Browse > Article
http://dx.doi.org/10.13045/jar.2019.00073

Effects of Snake Venom Pharmacopuncture on a Mouse model of Cerebral Infarction  

Choi, Chul-Hoon (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Gachon University)
Song, Ho-Sueb (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Gachon University)
Publication Information
Journal of Acupuncture Research / v.36, no.3, 2019 , pp. 140-146 More about this Journal
Abstract
Background: This study investigated the effects of Vipera lebetina turanica snake venom (SV) on cerebral infarction induced by middle cerebral artery occlusion in mice. Methods: Following cerebral infarction, SV was injected intravenously or added to BV2 cell culture. Tissue injury was detected using triphenyltetrazolium chloride (TTC) staining, neurological deficit score, NO, ROS, and GSH/GSSG assays, qPCR, Western blot, and cell viability. Results: Cerebral infarction caused by middle cerebral artery occlusion as observed by TTC staining, showed SV inhibited cell death, reducing the number of brain cells injured due to infarction. SV treatment for cerebral infarction showed a significant decrease in abnormal behavior, as determined by the neurological deficit score. The oxidation and inflammation of the cells that had cerebral infarction caused by middle cerebral artery occlusion (NO assay, ROS, GSH/GSSG assay, and qPCR), showed significant protection by SV. Western blot of brain infarction cells showed the expression of iNOS, COX-2, p-IkB-${\alpha}$, P38, p-JNK, p-ERK to be lower in the SV group. In addition, the expression of IkB increased. BV2 cells were viable when treated with SV at $20{\mu}g/mL$ or less. Western blot of BV2 cells, treated with 0.625, 1.5, $2.5{\mu}g/mL$ of SV, showed a significant decrease in the expression of p-IkB-${\alpha}$, p-JNK, iNOS, and COX-2 on BV2 cells induced by LPS. Conclusion: SV showed anti-inflammatory and anti-oxidant effects against cerebral infarction and inflammation.
Keywords
cerebral infarction; inflammation; middle cerebral artery occlusion; pharmacopuncture; snake venom;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke 1991;22:312-318.   DOI
2 Yang GE, Park DS, Lee SH, Bae DK, Yang YH, Kyung JB et al. Neuroprotective Effects of a Butanol Fraction of Rosa hybrida Petals in a Middle Cerebral Artery Occlusion Model. Biomol Ther 2013;21:454-461.   DOI
3 Chan PH. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 2001;21:2-14.   DOI
4 Vaughan CJ, Delanty N. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 1999;30:1969-1973.   DOI
5 Siigur E, Aaspollu A, Siigur J. Sequence diversity of Vipera lebetina snake venom gland serine proteinase homologs-result of alternative splicing or genome alteration. Gene 2001;263:199-203.   DOI
6 Alves RM, Antonucci GA, Paiva HH, Cintra ACO, Franco JJ, Mendonca-Franqueiro EP et al. Evidence of caspase mediated apoptosis induced by L-amino acid oxidase isolated from Bothrops atrox snake venom. Comp Biochem Physiol A Mol Integr Physiol 2008;151:542-550.   DOI
7 Kim KT, Song HS. Inhibitory Effect of Snake Venom Toxin on Colorectal Cancer HCT116 Cells Growth through Induction of Intrinsic or Extrinsic Apoptosis. J Korean Acupunct Moxib Soc 2013;30:43-55.
8 Kang J, Song HS. Snake Venom from Vipera lebetina turanica Inhibits Tumor in a PC-3 Cell Xenograft Model and PC-3 Cell Growth in Vitro. J Korean Acupunct Moxib Soc 2007;24:1-14. [in Korean].
9 Oh JW, Song HS. Snake Venom synergized Cytotoxic Effect of Natural Killer Cells on NCI H358 Human Lung Cancer Cell Growth through Induction of Apoptosis. Acupunct 2016;33:1-9.
10 Lee JI, Song HS. Snake Venom-enhanced Cytotoxic Effect of Natural Killer Cells on A549 Human Lung Cancer Cell Growth. Acupunct 2015;32:79-88.   DOI
11 Yang KR, Song HS. Effect of Snake Venom Toxin from Vipera lebetina turanica on Breast Cancer. J Korean Acupunct Moxib Soc 2009;26:27-38.
12 Lee BC, Song HS. Effect of Snake Venom on Cancer Growth through Induction of Apoptosis via Down Regulation of NF-${\kappa}B$ and STAT3 in the PA-1, Ovarian Cancer Cells. J Korean Acupunct Moxib Soc 2012;29:37-45.
13 Adibhatla RM, Hatcher JF, Sailor K, Dempsey RJ. Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats. Brain Res 2002;938:81-86.   DOI
14 Negishi H, Ikeda K, Nara Y, Yamori Y. Increased hydroxyl radicals in the hippocampus of stroke-prone spontaneously hypertensive rats during transient ischemia and recirculation. Neurosci Lett 2001;306:206-208.   DOI
15 Dawson TM, Snyder SH. Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J Neurosci 1994;14:5147-5159.   DOI
16 Marks L, Carswell HV, Peters EE, Graham DI, Patterson J, Dominiczak AF et al. Characterization of the microglial response to cerebral ischemia in the stroke-prone spontaneously hypertensive rat. Hypertension 2001;38:116-122.   DOI
17 Bennacef-Heffar N, Laraba-Djebari F. Evaluation of the effect of gamma rays on the venom of Vipera lebetina by biochemical study. Can J Physiol Pharmacol 2003;81:1110-1117.   DOI
18 Michalet S, Teixeira F, Gilquin B, Mourier G, Servent D, Drevet P et al. Relative spatial position of a snake neurotoxin and the reduced disulfide bond alpha (Cys192-Cys193) at the alpha gamma interface of the nicotinic acetylcholine receptor. J Biol Chem 2000;275:25608-25615.   DOI
19 Servent D, Winckler-Dietrich V, Hu HY. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem 1997;272:24279-24286.   DOI
20 Shin IC. Molecular cell biology. Seoul (Korea): Mari design; 2015. p. 185-195. [in Korean].
21 Park D, Lee SH, Choi YJ, Bae DK, Yang YH, Yang G et al. Improving effect of silk peptides on the cognitive function of rats with aging brain facilitated by D-galactose. Biomol Ther 2011;19:224-230.   DOI
22 Kondo K, Kurihara M, Miyata N, Suzuki T, Toyoda M. Scavenging mechanisms of epigallocatechin gallate and epicatechin gallate on peroxyl radicals and formation of superoxide during the inhibitory action. Free Radic Biol Med 1999;27:855-863.   DOI
23 Nicolis E, Lampronti I, Dechecchi MC, Borgatti M, Tamanini A, Bianchi N et al. Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial cells. Int Immunopharmacol 2008;8:1672-1680.   DOI