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ABSTRACT
The conflict between man and snake arises primarily from their overlapping habitats. Neutrali-
zation of snake venom toxicity by the application of serum antivenom is a development of the
last century. Traditionally people treated snake bite victims by medicinal plants alone or in
combination with processed edible items and various rituals. In spite of the success of antiven-
om treatment, the drug is still not available to a large number of people worldwide who are
vulnerable to snake bites. Thus the use of plants as snake venom antidotes will be continued in
future. It is also hypothesized that components isolated from plants together with antiserum
may yield better results in the neutralization of venom toxins. In this article, we have visited
continents to note the severity of snake bites and compiled various plants used as antidotes.
These plants warrant establishment of their anti-venom potential leading to a good possibility
of discovering new drugs or templates to design better drugs for various diseases.
KEYWORDS: Anti-snake venom, medicinal plants, snakebite, herbal therapy.
Medicinal plants as snake venom antidotes
Division of Structural Biology and Bioinformatics; CSIR-Indian Institute of Chemical Biology; 4, Raja S.C.
Mullick Road, Jadavpur, Kolkata-700032 – India
INTRODUCTION
There are over 3000 species of snakes
found worldwide including the sea and at high
altitudes like Himalayan range of Asia, Arctic
Circle in Scandinavia and extreme south of
Australia, although, snakes are absent in Ant-
arctica, Ireland, New Zealand and many small
islands of the Atlantic and central Pacific re-
gion (Bauchot 1994). Amongst the 600 spe-
cies of venomous snakes, about 410 are con-
sidered medically important (Pinho and Perei-
ra 2001). World Health Organization (WHO)
assessed the relative risk of each species and
divided them into two major categories, one of
highest medical importance and other of sec-
ondary medical importance (Warrel, 2010).
There are about 5 million snakebite cases per
year worldwide, among which 1,00,000 –
2,00,000 deaths are reported. Chippaux (1998)
has summarized the scenario of snake enven-
omation in different parts of the world. Many
people, who survive, however suffer from
snakebite related amputations or permanent
tissue damage leading to disability. Children
have both higher incidence of snakebites and
suffering than do adults, since they are ex-
posed to a larger amount of venom per unit ar-
ea of body surface and body weight. Snakebite
cases are higher in rural areas and show sea-
sonal variation, with the peak incidences ob-
Journal of Experimental and Applied Animal Science
Volume 1, Number 1, pp. 156-181, 2013
Print ISSN 2314-5684 | Online ISSN 2314-5692
REVIEW ARTICLE
Payel Bhattacharjee and Debasish Bhattacharyya
Bhattacharjee and Bhattacharyya, 2013
Journal of
Experimental and Applied Animal Sciences.
1, 1:156-181
157
served in the rainy and harvesting seasons
(WHO, 2008). Table 1 summarizes the names
of most relevant venomous snakes of the
world, their major toxic compounds, mecha-
nism of action of the toxins and their clinical
manifestations.
From ancient times indigenous com-
munities depended on herbal medicines to
cure variety of ailments including cases of
snakebites (Samy et al. 2008). There are am-
ple evidences of practice of herbal treatments
by aboriginal people from various sources like
written documents on parchment papers and
preserved stone monuments and even the orig-
inal medicines themselves. Since 5000 B.C.
Indians, Chinese, Babylonians, Hebrews,
Egyptians and Assyrians (an ethnic group
whose origin lies in ancient Mesopotamia)
were acquainted with medicinal plants. The
Greeks were familiar with many of the mod-
ern drugs as evidenced from the works of
Hippocrates, Theophrastus, Aristotle and Py-
thagoras. In spite of the relative geographical
isolation, however, there is a remarkable de-
gree of similarity in healing practices, found-
ing principles and beliefs when compared
among varied cultures. In India, specific
plants were used for the treatment of victims
bitten by specific snakes in ‘Ayurvedic’ sys-
tem of medicine. There is a complete descrip-
tion of Capparis deciduas in Brooklyn Papy-
rus, which is a medicinal plant used against
snakebite by Egyptians (Vinel and Pialoux
2005). ‘Cherokees’ - the native of America,
followed a general therapy for treatment of
snakebites. It consisted of both internal and
external applications of decoction of medici-
nal plants (Cozzo 2007). Houghton and Osi-
bogun (1993) compiled a list of flowering
plants used for the treatment of snakebite.
They also reviewed the methods of testing the
activity of the whole plant or parts thereof and
discussed the modes of action of the phyto-
chemicals. Many authors have mentioned the
versatility of antivenom plants. Rizzini et al.
(1988) enlisted 83 species, Mors (1991) com-
piled 578 species; Martz et al. (1992) enlisted
11 species, Duke (1993) enlisted 470 species,
Gomes (2010) and Dey and De (2012) enlisted
several flowering plants that are active against
snake venoms. Hashimoto (2002) in an ethno-
botanical database enlisted 66 species of
plants belonging to 31 families which are used
in the Brazilian folk medicine as antidotes
against snake venoms (Website 1). Amui et al.
(2011) have developed a plant-antivenom da-
tabase that contains information regarding an-
ti-venom medicinal plants, amino acid se-
quences of venom toxins and related publica-
tions. Continent wise details of the application
of the antivenom plants will follow in the later
sections.
Even today the traditional healers are
the first line of defense against illnesses in ru-
ral areas due to poor communication and lack
of emergency medical facilities in primary
health care centres. They serve more snake
bite victims as compared to the registered
medical practitioners. Direct testimonies from
victims confirm success of their treatment.
However, medical science ignores their prac-
tice partly due to unknown materials they use
and mystical nature of their practices (Chip-
paux 1998). Application of the plant or its sap
onto the bite area, chewing leaves and bark,
drinking plant extracts or decoctions are some
procedures intended to counteract snake ven-
om toxicity (Samy et al. 2008).
