Pharmacological and Evidence-based Review of Euphorbia neriifolia Linn. ( Snuhi ): An Upavisha ; A Strong Purgative; Exigencies to Verify its Potential to Act as an Anthelminthic Drug Especially in Paediatric Age Group in Local Regions of India Specifically in Chhattisgarh

Euphorbia neriifolia Linn. ( Snuhi ) (Euphorbiacea family) is a traditional medicine which is included under multiple catagories such as Upavisha, Purgatives and Anthelminthic drugs. Preferably, an anthelminthic agent should have comprehensive deed, high fraction of rehabilitation with a single analeptic hit, denuded noxiousness to the host and should be economical. Even the intricacy like retching, wobbliness and bowel interruption have been shown by the prevalent drugs like piperazine particles. High consequence of the existing drugs and hostility of the parasites to their action sanction the hunt for revived anthelminthic molecules. In the ritualistic remedy implementation, the genesis of many worthwhile drugs is found and to evaluate denizenlore healing herb for their proclaimed anthelminthic virtue, several researchers have undertaken studies. Reinforced governance integrated with Chemical command of helminthes has been the important world-wide worm constraint tactics. Still, global multiplying resistance of gastrointestinal trichostronglides of household petty ruminants hostile to accustomed antihelminthes. [1,2] The expertise of molding employ of even a solitary Drug with their sorting and amalgam to escort a concluding upgraded outcome is Yukti. Not forgetting the safety and fruitfulness of the medicament, it is the fundamental notion of empirical drug lay out. This review describes the key information related to botanical description of E. neriifolia , phytochemistry, pharmacological actions, its purification, clinical studies and better utilization as anthelminthic-purgative package. The author emphasizes the need for evidence-based clinical studies to expand Snuhi pharmacological activities


INTRODUCTION
Gent, the overseer of entire genus is always in thrust and hunt of one top-notch Target: "The paramount state of well-being".To execute the same, all the researches have been governed by the distinguished authority, from the Sacred text (Vedic span) to this epoch.The essence of the tenacity of our archaic oracle is the cherish of Ayurveda that has been lies in the literary texts.Greatest extent of these commentary is found only in fragments while some others are yet to be explored.Kashyapa Samhita has a lot to put under the hammer instead of being available as a Astamit Tantra (Obsolate literature).Ayurveda leaflets are tremendous fund of various drug articulation.Before the advent of calligraphy, the bygone sagacity of curing, precaution and eternity was a part of the non-secular ethic of a global faith.Along with the more spiritual insights of morality, grace, and self-exploration, Veda Vyasa the glorious mentor, preserved the complete insight of Ayurveda in written form.For assuring the restorative efficacy and safety of the formulations pertaining to its mode of action, the investigative study and survey are important areas.Krimi roga is being a typical presentation in pediatric age group.Despite the fact that, worm infestation is not mortal, sometimes on the growth and intellectual development of the little ones, they have greater influence.It may prove fetal if it involves other system.By robbing them of food, causing blood deficit, damaging organs, intestinal or lymphatic obstruction and by secreting toins, [3] they impair the host.Apathy to avert them by immunization is the major handicap in the battle against such parasite.Considering the aparipakwavastha of minor, the proposed action of medicament is further pertinent.As among all treatment criteria of Krimi, Samshamana is easier to be managed in children, so anthelminthic drugs are preferred to be administered.In the World Health Assembly, for sufferers inhabiting in tribal zone who are markedly susceptible to attack of several contagion due to awareness scarcity about convenient asepsis, the need to utilizes especially natural products with therapeutically approved efficacy has been highlighted by numerous settlements.Therefore it remains a budding area of investigation [4] to explore anthelminthic factors in plants.

Upavisha
In Ayurvedic point of view, the group of drugs which are less virulent in nature and not so baneful, but on intake. [5]Produces certain noxious symptoms are named as upavisha.Rasa Ratna Samucchaya described eleven number of upvisha. [6]Snuhi is one among upvisha.According to Acharya Charaka, even an acute poison become an exemplary medicament if delivered precisely and likewise in case that a drug not dispensed duly becomes an acute poison.A strong poison if used after proper shodhana, could be the best medicine in an acceptable remedial portion and formulation.Conversely, an authentic pill if not used for proper person with proper dose [7] may affect adversely.

