Alstonia scholaris (L.) R. Br.

Last updated: 27 May 2016

Scientific Name

Alstonia scholaris (L.) R. Br.

Synonyms

Echites scholaris L. [1]

Vernacular Name

Malaysia Pulai (Peninsular); kacau gitik (Kiput, Sarawak) [2]
English White cheesewood, milkwood, blackboard tree [2], common alstonia, devil tree, devil’s wood tree, dita bark, dita bark tree, dried njau, Indian pulai, milky pine, shaitan wood [3]
China Tang jiao shu, xiang pi mu [3]
India Aelele hale, ayugmachchhada, azhilaip-palai, bahuparna, bomudu, chatian, chitwan, daevasurippi, dieng rythen, edaakulaponna, gandhiparna, haale, haale mare, jantale, kadusale, lazarongpangtong, madagandha, paalagaruda, rukni, saitankajhad, shaitan, taala mraanu, thuam riat, vadirasi, visaltvak, yedakulapala [3]
Brunei Pulai lilin [2]
Indonesia Pulai (General); pule (Javanese); rite (Ambon) [2]
Thailand Sattaban, tin pet (Central); hassaban (Southwestern) [2]
Laos Tinpet [2]
Myanmar Taung meok, lettok [2]
Philippines Dita (Tagalog, Bikul, Sulu); dalipaoen (Iloko); tanitan (Bisaya) [2]
Vietnam M[of] cua, s[uwx]a [2]
Papua New Guinea Katung (Buang, Morobe Province); kambuu (Kanganaman, Sepik Province); herina (Hisui, Central Province) [2]
Tibet Lo ma bdun [3]
Nepal Chatiwan, chhatiwan, chition, palimara [3]
France Shaitan [2], arbre à lait [3].

Geographical Distributions

Alstonia scholaris is the most widely distributed Alstonia species, found from Sri Lanka and India through mainland Southeast Asia and southern China, throughout Malaysia, to northern Australia, the Bismarck Archipelago and the Solomon Islands. It has also been planted elsewhere. [2]

Botanical Description

A. scholaris is a member of the Apocynaceae family. It is a medium-sized to large tree that can grow up to 10-50(-60) m tall. The bole is cylindrical, massively fluted in older trees and measures up to 125 cm in diametre. [2]

The buttresses are stout, and measure up to 10 m tall which spread out at the base for up to 4 m. The outer bark is brown or yellowish-white, smooth but coming off evenly in small papery flakes, with horizontally enlarged lenticels and hoops while the inner bark is yellow to brown, usually tinged yellowish and with copious white latex. [2]

The leaves are in whorls of 4-8(-9), narrowly elliptical to obovate, measuring (5-)6-17(-22) cm x (1.5-)2.5-7.5(-8.5) cm, obtuse or rounded at apex and with 25-45(-55) pairs of secondary veins. The petiole is 5-20(-25) mm long. [2]

The inflorescence is mostly formed of dense bunches of flowers and many-flowered while the pedicel is 0-2 mm long. The sepal is soft hairy while the petal is hairy outside. Follicles are hairless. [2]

Cultivation

A. scholaris is most abundant in monsoon areas, and it tolerates various soils and habitats, including secondary vegetation. It occurs from sea level up to about 1250 m altitude. As an ornament, it has proved to be adaptable to the climates of southern Florida and California (United States). [2]

Chemical Constituent

A. scholaris leaves has been reported to contain picrinine-types of monoterpenoid indole alkaloids (e.g. 5-methoxyaspidophylline, picralinal and 5-methoxystrictamine) [4], C13-norisoprenoids (e.g. megastigmane-3β, 4α, 9-triol and 7-megastigmene-3, 6, 9-triol) [5], 2,3-secofernane triterpenoids (e.g. alstonic acids A and alstonic acids B) and indole alkaloid (e.g. N1-methoxymethyl picrinine) [6], 19-epischolarine, Nb-methyl-scholarine, Na- metylburnamine, vallesamine Nb-oxide, 6,7-seco-19,20-epoxyyanggustibobine B [7], lagunamine (19-hydroxytubotaiwine), angustilobine B acid, losbanine (6,7-seco-6-nor-angustilobine B), and tubotaiwine [8].

