Cicuta virosa L. Scientific Name : Cicuta virosa L. Synonym : Cicuta mackenzieana; Cicuta maculata; Cicuta douglasii,Cicuta californica, Cicuta vagans, Sium douglasii; Cicuta occidentalis; Cicuta bulbifera . Family: Apiaceae/Umbelliferae Genus: Cicuta Species: virosa English Vernacular Name: Mac Kenzie’s water hemlock Habitat: The plant is indigenous to Europe and Asia. Parts used: The homeopathic remedy Cicuta is prepared from the freshly expressed sap of the Cicuta or water hemlock plant. The root’s juice is collected when the plant is just beginning to blossom and blended with equal proportion of alcohol to prepare the medicine. Plant description: It is a native species of northern and central Europe , northern Asia and northwestern North America . It is a perennial herbaceous plant which grows up to 1–2 m tall. The stems are smooth, branching, swollen at the base, purple-striped, and hollow except for partitions at the junction of the leaves and stem. In cross section the stems have one flat side and the other sides are rounded. The leaves are alternate, tri-pinnate, only coarsely toothed, unlike the ferny, lacy leaves found in many other members of the family Apiaceae. The flowers are small, white and clustered in umbrella shaped inflorescences typical of the family. The many flowered umbellets have unequal pedicels that range from 5 to 11 cm long during fruiting. An oily, yellow liquid oozes from cuts to the stems and roots. This liquid has a rank smell resembling that of parsnips or carrots. The plant may be mistaken for parsnip due to its clusters of white tuberous roots . Chemical constituents: stigmasterol, falcarindiol , daucosterol .β-farnesene(22.7%), α-humulene (5.4%), humulene epoxide II (5.9%), caryophyllene oxide (3.4%), germacrene D (3.2%), α- farnesene (3.6%),myrcene(7.8%),hexadecanoic acid (8.4%),VirolA,Virol B, Virol C, isocicutoxin. Reported chemical constituents present in Cicutavirosa L. Cicutoxin Virol A 157 Virol B Isocicutoxin Virol C Farcarinol Falcarindiol β-farnesene α-humulene Humulene epoxide II Caryophyllene oxide 158 Germacrene D α-farnesene Myrcene Hexadecanoic acid Stigmasterol Daucosterol Mechanism of Action of Cicuta virosa : Cicutoxin the major toxic constituent of C. virosa acts as a GABA-receptor antagonist. Virol A another toxic component of C. virosa was found to selectively – inhibit the GABA A receptor Cl channel complexes at neuronal level in mammals . Medicinal uses: The root is analgesic, antispasmodic, emetic, galactofuge and sedative. The whole plant is highly toxic and is not used in herbal medicine. A homeopathic remedy has been made from this plant in the past. It was used in the treatment of epilepsy, meningitis and other ailments affecting the brain. In homoeopathy it is used for epilepsy, meningitis, ailments of brain, cancer of the skin, epithelioma, convulsive violence as in cerebrospinal meningitis, tetanus and other ailments that cause spasms. It is used effectively to treat migraine headaches, painful menstrual periods, skin inflammation, and worm infestations. Side effects & toxicity: Avoid water hemlock as it is highly toxic and may cause vomiting, acute renal failure, marked metabolic acidosis, drowsiness, seizures and convulsions, or unconsciousness that may lead to death. Taking water hemlock by mouth may cause severe illness with orthostatic hypotension or tachycardia. It may also cause dilated pupils, discoloration of the skin due a lack of oxygen in the 159 Actions of Herb: Used in trembling and sporadic jerks, particularly when the head is turned toward the back - for instance, in the case of meningitis, epilepsy, eclampsia and paralysis as well as for treating the repercussions of head injuries. In homeopathy, effective for skin eruptions or eczema on the beard or scalp, remedy for skin affections, pustules epileptic seizure convulsions/fits/seizures/epilepsy, heart disease, electric shock, alcohol use, barbiturates, intoxication or withdrawal, Brain illness or injury, brain tumor (rare), choking, drug abuse, heat illness, low blood sugar, meningitis, toxaemia of pregnancy, kidney failure (uraemia), very high blood pressure (malignant hypertension), venomous bites and stings, frequent micturition; the urine is propelled with great force, retention of urine. The characteristic properties are enuresis, vertigo, paralysis of bladder, hence involuntary urination, analgesic, anti-spasmodic, emetic, sedative, anti-carcinogenic, hepatoprotective, anxiolytic, lead antidote and dementia. Contraindications: Hyperlipidaemia, pregnancy and lactation. Incompatibilities with other medications: Water hemlock might have an effect like a water pill or "diuretic." Taking water hemlock might decrease how well the body gets rid of lithium. This could increase how much lithium is in the body and result in serious side effects. Talk with your healthcare provider before using this product if you are taking lithium. Your lithium dose might need to be changed . Range of