Anthelminthics
Snuhi is mainly recommended for preferred cure in Krimi due to its Samshamana as well as Prakritivighata effect, as it is halting the circumstances liable to cause krimi by the inherent pecularities of Snuhi that are further preverse to Pureesha and Kapha.

Purgative
An ideal anthelminthic medication is expected to wield its impact counter to the worm's excluding absorption.Portion is needed to be considerable that can ambush the worm instead of the host besides inducing any baneful reaction on victim.Safe doses of vermicides only depress or narcotize the parasites but do not kill them and these would recuperate if left in the intestine.For that reason, it is accustomed to ensure the use of vermicide with a purgative.This also abated the toxicity by precluding any drug absorption.As Snuhi itself is a strong purgative as given in Charaka samhita, kalpa sthana, and 10 th chapter so we can consider it as a single drug with package of anthelminthic (as having its chemical composition) and purgative effects if given in proper way.So, it can be considered as one among anthelminthic drugs with best results.
Species [24] The species of Euphorbia neriifolia are given in Table 2.
Species Distribution [25] Habitually, the plant crops up in rugged landscape all over the Deccan, Peninsula, and in villages, it is frequently cultivated for barricade all over India. [9,26,27] is considered as a little tree or an extensive luscious bush which extend up to 6-20ft high, with interconnected cylindrical or undistinguished 5-angled branches bearing short stippular thorns, more or less merging in vertical or slightly spiral lines.Fleshy and ephemeral leaves are prolonged 6-12 inch.The tinge of blooms is greenish yellow or yellowish green and emerge in springs with minute oil rich seeds.At the cold time, it turns into leafless vegetation.In due course, plant bear tricolcus fruits which comprises three arising radiating follicles.All over India, it is available.The other important points about botanical description are summarized in Table 3. [23] Common Therapeutic Uses of Snuhi are given in Table 4. Dosage, Toxic symptoms and Shodhana of Latex (Snuhi Ksheera) [19,23,28,29] (Figure 1).

Therapeutic Uses of Snuhi
Rasa Panchaka [30] The description about Rasa Panchaka is shown in Table 5.

Chemical Constituents in Parts of the Plant and their
Mode of Action [31,32] Chemical Constituents in different parts of the plant and their mode of action are given in (Figure 2).

Krimi Utpatti and Krimighna Effect of Snuhi according to Ayurvedic Concept
Samprapti [42] Samprapti of diseases consists of indulgence in causes of the diseases, resulting in Khavaigunya at any point in Srotas, vitiation of Doshas accompanied by Agnimandya and production of Ama and sthanasamshraya of Doshas at the point of khavaigunya producing the diseases.The improperly digested food item will have different effects.Firstly, the tissues of the body will be denied of nutrition.Secondarily, more or less, unwanted material in the body will get accumulated results in putrefaction and fermentation.This increased Amavisha induces more manufacture of Kapha and Purisha which are also considered as Krimikara nidana inturn forms Kaphaja and Purishaja krimi.The different types of Pakwa-Apakwa ahara which is moving downwards is digested by Jatharagni.Then the question was asked by Acharya Harita-Why this agni is not capable to burn Krimi.The answer given by Maharshi Atreya-Rakta gets vitiated in the body due to virudhanna and rasa.then these Krimi remained kaphavrita for one day, after that they gets their existence with shukra.They become chaitanya at the time when man becomes panchabhutatmaka and will not be burnt by Jatharagni. [43]de of action of Snuhi on Krimi [44] Snuhi is better option of drug for Samshamana as well as Prakritivighata line of treatment of Krimi, as it opposes the circumstances liable to cause Krimi by the inherent pecularities of Snuhi that are further preverse to Pureesha and Kapha.
The fundamental nature (prakriti) of Krimi subsists Kapha and Pureesha.
By virtue of inappropriate doing of agni, kitta bhaga deposited in pakwasaya, it can generate kotha alongwith Pureeshaja Krimi genesis responsible for pureesha prakriti of krimi.

Sanskrit name Snuhi
Hindi name Thuhara
Krimighna effect of Snuhi according to Rasa Panchaka-According to Rasa Panchaka, Krimighna effects of Snuhi are summarized in Table 8.

