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OBJECTIVE：To investigate the effects and mechanism of Jidesh eng anti-venom tablet on local wound inflammation and systemic inflammatory response of snake bite patients. METHODS ：Totally 64 patients with snake bite admitted to our hospital during Jun. 2018-Jun. 2020 were randomly divided into control group and observation group ，with 32 cases in each group. Both groups received routine treatment ，such as debridement ，drainage，flushing，sealing，anti-venom，anti-infection，anti-fibrinolysis and anti-shock. Observation group was additionally given Jidesheng anti-venom tablet for internal and external use ，for consecutive 7 d. Related indexes of systemic inflammatory response ，local wound condition ，hospital stay ，laboratory indexes of important organs，coagulation function index ，wound inflammatory cell counts ，serum levels of inflammatory cytokines and chemokine ，the occurrence of ADR were compared between 2 groups. RESULTS ：After treatment ，most of related indexes of systemic inflammatory response （RR，HR and WBC ），local wound condition （local pain disappearance time ，wound detumescence time ）， hospital stay ，laboratory indexes of important organs （AST，ALT，Scr，BUN，CKB，CK-MB），coagulation function index （t-PA， PAI-1，TAT，SFMC），wound inflammatory cell （macrophages，neutrophils，lymphocytes）count，serum levels of inflammatory cytokines（TNF-α，IL-1，IL-6，hs-CRP，NF-κB）and chemokine （MCP-1，CXCL-8）in 2 groups were significantly better than before treatment （P＜0.05）；most indexes of observation group were significantly better than those of control group （P＜0.05）. No severe ADR was found in 2 groups. CONCLUSIONS ：Jidesheng anti-venom tablet as auxiliary treatment can significantly reduce the local wound inflammation and systemic inflammatory response of snake bite patients ；the mechanism is probably related to reducing the levels of chemokine MCP- 1 and CXCL- 8 and inflammatory cytokines hs-CRP and NF-κB.
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Objective: To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial approaches. Methods: Synthetic flavonoids were assessed, either individually or in combination with antivenom, for their neutralization of phospholipase A
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Objective: To evaluate antioxidant, cytotoxic, and anti-venom capacity of crude bark extracts of Alstonia parvifolia Merr. Methods: Gas chromatography-mass spectrometry (GC-MS) and energy dispersive X-ray analyses were accomplished to characterize the chemical constituents of Alstonia parvifolia. Biochemical characterization was evaluated using an inhibitory phospholipase A 2 (PLA 2) assay, DPPH, and cytotoxicity assays. Using the constituents listed in the GC-MS analyses, molecular docking was conducted to inspect the binding energies between the chosen compounds and selected PLA 2 isoforms. Results: GC-MS analyses showed that the Alstonia parvifolia crude extract consisted predominantly of acetylmarinobufogenin (14.89%), γ-sitosterol (10.44%), 3-O-methyl-D-glucose (5.88%), 3,5-dimethoxy-4-hydroxyphenylacetic acid (5.30%), (2α,5α)-17-methoxyaspidofractinin-3-one (AFM) (4.08%), and 2,3,5,6,7,8,9-heptahydro-1-phenyl-5-(p-chlorophenylimino)-1H-benzo[e] [1],[4] thiazepine (HPT) (1.37%). The principal elemental components of Alstonia parvifolia were Ca (4.012%) and K (1.496%), as exhibited by energy dispersive X-ray examination. Alstonia parvifolia showed significant free radical scavenging ability (IC 50: 0.287 mg/mL) and was non-cytotoxic to normal HDFn cells (IC 50 >100 μg/mL). Moreover, Alstonia parvifolia was favorably cytotoxic to MCF-7 (IC 50: 4.42 μg/mL), followed by H69PR, HT-29, and THP-1, with IC 50 values of 4.94, 5.07, and 6.27 μg/mL, respectively. Alstonia parvifolia also displayed notable inhibition against PLA 2 activity of Naja philippinensis Taylor venom with IC 50 of (15.2 ± 1.8) μg/mL. Docking and cluster analyses projected negative binding energies from AFM (-6.36 to -9.68 kcal/mol), HPT (-7.38 to -9.77 kcal/ mol), and acetylmarinobufogenin (-7.22 to -9.59 kcal/mol). These calculations were for the particular interactions of Alstonia parvifolia constituents to PLA 2 homologues where the utmost affinity was detected in HPT owing to the dipole interactions with amino acid residues. Conclusions: The bark extract of Alstonia parvifolia shows great potential as an anti-venom agent due to its low cytotoxic profile, remarkable PLA 2 inhibition, and docking binding energies between its bioactive constituents and PLA 2 homologues.