application: 2-3 gram of root is potentially toxic. Chemical Identification Tests of C. virosa The presence of following chemical class compounds was detected in C. virosa extract by chemical colour reaction test: saponins, carbohydrates, sterols and steroids Microscopic examination of C. virosa Rhizomes of C. virosa of any age were covered with multi-layer cover tissue; no connective tissue was found. Starch granules were seen in the parenchyma cells surrounding secretory ducts, especially in phloem. Colorless droplets of fat and gold-yellow cicutoxin were found in most of the basal tissue cells (Blackwell 1773; Köhler 1890) See figure below. Figure: Cicuta virosa L. and its diagnostic features 160 Thin-layer Chromatography of C. virosa In chloroform: ethanol: water (80: 20: 2) at 254nm following Rf values were observed 0.09, 0.12, 0.28, 0.39, 0.60, 0.66, 0.78 while at 366 calculated Rf values were. In ethyl acetate: methanol: water (100: 16.5: 13.5) solvent system Rf values at 254nm were 0.12 and 0.22 whereas at 366nm were 0.07, 0.15, 0.26, 0.35, 0.46, 0.73 and 0.91. Fourier Transform Infrared Spectroscopy of C. virosa In FT-IR spectrum of C. virosa diagnostic peaks were found at 3300 (OH), 2917.14 (C-H), 1593.19 and 1503.29 (aromatic ring), 1050 (C-O-C) cm -1. High Performance Liquid Chromatography of C. virosa HPLC profiles of the lipophilic extracts of different organs, individuals, and provenances of C. virosa harvested at different seasons revealed quantitative but not qualitative variations of the polyacetylene composition. Insecticidal activity of C. virosa C. virosa exhibited mean mortality time 4.8±2.25 hours at the dose of 10mg/2ml. At the dose of 50mg/2ml of C. virosa , mean mortality time 5.6±2.19 was found. C. virosa at the dose of 100mg/2ml showed mean mortality time i.e. 10.8±2.55 hours as compared to control and Permethrin (Standard drug). Anthelmintic activity of C. virosa C. virosa at dose of 100mg/ml exhibited paralysis and means paralysis time is 3±0 hours, and mean mortality time 24 ±0 hours. The results were compared with control and standard drug Albendazole. Molluscicidal activity of C. virosa C. virosa showed significant dose and time dependent molluscicidal activity. At 25 mg/ml mean paralysis time was found 24 ±16.62 hours and mortality time 48 ±16.62. At 50 and 75mg/ml mean paralysis time was 48 ±8.31 hours and mean mortality time was 48 ±16.62 hours. At 100 and 500 mg/ml mean paralysis time observed was 48 ±0 hours and mean mortality time 72 ±0 hours. Mean paralysis time was found 24±0 hours and mean mortality time 48 ±0 hours at 1000mg/ml of C. virosa . 161 Anti-fungal activity of C. virosa C. virosa showed anti-fungal activity in terms of zone of inhibition against yeast ( Candida albicans , Candida albicans ATCC 0383 , Candida galbrata ), dermatophytes ( Microsporum canis, Trichophytontons urans ), Saprophytes ( Aspergillus flavus, Aspergillus niger and Penicillium sp). C. virosa exhibited minimum inhibitory concentration against following fungal pathogens (Yeasts - Candida albicans, Candida albicans ATCC 0383 and Candida galbrata ; Saprophytes – Aspergillus flavus , Aspergillus niger and Penicillium sp. ). Anti-oxidant effects of C. virosa At dose of 1mg/ml of C. virosa 80% DPPH scavenging activity was found. Total anti-oxidant activity observed was 74.27% while IC 50 was found 0.6µg/ml. Neuropharmacological activity of C. virosa The anxiolytic activity was assessed using open field, head dip, light and dark, cage cross and swimming. At the dose of 100mg/kg of C. virosa , CNS inhibitory effects were observed in following activities: In open field activity 73.33 ±3.28 counts in 30 minutes were observed; in light and dark activity, mice entries in light compartment were 5.16 ±1.07 times; and in forced swimming test (FST) the mean forced mobility time recorded was 1.16 ±0.02 seconds. While at the dose of 500mg/kg of C. virosa , central nervous system inhibition was observed in cage cross test and dip cage activity. The readings of cage cross were found 13.83 ±3.75 times and during dip cage activity, the mice dipped its head 6.5 ±0.83 times. Locomotor and exploratory activity was observed to be substantially reduced in comparison to control and standard Diazepam (2 mg/kg -1). Analgesic activity of C. virosa using Acetic acid Analgesic activity is widely assessed by acetic acid method. The abdominal constrictions were observed. C. virosa at the dose of 50 mg/kg exhibited maximum inhibition of writhes, in first phase (57.67%) second (3.26%) and third phase (0%). While at the dose of 25 mg/kg C. virosa inhibition of writhes were observed as follow: 46.25% (first phase), 4.17% (second phase) and 28.57% (third phase). Analgesic activity of C. virosa using Formalin The results of analgesic activity using formalin exhibited prominent analgesic effect in comparison with aspirin (orally administered, 300 mg/kg). The analgesic effect of aspirin in phase 1, 2 and 3 were 32.88%, 61.54% and 41.41% respectively.