1.The protection of scorpion venom derived activity peptide against the change of dynorphin in the early Parkinson's disease rats.
Dong-mei WANG ; Dan ZHAO ; Sheng-ming YIN ; Dong AN ; Wei CHEN ; De-qin YU ; Hong XU ; Jie ZHAO ; Wan-qin ZHANG ; Yu-xiang TIAN
Chinese Journal of Applied Physiology 2015;31(2):120-122
Animals
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Dynorphins
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metabolism
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Parkinson Disease
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drug therapy
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metabolism
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Peptides
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pharmacology
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Rats
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Scorpion Venoms
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pharmacology
2.Anti-epileptic/pro-epileptic effects of sodium channel modulators from Buthus martensii Karsch.
Qian XIAO ; Zhi-Ping ZHANG ; Yang-Bo HOU ; Dong-Xiao QU ; Le-Le TANG ; Li-Ji CHEN ; Guo-Yi LI ; Yong-Hua JI ; Jie TAO ; Yu-Dan ZHU
Acta Physiologica Sinica 2022;74(4):621-632
The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals
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Anticonvulsants/therapeutic use*
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Neurotoxins/pharmacology*
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Scorpion Venoms/pharmacology*
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Scorpions/chemistry*
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Voltage-Gated Sodium Channels
3.Bioactive peptides from scorpion venoms: therapeutic scaffolds and pharmacological tools.
Kamau PETER MUIRURI ; Jian ZHONG ; Bing YAO ; Ren LAI ; Lei LUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(1):19-35
Evolution and natural selection have endowed animal venoms, including scorpion venoms, with a wide range of pharmacological properties. Consequently, scorpions, their venoms, and/or their body parts have been used since time immemorial in traditional medicines, especially in Africa and Asia. With respect to their pharmacological potential, bioactive peptides from scorpion venoms have become an important source of scientific research. With the rapid increase in the characterization of various components from scorpion venoms, a large number of peptides are identified with an aim of combating a myriad of emerging global health problems. Moreover, some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development. In this review, we summarize the promising scorpion venoms-derived peptides as drug candidates. Accordingly, we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms, as potential drugs that can treat related diseases.
Animals
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Scorpion Venoms/pharmacology*
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Peptides/pharmacology*
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Scorpions
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Drug Development
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Medicine, Traditional
4.Inhibitory effects of immunotargeting of Chinese cobra cytotoxin and iodine-131 against nasopharyngeal carcinoma cells in vitro.
Yong-sheng ZHAO ; Hui-ling YANG ; Chang-zheng LIU
Journal of Southern Medical University 2008;28(7):1235-1236
OBJECTIVETo explore a new specific therapy of nasopharyngeal carcinoma (NPC) using an anti-nasopharyngeal carcinoma (NPC) monoclonal antibody BAC5 conjugate with Chinese cobra (CT) and iodine-131(131I).
METHODSBAC5 was labeled with 131I by chloramine-T method, CT was labeled with 125I using iodogen method, and BAC5 and 125I-CT were conjugated by SPDP method. The inhibitory effect of the conjugate on cultured human NPC CNE2 cells was observed using MTT assay.
RESULTSThe IC50 of 125I-CT-BAC5 conjugate was 9.17x10(-8) mol/L, and that of 131I-BAC5 was 5.83x10(8) Bq/L, and their combined administration showed obvious inhibitory effect on the NPC cells.
CONCLUSIONBoth 125I-CT-BAC5 and 131I-BAC5 have obvious inhibition effects against NPC cells, but their combined use shows stronger effects.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cytotoxins ; pharmacology ; Elapid Venoms ; pharmacology ; Humans ; Immunoconjugates ; pharmacology ; Iodine Radioisotopes ; pharmacology ; Nasopharyngeal Neoplasms ; pathology
5.Progress in sodium channelopathies and biological functions of voltage-gated sodium channel blockers.
Hongyan WANG ; Meng GOU ; Rong XIAO ; Qingwei LI
Chinese Journal of Biotechnology 2014;30(6):875-890
Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.
Animals
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Channelopathies
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physiopathology
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Hippocampus
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drug effects
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Neurons
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drug effects
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Neurotoxins
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pharmacology
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Venoms
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chemistry
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Voltage-Gated Sodium Channel Blockers
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pharmacology
6.Effects of BmkTXK beta on electrophysiological properties of rabbit atrial myocytes.
Dan HU ; Congxin HUANG ; Hong JIANG ; Gengshan LI ; Zhijian CAO ; Wenxin LI ; Shimin WANG
Chinese Medical Journal 2003;116(11):1691-1696
OBJECTIVETo investigate the effects of BmkTXK(beta), a newly purified 'long chain' peptide inhibitor of K(+) channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit atrial myocytes.
METHODSThe standard whole-cell patch-clamp technique was used to study the effects of multiple concentrations of BmkTXK(beta) on potassium currents and action potentials.
