Available online on www.ijtpr.com International Journal of Toxicological and Pharmacological Research 2016; 8(3); 163-172 ISSN: 0975-5160 Research Article Evaluation of Potential Toxicity of Bioactives of Anagallis arvensis- A Toxic Plant Pande A*, Vaze A, Deshpande V, Hirwani R CSIR Unit for Research and Development of Information Products “Tapovan”, S.No.113,114, NCL Estate, Pashan Road, Pune 411 008, Maharashtra, India. Available online:10th June, 2016 ABSTRACT Toxic plants are found to have potential therapeutic activities. They have been used in the treatment of a number of dis- eases. Recently there is an increasing demand and interest in bioactive natural products from plants for the purpose of their use in herbal medicine. So critical evaluation of their toxicity has become necessary. This article provides the de- tailed toxicity information of the phytochemical constituents from the toxic plant Anagallis arvensis (Family Primula- ceae). The plant is toxic to ruminants but it has great potential to treat diseases like Gout, Leprosy, Epilepsy, Urinary infection etc. The phytochemical constituents isolated from the toxic plant have Antibacterial, Antifungal, Antiviral, An- titumour, Antidiabetic, Antidepressant, Anti-inflammatory and Hepatoprotective activities. Some bioactives are having therapeutic activity, no reported toxicity and were predicted to be less toxic. Many actives from this plant have not been explored for any activity and their toxicity has not been determined. These actives were found to be less toxic through the toxicity prediction tool. This study would be important for exploiting the potential of such actives which may further prove to be promising natural products for medicinal and cosmetic use. Keywords: Anagallis, Primulaceae, Toxicity, Prediction, Bioactive, Traditional medicine INTRODUCTION Poisonous plants are distributed all over the world. Plants MATERIALS AND METHODS produce poisonous compounds as defensive mechanism. The literature search for biological activity and toxicity of These plants can cause serious illness, injury, or death to the plant was carried out on free and subscribed databases humans or animals following accidental ingestion, skin viz. Toxnet, PubMed and SciFinder. contact, eye exposures or inhalation. Poisonous plants are In silico Toxicity Prediction used for different purposes such as hunting, fishing, wars Toxicity of the actives for which there was no existing and treating diseases. Anamirta cocculus is used for pis- toxicity data was predicted using DEREK Nexus version cidal activity1. Poisonous plants are source of various 4.1.0, Nexus: 2.0.0. DEREK is a knowledge based expert drugs viz. Digoxin and Digitoxin from Digitalis spp. used system which predicts the potential toxicity of molecules. as cardiotonic, Vincristrine and Vinblastine from The qualitative predictions made by DEREK are based on Catharanthus roseus act as anticancer agent, Atropine rules and reasonings which describe the relation between from Atropa belladonna act as anticholinergic while chemical structure and toxicity. morphine and codeine from Papaver somniferum act as analgesic2. Poisonous plants have also been proved as a RESULTS AND DISCUSSION source of bioactives showing therapeutic activity and On searching the existing toxicity data for the whole plant lower toxicity. Bioactive compounds of known scaffold and its active constituents, it was found that the plant is can be used to synthesize molecules showing higher ther- toxic to cattle and sheep. Plant is reported to produce gas- apeutic activity and lower toxicity e.g., metformin, na- trointestinal symptoms in dogs and horses. It is also toxic bilone, oxycodon (narcotic analgesics), taxotere3. There to poultry animals, rabbits and birds. Clinical signs in- are still many poisonous plants in nature which are unex- clude difficulty in breathing, stiffness in gait, leg weak- plored for their bioactivity. We have focused our study to ness, and recumbancy. Post mortem lesions are haemor- one of such poisonous plant Anagallis arvensis. Toxic rhage in kidney, heart and intestine, congestion of lung effect of Anagallis arvensis on humans has not yet been and liver. In another case reported by Riet-Correa4 four reported. Detail toxicity studies and clinical studies are cases of poisoning were diagnosed in barely and stubble not being carried out. Objectives of this article are: 1) field. Cattle of different ages were affected. Morbidity Detail literature search for biological activity and toxicity was 7-30% and fatality was 50-86%. LD50 of the extract of the active constituents of the plant, 2) Toxicity predic- was determined by dosing rats intraperitoneally at the tion of the actives using DEREK. dose of 5, 10, 20, 40 mg/kg body