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Abstract In this study, mango seed kernels extract contained a considerable amount of phenolics and flavonoids (17,400 and 3325 mg/100 g seed, respectively). The HPLC profiling revealed that hesperidin was the major phenolic compound of the mango seed kernels extract. This is the first report find hesperidin in mango extracts. The phenolic compounds of mango seed kernels extract were effective in scavenging free radicals of DPPH and ABTS with IC50 values of 47.3 and 7.9 µg/ml, respectively. The total antioxidant activity of mango seed kernels extract based on the reduction of molybdenum was also measured. The phenolic compounds of mango seed kernels extract potentially inhibited the protease, fibrinogenase, phospholipase A2, l-amino acid oxidase, hyaluronidase, and hemolytic activities of the most dangerous Cerastes cerastes and Echis coloratus viper venoms. The phenolic compounds of mango seed kernels extract could completely neutralize the hemorrhage and lethality of both venoms in experimental animals. It could be concluded that the mango seed kernels extract phenolic compounds with potential antioxidant activity are considered as a new avenue in the viper bite treatment.
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Objective To assess the clinical efficacy of vacuum sealing drainage (VSD) in the treatment of mixed poisonous snake bite. Methods A prospective study was conducted. Forty-three snake bite patients by mixed poisonous snakes admitted to Department of Emergency of the 175th Hospital of People's Liberation Army from February 2015 to February 2017 were enrolled. All patients were divided into routine treatment group (n = 20) and VSD treatment group (n = 23) according to whether early incision decompression and using the VSD technique. The patients in the routine treatment group were treated with injection of antivenoms, Jidesheng snake tablets external coating, and wound incision detoxification. Beside the routine treatments, patients in the VSD treatment group were treated with incision decompression and the VSD suction aspiration for the swelling limb. Bite wound infection rate, local skin necrosis area, maximum level of C-reactive protein (CRP), length of hospital stay and disability rate were compared between the two groups. Results Forty-three patients were followed up for 6-12 months with average of (10.3±1.4) months postoperatively. There were no deaths in both groups. Compared with the routine treatment group, wound infection rate in the VSD treatment group was significantly lowered [8.7% (2/23) vs. 40.0% (8/20)], local skin necrosis area was significantly reduced (cm2: 4.2±0.8 vs. 6.0±1.3), the maximum CRP was significantly lowered (mg/L: 50.0±12.1 vs. 68.0±13.4), the hospitalization time was significantly shortened (days: 11.7±2.9 vs. 17.7±4.9), and the difference above was statistically significant (all P < 0.05). The disability rate of the VSD treatment group was lowered as compared with routine treatment group [13.0% (3/23) vs. 13.0% (6/20)] without statistically significant difference. Conclusion Early incision decompression and VSD pressure suction of the swelling limb associated with combination therapy of drugs is a reliable and effective method for severe snakebite, and can promote physical rehabilitation and shorten hospital stay.
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Specific anti-venom used to treat scorpion envenomation is usually obtained from horses after hyperimmunization with crude scorpion venom. However, immunized animals often become ill because of the toxic effects of the immunogens used. This study was conducted to evaluate the toxic and immunogenic activities of crude and detoxified Tityus serrulatus (Ts) venom in sheep during the production of anti-scorpionic anti-venom. Sheep were categorized into three groups: G1, control, immunized with buffer only; G2, immunized with crude Ts venom; and G3, immunized with glutaraldehyde-detoxified Ts venom. All animals were subjected to clinical exams and supplementary tests. G2 sheep showed mild clinical changes, but the other groups tolerated the immunization program well. Specific antibodies generated in animals immunized with either Ts crude venom or glutaraldehyde-detoxified Ts venom recognized the crude Ts venom in both assays. To evaluate the lethality neutralization potential of the produced sera, individual serum samples were pre-incubated with Ts crude venom, then subcutaneously injected into mice. Efficient immune protection of 56.3% and 43.8% against Ts crude venom was observed in G2 and G3, respectively. Overall, the results of this study support the use of sheep and glutaraldehyde-detoxified Ts venom for alternative production of specific anti-venom.
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Animals , Mice , Antibodies , Horses , Immunization Programs , Scorpion Venoms , Scorpions , Sheep , VenomsABSTRACT
The study was done to investigate the anti-venom activity of Mucuna pruriens leaves extract against cobra snake (Naja hannah) venom. Study Design: The mice were randomly grouped into six groups (A, B, C, D, E, and F) of five rats each. Group A served as the normal control (no induction), and the mice in the group were given normal saline (1ml/kg/body weight).Group B served as the test control (snake venom was induced but no treatment administered), Group C served as the standard control (snake venom was induced and treated with antivenin, a standard drug), Group D, E and F were all induced with the cobra snake venom and treated with ethanolic extracts of the leaves of M. pruriens for 14 days. Methodology: The induction with cobra snake venom was done with 0.075mg/kg b.w of venom and thereafter the treatment with M. pruriens extract for Group D, E and F were done with 40 mg/ kg, 60 mg/ kg and 80 mg/ kg respectively intraperitoneally in the mice. Serum blood of the animals was used to assay for total cholesterol, bilirubin, AST, ALT, GSH and catalase levels after 14days. Result: The injection of crude venom of cobra snake (Naja hannah) caused an increase in cholesterol, AST, ALT, bilirubin, catalase and glutathione in envenomated mice which significantly reduced (p<0.05) compared to all the controls after 14 days of treatment with the extract. Conclusion: The results suggests that 80 mg/ kg of the plant extract is more effective than the standard drug, therefore M. pruriens leaves has a greater anti-venom potential for curing snake bite, than antivenin.
