Analysis of the active fraction of Iranian Naja naja oxiana snake venom on the metabolite profiles of the malaria parasite by 1HNMR in vitro (original) (raw)
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Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review
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Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7...
In Vitro Neutralization of Naja naja Venom Enzymes by Folk Medicinal Plant Extracts
Journal of Biologically Active Products from Nature, 2019
Medicinal plants are known to possess pharmacologically active compounds which have therapeutic properties and number of plants have been evaluated in disease management including venomous bites. Products of plant extracts are thus gaining importance because of their easy availability, low cost and less side effects and are evaluated for their antidote potential against Indian cobra (Naja naja) venom enzymes. In vitro enzyme inhibitions such as anti-proteolytic, anti-phospholipase, anti-hyaluronidase, anti-acetylcholine esterase and pharmacological studies (anti-hemolytic activity and anti-fibrinogenolytic activity) were evaluated for aqueous ethanolic extracts and organic extracts of Clerodendrum serratum, Azadirachta indica, Aegle marmelos, Aristolochia indica, Citrus limon, Calotropis gigantea, Cryptolepis buchanani and Butea monosperma on N. naja venom. Significant inhibitions were observed by both the extracts. However, it is interesting to note that aqueous extracts significantly inhibited phospholipase activity and organic extracts inhibited fibrinogenolytic activity of venom. The hyaluronidase activity was not observed in the venom. Indirect hemolytic assay revealed the potential of Butea monosperma extracts to completely neutralize the lysis of red blood cells (RBC) induced by cobra venom. The isolation of bioactive principles or a combination of these active principles, from the tested medicinal plants for ex vivo and in vivo anti-venom activity has to be validated by active isolated compound from extract which is responsible for neutralizing toxic snake venom enzymes.
The crude extract of Tribal Medicine Formulation (TMF), an herbal drug was taken to appraise the pharmacognos-tic status through antioxidant activity and anti-snake venom properties. The antioxidant activity has been evaluated by ABTS, TBARS and Hydroxyl radical scavenging assay methods, respectively. Since, ethno-medicinal plants and their formulation contain generally diverse class of active metabolites and phenolic compounds which possess wide-ranging amount of antioxidant activities; the anti-venom activity was evaluated for the enzymes like PLA2 and protease which are present in the snake venom by interaction of proteins between Naja naja and protein of TMF drug. The Anti-PLA2 activity was done to facilitate neutralizing effect of PLA2 in association with the different fractions of TMF drug. Accordingly, the efficacy of TMF drug was employed to neutralize snake venom and the significant neutralization effect was noticed, which may be due to presence of certain active class of chemical compounds in TMF drug that acquired anti-lethal effects. Among them, presence of terpenoids, flavonoids, poly-phenols, total sugars and ascorbic acid have contributed significantly as anti-venom potential. Therefore, multi-functionality of TMF drug has clearly indicated the competence of such active chemical constituents that make possible of binding between two proteins. Consequently, the obstruction in the functions of many macromole-cules could be accomplished due to interaction of these two proteins. Later, the hemorrhage activity was conducted to assess the anti-snake venom activity through myonecrosis-lung hemorrhage activity. In the study, the mouse lung tissue and also the muscle tissue layer was collected and added with saline buffer to one layer in which, the cell death did not occur. Then, the other layer added with snake venom was found to be the cells started dying by forming tumors; whereas, the third layer which was added with both snake venom along with the extracts of TMF drug diminishes the activity of inflammatory enzyme. This confirms the better activity of TMF drug over venom which further influences neutralization of snake venom. However, it can be suggested that, the active metabolites present in the TMF drug extract are most responsible in inhibiting the PLA2 activity and the fortification in the efficiency of drug was justified. This will facilitate the rationale factor pharmacologically which admits the traditional evidences for these Ethno-medicinal plants in the form of TMF drug as antidote for snake victims. Therefore, the TMF drug was found to have high potential active constituents which make possible of neutraliza-tion competence in treating snake bite. Further, the TMF drug can be explored for its therapeutic authentication through analyzing probable mechanism of action by lead molecules present in the formulations via clinical studies which can be recommended further as counteractive doctrine in case of snakebite envenomation.
A Review on Venom Enzymes Neutralizing Ability of Secondary Metabolites from Medicinal Plants
Journal of pharmacopuncture, 2017
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. 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. Recent interest in different plant has focused on isolating...