Herbal medicines are in great demand
in both developed and developing countries as
a source of primary health care due to their
wide biological and medicinal activities, high
safety margins, availabilities and cost consid-
erations. WHO estimated that, more than 80%
of the world’s population relies on traditional
healing practices and herbal medicines for
primary health care. In United States, about
25% of all prescribed drugs are derived from
herbal sources and most of them were discov-
ered owing to their prior use by traditional
healers (Rawat 2006). The demand of herbal
medicine in global market is increasing day by
day. Near the turn of the century, there was a
Bhattacharjee and Bhattacharyya, 2013
Journal of
Experimental and Applied Animal Sciences.
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158
rise of spending on herbal medicines by 4.6
billion US dollar in a decade; 19.6 in 1992 to
24.2 in 2002 (Vasisht and Kumar 2002). Eu-
romonitor International has reported the latest
market trends and sources of future market
growth for the industry of herbal/traditional
products in 80 countries (Website 1). Balick
and Cox (1996) have noted that even with the
advent of modern or allopathic medicines, a
number of essential drugs have been derived
from plants that are used by indigenous peo-
ple. At this stand point it is crucial to evaluate
antivenom plants to gather an overall idea for
future research and drug development. In this
review, we survey snake bite incidents conti-
nentwise and describe the variety of plants
used to save the snakebite victims. As the
trend shows, the use will be continued in near
future demanding their rational evaluation.
Epidemiology of snakebite and traditional
herbal treatment
Asia: People of South Asia are most
affected by snake bites. India has the highest
number of snake bite related deaths in the
world; 35,000–50,000 people dye per year
(David, 2005). In Pakistan, 40,000 bites are
reported annually, resulting in 8,200 fatalities
(Ali 1990; Kasturiratne et al. 2008). In Nepal,
1,000 recorded deaths occur among 20,000
cases of envenomation annually (Alirol et al.
2010). In Sri Lanka, around 33,000 cases of
envenomation are reported annually from
government hospitals (Kularatne 2003; Kastu-
riratne et al. 2008). In Bangladesh, the annual
incidence of snake bite is 4.3 per 1,00,000
population, where 20% are fatal (Sarker et al.
1999). In Iran, 5,000-7,000 snake bite cases
with 7 deaths were recorded annually between
2001-2009 (Kohli and Sakhuja 2003). In
Sayyed Dakhil district of Iraq, there are 150
cases of snake bites leading to the death of
more than 40 people since 2003. In 2011, lo-
cal Government admitted for the first time that
saw-scaled viper is responsible for the majori-
ty of the death cases (Website 2). In Vietnam,
between 1992-1998, 3,00,000 bites by Ma-
layan pit vipers (Calloselasma rhodostoma)
per year with 22% fatality, was recorded. In
Mynamar, 14,000 bites with 1,000 deaths
were recorded in 1991 (Cruz et al. 2009).
Warrell (2010) and Eriksson (2011) have
compiled the reports on snake bite cases in
South-East Asian countries. In Japan, the ma-
jority of venomous bites are inflicted by the
Asian pit vipers. The Palestine viper (Vipera
palaestinae) and Lebetine viper (Macrovipera
lebetina) are the most important species in
Western and South East Asia (Warrell 2010).
However, existing epidemiological data re-
main fragmented and the factual impact of
snake bites is possibly underestimated. More-
over, total area and the size of the whole
population of a country should be considered,
otherwise the true epidemiological picture of
snakebite in different regions would not be re-
flected.
In the Indian subcontinent, almost all
snakebite deaths are attributed to the ‘big
five’, consisting of the Russell's viper (Daboia
russelli), Indian cobra (Naja naja), saw-scaled
viper (Echis carinatus), common krait (Bun-
garus caeruleus) and king cobra (Ophiopha-
gus hannah). However, hump-nosed viper
(Hypnale hypnale), banded krait (Bungarus
fasciatus), monocled cobra (Naja kaouthia)
and Asian pir viper (Trimeresurus sp.) are ca-
pable of delivering fatal bites.
The tribal and rural people of Asia
have preserved a huge traditional knowledge
regarding the applicat ion of medicinal plants
growing around their habitat. More than 100
species of Indian plants have been reported as
snake venom antidotes (Chopra et al. 1956;
Usher 1974; Nadkarni 1976; Lewis and Elvin-
Lewis 1977; Alam and Gomes 2003). Plants
are used either as single or in combination
(Kirtikar and Basu 1975). Indian plants that
are most effective as antivenom are Aris-
tolochia sp., Cissus assamica, Echinacea sp.,
Excoecaria agallocha, Gloriosa superba,
Guiera senegalensis, Hemidesmus indicus,
Nerium oleander, Parkia biglobosa, Sarsapa-
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159
rilla hemidesmus, Securidaca longipeduncula-
ta, Tamarindus indica, Thea sinensis, Triano-
sperma tayuya, Withania somnifera etc (Das
2009). The traditional healers first tie a piece
of cloth with a knot immediately above the
bitten area to minimize spread of poison into
the entire body with flow of blood. The place
of wound is properly cut to ooze out the in-
fested blood from the victim’s body and then
the paste prepared from the herbal plant is ap-
plied over the wound for a time period for
healing. Such pastes are generally prepared
from rhizomes, stems, roots or leaves of
plants, e.g. the paste from rhizome of Acorus
calamus, stem and bark of Buchnania lanzan,
shoot and leaves of Bombax ceiba and
Moringa oleifera are applied on wounds as an-
tidote of snake-bite. The seed oil of Madhuca
indica is applied on the wounds due to snake-
bite and scorpion sting for instant healing.
Rhapidophora pertusa has analgesic and anti-
inflammatory effects that help to reduce pain
caused by snake bite (Rai and Nath 2003).