RESULTSBmkTXK(beta) produced concentration-dependent prolongation of action potential duration at 20%, 50%, and 90% repolarization (APD(20,50,90)) without any use-dependence. Meanwhile, it had no significant effect on RMP, APA, or V(max) (n = 9). At a dose of 1 micro mol/L, BmkTXK(beta) decreased I(to) by 41.4% (n = 10, P < 0.01) at a membrane potential of +50 mV [from (13.63 +/- 0.87) pA/pF to (7.98 +/- 0.78) pA/pF]. I(to) was reduced significantly with an IC(50) value of 1.82 micromol/L (95% confidence interval: 1.47 - 2.17 micro mol/L), in a clear concentration-dependent manner. BmkTXK(beta) blocked I(Ks) and I(Ks),tail with an IC(50) of 20.15 micromol/L and a 95% confidence interval of 16.93 - 23.37 micromol/L. At a concentration of 10 micromol/L, BmkTXK(beta) blocked both I(Ks) (mean reduction 37.3% +/- 4.2%, P < 0.01, n = 7) and I(Ks), tail (mean reduction 35.8% +/- 4.1%, P < 0.01, n = 7). At 0 mV, 10 micromol/L BmkTXK(beta) inhibited both I(Kr) (mean reduction 40.5% +/- 2.6%, P < 0.01, n = 6) and I(Kr), tail (mean reduction 42.3% +/- 2.9%, P < 0.01, n = 6). Blocking of I(Kr) by BmkTXK(beta) occurred in a concentration-dependent manner, with an IC(50) of 17.21 micromol/L (95% confidence interval: 14.76-19.66 micromol/L). An absence of effects on I(K1) was observed for BmkTXK(beta), with no change in reversal-potential (n = 6, P > 0.05).
CONCLUSIONSBmkTXK(beta) exerts direct blocking effects on several potassium channels involved in cardiac repolarization, and has a strong effect on prolonging the repolarization of rabbit cardiomyocytes without reverse frequency dependence. This finding suggests that BmkTXK(beta) could be a promising class III drug for anti-arrhythmic therapy without the risk of proarrhythmia.
Action Potentials ; drug effects ; Animals ; Cells, Cultured ; Heart Atria ; Myocardium ; cytology ; Patch-Clamp Techniques ; Rabbits ; Scorpion Venoms ; pharmacology
7.Cytotoxicity of Naja Naja Actra Venom Component combined with activated immune cells on leukemia cell line KG1a.
Yan-Jie HE ; Yu-Hua LI ; San-Fang TU ; Hai-Yan WU ; Kun-Yuan GUO
Journal of Experimental Hematology 2013;21(5):1133-1136
This study was aimed to investigate the cytotoxic effect of the Naja Naja Actra Venom Component (NNAVC) combined with activated immune cells on human acute myeloblastic leukemia line KG1a cells. The cytotoxic effects of NNAVC at different concentrations on KG1a cells were measured by CCK-8 method. LDH releasing assay was used to detect the cytotoxic effects of activated immune cells, NNAVC combined with activated immune cells on KG1a cells and the sensitivity of KG1a treated with NNAVC to activated immune cells. The results showed that the inhibitory rate of NNAVC on KG1a cells increased with the concentration enhancement, the cytotoxicity of activated immune cells at the different effector to target (E:T) ratios(6.25:1, 12.5:1, 25:1) on KG1a cells were 12.30%, 24.85% and 52.26%. The cytotoxicity of NNAVC combined with activated immune cells at the different E:T cell ratios (10:1, 20: 1) on KG1a cells were 56.21% and 85.59%, which were higher than that of NNAVC or activated immune cells alone. The cytotoxicity of activated immune cells at the E: T cell ratio of 10:1 on KG1a cells treated with NNAVC at different concentrations were 25.65%, 31.33%, 28.63% and 16.78%, respectively, and that at the E:T cell ratio of 20: 1 were 40.62%, 44.70%, 44.62% and 40.72%. It is concluded that:both of NNAVC and activated immune cells have lethal effect on KG1a cells, and the combination of NNAVC and activated immune cells can strengthen their effect on KG1a.
Animals
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Cell Line, Tumor
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drug effects
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Cytotoxicity, Immunologic
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Elapidae
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Humans
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Immunocompetence
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Leukemia, Myeloid, Acute
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immunology
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pathology
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Venoms
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pharmacology
8.Mechanisms of Chansu Injection in reversing multidrug resistance of HL60/ADM cells.
Journal of Southern Medical University 2012;32(3):337-340
OBJECTIVETo investigate the mechanisms underlying the effect of Chansu Injection (CHS) in reversing multi-drug resistance (MDR) of HL60/ADM cells.
METHODSMTT assay was used to investigate the effect of CHS on adramycin (ADM) sensitivity of HL-60/ADM cells. Flow cytometry was used to observe the effect of CHS on the cell cycle of HL60/ADM cell. The expressions of NF-κB, MRP, GST-π, and iNOS were detected by immunocytochemistry.