Worm Infestation and Anthelminthic Effect of Euphorbia neriifolia according to Modern Concept
Etiology and Epidimiology of Round worm [45] Within the lumen of the small intestine, mature worms of Safaris lumbricoids lodges having a life cycle of 10   [30] Figure 2: Chemical Constituents in Parts of the Plant and their Mode of Action. [31,32]erapeutic Uses [23] Vrana By applying the streamed leaves of Snuhi for 5-6 days, gashes are healed.
Kshara Sutra The preparation of Kshara Sutra by using Snuhi Kshira and Haridra was recited by Cakradatta.Pathogenesis [46] Following ingestion by the human host, Safaris ova contrive in the small intestine.After release, Larvae penetrate the intestinal wall and migrate to the lungs via venous circulation.The parasites cause pulmonary ascariasis while enter into the alveoli and migrate through the bronchi and trachea.Later on, they are swallowed and return to the intestines, where they mature into adult worms.Female Safaris begin depositing eggs in 8-10 wk.

Mechanism of Action of Euphorbia neriifolia as Anthelminthic
A Kind ofdrugs thrusting out parasitic worms and other immanent parasites from the body are specified as antihelminthics.
Besides instigating remarkable harm to the host, such drugs acted by either stunning (vermifuges) or killing (vermicides) parasites.To warrant their competence, anthelmintic drugs require efficient concentrations to be attained at parasitic site for a concluded duration.Drug concentration and length of its withdrawal time is influenced by the processes of absorption, dispersal, integration and elimination (pharmacokinetic aspect) promptly accomplished at the activity site and the pharmacological consequences.
After consumption, anthelmintic drugs like Euphorbia neriifolia are frequently taken into the blood flow, then deported to body different parts, including the liver, where they feasibly metabolized and subsequently evacuated in the poop and pee.

Structure Pharmacological Value
Esters of Phorbol (PubChem CID 442070) Tumour promoting activity is owned by esters of phorbol (basically found in croton oil) and trigger the process allied with cell growth.A range of these chemicals adopted as protein kinase catalyst.

Sl. No Pharmacological properties
References of study done
September-November 2009.The temperament of the drug is more intricated all through the body than can be depicted by a set of pharmacokinetic criterions in the circumferential circulation.Upgraded drug execution requisite expertise drug aspects comprising the convoluted interactivity amidst formulation and course of administration, physicochemical aspects of the compound, and physiology of the compartment into which the drug is disseminated.For combating these worms, absorption of drug from the GI tract, injection site, or skin is mandatory by reason of lodging of worms in the lumen or close to the mucosa, others reside at locations of the liver and lungs.Not only with the unabsorbed drug going across the GI tract, intestinal parasites approach furthermore along the absorbed fraction in the blood as they sustain on the intestinal mucosa, and with some other that is recycled into the gut.To the parasite, anthelminthics ought to be specifically virulent by its inherent pharmacokinetic features that cause parasite to be in special mode of action or this is also executed by hindering metabolic processes that are only vital to the parasite but not vital to or absent in the host.Along with that, their site of action and biochemical mechanisms are needed to be understood properly.For nurturing, an appropriate site needs to be perpetuated by parasitic helminthes.Despite host immune reactions, parasite also required to be maintained homeostasis.
The pharmacologic premise of anthelminthic aid basically includes, Defensive mechanism against host immunity which prompt starvation, paralysis, expulsion or digestion of the parasite.
Inference with integrity of parasitic cells and neuromuscular collaboration.

Role of Euphorbia neriifolia as Purgative as well as Anthelminthic drug
The anthelminthic type used is the basis to select a preliminary aperient.Since oil helps drug absorption, on that account, purgatives oil has to be evaded for drugs like male fern, thymol, carbon tetrachloride except castor oil which can be used with oil of chenopodium having the vantage of thvarting the paralyzing act of chenopodium oil on the intestine.In large doses, most anthelminthics acts as gastrointestinal irritants.In that instance of tapeworm or hook worm infection, anthelminthic intake is typically preceded by food abstinence with the intention that parasite will not be secured by intestinal constituents and also helping drug absorption.In spite of all these facts, patient debility is the drawback, thus, in any case, Fast should not be severe like starving.Succeeding light supper, purgative hit is supplied, also anthelminthic is taken.Primarily in the next Rasa Katu rasa Rasa of a substance can be scientifically used to presume its pharmacological behavior which in drug research will reduce the time and cost and it can provide lead optimization.For safer and effective drugs, rasa can help focused and intentional search.Katu rasa dilates the body channels, allays kapha humor and acts as a anthelminthic.It is an art of a writer to express the action of drug more precisely and correctly.Haret, ghna, hanti are the upsarga used by Bhavprakash Nighantu which attracts a special attention which requires to be understand by physician and research.All these upsarga are a part of Amashamsha Vikalpana subject to the karma mentioned by Nighantu and also indicates a special action.