Rauvolfia serpentina grows in the foothills of
Himalaya. Local people use the root of this
plant to treat snake bite victims. They claim
that the practice has been evolved through
generations after observing that mongoose
(Helogale parvula) feed on this plant before
combating with snakes (Balick and Cox
1996).
The Kani tribes of the state of Kerala,
India use Aristolochia indica and Aristolochia
tagala to treat krait and cobra bites. Paste of
fresh leaves or roots of the plants are applied
externally over the bitten area and 10 – 15 ml
of fresh juice from leaves or roots with a pinch
of black pepper is administered orally 6 times
a day to recover from the pain and coma.
Aristolochia tagala is more potent than Aris-
tolochia indica as a snake venom antidote.
The Malapandaram tribe of Kerala uses leaves
of Cipadessa baccifera mixed with pepper and
administer orally against snake bite (Latha et
al. 2008). The Sugali tribes of Yerramalais ar-
ea, Tamil Nadu, India use 23 species of ethno-
medicinal plants in the form of paste, powder,
juice, decoction, infusion and also in crude
form to treat snake bite victims. Some of them
claim that there is no death due to snake bites
till date (Basha and Sudarsanam 2012). Kun-
jam et al. (2013) described the application of
herbal medicines by the Cherwa and Pando
tribes of Chattisgarh, India. They prepare
paste, pills, powder, decoction, infusion and
aqueous extracts of medicinal plants, either
separately or in combination with other plants
and minerals. The main tribal communities of
Rajasthan, India viz., Bhil, Meena, Garasia,
Damor, Sahariya and Kathodia etc use nearly
44 plants for the treatment of snake bite,
among which 5 are monocotyledonous and 39
are dicotyledonous (Jain et al. 2011). Tribal
people of Kalahandi, Orissa, India use the
term ‘Gada’ for antivenom plants. Similar
terms like ‘Sarpairi’ or ‘Sapabisha-jhada-
gada’ literally means ‘snake medicine’ and is
used by the people in coastal districts of Oris-
sa. Mund and Sathpathy (2011) compiled the
widely used antivenom plant species used by
these ethnic people. Sometimes the snake
teeth were mixed with roots of Aristolochia
indica to treat victims. Herbal therapy of the
tribals also involved oral consumption of leaf
powder of Ocimum sanctum or rhizome pow-
der of Curcuma longa before treatment (Mund
and Satapathy 2011). In North East India, the
leaves and flowers of Mesua ferrea are used
against snake bite (Sahni 1998). Some species
are grown around houses or their extracts are
sprinkled on the floor to repel snakes. e.g., Al-
lium sativum (garlic) and Pseudocalyma alli-
ceaum (garlic vine). Aristolochia indica root
has a strong aromatic smell which is believed
to repel snakes (Latha et al. 2008). Figure 1
shows the demand for medicinal plants in
West Bengal, India. Aristolochia indica, Aza-
dirachta indica, Ocimum sanctum and An-
drographis paniculata are some of the plants
widely used as a snake venom antidote. In ru-
ral areas of West Bengal, people tie small
piece of roots of Aristolochia indica with a
thread on upper arm and use as amulet to pro-
tect them from Russell’s vipers (information
Bhattacharjee and Bhattacharyya, 2013
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Experimental and Applied Animal Sciences.
1, 1:156-181
160
obtained from interviewing a local medicinal
herbs seller).
Asad et al. (2011) enlisted 35 plants
having application as folklore (ethno-
botanical) antidotes in Pakistan. The tradit ion-
al use of leaves (35%) is higher than roots
(25%), whole plant (21%), flower (7%), wood
(5%), fruit (5%) and milky juice (2%) as a
snake venom antidote. The herbs (55%) are
mostly used as snake bite remedy than shrubs
(31%) and trees (14%). Achranthes aspera,
Albizia lebek, Cassia occidentalis and Verbe-
na officinalis are used against snakebites in
Pakistan (Ahmed 2007). Glycine max, Hedyo-
tis diffusa and Ruta graveolens are used in
traditional Chinese medicine as snake bite an-
tidote. Ash of leaves and stem of Launea
acanthodes is used as herbal antidote for
snake bites and insect sting in Iran (Rajaeia
and Mohamadi 2012).
Africa: Africa is the habitat of four
venomous snake families- Atractaspididae,
Colubridae, Elapidae and Viperidae. Vipers
alone cause approximately 60% of all bites. In
drier regions of the continent, 90% of bites are
inflicted by the saw-scaled vipers. Snakebites
are most common in the sub-Saharan regions
with approximately 1 million reports annually,
resulting 5,00,000 envenomations and 25,000
deaths (Chippaux 1998). The annual incidence
of snake bites in the Benue Valley of North-
Eastern Nigeria is 500 per 1,00,000 population
with 12.2% fatality (Cruz et al. 2009).
In Kenya, up to 80% of snakebite vic-
tims take help from traditional practitioners
before visiting a medical center (Snow et al.
