Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence
Juliana Félix-Silva,1Arnóbio Antônio Silva-Junior,1Silvana Maria Zucolotto,2 and Matheus de Freitas Fernandes-Pedrosa1
1Laboratório de Tecnologia & Biotecnologia Farmacêutica (TecBioFar), Faculdade de Farmácia, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil
2Grupo de Pesquisa em Produtos Naturais Bioativos (PNBio), Laboratório de Farmacognosia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil
Academic Editor: Rainer W. Bussmann
Received23 Feb 2017
Accepted09 Jul 2017
Published21 Aug 2017
Snakebites are a serious problem in public health due to their high morbimortality. Most of snake venoms produce intense local tissue damage, which could lead to temporary or permanent disability in victims. The available specific treatment is the antivenom serum therapy, whose effectiveness is reduced against these effects. Thus, the search for complementary alternatives for snakebite treatment is relevant. There are several reports of the popular use of medicinal plants against snakebites worldwide. In recent years, many studies have been published giving pharmacological evidence of benefits of several vegetal species against local effects induced by a broad range of snake venoms, including inhibitory potential against hyaluronidase, phospholipase, proteolytic, hemorrhagic, myotoxic, and edematogenic activities. In this context, this review aimed to provide an updated overview of medicinal plants used popularly as antiophidic agents and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation. The present review provides an updated scenario and insights into future research aiming at validation of medicinal plants as antiophidic agents and strengthens the potentiality of ethnopharmacology as a tool for design of potent inhibitors and/or development of herbal medicines against venom toxins, especially local tissue damage.
Snakebites are a serious public health problem in many regions around the world, particularly in Africa, Asia, Latin America, and parts of Oceania . Conservative data indicate that, worldwide, there are between 1.2 and 5.5 million snakebites every year, leading to 25,000 to 125,000 deaths . Despite its significant impact on human health, this condition remains largely neglected by national and international health authorities, funding agencies, pharmaceutical companies, patients’ organizations, and health advocacy groups . Thus, snake envenomation is included since 2009 in World Health Organization (WHO) list of Neglected Tropical Diseases (NTDs) . Envenoming and deaths resulting from snakebites are a particularly important public health problem in the rural tropics. Populations in these regions experience high morbidity and mortality because of poor access to health services, which are often suboptimal, as well as other NTDs, which are associated with poverty [3, 4].
Snakes with major clinical importance belong to the families Elapidae (African and Asian cobras, Asian kraits, African mambas, American coral snakes, Australian and New Guinean venomous snakes, and sea snakes) and Viperidae (Old World vipers, American rattlesnakes and pit vipers, and Asian pit vipers) . After production, snake venom is injected in the victim via tubular or channeled fangs . Biochemically, venoms are complex mixtures of pharmacologically active proteins and polypeptides, acting in concert to help in immobilizing the prey . The most common toxins in snake venoms are snake venom metalloproteinases (SVMPs), phospholipases A2 (PLA2s), snake venom serine proteinases (SVSPs), acetylcholinesterase (AChE), L-amino acid oxidases (LAAOs), nucleotidases, and snake venom hyaluronidases (SVHs) .
Biological properties of snake venom components are peculiar to each species, but in general, the main clinical effects of snake envenomation are immediate and prominent local tissue damage (including myonecrosis, dermonecrosis, hemorrhage, and edema), coagulation disorders (consumption coagulopathy and spontaneous systemic bleeding), cardiovascular alterations (hypotension, hypovolemic shock, and myocardial damage), renal alterations (which could evolve into acute kidney injure), neurotoxic action (descending paralysis, progressing from ptosis and external ophthalmoplegia to bulbar, respiratory muscle, and total flaccid paralysis), generalized rhabdomyolysis with myoglobinuria, and intravascular haemolysis [5, 8].
The only available specific treatment is the antivenom serum therapy, which consists of a pool of neutralizing immunoglobulins, or immunoglobulin fragments, purified from the plasma of animals hyperimmunized against snake venoms or specific toxins. Its effectiveness consists in its ability to provide to the patient antibodies with a high affinity to snake venom, aiming to eliminate the toxins responsible for toxicity of the envenoming, mitigating the progress of toxic effects induced by snake venom components . However, the antivenom has some limitations, such as poor ability to treat local effects, risk of immunological reactions, high cost, and difficult access in some regions [8–10]. If antivenom administration is initiated rapidly after envenomation, neutralization of systemic effects is usually achieved successfully; however, neutralization of local tissue damage is more difficult . Furthermore, the availability and accessibility of antivenoms is limited in many regions, such as Sub-Saharan Africa, Asia, and, to a lesser extent, Latin America, which could aggravate even more this picture . Thus, this inability to treat local effects, as well as the increased time between accident and treatment, is the main reason for the temporary or permanent disability observed in many victims, which can lead to serious social, economic, and health negative impacts, given that most victims live in rural areas .
