Rhazya Stricta Decne

Rhazya stricta Decne.

Scientific name: Rhazya stricta Decne. Family: Apocynacaea Genus: Rhazya Species: stricta Common name: Rangboul, Sewar, Gandera, Ishwang, Vergulam, Harmal, Dogbane Part used: Leaves, Legumes, Fruit and root Plant Description: R. stricta is a small glabrous, erect under shrub or shrub about 90 cm high with a smooth central stem and dense semi-erect branches.Leaves are alternate, 6 to 10 × 1 to 2 cm, elliptic–lanceolate, thick or leathery, sessile, turning yellow with age.Flowers are white in short branched cymes.Fruits are pale yellow follicles and seeds are shortly winged. Constituents: 16-Epi-Z- isositsirkine, Akuammidine, rhazinilam, and tetrahydrosecamine, Rhazimine, Rhazimanine, Methoxy-1,2- dihydrorhazimine , aspidospermiose, strictibine, 1 carboxymethoxy-b-carboline, stemmadenineakuammidine, 15-b-hydroxyvincadifformine, isorhazicine, 2-methoxy-1,2-dihydrorhazimine, bharhingine, rhazimal (16formylstrictamine), rhazimol (deacetylalkuammiline), rhazinol (a hydroxymethyl analogue of strictamine), stricticine, strictine, rhazimine 2-methoxy-1-,2-dihydrorhazimine. Four indole alkaloids from its leaves and roots, namely: vallesiachotamine, sewarine and tetrahydrosecamine and polyneuridine. Rhazimanine, A new piperidine alkaloid termed strictimine and another new alkaloid, 1, 2-dehydroaspidospermidine-N-oxide were isolated. Structures of isolated chemical constituents of Rhazya stricta Decne.

Rhazicine Strictamine-N-oxide Rhazimin

2-methoxy 1, 2-dihydrorhazim Strictimine Postsecamidine

391

1, 2-dehydroaspidospermidine N-oxide Actions of herb: anti-diabetic, anti-helminthic, anti-inflammatory, vermifuge, purgative, anti- hyperglycaemic, anti-depressant, anti-spasmodic, anti-oxidant, anti-microbial, anti-cancer, analgesic, anti-rheumatic. Medicinal Uses: The fruits and leaves of R. stricta are used as a tonic to cure sore throat and skin diseases.Leaves and branches are used to cure tooth diseases, diabetes, constipation and intestinal diseases. Arabian communities use R. stricta to cure diabetes, inflammatory conditions, stomach disorders and helminthiasis. The leaf of the plant is used to treat tumors. In the indigenous system of medicine, it is used for the treatment of chronic rheumatism, sore throat and general debility. R. stricta is used to cure urinary tract diseases, fever, allergy, dysentery, headache, asthma, syphilis, pharyngitis. Side effects and Toxicity The toxicity of Rhazya stricta leaves for Najdi sheep is described in 9 sheep assigned as untreated controls, Rhazya-treated at 0.25 g/kg/d and Rhazya-treated at 1 g/kg/d. The oral use of 1 g/kg/d caused body weight depression, ruminal bloat, diarrhea, dyspnea and weakness of the hind limbs. Entero-hepato-nephropathy, pulmonary congestion, hemorrhage and emphysema, lymphocytes in vital organs, and congestion of the blood vessels of the heart were associated with increases in serum AST and LDH, in elevated bilirubin and urea concentrations, and decreased total protein, albumin and calcium concentrations, and leucopenia and anemia. Dosage: Dried leaves: 6.000 g Leave juice: 12.000 ml

(a). TS of the leaf showing a papillose epidermis covered with a thick raised cuticle forming small curves. The underlying palisade layer consists of rectangular slightly broad cells underlain by spongy tissues. (b). A surface view of the leaf upper epidermis showing polygonal cells with oval anomocytic stomata. (c). A surface view of the leaf lower epidermis showing polygonal cells with warty cell walls; stomata are oval, anomocytic and abundant. Microscopic examination of R. stricta leaf A transverse section of the R. stricta leaf shows its unilateral characteristic. The epidermal cells are ovoid to round with thin cell walls and they are covered with a very thick cuticle having faint striations and it is somewhat raised forming small curves. The palisade tissues consist of one layer of rectangular and slightly broad loosely packed cells with thin wavy cell walls. The