1994). For treatment, plants belonging to
Asteraceae family are used extensively fol-
lowed by Annonaceae, Fabaceae, Combreta-
ceae and Tiliaceae families. Among the Baka
community, nearly all remedies are from
Apocynaceae and Annonaceae. The Luo and
Kamba ethnic groups of Kenya are highly ex-
posed to snake bites, especially Bitis sp., Den-
droaspis polylepis and Naja melanoleuca. The
traditional healers make an incision around the
bite and herbal remedies applied on the wound
site. Antidotes are administered within half an
hour after the bite. Owuor and Kisangau
(2006) have reported use of several indige-
nous plants by these communities. Both com-
munities had two exotic species. Allium cepa
and Tagetes minuta are used by Kambas and
Senna siamea and Tithonia diversifolia are
used by Luos of South Western Kenya. Only
Combretum sp. is shared by these two ethnic
groups. Similar practice of using Combretum
sp. is reported in Tanzania. In some cases, the
snake teeth were mixed with Opilia
amentecea, a woody vine for the treatment of
poisoning. Despite this difference, there are
significant similarities among the Luo and
Kamba beliefs of snake bite perception and
etiology (Owuor and Kisangau 2006). Com-
bretum collinum, Sebaea hymenosepala, Sola-
num incanum, Steganotaenia araliacea and 3
species of Grewia (G. bicolor, G. fallax and
G. truncata) are used by the native people in
East Africa. In addition, application of plants
like Erythrina abyssinica, Sansevieria kirkii
and Vernonia sp. are recorded (Reis and Lipp
1982). In South Nigeria, an infusion of the
leaves of Clerodendron polycephalum and
Sansevieria liberica are applied on the bitten
area (Dalziel 1948; Gill 1992; Osabohien and
Egboh 2008; Adeyemi et al. 2009). In South
Africa and tropical America, Sansevieria
trifasciata is used for the treatment of inflam-
matory conditions and sold as a crude drug in
the market to treat victims of snakebite (Mor-
ton 1981). ‘Vemkill’ is a standardized ethanol-
ic extract of a combination of three plants,
which has been used successfully to abolish or
reduce lethality of snake bites in Ghana (Na-
omesi et al. 1996). Hoodo, a traditional Afri-
can-American community treats victims by
applying a boiled mixture of Argentina anser-
ine, Musa sp. and milk to the site of snake bite
(Yonwode C).
Bhattacharjee and Bhattacharyya, 2013
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Table 1: Major venomous snakes of the world
Family
Species
Major components
a
Mechanisms of action
Clinical manifestations
b
Viperidae
Daboia
russelli
Echis carinatus
Hypnale hypnale
Trimeresurus sp.
Vipera sp.
Macrovipera sp.
Calloselasma sp
Bitis sp.
Bothrops sp.
Crotalus sp.
Agkistrodon sp.
Lachesis sp.
Phospholipase A
2
(PLA2) isoforms
Hydrolyse membrane phospholipids in a Ca2+
dependent manner and incr ease release of free
proteins
Hemorrhage, coagulation
defects, acute renal failure,
cardiotoxicity, local tissue
necrosis, pulmonary hemor-
rhagic edema, renal failure
and hematuria.
Serine protease like
factor V and X activator
Affect
blood coagulation system of victim
Haemorrhagic metalloprotease
Degrade extracellular matrix proteins and shows
cytotoxicity on endothelial cells
Hyaluronidases
Degradation of hyaluronic acid in the extracell
u-
lar matrix facilitates the diffusion of toxins from
the site of a bite into the circulation
Nucleases, nucleotidases and
phosphoesterases
Release of purines, a multitoxin, during snake
envenomation
L
-
amino acid oxidase (LAAO)
Generates hydrogen peroxide and affects
platelet
aggregation, induction of apoptosis, haemor-
rhagic effects, and cytotoxicity
Disintegrins
C-type lectins Cysteine-rich se-
cretory protein and vascular en-
dothelial growth factor (VEGF)
Hemagglutination, platelet aggregation and va
s-
culogenesis
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Table 1: Major venomous snakes of the world (Continued)
Family
Species
Major components
a
Mechanisms of action
Clinical manifestations
b
Elapidae
Naja sp.
Bungarus sp.
Dendroaspis sp.
Micrurus sp.
Acanthophis sp.
Micropechis sp.
Pseudonaja sp.
Oxyuranus sp.
Notechis sp.
Austrelaps sp.
Hoplocephalus sp.
Acetylcholinesterase (Except
Mamba snakes)
Depletion of neurotransmitter from the
nerve terminals, degeneration of nerve ter-
minals and intramuscular axons.
Neurological and neuromuscular
problem, paralysis, ventilatory
failure, diuresis and death in a
short duration of time.
Cardiotoxin
Depolarization and degradation of the
plasma membrane of skeletal muscle cells.
Neurotoxic
PLA2
Degrades synaptosomal phosphatidylch
o-
line
Pre or
post
-
synaptic neur
o-
toxin
Reversible blocking of neural transmission
by competitively binding to the nicotinic
acetylcholine receptors (nAChRs)
Metalloproteases
Bleeding disorder due to degradation of f
i-
brinogen
Disintegrins, warparins
Affects
Na
+
-K
+
ATPase
Phosphoesterase (low
amount)
Release of purines, a multitoxin
a These major components are common to the family of snakes.
b These clinical manifestations are common to the family of snakes.
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Table 2: List of plants having antivenom potentiala
Name of plant Parts/extracts used
Inhibition of snake venom
(whole venom/ components)
Reference
Aristolochia bracteolata
,
T
y-
lophora indica and Leucas
aspera (1:1:1)
Aqueous extracts of leaves and roots Daboia russelli russelli and Naja naja Sakthivel et al. 2013
Piper longum
Ethanolic extract of fruits, especially piperin.
Daboia russelli
Shenoy et al. 2013
Aristolochia indica Aqueous extract of root Daboia russelli russelli
Bhattacharjee and Bhattacharyya
2013; Meenatchisundaram et al. 2009
Bombacopsis glabra
Triacontyl p
-
coumarate (PCT) isolated from
root bark Bothropoides pauloensis Mendes et al. 2013
Crocus sativus
Crocin
Daboia russelli
Sebastin et al. 2013
Renealmia alpinia Alcoholic extract
Metallo
-
and serine proteinases present
in snake venoms Patiño et al. 2013
Artemisia absinthium
Methanolic extract
Montivipera xanthina
Nalbantsoy et al. 2013
Solanum campaniforme
Alcoholic extract of leaves
Bothrops pauloensis
Torres et al. 2013
Sapindus saponaria
Callus
Bothrops
and
Crotalus sp.
da Silva et al. 2012
Persimmon proanthocyanidin
Alcoholic extract
Naja atra
Xu et al. 2012
Butea monosperma
Ethanolic extract of stem bark
Daboia russelli
Tarannum et al. 2012
Mikania laevigata
Ethanolic extract of leaves
Philodryas olfersii
Collaço et al. 2012
Tanacetum parthenium, A
n-
drographis paniculata and
Curcuma sp.
