• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.165-177
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• 2003

The study was carried out to investigate the researches of Snake which was published papers in the TOXlCON(1990-2000), one of the most famous Journal of toxicology. And the results were as follows : 1. The number related with Snake is 195papers. 2. There were great papers related wih Cobra, and next is Tigris, Viper, etc. 3. There were great papers related wih protein in the composition of snake venom. 4. There were great papers related wih neurotoxin in the research of poisonous character. 5. There were great papers related wih Viper according to the anticoagulation. 6 Eight papers were published to study the immune response of snake venom. 7. The papers of molecular study of snake venom were seven. 8. The papers of anti-snake venom study were three.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.1-9
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• 2016

Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with $4{\mu}g/m{\ell}$ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase-8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-${\kappa}B$ activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of $4{\mu}g/m{\ell}$ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.106-113
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• 2014

In the present study, we investigated anti-cancer effect of snake venom activated NK cells (NK-92MI) in lung cancer cell lines. We used snake venom ($4{\mu}g/ml$) treated NK-92MI cells to co-culture with lung cancer cells. There was a further decrease in cancer cell growth up to 65% and 70% in A549 and NCI-H460 cell lines respectively, whereas 30-40% was decreased in cancer cell growth by snake venom or NK-92MI alone treatment. We further found that the expression of various apoptotic proteins such as that Bax, and cleaved caspase-3 as well as the expression of various death receptor proteins like DR3, DR4 and Fas was also further increased. Moreover, consistent with cancer cell growth inhibition, the DNA binding activity of NF-${\kappa}B$ was also further inhibited after treatment of snake venom activated NK-92MI cells. Thus, the present data showed that activated NK cells could further inhibit lung cancer cell growth.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.173-178
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• 2017

Objectives: Medicinal plants are vital sources of bioactive compounds that are useful for the treatment of patients with snake bites or are indirectly applicable for boosting the effects of conventional serum therapy. These plants are being used traditionally by local healers and tribes for the treatment of patients with snake bites and therefore can be used as an alternative against snake envenomation. Scientifically, using the secondary metabolites of plants to neutralize venom enzymes has an extra benefit of being based on traditional knowledge; also, the use of such metabolites for the treatment of patients with snake bites is cheaper and the treatment can be started sooner. Methods: All the available information on various secondary metabolites exhibiting venom neutralizing ability were collected via electronic search (using Google books, Pubmed, SciFinder, Scirus, Google Scholar, and Web of Science) and articles of peer-reviewed journals. Results:Recent interest in different plant has focused on isolating and identifying of different phytoconstituents that exhibit Phospholipase A2 activity and other venom enzyme neutralizing ability. In this support convincing evidence in experimental animal models are available. Conclusion: Secondary metabolites are naturally present, have no side effect, are stable for a long time, can be easily stored, and can neutralize a wide range of snake enzymes, such as phospholipase A2, hyaluronidase, protease, L-amino acid oxidase, 5'nucleotidase, etc. The current review presents a compilation of important plant secondary metabolites that are effective against snake venom due to enzyme neutralization.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.181-188
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• 2002

Objective: Through the literatures on the effects of Buthus martensii Karsch, we are finding out the clinical possibility and revealing the more effctive to intractable diseases. Method: We investigated the literatures of Oriental Medicine and experimental reports about Buthus martensii Karsch. Results: 1. The taste of Buthus martensii Karsch is salty, hot and toxic, and the effect of this is tetanus, headache, facial palsy and convulsion. 2. The venom of Buthus martensii Karsch is anaesthetic and toxic protein, composed of buthotoxin, lecithin, trimethylamine, betaine, taurine, cholesterol, stearic acid and palmitic acid and similar to the snake venom. 3. The pharmacological effects ofButhus martensii Karsch are anti-convulsion, depressor, anesthesia, anti-thrombosis and anti-cancer. 4. Symptoms of Buthotoxin poisoning are local pain, vomiting, fever, hypertension and palpitaion, and critical condition to Dyspnea, coma and death.

• Journal of Acupuncture Research
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• v.31 no.2
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• pp.87-98
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• 2014

Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

• Journal of Acupuncture Research
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• v.36 no.3
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• pp.140-146
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• 2019

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.