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Introduction: Snakebites are a major health problem in several rural areas of tropical countries worldwide. Timely administration of appropriate antivenoms (AV) has been shown to significantly improve outcome. It has been hypothesized that presence of blisters may lead to poor outcome because of potential sequestration of snake venom with gradual systemic absorption. We explore the impact of blisters on outcome of snake bite envenomation. Methods: The study was a prospective cohort, enrolling all snake bite victim reporting to hospital in Febuary-April 2013. Data on demography, type of snake, circumstances of bite, presence or absent of blisters, systemic bleeding, 20min Whole Blood Clotting Time (WBCT), amount of anti-venom needed to restore clotting, and outcomes were recorded. Analyses explored relationship between blister and poor outcome (PO) defined as deaths, gangrene, prolonged Length of Hospital Stay (LOS), amputation, altered consciousness or requiring more than 10mls or 30mls of Echitab or Echitab plus respectively to restore clotting. Results: A total of 128 cases were studied, 101 were males. The mean age of the victims was 25.19 years ±17.51. Carpet viper was the most common responsible snake 89/106(84.0%). Local 84/128(65.6%), systemic bleeding 33/128(25.8%) and non-clotting 20WBCT 100/128(78.1%) were common while amputations 3/128(2.3%), gangrene 5/128(3.9%), altered consciousness 2/128(1.6%) and deaths 4/128(3.1%) were fewer. Blister was present in 42/128(32.8%) which had no relationship with gender (P=.39). Patients with blisters compared to those without blisters had more gangrene 4/42(9.5%) vs 1/86(1.2%) (P=.04), non-clotting 20WBCT 40/42(95.2%) vs 60/86(69.8%) (P<.001) and required more amount of antivenom to restore clotting >10mls (Echitab) or 30mls (Echitab plus) in 8/32(25%) vs 3/57(5.3%) (P=.03). Using Wilcoxon Rank-Sum test patients with blisters had a median LOS of 6.0±2.3 days compared to those without blisters 5.0±3.5 days (P=.02). In a logistic regression adjusting for LOS and systemic bleeding, blister predicted PO with P=.043 (95%CI: 0.110- 0.963). Conclusion: Presence of blister predicts PO (LOS, gangrene and large amount of antivenom needed to restore clotting). Deblistering of blister in snake bite patients may improve outcome. A randomised control trial is recommended to look at the effect of deblistering on outcome among patients with snake bite envenomation.
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OBJECTIVE@#To determine the altitudinal variation of stigmasterol, a potential antivenin, in roots from seven populations of Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) (R. serpentina), an important herb found in Indian subcontinent which has long been used in the treatment of snakebite, blood pressure and schizophrenia.@*METHODS@#Altitudinal variation of stigmasterol content in R. serpentina roots was analyzed by high performance thin layer chromatography. Chromatography was performed on silica gel 60 F254 thin layer chromatography plates with benzene-acetone 86:14 (v/v) as mobile phase. Densitometric analysis was done at λ=366 nm after derivatization with vanillin-10% (v/v) sulphuric acid alcohol reagent. The method was validated for precision and recovery.@*RESULTS@#The present experiment demonstrates a simple, rapid, precise and sensitive high performance thin layer chromatography protocol for qualitative and quantitative determination of stigmasterol from different populations of R. serpentina. Results demonstrated that in root samples stigmasterol was present at Rf value of 0.44.@*CONCLUSIONS@#This investigation demonstrates that stigmasterol content in R. serpentina roots varies in different altitudes. Popular ethnomedicinal use of this herb against snakebite may be contributed by the occurrence of stigmasterol in its roots.
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Objective: To determine the altitudinal variation of stigmasterol, a potential antivenin, in roots from seven populations of Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) (R. serpentina), an important herb found in Indian subcontinent which has long been used in the treatment of snakebite, blood pressure and schizophrenia. Methods: Altitudinal variation of stigmasterol content in R. serpentina roots was analyzed by high performance thin layer chromatography. Chromatography was performed on silica gel 60 F