Laghu, Tikshna and snigdha guna
It is surprisingly observed that there are 132 krimighna drugs out of 426 drugs.From Ayurveda to microbiology, It can be a novel contribution for screening the herbs.Among them for krimighna karma, Laghu and Tikshna guna pradhana dravyas are maximum.
Laghu guna dravyas are easy to digest and very less nutrient is made available for microbes for growth (static effect) while Tikshna guna opens the microchannels, irritating actions pressurize the microbes to excrete/kill (cidal effect).So, tikshna guna can have better actions in the apakarshana treatment in which the unwanted components i.e; Krimi and dosha are removed or eliminated from body, Tiksna and snigdha guna of Snuhi also promotes Panchakarma therapies to expel out doshas, also Krimi.

Virya-Ushna Virya
Kapha and vata dosha are the basic promoters of Krimi in the body and pacified by ushna virya of Snuhi.The ushna virya also promotes to release various hormones to destroy Krimi.

Vipaka Katu vipaka
Katu vipaka have direct action on Krimi.As it is kapha shamaka, it restricts the nutrient value (End digestive material) for Krimi growth.

Doshaghnta Kaphavatahara
The doshagnta of Snuhi is Kaphavatahara.As kapha is enriched with favourable atmosphere for progress of flora for Krimi which is kleda, jala, drava, sneha.The destruction of kapha will exert a static as well as cidal effect on all Krimi.AM, either in one dose or in 2 or 3 splitted doses prescribed per hour, to be followed 2 hr after last dose by another laxative shot.
A preliminary saline purgative usually facilitates expulsion of intestinal mucus which aids worms' exposure to anthelminthic action.For that, Magnesium sulphate or sodium sulphate or both are practiced feasibly.Owing to its reaction on retina, Santonin is chiefly granted at sleep time.As we know, for safe doses of any anthelminthic drug, a purgative is must.Etymological derivation of drug Snuhi reflects it secretes milky white latex which is used as drastic purgative. [47]

Clinical Trials on Euphorbia neriifolia and its obligation in most Prevalent Areas like Chhattisgarh
In vitro Study [48] Anatomical and physiological similitude between Human intestinal round worm parasite and Adult Indian Earthworm, Pheretima posthuma is the base of the study performed on anthelminthic activity.By escalating chloride ion conductance of worm muscle membrane, Piperazine citrate initiate hyperpolarization and diminished the excitability that trigger muscle relaxation and flaccid paralysis.Euphorbia neriifolia juice manifested paralysis and also caused death of worms specifically at great concentration of 100mg/mL, in short while as compared to reference drug Piperazine citrate.Presence of tannin as one of the main components is disclosed by phytochemical investigation of the crude extracts.Tannins are poly phenolic compounds shown to produce anthelminthic activity by interfering with energy generation in helminth parasites via uncoupling oxidative phosphorylation.They also can stick to free polypeptides in the gastrointestinal passage of host animal or glycoprotein on the cuticle of the parasite and cause loss of life.
In a Survey Study [49] Around the time of November 2015 and January 2016, in the Indian States of Chhattisgarh, Telangana, and Tripura, amid the children of government schools learning in 1 st to 5 th standard, school-based surveys were conducted to assess the ubiquity and severity of STH (Soil Transmitted Helminthes) infections.
As per the 2011 census, the total population of Chhattisgarh was 25,540,196.Based on soil type, average annual rainfall, and temperature, Chhattisgarh is divided into three agro-climatic zones: the Bastar plateau consisting of six districts, Chhattisgarh plains consisting of 16 districts, and hilly areas consisting of five districts. [50]Stool samples from 3,313 students (Chhattisgarh: In another Study [51] In the Department of Microbiology, CCMMC, Bhili, Durg Dist., Chhattisgarh; India, the present survey was organized to evaluate prevalence of parasitic infection and their affiliation with environmental, socio-demographic and behavioral habits of school children.Out of total, 250 stool samples were picked up from students, 160 were male and 90 were female.A total of 78