• Journal of Acupuncture Research
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• v.34 no.1
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• pp.23-30
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• 2017

Objectives : In this study, the roles of Interleukin (IL)-4 and Signal transducer and activator of transcription 6 (STAT6), which have been reported to play a role in the pathogenesis of inflammation and cancer, were evaluated in snake venom toxin (SVT)-induced apoptosis. Methods : Inflammation was induced in human HaCaT kerationocytes, by lipopolysaccharide (LPS; $1{\mu}g/mL$) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), followed by treatment with SVT (0, 1, or $2{\mu}g/mL$). Cell viability was assessed by MTT assays after 24 h, and the expression of levels of IL-4, STAT6, and the apoptosis-related proteins p53, Bax, and Bcl-2 were evaluated by western blotting. Electro mobility shift assays (EMSAs) were performed to evaluate the DNA binding capacity of STAT6. Results : MTT assays showed that inflammation-induced growth of HaCaT cells following LPS or TNF-${\alpha}$ stimulation was inhibited by SVT. Western blot analysis showed that p53 and Bax, which promote apoptosis, were increased, whereas that of Bcl-2, an anti-apoptotic protein, was decreased in a concentration-dependent manner in LPS- or TNF-${\alpha}$-induced HaCaT cells following treatment with SVT. Moreover, following treatment of HaCaT cells with LPS, IL-4 concentrations were increased, and treatment with SVT further increased IL-4 expression in a concentration-dependent manner. Western blotting and EMSAs showed that the phosphorylated form of STAT6 was increased in HaCaT cells in the context of LPS- or TNF-${\alpha}$-induced inflammation in a concentration-dependent manner, concomitant with an increase in the DNA binding activity of STAT6. Conclusion : SVT can effectively promote apoptosis in HaCaT cells in the presence of inflammation through a pathway involving IL-4 and STAT6.

• Journal of Pharmacopuncture
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• v.25 no.2
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• pp.114-120
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• 2022

Objectives: Antivenom serums have been used extensively for over a century and are the only effective treatment option for snake bites and other dangerous animal envenomations. In therapeutic serum centers, a wide range of antivenoms is made from animal serum, mainly equine and sheep, that are immunized with single or multiple venoms. This work aimed to use caprylic acid (CA) to purify therapeutic snake antivenom. Methods: Plasma was obtained from equine immunized with a mixture of venoms. Immunized plasma was obtained by precipitation of different concentrations (2-5%) of CA. This methodology was compared to that based on ammonium sulfate (AS) precipitation. Sediment plasma proteins were purified by ion-exchange chromatography. Protein assay, SDSPAGE, and agar gel diffusion were performed. Results: The total protein precipitation with AS was higher than precipitation with CA, but the best results were obtained when CA was added to the plasma until a final CA concentration of 5% was reached. Chromatography and electrophoresis indicated a stronger band for the 5% CA, and the gel diffusion assay showed antigen-antibody interaction in the purified serum. Conclusion: The use of CA compared to the routine method for purifying hyperimmune serums is a practical and cost-effective method for preparing and producing therapeutic serums. It constitutes a potentially valuable technology for alleviating the critical shortage of antivenom in Iran.

• CELLMED
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• v.10 no.4
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• pp.30.1-30.4
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• 2020

Background: Tiryaq-e-arba is a polyherbal Unani antidote/antivenom formulation used in the management of poisoning due to snake bite, scorpion bite as well as in cold poisons since time immemorial. Objectives: Tiryaq-e-arba was not evaluated scientifically before this study carried out, therefore it was studied for antivenom activity by testing on plasma fibrinogen level in Russell's Viper envenomation in rabbits. Material &Methods: The anti-venom activity of the test drug was studied by observing its effect on plasma fibrinogen level in Russell's Viper envenomation in rabbits by the method of Netelson. Results: The plasma fibrinogen level was found to be 171±665.04 mg/100 ml of blood, 36.18±1.12 mg/100 ml of blood, 33.14±0.52 mg/100 ml of blood and 17.9±1.65 mg/100 ml of blood at 0, 1, 3 and 6 hours respectively in control animals while in the test animal it was found to be 157.13±3.44 mg/100 ml of blood, 41.13±2.69 mg/100 ml of blood, 62.09±1.65 mg/100 ml of blood and 54.39±0.73 mg/100 ml of blood respectively. The test showed that though the plasma fibrinogen level in the test lower at 0 hour but it was greater in the control animals at 1, 3 and 6 hours. The increase in plasma fibrinogen level in the test animals at 3 and 6 hours was statistically significant (P<0.001). Conclusions: The finding of the present study was that Tiryaq-e-arba possesses antivenom activity which scientifically support the Unani claim that it is Dafe-Sumoom-al-Hevan (Antivenom or Antidote) and the use of this preparation in corresponding diseases.