weight. LD50 was *Author for Correspondence Pande et al. / Evaluation of Potential… Table 1: The reported toxicity and biological activities of the plant bioactives. Sr. Active name Phytochem- Toxic Structure Biological activity No. and CAS No. ical groups endpoints Acute/ subacute Anticancer9, Beta Sitosterol 1 Saponin toxicity7, Devel- Angiogenic activity 10, (83-46-5) opmental toxicity8 Antihyperglycemic activity11 Acute toxicity 12, Chelating and free radical Developmental scavenging activities16, An- Quercetin toxicity13, Geno- tioxidant activity17, Anti- 2 Saponin (117-39-5) toxicity14, Neuro- inflammatory activity18, toxicity15 Antidiabetic activity19, Anti- cancer activity20 Hepatoprotective effects24, Acute toxicity21, Antibacterial activity25, An- Kaempferol Developmental 26 3 Saponin 22 ti-asthmatic effect , Anxio- (520-18-3) toxicity , Geno- 27 23 lytic activity , Treatment toxicity 28 of atherogenesis CNS depressant32 Antino- ciceptive effects33, Antihy- Acute toxicity29, perglycemic Effect34, Hepa- Rutin Developmental 4 Triterpene toprotective activity 35, An- (153-18-4) toxicity30, Geno- thelmintic, antibacterial, toxicity 31 antifungal, cytotoxic, larvi- 36 cidal Table 2: summarizes biological activity, reported toxicity and toxicity prediction for those actives which have less or no reported toxicity. Sr. Actives Phyto- Structure Toxic endpoints Biological activity Prediction/ no Name and chemical likelihood CAS No. groups 1 β- Saponin Acute Thyroid inhibitory, No alert Stigmasterol Toxicity37 antiperoxidative and (83-48-7) hypoglycemic effects 37, spasmolytic and anti-inflammatory 38, Viper and cobra ven- om neutralization39, antitumor40 2 Beta Amyrin Triterpe- Acute Anxiolytic Nephrotoxicity, (559-70-6) noid Toxicity41 and antidepressant Skin sensitisa- effects42 tion Cucurbitacin Triterpe- Acute Antitumor44 Carcinogenici- I noid toxicity43 ty, Hepatotoxi- 3 (2222-07-3) city, Ne- phrotoxicity, Skin sensitisa- tion 4 Cucurbitacin Triterpe- Acute toxicity45 Anti-inflammatory46 Carcinogenici- B noid anti-cancer47 ty, Nephrotox- (6199-67-3) icity, Skin sen- sitisation IJTPR, Volume 8, Issue 3, June - July 2016 Page 164 Pande et al. / Evaluation of Potential… 5 Alpha Elater- Triterpe- Acute toxicity45 Anti-inflammatory48 Carcinogenici- in noid ty, Skin sensi- (18444-66-1) tisation 6 Isorhamnetin Flavonoid Acute toxicity49 Anti-tumor50 Chromosome (480-19-3) glycoside damage in vitro, Muta- genicity in vitro, Skin sen- sitisation 7 α-spinasterol Higher Acute toxicity51 Antinociceptive 52 No alert (481-18-5) alkanes 8 n-hexacosane Lipid Acute toxicity53 Anti-inflammatory53 No alert (630-01-3) 9 α-Spinasterol Steroids Not available Anti-inflammatory54 No alert glucoside (1745-36-4) 10 Cucurbitacin Phytoster- Not available Anti-tumor55, treat- Carcinogenici- D ols ment of β- ty, Hepatotoxi- (3877-86-9) hemoglobinopathies, city, Ne- including sickle cell phrotoxicity, anemia and β- Skin sensitisa- thalassemia56, im- tion munomodulating activity57 Table 3: provides a list of the actives with no reported toxicity and biological activity with their toxicity predictions. Substructures which might have the toxicity potential are highlighted. Actives Name and Matching alert Prediction/ likeli- Sr. no Structure of active Matching alert CAS No. detail hood 1 Lacceric acid -- -- (3625-52-3) No alert 2 Anagalligenin B 1,1- Nephrotoxicity (33722-92-8) Dimethylcyclo- hexane 3 Anagalligenone B 1,1- Nephrotoxicity (33809-48-2) Dimethylcyclo- hexane 4 Arvenin I alpha,beta- Carcinogenicity (65247-27-0) Unsaturated aldehyde, ke- tone or imine IJTPR, Volume 8, Issue 3, June - July 2016 Page 165 Pande et al. / Evaluation of Potential… 1,1- Nephrotoxicity Dimethylcyclo- hexane alpha,beta- Skin sensitisation Unsaturated ketone or pre- cursor 5 Arvenin II 1,1- Nephrotoxicity (65247-28-1) Dimethylcyclo- hexane 6 alpha,beta- Carcinogenicity Arvenin III Unsaturated (65597-45-7) aldehyde, ke- tone or imine Tertiary alcohol Hepatotoxicity, or ether Nephrotoxicity 1,1- Nephrotoxicity Dimethylcyclo- hexane alpha,beta- Skin sensitisation Unsaturated ketone or pre- cursor 7 Arvenin IV Tertiary Hepatotoxicity, (69312-48-7) alcohol or ether Nephrotoxicity 1,1- Nephrotoxicity Dimethylcyclo- hexane 8 Anagalloside A Alkyl Chromosome dam- (114318-81-9) aldehyde or age in vitro, Muta- precursor genicity in vitro, Non-specific geno- toxicity in vitro IJTPR, Volume 8, Issue 3, June - July 2016 Page 166 Pande et al. / Evaluation of Potential… Aldehyde pre- Skin sensitisation cursor 1,1- Nephrotoxicity Dimethylcyclo- hexane 9 Anagalloside B 1,1- Nephrotoxicity (114318-82-0) Dimethylcyclo- hexane 10 Anagalloside C 1,1- Nephrotoxicity (114318-83-1) Dimethylcy- clohexane 11 Deglucoanagallo- 1,1- Nephrotoxicity side B Dimethylcy- (114318-84-2) clohexane