In this context, the search for complementary therapies to treat snakebites is relevant and medicinal plants could be highlighted as a rich source of natural inhibitors and pharmacologically active compounds [6, 11–13]. There are several reports of the popular use of medicinal plants against snakebites around the world, especially in tropical and subtropical regions such as Asia, Africa, and South America [14, 15]. The rural and tribal people living in remote areas greatly depend on folk medicines for the treatment of bites from any venomous creatures . The use of medicinal plants against snakebites is a historical practice throughout the human history, and this knowledge has been transferred among the rural communities from generation after generation . Nowadays, these herbal antidotes used in folk traditional medicine gained much attention by toxinologists worldwide as a tool for design of potent inhibitors against snake venom toxins. The potential advantages of antiophidic plants are their possible low cost, easy access, stability at room temperature, and ability to neutralize a broad spectrum of toxins, including the local tissue damage [12, 15–17].
So, the objective of this review is to provide an updated overview of medicinal plants used popularly as antiophidic and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation, since this is a critical effect of snake venoms that could lead to relevant sequel to victims. A review of the main botanical families popularly used as antiophidic is presented, including the main species and forms of popular use of them. Then, studies supporting their popular use are discussed, as well as the advantages of this kind of approach for treatment of snake venom accident.
The study database included original articles published in peer-reviewed journals, as well as books, thesis, dissertations, patents, and other reports covering antiophidic plants (ethnopharmacological surveys, original articles, or reviews), dated until December 2016. For the online search, where applicable, the following search strategy was employed: (“plant” OR “plants” OR “plant extract” OR “vegetal” OR “vegetal species” OR “vegetal extract” OR “traditional medicine” OR “alternative medicine” OR “complementary therapy” OR “natural medicine” OR “ethnopharmacology” OR “ethnobotany” OR “herbal medicine” OR “herb” OR “herbs” OR “decoction” OR “tea” OR “infusion” OR “macerate”) AND (“snake venom” OR “snake” OR “snakes” OR “snakebite” OR “snakebites” OR “antivenom” OR “antivenoms” OR “anti-venom” OR “anti-venoms” OR “antivenin” OR “antivenins” OR “anti-venin” OR “anti-venins” OR “antiophidian” OR “antiophidic” OR “snake envenomation” OR “antitoxin” OR “antitoxins” OR “snake antidote” OR “snake antidotes” OR “snake venom neutralization” OR “snake venom inhibition” OR “snake toxins inhibition” OR “snake toxins neutralization” OR “viper” OR “viperidae” OR “crotalinae” OR “viperinae” OR “elapidae” OR “pit-viper” OR “bothrops” OR “jararaca” OR “crotalus” OR “micrurus” OR “lachesis” OR “cobra” OR “naja” OR “bitis” OR “vipera” OR “daboia” OR “trimeresus”).
All abstracts and/or full-text data were considered, without language restriction. Then, the publications covering ethnobotanical and/or pharmacological studies of antiophidic plants were selected and carefully analyzed. With the information gathered in these studies, the actual scenario of the use of plants against snake venom was pointed out. Main botanical families used, main countries where antiophidic plants are reported, and mode of use mostly employed in folk medicine were described. Regarding studies of pharmacological evidence, the snake species that were most studied, which plant species were tested and presented positive results, correlating with those species that also presented record of ethnopharmacological use, were also reported.
3. Medicinal Plants as a Popular Source of Antidotes for Snakebites: Traditional Use
According to the literature search performed, a lot of ethnopharmacological studies showing medicinal plants claimed as antiophidic were found. A summary of these vegetal species can be observed in Table 1.
In parentheses is the synonym used in the original work; out of the parentheses is the accepted name (in case of more than one paper treating the same species with different names); ND = information not described in the work; I = internal use; E = external use. Species evaluated on antiophidic activities in previous studies (see Tables 2–8) showing good inhibitory potential against venom induced local effects. #Species evaluated on antiophidic activities in previous studies, however, with poor inhibition potential against venom induced local effects.