392 spongy tissues consist of rounded to oblong loosely packed cells that contain many small whitish prisms or light green rounded particles. They also embed vascular tissues that include spirally thickened vessels. The lower epidermis consists of oblong to rounded cells that have covering trichomes with thick warty cell walls found mainly near to the margins. They also bear glandular trichomes with large spherical heads and thick curved stalks. Stomata are oval in shape and anomocytic and they are abundant on both epidermises. Organoleptic characteristics: Appearance: Powder Colour: Greenish yellow Odour: Odourless Taste: Bitter Physicochemical constants: Loss in weight on drying at 1050C (%): 7.40 Solubilities (%) Alcohol solubility: 20.00 Water solubility: 37.60 10% ethanolic extractive: 47.00 Ash values (%) Total ash: 7.80 Water soluble ash: 4.20 Acid-insoluble ash: 0.30 Successive extractive (%) Petroleum ether (60-80C): 8.00-8.80 Chloroform: 12.11-13.30 Absolute alcohol: 19.80-20.20 Distilled water: 18.60-19.30 pH values pH of 1% solution : 5.13 pH of 10% solution: 4.86 Ambulatory activity Ali et al. (1999) studied the effect of leaves extract of R. stricta on ambulatory activity in rats in case of acute and chronic treatment respectively. For the purpose of acute treatment a single oral doses of 1, 2, 4, and 8 g/kg body weight of R. stricta extract were given that produced dose- dependent decreases in total activity and ambulatory activity. Diazepam (20 mg/kg p.o.) produced a decrease in rat activity comparable to that produced by a dose of 1 g/kg of the extract. An oral dose of 2 g/kg daily for 21 consecutive days produced on the last day of treatment significant decrease in activity amounting to about 30% of control activity levels. Anti-neoplastic activity Zaman, 1990 explored that tetrahydrosecamine and 16-epi-Z-isositsirikine, isolated from R. stricta displayed anti-neoplastic activity in KB test system in vitro and P-388 test system in vivo . Effect of R. stricta on central nervous system Ali et al. (1995) explored the effects of orally administered aqueous lyophilized extract of the leaves of R. stricta (2, 4 and 8 g/kg) on central nervous system function in mice. The extract exhibited significant dose-dependent activities in anti-nociceptive tests. Anti-spasmodic activity of R. stricta: Tanira et al. (1996b) studied the anti-spasmodic effect of R. stricta on isolated intestinal muscles of rat.

393 Nematicidal activity of R. stricta AL-Rajhi et al. (1997) explored the nematocidal activity of R. stricta extracts against nematode Meloidogyne javanica and found potent nematicidal activity at a rate of 100 ppm. Pesticidal activity of R. stricta : In research work carried out by El-Hag et al. (1996)it was found that R. stricta leaves extract in the concentration range from 100 to 500 ppm affected the growth and caused mortality to mosquitoes, Culex pipiens . Effect of R. stricta on lipid profile, liver enzymes and kidney function Baeshen et al. (2010) carried out biochemical evaluation of the effect of Rhazya stricta aqueous leaves extract in liver and kidney functions in rats. The aqueous extract of the R. stricta leaves significantly decreased concentrations of triglycerides, low density lipoprotein, cholesterol, uric acid and creatinin, but increased concentration of high density lipoprotein. It triggered all these activities without affecting liver enzyme activities or kidney functions. These study findings may have a positive impact on the cardiovascular patients and may provide a new therapeutic strategy to reduce hypertriglyceridemia. Anti-dermatitis activity of R. stricta: Anti-dermatitis activity was evaluated by Ahmad et al. 2014 using intensity score, scratching behaviour and histological evaluation. The results of the anti-dermatitis activities were comparable with the standard drug, Betnvat-N. Table: Anti-dermatitis activity intensity score of mice treated with R. stricta

Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486 . Analgesic activity of R. stricta Analgesic activity was assessed by Ahmad et al. 2014 acetic acid induced writhing test and hot plate method. Acetic acid induced writhing test produced significant result comparable to that of Aspirin. Table: Effect of R. strict a crude extract on acetic acid induced writhes in mice

Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486.