RESULTSTreatment with CHS lowered the IC(50) of ADM in HL60/ADM cells from 34.1971 µmol/L to 17.4393 µmol/L, and caused an increase in G(0)/G1 and G(2)/M phase cells with decreased S phase cells. CHS decreased the expressions of MRP mRNA and GST-π and MRP proteins but increased the expressions of iNOS and NF-κB proteins in the cells.
CONCLUSIONCHS can partly reverse MDR in HL60/ADM cells possibly by down-regulating MRP and GST-π, up-regulating NF-κB and iNOS, and promoting cell apoptosis, thereby increase ADM sensitivity of HL-60/ADM cells.
Amphibian Venoms ; pharmacology ; Bufanolides ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; HL-60 Cells ; Humans
9.Effect of exendin-4 on monocyte chemoattractant protein-1 expression in cultured rat glomerular mesangial cells induced by tumor necrosis factor-α in vitro.
Yingjuan JIANG ; Yaoming XUE ; Qian ZHANG ; Yanfei ZHANG ; Yuan YUAN
Journal of Southern Medical University 2013;33(6):930-933
OBJECTIVETo investigate the effect of exendin-4 on the expression of monocyte chemoattractant protein-1 (MCP-1) and fibronectin (FN) in rat glomerular mesangial cells in vitro.
METHODSRat glomerular mesangial cells were divided into 5 groups, namely control group, tumor necrosis factor-α (TNF-α) group (10 ng/ml), TNF-α (10 ng/ml)+E1 (1 nmol/L exendin-4) group, TNF-α (10 ng/ml)+E5 (5 nmol/L exendin-4) group, and TNF-α (10 ng/ml)+E10 (10 nmol/L exendin-4) group. After cultured 24 h or 48 h, RNA were extracted to determine the expression of MCP-1 with real-time PCR, the supernatant were collected to determine the expression of MCP-1 and FN with ELISA.
RESULTSCompared with control group, the cells treated with TNF-α for 24 h showed significantly increase the expression of MCP-1 and FN (P<0.01), exendin-4 significantly reduced the expression of MCP-1 and FN in TNF-α+E5 group and TNF-α+E10 group (P<0.05). After 48h incubation, the expression of MCP-1 and FN increased significantly in TNF-α group (P<0.01), which was lowered by exendin-4 in TNF-α+E1,TNF-α+E5 and TNF-α+E10 groups (P<0.05).
CONCLUSIONExendin-4 has an intrinsic capability to concentration- and time-dependently inhibit TNF-α-induced expression of MCP-1 and FN in rat mesangial cells, suggesting the beneficial effect of exendin-4 in preventing and treating diabetic nephropathy.
Animals ; Cells, Cultured ; Chemokine CCL2 ; metabolism ; Diabetic Nephropathies ; metabolism ; Glomerular Mesangium ; cytology ; Mesangial Cells ; drug effects ; metabolism ; Peptides ; pharmacology ; Rats ; Tumor Necrosis Factor-alpha ; pharmacology ; Venoms ; pharmacology
10.Effects of exendin-4 on rat cardiomyocyte apoptosis early after severe scald injury.
Yun-hui CHEN ; Jia-han WANG ; Zhi-qing LI ; Zhao-hui YI
Journal of Southern Medical University 2011;31(6):1101-1104
OBJECTIVETo observe the effect of exendin-4 on cardiomyocyte apoptosis in the early stage after scald injury in rats and explore the mechanisms.
METHODSFifty-four healthy adult SD rats were randomly divided into normal control group (n=6), scald group (n=24) and scald with exendin-4 treatment group (n=24). In the latter two groups, the rats were subjected to 30% TBSA full-thickness scald burns on the back, and Parkland formula was used for determining the resuscitation fluid volume. In exendin-4 treatment group, the rats received intraperitoneal injection of 5 µg/kg exendin-4 after the scald. Apoptosis of the cardiomyocytes from the left ventricle was determined by TUNEL assay and the activity of caspase-3 in the myocardium was assessed.
RESULTSIn the scald group, the apoptotic index of the cardiomyocytes was increased at 6 h post-burn, reaching the peak level at 12 h, and maintained a significantly higher level than that in the normal control at 48 h (P<0.05). Myocardial caspase-3 activity in the scald group was increased at 6 h post-burn and reached the peak at 12 h, still maintaining a high levels at 24 h (P<0.05). In exendin-4 treatment group, the apoptotic index of the cardiomyocytes was significantly lower than that in the scald group at 6, 12, 24 and 48 h post-burn (P<0.05), and so was the caspase-3 activity at 6, 12 and 48 h (P<0.05). A significant positive correlation was found between the apoptotic index of the cardiomyocytes and myocardial caspase-3 activity in the rats (P<0.05).
CONCLUSIONExdendin-4 can inhibit rat cardiomyocyte apoptosis early after scald injury possibly by suppressing caspase-3 activity in the myocardium.
Animals ; Apoptosis ; drug effects ; Burns ; pathology ; Caspase 3 ; metabolism ; Myocytes, Cardiac ; cytology ; pathology ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Venoms ; pharmacology