Crude extracts, purified
compounds
Ophiophagus
hannah
Salama et al. 2012
Bhattacharjee and Bhattacharyya, 2013
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Table 2: List of plants having antivenom potentiala (Continued)
Name of plant Parts/extracts used
Inhibition of snake venom
(whole venom/ components)
Reference
Mucuna pruriens Seed
Echis carinatus
Calloselasma rhodostoma and Naja
sputatrix
Hope-Onyekwere et al. 2012; Scirè et al.
2011; Fung et al. 2010; 2011; Guerranti
et al. 2008
Nectandra angustifolia
Ethanolic extract of leave and essential oil
Bothrops neuwiedi diporus
Torres et al. 2011a
Solanum campaniforme
Solanidane steroidal
alkaloids isolated from
leaves Bothrops pauloensis Torres et al. 2011b
Mangifera indica
Aqueous extract of stem bark
Ethanolic extract from seed kernels
Daboia russelli russelli
Calloselasma rhodostoma and Naja
naja kaouthia
Dhananjaya et al. 2011
Leanpolchareanchai et al. 2009
Schizolobium parahyba Aqueous extract of leaves Bothrops sp.
Vale et al. 2011; 2008; Mendes et al.
2008
Fagonia cretica
Methanolic extract from the leaves and twigs
Naja naja karachiensis
Razi et al. 2011
Mimosa pudica
Tannin isolate
Aqueous root extracts
Naja kaouthia
Echis carinatus and Daboia russelli
russelli
Ambikabothy et al. 2011
Meenatchisundaram and Michael 2009
Marsypianthes chamaedrys
Inflorescence and leaf extracts
Bothrops atrox
Magalhães et al. 2011
Hibiscus aethiopicus
Aqueous extract of whole plant
Echis ocellatus
and
Naja n. nigricollis
Hasson et al. 2010
Argusia argentea
Rosmarinic acid
Trimeresurus flavoviridis
Aung et al. 2010
Dipteryx alata
Hydroalcoholic extract of bark
Bothrops jararacussu
Puebla et al. 2010; Nazato et al. 2010
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Table 2: List of plants having antivenom potentials a (continued)
Name of plant Parts/extracts used
Inhibition of snake venom
(whole venom/ components)
Reference
Curcuma
zedoaroides
Acetone extract of rhizome
Ophiophagus hannah
Lattmann et al. 2010
Mikania glomerata
Aqueous leaf extract
Crotalus durissus
Floriano et al. 2009
Anacardium occidentale Bark extract
Neutralize the viper venom hydrolytic
enzymes such as phospholipase, prote-
ase, and hyaluronidase
Ushanandini et al. 2009
Vitis vinifera Methanolic extract of seed
Daboia russelli
Echis carinatus
Mahadeswaraswamy et al. 2009
Mahadeswaraswamy et al. 2008
Eclipta alba
Extracts from both native and
genetically mod
i-
fied plant
Crotalus durissus terrificus
and
Bot
h-
rops jararacussu Diogo et al. 2009
Mouriri pusa, Byrsonima cra
s-
sa, Davilla elliptica and
Strychnos pseudoquina
Methanolic extracts of leaves Bothrops jararaca Nishijima et al. 2009
Morus
alba
Leaf extract
Daboia russelii
Chandrashekara et al. 2009
Azadirachta indica
Methanolic leaf extract
Cobra and viper venom
Mukherjee et al. 2008
Casearia sylvestris
Ellagic acid derivatives from aqueous extract
Bothrops jararacussu
Da Silva et al.
2008
Galactia glauscescens
Ethanolic extract of leaves
Crotalus durissus terrificus
Dal Belo et al. 2008
Curcuma longa Turmerin protein Naja naja
Chethankumar and Srinivas 2008
Ferreira et al. 1992
Echinacea purpurea
Aqueous extract of root
Bothrops
asper
Chaves et al. 2007
Pentaclethra macroloba Aqueous extract of bark Triterpenoid saponin
inhibitors
Bothrops sp.
da Silva et al. 2005; 2007
Bhattacharjee and Bhattacharyya, 2013
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Table 2: List of plants having antivenom potentialsa (continued)
Name of plant Parts/extracts used
Inhibition of snake venom
(whole venom/ components)
Reference
Pluchea indica
Beta
-
sitosterol and stigmasterol isolated from
the root extract viper and cobra venom Gomes et al. 2007
Tamarindus indica
Seed extract
Daboia russelli
Ushanandini et al. 2006
Bridelia ndellensis
Alcoholic extract of bark
Neutralize snake venom toxicity
Mostafa et al. 2006
Crinum jagus Methanolic extract of the bulb
Echis ocellatus
,
Bitis arietans
and
Naja
nigricollis Ode and Asuzu 2006
Hemidesmus indicus
Methanolic root extract
Daboia russellii
and
Naja kaouthia
Chatterjee et al. 2006
Croton urucurana
Aqueous extract
Bothrops jararaca
Esmeraldino et al. 2005
Cordia verbenacea
Rosmarinic acid
Bothrops jararacussu
Ticli et al. 2005
Bauhinia forficate
Aqueous extract from aerial parts
Bothrops
and
Crotalus sp.
Oliveira et al. 2005
Musa paradisiacal
Juice
Crotalid venom
Borges et al.