DISCUSSION
Krimi cannot be produced in our intestines unless their eggs are ingested, but to get totally sterile food in our country is improbable, so contaminated food articles and unclean water as by Maharshi Kashyapa serve as vehicle for the eggs to get into the gut, in turn, provides optimal conditions for Krimi growth in intestine.The parasite twists the foundation of the health of child mainly at developmental stage.Infections of man and animals with different varieties of worms is a common occuranace and drugs which are used to kill or throw out these worms are known as anthelminthics.Either they live in the tissues or in the intestinal canal of the victim responsible for somatic infections.Medicament which expels the worms besides certainly destroying them are named as Vermifuges while Vermicides are remedies which kill them.Along with other intestinal contents, intestinal parasites are cleared away by active peristalsis.Therefore, in an effort to dislodge the worms, harsh laxatives are rarely used with imperfect profit.Considering the fact that the worms anchor themselves with the aid of their hooks, suckers or serrated margins, they must be weakened or narcotized or destroyed prior to their expulsion effectively.Snuhi is referred by Brahat Trayi texts along with all the Nighantus. [52]As Snuhi itself is mentioned as strong purgative by Charaka samhita and also by other texts.So, we can consider it as a solitary medication wrap up with anthelminthic (as having its chemical composition) and purgative effects if given in proper way.So, it can be considered as one among anthelminthic drugs with best results.

CONCLUSION
This review compiles the different aspects about Upavisha Snuhi, its anthelminthic and purgative potential, its botanical description, therapeutic contribution, purification of its toxic but useful part (latex), its pharmacological actions, chemical constituents with structure and anthelminthic properties and different clinical studies.The above attempt is for concluding the classical and modern concept of anthelminthic enterprise of Euphorbia neriifolia.The preclinical studies discovered that Euphorbia neriifolia holds Analgesic, Anti-inflammatory, Anti-parasitic, Wound healing, Antimicrobial, Anticancer, Antipsychotic, Antidiabetic, Antihyperlipidemic, Hepatoprotective and Immunomodulatory attributes.
These vast ranges of pharmacological activities may be ascribed due to phytoconstituents present in its different parts like stem, root, leaves, bark, latex, etc. and the anthelminthic act is shown by major phytoconstituents of Euphorbia neriifolia like Esters of Phorbol, Tannin, Piperazine citrate.Worm infestation in Chhattisgarh has been a concern, so to promote awareness about deworming and sanitation, the clinical trials has been conducted in most prevalent areas, the facts about those trials are summarized by the author to reveal the anthelminthic potential of Euphorbia neriifolia and also the call of time and context to amplify its more use considering its clinical efficacy and safety.
phosphorylation, polyphenolic compounds hinder energy genesis in helminth worm.Tannin in juice of snuhi can cohere with free proteins in the gastrointestinal tract of host animal or glycoprotein on the cuticle of parasite and causes death.escalating chloride ion conductance of worm muscle membrane and creating hyperpolarization and diminishing excitability that elicit muscle leisure and flaccid apathy.
Singh, et al.: Snuhi with Special Reference to its Anthelminthic Potential

Table 8 : Anthelminthic Effect of Snuhi according to Rasa Panchaka.
Singh, et al.: Snuhi with Special Reference to its Anthelminthic Potential

Table 9 : The Prevalence of STH in different agro-climatic zones of Chhattisgarh, [50] 2015-2016. were
positive for one or more parasite.Out of total positive 53.9% were protozoan, 38.5% were helminthes and 7.7% were mixed type.Entamoeba histolytica 38.5% and Safaris lumbricoides 19.2% were the commonest protozoan and helminthes respectively.The other parasite found were Giardia lamblia 19.2%, Hookworm 10.3%, Taenia spp 5.1%.Multiple parasitism's were found in 7.7% children.The present study shows 31.2%parasitic infection which is still important health issue in our zone.Health alertness agenda, individualized sanitation, hand cleaning as well as uses of sanitary latrine and food treatment to minimize the occurrence of parasitic infection should be executed in these societies.