASMCs in vitro by a mechanism that involves the MAPK pathway, altering cell cycle progression, and the inhibitory action cannot be limited to its Ca(2+) modulation.
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PMID:Inhibitory effects of tetrandrine on the serum- and platelet-derived growth factor-BB-induced proliferation of rat aortic smooth muscle cells through inhibition of cell cycle progression, DNA synthesis, ERK1/2 activation and c-fos expression. 1513 51

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known to possess activities including antioxidant, anti-inflammation, anti-fibrotic and anticancer. It is used clinically to treat hypertension and silicosis. In the present study, the anti-proliferative and apoptotic effects of TET were evaluated on three different hepatoma cell lines, namely Hep G2, PLC/PRF/5 and Hep 3B. Using XTT assay, results showed that the IC50 values of TET were 4.35 microM for Hep G2, 9.44 microM for PLC/PRF/5 and 10.41 microM for Hep 3B cells. The CC50 of TET against BNL-CL.2 mouse normal liver cells was 31.12 microM. Interestingly, TET exhibited a lower IC50 value and better selectivity against Hep G2 and PLC/PRF/5 cells than cisplatin. Microscopic observation study, DNA fragmentation assay and flow cytometric analysis further supported apoptotic effect of TET on both PLC/PRF/5 and Hep 3B cells. The cell cycle of PLC/PRF/5 treated with TET appeared to arrest at G2/M phase in a dose-dependent manner, whereas no effect was noted on the cell cycle of Hep 3B cells. The present study concludes that TET exhibited anti-proliferative effect on Hep G2, PLC/PRF/5 and Hep 3B cells in a dose-dependent manner. TET also possesses a lower IC50 and better SI value than cisplatin against Hep G2 and PLC/PRF/5 cells. The effect of TET on cell cycle progression was found to vary with the type of hepatoma cells, suggesting the genetic make-up of the cells play an important role in the response to drug treatment.
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PMID:Antiproliferative and apoptotic effects of tetrandrine on different human hepatoma cell lines. 1643 45

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root of hang-fang-chi (Stephania tetrandra S. Moore), is traditionally used in China for treating inflammation, hypertension and silicosis. In this study, our aim was to examine the anti-inflammatory mechanism of TET through measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-1, and -2 (COX-1 and COX-2) expression, cytokines (TNF-alpha, IL-4 and IL-8) formation, nitric oxide (NO) release and prostaglandin E2 (PGE2) generation in lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. Results showed that TET remarkably suppressed the LPS (1 microg/ml) induction of NO release and PGE2 generation. It also significantly attenuated the LPS-induced transcription of proinflammatory cytokines (TNF-alpha, IL-4 and IL-8) in a dose-dependent manner. Furthermore, TET at 100 microM significantly blocked the LPS induction of iNOS and COX-2 expression, but not the COX-1. Taken together, these results suggest that TET exerts anti-inflammatory effects probably through the suppression of COX-2 and iNOS expression.
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PMID:Tetrandrine inhibits proinflammatory cytokines, iNOS and COX-2 expression in human monocytic cells. 1720 60


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