2005
Annona senegalensis
Methanol extract of root bark
Naja nigricotlis nigricotlis
Adzu et al. 2005
Acalypha indica
Ethanolic extract of leaf
Daboia russelli russelli
Shirwaikar et al. 2004
Baccharis trimera
Alcoholic extract
Bothrops neuwiedi
and
B.
jararacussu
Januário et al. 2004
Eclipta prostrata
Butanolic extract
Calloselasma rhodostoma
Pithayanukul et al. 2004
Tabernaemontana catharinensis
Aqueous extract
Crotalus durissus terrificus
de Almeida et al. 2004
Thea sinensis
Melanin
Agkistrodon
sp.
and
Crotalus sp.
Hung et al. 2004
Parkia biglobosa
Water
-
methanol extract of stem bark
Naja nigricollis
and
Echis ocellatus
Asuzu and Harvey 2003
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Table 2: List of plants having antivenom potentials a (continued)
aThe table provides information about antivenom plants reported in the last 20 years (1993-2013).
Additional information is available from cross references.
Name of plant Parts/extracts used
Inhibition of snake venom (whole
venom/ components) Reference
Mandevilla velutina Aqueous extract
Inhibit some enzymatic and pharmac
o-
logical activities of some snake ven-
oms
Biondo et al. 2003
Casearia mariquitensis
Aqueous extract of leaves
Bothrops neuwiedi pauloensis
Izidoro et al. 2003
Marsypianthes chamaedrys Methanolic extract
Antifibrinoclotting action against
thrombin-like enzymes of snake ven-
oms
Castro et al. 2003
Symplocos racemosa Phenolic compound
Inhibitory activity against snake ve
n-
om phosphodiesterase I Ahmad et al. 2003
Mitragyna stipulosa Non-alkaloidal extract of bark
Inhibit snake venom phosphodieste
r-
ase I activity Fatima et al. 2002
Ehretia buxifolia
Ehretianone in the methanolic extract of the
root bark Echis carinatus Selvanayagam et al. 1996
Brongniartia podalyrioides
and
B. intermedia
(
-
)
-
Edunol a prenylated pterocarpan isolated
from the roots Bothrops atrox Reyes-Chilpa et al. 1994
Bhattacharjee and Bhattacharyya, 2013
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Central and South America: South
America is the third most affected area by
snake envenomation after Africa and Asia
(Chippaux 1998). Epidemiological data on
snakebite envenomation in Latin America are
limited due to improper reporting to health
centers. In Brazil, there are 25,000 snake bite
incidences per year with a mortality rate of
about 0.45%. The snakes responsible for ven-
omous bite are Bothrops (83.8%), Crotalus
(8.5%), Lachesis (3.4%) and Micrurus sp.
(0.4%) (Sousa et al. 2013). Mexico and Cen-
tral America collectively have an estimated
193 fatalities per year. The tropical areas of
the Amazon basin and the southern tip of
South America contribute an additional 100
and 4 death per year on an average respective-
ly (Miller L). In Costa Rica, 22.4 per 1,00,000
inhabitants are admitted to hospitals annually
due to snake bites (Rojas et al. 1997).
Figure 1: Handling of traditional medicinal plants in India. a. Series of shops selling medicinal herbs
even at late evening in a suburban railway station near Kolkata, India; b. Aristolochia indica; c. Aza-
dirachta indica; d. Ocimum sanctum and e. Andrographis paniculata grown in herbal gardens near Kol-
kata. Photographic credits, PB (a, c-e) and Angana Bhattacharyya (b).
Bhattacharjee and Bhattacharyya, 2013
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Sciences.
1, 1:156-181
169
Brazilian Indians have an ancient tradi-
tion of using ‘guaco’ (Mikania cordifolia and
M. glomerata) for snake bites. They prepare a
decoction of the leaves and administer orally.
They also apply the juice of leaves or stem di-
rectly onto the bitten part. Other Red Indian
tribes in Amazonian rainforest use the crushed
leaf and stem topically on snake bites and the
decoction of leaves/stem as a drink. Several
Indian tribes also believe that the fresh aro-
matic smell of crushed leaves may drive
snakes away (Ruppelt et al. 1991; Maiorano et
al. 2005; Floriano et al. 2009; Collaço et al.
2012). People of Serra da Jibóia, Brazil, use
homemade remedies against snake enven-
omation from the plants like Allium cepa, Al-
lium sativum, Anacardium occidentale, An-
nona crassiflora, Amburana cearensis, Euter-
pe edulis, Joannesia princeps, Mucuna urens,
Zephyranthes sp. etc (Fita et al. 2010).
Otero et al. (2000a) reported an inven-
tory of plants used by traditional healers to
treat snake bites in Colombia. They docu-
mented the methods of preparation, mode of
administration, dosage and results of treat-
ment. They reported 77 species of plants be-
longing to 41 families like, Acrocomia ieren-
sis, Aristolochia rugosa, Aristolochia trilo-
bata, Barleria lupulina, Bauhinia cumanensis,
B. excisa, Cecropia peltata, Cola nitida,
Costus scaber, Nicotiana tabacum, Allium sp.
and Renealmia alpinia. Eclipta prostrate is
highly recognized as snakebite antidote in the
vast region of Southern United States to South
America. Mesua ferrea bark is mostly used to
treat snake bites (Santamaría 1978). The Maya
text recommended the application of boiled
leaves of Clerodendrum ligustrinum as a wash
for snake bites (Roys 1931). The Choco and
Cuna Indians in Panama use Chrysothemis
friedrichsthaliana as a snakebite treatment re-
gime. Negroes in Panama apply boiled shoots
of Heliconia bihai on foul ulcers resulting
from snakebites (Morton 1981). In Venezuela,
Serpicula brasiliensis is boiled in water and
used for snakebite (Reis and Lipp 1982).