Antiplasmodial and Cytotoxic Activities of Toad Venoms from Southern Amazon, Brazil
The Korean Journal of Parasitology, 2016
The drug-resistance of malaria parasites is the main problem in the disease control. The huge Brazilian biodiversity promotes the search for new compounds, where the animal kingdom is proving to be a promising source of bioactive compounds. The main objective of this study was to evaluate the antiplasmodial and cytotoxic activity of the compounds obtained from the toad venoms of Brazilian Amazon. Toad venoms were collected from the secretion of Rhinella marina and Rhaebo guttatus in Mato Grosso State, Brazil. The powder was extracted at room temperature, yielding 2 extracts (RG and RM) and a substance ('1') identified as a bufadienolide, named telocinobufagin. Growth inhibition, intraerythrocytic development, and parasite morphology were evaluated in culture by microscopic observations of Giemsastained thin blood films. Cytotoxicity was determined against HepG2 and BGM cells by MTT and neutral red assays. The 2 extracts and the pure substance ('1') tested were active against chloroquine-resistant Plasmodium falciparum strain, demonstrating lower IC50 values. In cytotoxic tests, the 2 extracts and substance '1' showed pronounced lethal effects on chloroquine-resistant P. faciparum strain and low cytotoxic effect, highlighting toad parotoid gland secretions as a promising source of novel lead antiplasmodial compounds.
Review on Snake Venom, Venom Chemistry, Anti-Venom and Traditional Treatment Treatment
http://www.sciencepub.net/nature., 2019
Snake venom is highly modified saliva containing zootoxins which facilitates the immobilization and digestion of prey, and defends against threats. It is injected by unique fangs after a bite, and some species are also able to spit. envenomation has very high rate of mortality resulting from snakebites. From the seventeen families twenty-three plants were collected and explored for the first time for antisnake venom activity. According to scientific reports, the methanolic root extract of the medicinal plants Vitex negundo, Hemidesmus indicus, Pluchea indica and Emblica officinalis significantly neutralized the Viper and Cobra venom-induced pathophysiological changes. For the time being, four plants extracts explored (Curcuma Aristolochia indica, aromatica, Androgrphis paniculata and Curcuma zeodaria) for their inhibitory activity snake venom. Echis carinatus, Ophiophagus hannah, Daboia russelli and Naja kaouthia venom-induced lethal activity was significantly antagonized by the extracts of plant both in in vitro and in vivo studies. So the venom-induced coagulant, haemorrhage, defibrinogenating and PLA2 activity from Daboia russellii were significantly neutralized by the extracts. Precipitating bands between the plant extract and venom were not observed. The role of active constituents of plants and plant materials involved in snake venom inhibition was confirmed by this observation. Further studies are going on in our laboratory for the identification of active molecules as well as their mechanism of venom inhibition.
The Effect of Naja naja oxiana Snake Venom Against Leishmania tropica Confirmed by Advanced Assays
Purpose The aim of this study was to explore the activity of Naja naja oxiana venom on Leishmania tropica and its modes of action. Methods Different fractions of Naja naja oxiana venom (NNOV) were prepared and characterized by high-performance liquid chromatography. The superior component, fraction k (FK) was selected. The activity of the fraction was assessed using advanced assays. Results Interleukin (IL)-12, TNF-α and iNOS gene expression as the indicators of Th1 significantly increased. In contrast, the level of IL-10, as the marker of T helper 2 substantially decreased (p < 0.001). Reactive oxygen species (ROS) detection showed a significant increase (p < 0.001) after treatment with different concentrations of NNOV-FK, unlike arginase (L-ARG) activity which showed a significant reduction (p < 0.001). The NNOV-FK showed significant lethal activity on the L. tropica stages. Conclusion The findings demonstrated that NNOV-FK represented a strong leishmanicidal activity on L. tropica stages. The major modes of NNOV-FK action are multidimensional, which perceives the induction of a synergistic response and upregulation of the immune-modulatory role towards Th1 response against L. tropica stages as well as apoptotic and anti-metabolic action as a model drug to generate ROS, block the polyamine synthesis and lead to parasite death.
In-Vitro Assays for Neutralization of Snake Venom Using Herbal Drugs: A Review
Sipra Sarkar., et al.: In-Vitro Assays for Neutralization of Snake Venom. Snakebite is a major health hazard that leads to high mortality rate especially in India. The present review article focuses on the point of view of different in –vitro neutralization assays that serve as an index for assessing the status of therapy. For this purpose bibliographic and scientific literature articles in indexed journal databases were comprehensively researched and contemporary articles were studied from different abstracting and indexing systems like PubMed using relevant keywords. It was found that some of the in-vitro assays like Phospholipase A2, Hemorrhagic activity assay, agglutination assay for potency assessment, general proteolytic activity assay, snake venom metalloprotease activity (SVMP), hemolytic activity, neutralization of serum inhibitory activity assay, neutralization of fibrinolytic activity, inhibition of venom cardiotoxic activity assay and brine shrimp lethality test are prevalent in use. Performing these in –vitro tests is essential for the development of therapy against envenomation. Antisnake venom serum (ASVS) for snake bite therapeutics is available but suffers from many drawbacks; herbal plants provide a solid platform for the natural treatment of this serious issue. Herbal medications have excellent potential to treat snake bite. Herbal medicinal plants are an important element of indigenous medical systems globally. Many of the active plant constituents are promising contenders for the development of antivenom drug molecules. So our objective is to find different alternative in-vitro processes for anti venom activity. The rationale behind choosing the in-vitro assays is to enable to generate basic data and understand the probable basic mechanism of snake venom and herbal antisnake venom without sacrificing or using invasive procedures on the experimental animal.