A. scholaris bark has been reported to contain 17-O-Acetylechitamine and echitamine. [8]

A. scholaris stem bark has been reported to contain alkaloids (e.g. alstonidine, alstonine, alstovenine, chlorogenic acid, chlorogenine, ditain, ditaine, ditamine, echicaoutchin, echicerin, echiretin, echitamine, echitein, echitenin, echitin, porphyrine, porphyrosine, reserpine, venenatine, villalstonine pleiocarpamine, O-methylmacralstonine, macralstonine O-acetylmacralstonine, villalstonine, macrocarpamine, corialstonine and corialstonidine) and triterpenoids (e.g. lupeol linoleate, lupeol palmitate and alpha-amyrin linoleate) [9][10]. Other alkaloids that had been isolated are nareline methyl ether, nareline ethyl ether , 5-epi-nareline ethyl ether, picrinine, scholaricine and scholarine-N(4)oxide, 12-methoxyechitamidine [11], 19,20-[E]-vallesamine, angustilobine, B-N4-oxide, 20(S)-tubotaiwine and 6,7-seco-angustilobine [12].

Plant Part Used

Bark, leaves. [13]

Traditional Use

In Ayurveda, the poultice of the roasted and pulverised A. scholaris tender leaves is used as a local stimulant to unhealthy ulcers with foul discharges. The leaves juice together with fresh ginger or zedoary is given to women after confinement. [13]

The inhabitants of Macassar use the petioles as an antidote to poison of ipoh tree. [13]

The milky juice has been traditionally used to treat ulcers, and mixed with oil as a remedy for ear-ache. [13]

In Ayurveda, the bark is considered acrid, bitter, heating, oleaginous, appetiser, laxative, anthelmintic, galactagogue, heart problems, asthma, leucoderma, ulcersm, blood problems, “tridosha”, pains, tumours, very good for chronic ulcers and carries of the teeth. It has been used as an astringent tonic, anthelmintic, alterative and antiperiodic. The bark is a valuable remedy in chronic diarrhoea and dysentery, as well as catarrhal fever. [13]

A. scholaris bark is used for snake-bite and scorpion-sting in combination with the other drugs. It also used for stomachache by ground the bark with water, strained and drinks it while the residue is being rubbed over the pit of the stomach. Furthermore, the fresh bark in milk is given for leprosy, dyspepsia, and as anthelminthic. The bark has been used for fever and dysentery in Philippine Islands and as an astringent, antidysenteric and emmenagogue in Cambodia. It also has been used for chronic paludism with enlargement of the spleen and liver complaints. [13]

The root is used to treat pain because of the enlarged liver. [13]

Preclinical Data

Pharmacology

Broncho-vasodilatory activity

Ethanol extract of the of A. scholaris leaves showed broncho-vasodilatory activity.  Administration of the plant extract (25, 37 and 50 mg/kg, via the jugular vein) to anaesthetised rats at 5 min before the administration of carbachol (10 µM/kg) led to a transient decrease in the normal blood pressure by 54±13% and 81±7% at doses of 25 and 37 mg/kg, respectively. In contrast the inspiratory pressure was increased by 50±13% and 83±12%, respectively, while the expiratory pressure and heart rate remained unchanged. Isoprenaline and salbutamol were the positive controls for the effects of the leaf extract on the carbachol-induced changes. The highest dose of the leaf extract (50 mg/kg) caused a severe decrease in the blood pressure and disturbed the respiratory rhythm. [14]

The bronchodilation cannot be attributed to direct tracheal smooth muscle relaxation as in the guinea pig trachea, the leaf extract (100-700 µg/mL) did not antagonize histamine (10 µM) or potassium chloride (50 mM)-induced contraction. The vasodilatory activity of the extract was attributed to nitric oxide, independent of adrenergic or muscarinic receptors or prostaglandins. The leaf extract directly interfered with the influx of calcium ions into cells as it reduced guinea pig ileum and pulmonary artery contractions induced by barium chloride, potassium chloride or calcium chloride. [14]