394 R. stricta crude extract exhibited slight increase in pain threshold by hot plate method. Table: R. stricta crude extracts effect on hot plate analgesiometer in mice

Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486. Anxiolytic effect of R. stricta Anxiolytic effect of R. stricta extract was evaluated by Ahmad et al. 2014 using open field test, head dip test, cage crossing test, rearing test, traction test and mean mobility time test. Table: Assessment of anxiolytic effect of R. stricta in mice

Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486. Insecticidal activity of R. stricta Insecticidal activity was performed by Ahmad et al. 2014. The insecticidal activity was performed on Tribolium castaneum, Sitphilus oryzae, Rhyzopertha dominica, Callosbruchus analis . Results revealed that the R. stricta crude extract have insecticidal activity against Callosbruchus analis . The percentage mortality was found 40%. Table: Insecticidal activity of R. stricta extract

Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486. Brine Shrimp Bioassay of R. stricta Brine shrimp bioassay of R. stricta extract was carried out by Ahmad et al. 2014 and dose dependent response was observed.

395 Table: Brine Shrimp Bioassay of R. stricta

Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486. Anti-leishmanial activity R. stricta Al-Kahraman et al. 2012 explored anti-leishmanial activity of R. stricta extract. Crude methanolic extract (CME) and its fractions; n-hexane fraction (NHF), chloroform fraction (CCF), acetone fraction (ACF) and aqueous fraction (AQF) exhibited good inhibition activity against the promastigotes of L. major . Table: In-vitro efficacy of Rhazya stricta Decne. leaves extract and its fractions. % Inhibition of death L. major parasite

Khan MJ, Baloch NU, Nabi S, Ahmed N, Bazai Z, Yasinzai M, Al-Kahraman YMSA. 2012. Antileishmanial, cytotoxic, antioxidant activities and phytochemical analysis of Rhazya stricta Decne. leaves extracts and its fraction. Asian J Plant Sci Res; 2(5): 593-598. Anti-oxidant activity of R. stricta Al-Kahraman et al. 2012 used DPPH free radical scavenging method for the evaluation of antioxidant potential of R. stricta . Crude extract of R. stricta and its fractions revealed effective free radical scavenging activity as determined of DPPH method. Table: DPPH free radical scavenging activity of R. stricta crude extract and its fractions

396 Phytochemical analysis of R. stricta Phytochemical analysis of R. stricta crude extract and its fractions was carried out by Al- Kahraman et al. 2012. Table: Phytochemical analysis of R. stricta crude extract and fractions

Khan MJ, Baloch NU, Nabi S, Ahmed N, Bazai Z, Yasinzai M, Al-Kahraman YMSA. 2012. Antileishmanial, cytotoxic, antioxidant activities and phytochemical analysis of Rhazya stricta Decne. leaves extracts and its fraction. Asian J Plant Sci Res; 2(5): 593-598. Invitro anti-fungal activity of R. stricta Khan & Khan 2007 carried out anti-fungal activity of R. stricta against five fungal strains; Trichophyton longifusis, Aspergillus flavus, Candida albicans, Microsporum canis and Fusarium solani . The results revealed significant anti-fungal activity. Table: Anti-fungal activity of R. stricta

Khan S, Khan GM. 2007. In vitro antifungal activity of Rhazya stricta . Pak. J. Pharm. Sci. 20(4): 274-279.

References

Adam SE. 1998 Toxicity of Rhazyastricta to sheep. Vet Hum Toxicol. 40(2): 68 -9. Ahmad M, Muhammad S, Mehjabeen, Jahan N, Jan SU, Qureshi ZR. 2014. Anti-dermatitis, anxiolytic and analgesic effects of Rhazya stricta from Balochistan. Pak. J. Pharm. Sci. 27(3): 481-486. Alami, R. & Macksad, A. Medicinal Plants of Kuwait. Al-Assriya Printing Press. Kuwait. Al-Homidan A, Al-Qarawi AA, Al-Waily SA, Adam SE. 2002. Response of broiler chicks to dietary Rhazya stricta and Nigella sativa . Br Poult Sci.43(2): 291-6. Ali BH. (2002). The effect of treatment with the medicinal plant Rhazya stricta Decne on gentamicin nephrotoxicity in rats. Phytomedicine. 9(5): 385-9. Ali BH. 1997. The effect on plasma glucose, insulin and glucagon levels of treatment of diabetic rats with the medicinal plant Rhazya stricta and with glibenclamide, alone and in combination. J Pharm Pharmacol. 49(10): 1003-7. Ali BH, Alqarawi AA, Bashir AK, Tanira MO.2000 Antioxidant action of extract of the traditional medicinal plant Rhazya stricta Decne. in rats. Phytother Res. 14(6): 469 -71.