Journal of Ayurveda and Integrative Medicine, 2017
Background: Indigenous medicinal practice in Sri Lanka talks about powerful compounds extracted from native plants for treating venomous snake bites which are hardly documented in literature but are used by the indigenous doctors for thousand years. Objective: We screened the neutralizing ability of a herbal preparation practiced in indigenous medicine of Sri Lanka, consisting of Sansevieria cylindrica, Jatropha podagrica and Citrus aurantiifolia, for its ability to neutralize venom toxins of Naja naja (Common Cobra) and Daboia russelii (Russell's viper). Materials and methods: The venom toxicity was evaluated using a 5-day old chicken embryo model observing the pathophysiology and the mortality for six hours, in the presence or absence of the herbal preparation. The known toxin families to exist in snake venom, such as Phospholipase A 2 , Snake venom Metalloprotease, were evaluated to understand the mechanism of venom neutralizing ability of the herbal preparation. Results: The LD 50 of D. russelii venom, as measured using the 5-day old chicken embryo model, was 4.8 ± 0.865 ug (R 2 ¼ 84.8%, P ¼ 0.079). The pre-incubation of venom with the herbal preparation increased the LD 50 of D. russelii venom to 17.64 ± 1.35 mg (R 2 ¼ 81.0%, P ¼ 0.100), showing a clear neutralizing action of D. russelii venom toxicity by the herbal medicine. Whereas the pre-incubation of venom with the 1Â venom neutralizing dose of commercially available polyvalent anti-venom serum shifted the LD 50 venom only up to 5.5 ± 1.35 mg (R 2 ¼ 98.8%, P ¼ 0.069). In the presence of the herbal preparation, Phospholipase A 2 activity of D. russelii venom was significantly reduced from 9.2 Â 10 À3 mM min À1 to 8.0 Â 10 À3 mM min À1 and that of N. naja from 2.92 Â 10 À2 mM min À1 to 0.188 Â 10 À2 mM min À1. Further, the pre-incubation of N. naja venom with the herbal preparation significantly reduced its Metalloprotease activity from 0.069 units min À1 to 0.019 units min À1. Conclusion: The herbal preparation shows a clear neutralizing action against the toxicities of D. russelii and N. naja venoms demonstrating the potential to be used as a plant based antidote for snake envenomation.
Antimalarial activity and toxicity evaluation of a quantified Nauclea pobeguinii extract
Journal of Ethnopharmacology, 2010
Aim of the study: To evaluate the in vitro and in vivo antiplasmodial activity and toxicity of the aqueous and 80% EtOH extract of the stem bark of Nauclea pobeguinii (Pob. Ex. Pell.) Petit (Rubiaceae), a plant used in traditional medicine in DR Congo against malaria. Materials and methods: The aqueous and 80% EtOH extract from N. pobeguinii stem bark, and its constituents (5S)-5-carboxystrictosidine, 19-O-methylangustoline, 3-O--fucosylquinovic acid, 3ketoquinovic acid and strictosamide, were evaluated for their in vitro activity against Plasmodium falciparum (chloroquine-sensitive Ghana-strain). The 80% EtOH extract, containing 5.6% strictosamide, was evaluated in vivo in the 4-day P. berghei mouse model, and in the P. yoelii N67 model. Results: All compounds were inactive or only moderately active in vitro. The aqueous and 80% EtOH extract displayed moderate in vitro activity with IC 50 values of 44 and 32 g/mL, respectively, without apparent cytotoxicity on MRC-5 cells (CC50 > 64 g/mL). Daily oral dosing of the 80% EtOH extract, at 300 mg/kg, resulted in 86% reduction of parasitaemia in the 4-day P. berghei mouse model, and 75% reduction in the P. yoelii N67 model. Prolonging oral dosing to 2 × 5 days, with an interval of 2 days, and oral administration of the 80% EtOH extract at 300 mg/kg induced 92% reduction of parasitaemia, and a mean survival time of 17 days. Strictosamide, the putative active constituent, may be metabolically activated in the gastrointestinal tract after oral administration. Levels of creatinin, urea, ALAT and ASAT remained unchanged after treatment. No acute toxicity was observed in mice after a single 2 g/kg oral dose, nor after 4 weekly doses. No significant macroscopic or microscopic lesions were observed in heart, lung, spleen, kidney, liver, large intestine and brain. Conclusions: These results can partly support and justify the use of N. pobeguinii in traditional medicine in the DR Congo for the treatment of uncomplicated malaria.