Mestizos and the native peoples in the
Upper Amazon use a wide variety of plants to
treat snakebites. Ethnobotanists Evans and
Raffauf (1990) enlisted 29 plants while Duke
and Vasquez (1994) enlisted 12 plants used
for this purpose. Local inhabitants use to ap-
ply a poultice, made up of banana leaf, filled
with the finely chopped tuber of Dracontium
loretense around the site of envenomation.
They also apply Laportea aestuans and Sola-
num sessiliflorum, as well as chewed leaves of
Nicotiana rustica and applied directly to the
wound. The patient was also given a cold-
water infusion of Dracontium loretense to
drink or Solanum sessiliflorum fruit boiled
with sugar (Beyer 2008). Bauhinia cumanen-
sis or Bauhinia excisa were used to treat
snakebites in Trinidad and Tobago. They
made tinctures with alcohol or olive oil and
kept in rum flasks called 'snake bottles'. The
other plants used are Aristolochia rugosa, Ac-
rocomia aculeate, Barleria lupulina, Cola ni-
tida, Nicotiana tabacum and Pithecellobim
unguis-cati. Emergency medicines are ob-
tained by chewing a three-inch piece of the
root of Cecropia peltata and administering
this chewed-root solution to the bitten area.
Another indigenous plant used is Renealmia
alpinia that are crushed together with the juice
of Costus scaber (Lans et al. 2001). Guahibo,
the nomadic people of Savannas and gallery
forests of South America, extensively used
plants as antidotes. The traditional healers,
known as ‘shaman’ play significant role for
curing snake envenomations. They produce
tobacco smoke along with chanting and then
the cigarette was soaked in a cup of water to
produce ‘tobacco water’, which was sprinkled
on the patient’s head and extremities. Accord-
ing to their belief, this smoke-blowing treat-
ment had a strong psychological effect on pa-
tient (Zethelius and Balick 1982).
North America: Approximately
45,000 snakebites occur annually in the Unit-
ed States, 8000 of which are from venomous
snakes and among them only 5 people die
each year. This number is quite low due to
Bhattacharjee and Bhattacharyya, 2013
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availability of good transportation and medical
facility. The state of North Carolina has the
highest frequency of snakebites with an aver-
age of 19 bites per 1,00,000 people followed
by Arkansas, Texas, Georgia, West Virginia,
Mississippi, Louisiana, and Oklahoma (Par-
rish 1966; Russell 1980). Between 1960 and
1990, only 12 fatalities per year from snake-
bite were reported (Juckett and Hancox 2002).
There are about 25 species of venomous
snakes among the 120 species indigenous to
United States. Western and Eastern diamond-
back rattlesnakes cause up to 95% of all
snakebiterelated deaths in the United States
(Gold et al. 2002). The majority of the snakes
are pit vipers (subfamily Crotalinae), e.g. rat-
tlesnakes, cottonmouths and copperheads. The
coral snake (Elapidae) is the native venomous
snake in United States (Gold et al. 2004).
Artemisia fillifolia, Echinacea sp.,
Eryngium yuccifolium, Gentiana villosa,
Gutierrezia sarothrae, Hypericum perforatum,
Juniperus sp., Lesquerella fendleri, Ligusti-
cum poteri, Nicotiana sp., Podophyllum pelta-
tum and Polygala senega are used as folklore
plants to treat snake bite by Native American
(Huntley et al. 2005). There is little infor-
mation on how the Ohlone, Native American
people of the Central and Northern California
coast, dealt with snakebites. They generally
treat a person who was bitten by a rattlesnake,
by giving a tea made from rattlesnake weed
(Daucus pusillus). They also use to make an
incision followed by suction to the area of the
bite. The Ohlone protect themselves from
snake bites by placing fresh leaves of the Ore-
gon ash tree (Fraxinus latifolia) in their san-
dals (Website 4). Comanche tribe of Texas,
Oklahama and New Mexico use Ageratina sp.,
Lophophora williamsii and the bark of Alnus
sp. for treating snakebite (Graham JS).
Australia: Despite the enormous spe-
cies of venomous snakes in Australia, only 2
to 4 deaths occur every year from snakebites.
In Australasia ecozone, like Papua New Guin-
ea, Solomon Islands and Vanuatu where hu-
man settelement in the fringe area of dense
rain forest causes human-snake habitat con-
flict, snakebite is an almost daily occurrence
and venomous snakebite is a serious public
health problem (Kasturiratne et al. 2008). In
New Guinea, majority of the bites are caused
by the death adders (Acanthophis sp.) and few
are by the endemic small-eyed snake (Microp-
echis ikaheka) and other local species. Few
numbers of terrestrial snakes like eastern
brown snakes (Pseudonaja textilis), death ad-
ders, mulga snake (Pseudechis australis), tai-
pans snake (Oxyuranus sp.), tiger snakes
(Notechis scutatus), copperheads (Austrelaps
sp.) and broad-headed snake (Hoplocephalus
sp.) are found in the Pacific Islands, although
sea snakes are common in coral reefs. Among
these the eastern brown snake is highly ven-
omous resulting in up to 60% of all deaths due
to snakebites (Mirtschin et al. 2002). Williams
et al. (2003) reported the snakebite incidences
in Mekeo region of Central province between
1997 and 2001 as 561.9 cases per 100,000
populations per yaer. At present, there is no
data on the incidence of snakebite related
morbidity or mortality in other regions of Pa-
pua New Guinea.
In some areas of Papua New Guinea,
the following plants are used for treating
snakebites: Alphitonia incanea, Cerbera flori-
bunda, Maclura sp., Mangifera minor,
Melanolepis multiglandulosa, Musa paradisi-
ca, Nicotinia tabacum, Osmoxylon micran-
thum, Osmoxylon micranthum and Passiflora
foetida. People use to apply the sap or extract
of bark onto the bitten area and sometimes in-
gest the juice of the plant/ plant parts (Mebs
1996; 2000). In the Morobe province of Papua
New Guinea, the sap of the stem of cooked
banana (Musa paradisiaca) is smeared onto
the site of bite. The sap of the leaf of Codi-
aceum variegatum is also ingested and rubbed
into the bite area (Woodley 1991). In Madang
province of Papua New Guinea, the dry leaf of
Nicotiana tabacum is consumed to treat snake
envenomation (Petir et al. 1997).