397 Ali BH, Al-Qarawi AA, Bashir AK, Tanira MO. (2000). Phytochemistry, pharmacology and toxicity of Rhazya stricta Decne: a review. Phytother Res. 14(4): 229-34. Ali BH, Bashir AK, Tanira MO.1998. The effect of Rhazya stricta Decne, a traditional medicinal plant, on the forced swimming test in rats. Pharmacol Biochem Behav. 59(2): 547-50. Atta-ur-Rahman, Qureshi, M.M.,Zaman, K., Malik, S. & Ali SS. 1998. The alkaloids of R hazya stricta and R. orientalis . Fitoterapia V. LX, No. 4. Baeshen NA, Lari SA, Aldoghaither HA, Elkady AI. 2010. Biochemical evaluation of the effect of Rhazya stricta aqueous leaves extract in liver and kidney functions in rats. Nature and Science 2010;8(4): 136-142. El-Ghonemy, A. A. Encyclopedia of Medicinal Plants of the United Emirates.1993. 1st Edition, University of UAE. El-Kadi AO, Tanira MO, Ali BH, Bashir AK, Souich PD. 2003 The effect of a strongly basic alkaloidal fraction of Rhazya stricta , a traditional medicinal plant, on cytochrome P450-mediated metabolism of theophylline in mice. Phytother Res. 17(6): 688-90. Ghazanfar S A. Handbook of Arabian Medicinal Plants. p.26, CRC Press, 1994. Islam, M.W., M.N.M. Zakaria, R. Radhakrishnan, A. Ismail, X.M. Liu,M. Habibullah and K. Chan.Anti- inflammatory, gastric anti-ulcer and cytoprotective properties of ethanolic extract of Rhazya stricta Decene. (Fam.Apocynacea). “2000 Years of Natural Products Research–Past Present andFuture”, Amsterdam, July26-30 1999. Jongbloed M. V.The Comprehensive Guide to the Wild Flowers of the United Arab Emirates, Erwda. 2003. Emirates Printing Press, Dubai, UAE. ISBN9948-408-24-1. Kamil M , Ahmad F, Sheikh M O, Jayarag AF, Gunaskhar C, Thomas S,Habibullah M, Chan K & Attas A. Quality Control Studies for the plant Rhazya stricta . European Journal of Pharmaceutical Sciences, Vol. II. Supp.1,Elsevier, Sept. 2000. Khan S, Khan GM. 2007. In vitro antifungal activity of Rhazya stricta . Pak. J. Pharm. Sci. 20(4): 274-279. Khan MJ, Baloch NU, Nabi S, Ahmed N, Bazai Z, Yasinzai M, Al-Kahraman YMSA. 2012. Antileishmanial, cytotoxic, antioxidant activities and phytochemical analysis of Rhazya stricta Decne. leaves extracts and its fraction. Asian J Plant Sci Res; 2(5): 593-598. Kotb, T. F. Medicinal Plants in Libya.(1985) Arab Encyclopedia House. Tripoli-Libya. Mandaville, J P. Flora of Eastern Saudi Arabia. (1990). Kegan Paul International Ltd. England. Miller A.G., Morris M. Plants of Dhofar, The southern Region of Oman: Traditional, Economic and Medicinal Uses.1987. Office of the Advisor for conservation of the Environment, Sultanate of Oman. Quality Control Studies for the plant Rhazya stricta ., EUFEPS 2000 Congress, Budapest (Hungary) , Po-154, Sept. 2000. Radhakrishnan R, Zakaria MNM, Islam MW, Liu XM, K. Chanand Al-Attas. Anti Hyperglycaemic Effects of Rhazya stricta in Diabetic Mice.1 st International Congress on Traditional Medicine & Materia Medica, Tehran 2000. Tanira, M.O., Ali, B. H., Bashir, A.K;, Wasfi, I.A & Chandranath, I. 1996.Evaluation of the relaxant activity of some United Arab Emirates plants on intestinal smooth muscle. J. Pharm Pharmacol. 48(5) 545-550. Wasfi IA, Bashir AK, Amiri MH, Abdalla AA.1994. The effect of Rhazya stricta on glucose homeostasis in normal and streptozotoc in diabetic rats. J Ethnopharmacol. 8; 43(2): 141-7. Western, A. R. The Flora of United Arab Emirates, an introduction. 1986. Publication of the UAE University.

398