Bhattacharjee and Bhattacharyya, 2013
Journal of Experimental and Applied Animal
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171
Europe: Snakebite is relatively a rare
medical emergency in Europe due to cold cli-
matic conditions, better standard of living and
thin population density. In this continent in-
cluding European Russia and Turkey, the an-
nual number of snakebite cases is estimated to
be 8,000 with only 15% severe cases (Chip-
paux 2012). Average estimated death is 5 and
6 per year in Western and Central Europe re-
spectively. Eastern Europe has relatively more
deaths of about 37 per year. In Europe, most
of the venomous bites are caused by coastal
viper (Vipera xanthina), nose-horned viper
(Vipera ammodytes), asp viper (Vipera aspis)
and Lataste's viper (Vipera latastei) (Chip-
paux 1998). In 16th century, Ribes nigrum
was used by French monks to treat snakebite
victims. European settlers use Sanicula
marilandica roots to draw out snakebite ven-
om (Website 5). Thymus vulgaris was used by
the Greek and Roman as treatment for snake
bite poisoning (Website 6). Overall, there is
little information of antivenom plants in Eu-
rope.
Need for scientific validations of antivenom
plants
Snake bite victims are generally treat-
ed by administration of horse or sheep-derived
polyclonal antivenoms. However, despite be-
ing the only recommended treatment for the
registered medical practitioners and success of
the therapy, it is still important to search for
synthetic and natural product inhibitors of
venom that could complement serum therapy
in terms of reducing morbidity and mortality
and also to alleviate the side-effects of antise-
rum therapy. There is a wide gap between the
supply and demand of the antivenoms. It will
be wider in future because of procurement of
snake venoms arising from stringency in ani-
mal ethics regulations.
In contrast, among the enormous varie-
ties of antiophidian plants used worldwide,
only a few species have been scientifically in-
vestigated to explore the underlying secret of
this gift of nature to identify antivenom mole-
cules and their mode o f actions. Pereira et al.
(1994) have screened 15 compounds, isolated
from reputed antiophidian plants that showed
significant protection to mice against the le-
thal action of the venom of Bothrops jararaca.
Otero et al. (2000b) described the antivenom
activity of ethanolic extracts of 12 plants
among 74 plants used by traditional healers
for snakebites in the North-West region of Co-
lombia. Núñez et al. (2004) determined the
neutralizing activity of ethanolic extracts of
leaves and branches of 12 plants against the
edema-forming, defibrinating and coagulant
effects of Bothrops asper venom in Swiss
Webster mice. Several researchers have com-
piled the reports on inbitory properties of var-
ious plants against snake venom induced tox-
icity (Daduang et al. 2005; Soares et al. 2005;
Memmi et al. 2005; Samy et al. 2008; Gomes
et al. 2010; Makhija and Khamar 2010; Dey
and De 2012; Gupta and Peshin 2012). Table
2 summarizes the description and references
of major antivenom plants that neutralize the
toxic effects of different snake venoms in vitro
and in vivo. Certainly, this list is not exhaus-
tive.
CONCLUSION
There is an intricate relationship be-
tween human beings and plants from the be-
ginning of civilization. At first, the use of me-
dicinal plants for various ailments was instinc-
tive similar to other animals. During evolution
healing properties of certain plants were iden-
tified, noted and conveyed to the successive
generations. Sometimes plants believed to
possess antivenom properties do not show ex-
pected results in experiments done in vitro
(Mebs 2000). It is possible that some plants
may act as placebo to reduce fear and recov-
ery from traumatic conditions of the victim. It
should be acknowledged that snakes are one
of the ten major causes of fear experienced by
the human race (Tancer 2008). Therefore, the
physiological changes associated with intense
fear of a snake bite victim must not be over-
looked.
Bhattacharjee and Bhattacharyya, 2013
Journal of Experimental and Applied Animal
Sciences.
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172
In parallel, with the advancement of
immunology, application of antivenom serum
emerged to treat snake bite cases. Major limi-
tation of this treatment is that serum proteins
of the aminals used for raising the antibodies
are invariably contaminated in the antisera.
Further, in cases of polyvalent antisera, anti-
bodies of unrelated snake venoms also act as
contaminations. The combined effect often
leads to severe allergic reactions in patients.
Plant products within safe margin of their tox-
icity, if any, are less probable to react immu-
nologically. Medicinal plants are gaining at-
tention for discovery of drugs as phytomedi-
cine with a hope to develop antivenom agents
that could complement serum therapy. It is al-
so possible that these plants may yield effi-
cient remedies for diseases unrelated to
snakebites (P.B. and D.B., unpublished obser-
vation).
ACKNOWLEDGEMENTS
PB was supported by National Eligibil-
ity Test-Senior Research Fellowship, Univer-
sity Grants Commission, New Delhi. We
thank Ms Kanika Sharma for critical reading
of the manuscript.
CONFLICT OF INTEREST
The authors have no conflict of interest.
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Received:
13 November 2013
Accepted: 17 December 2013
Corresponding author:
Debasish Bhattacharyya
Division of Structural Biology and Bioinformatics;
CSIR-Indian Institute of Chemical Biology 4, Raja
S.C. Mullick Road, Jadavpur, Kolkata-700032 India
Phone: +91 33 2499 5764
Fax: +91 33 2473 0284
E.mail: debasish@iicb.res.in, payel.iicb@gmail.com