Anticancer activity

The cytotoxicity of different fractions of A. scholaris in HeLa cells was dependent on the season of collection be it, the monsoon, winter or summer. The most toxic extract was obtained from the bark collected in the summer followed by that collected in the winter and the least toxic was when collection was in the monsoon season.  Cytotoxicity was highest with the residue fraction and lowest for the steroidal fraction. Cytotoxicity, in the order of most toxic to least toxic, was the residue fraction>whole extract>chloroform extract>chitamine chloride (an active principle of A. scholaris)> ethyl acetate fraction>diethyl ether fraction>petroleum ether fraction>n-butanol fraction>aqueous fraction>steroidal fraction. [12]

A major alkaloid, alstonine has antitumor activity in YC8 lymphoma and Ehrlich ascites carcinoma cells.  Bisindole and villalstonine showed marked activity against human cancer cell lines, MOR-P (adenocarcinoma), COR-L23 (large cell carcinoma) cell lines although in these cells, pleiocarpamine, Omethylmacralstonine and macralstonine were much less active than villalstonine.  Oacetylmacralstonine, villalstonine and macrocarpamine were cytotoxic to human cancer cell lines, MOR-P, COR-L23 StMI1 1a (melanoma), Caki-2 (renal cell carcinoma), MCF7 (breast adenocarcinoma) and LS174T (colon adenocarcinoma). [12]

Hydroalcohol extract of A. scholaris protected against benzo(a)pyrene-induced forestomach carcinoma in female mice when added to drinking water at doses of 1, 2 and 4 mg/mL for 2 weeks before, during and 2 weeks after the carcinogen exposure. These doses reduced tumour multiplicity by 21.43, 28.57 and 50%, respectively.  The greatest protection was afforded by the highest dose which reduced tumour incidence by 6.67%. Tumour multiplicity incidence was significantly reduced (91.93% with extract versus 100% in benzo(a)pyrene-treated mice) by 4 mg/mL dose that was added to the drinking water during the post-initiation period, starting at 48 h after the last dose of benzo(a)pyrene (post-treatment) and continued for 8 weeks. These findings were corroborated by the observation that micronuclei frequency reached the lowest point at 4 mg/mL of the extract.  The extract was able to inhibit benzo(a)pyrene-induced mutagenic changes as the frequency of splenocytes bearing one micronuclei and also cells which bear multiple micronuclei were reduced by the extract.  Mice that were pretreated with 4 mg/mL of the extract were not changed with regards to tumor multiplicity and tumor incidence. [10]

The extract of A. scholaris was reported to possess immunostimulatory activity and was able to enhance phagocytic activity in normal and immunosuppressed mice. Thus immunomodulation may also have played a part in the chemopreventive activity of A. scholaris. [10]

The extract of the A. scholaris  leaves have antimicrobial properties while the alcoholic extract from the stem bark showed anticancer activity in HS1 human sarcoma in embryonated egg. An 85% ethanolic bark extract of A. scholaris showed antitumor and radiation sensitising activity against a mouse transplantable tumor and is cytotoxic to human tumour cell lines. [9]

Antimalarial activity

Corialstonine and corialstonidine, alkaloids of Alstonia scholaris, are active against P. falciparum. [12]

Antifertility activity

A. scholaris bark extract (200 mg/day for 60 days, orally) showed significant antifertility effects in male rats as evidenced by marked reductions in the weights of testes, epididymides, seminal vesicle and ventral prostate. Step-19 spermatids production was reduced by 79.6 % while the population of preleptotene and pachytene spermatocytes were decreased by 61.9 % and 60.1 %, respectively. Spermatogonia, Sertoli cell population and areas of the seminiferous tubule and Leydig cell nuclear,were significantly reduced as were other indicators of male fertility. [15]

Antidiabetic activity

The leaves of Alstonia scholaris possessed the highest inhibitory effect for two sugar compounds which are sucrase and maltase when compared with Cratoxylum mangayi and Dillenia indica. However more studies need to be conducted to further understand the mechanism of inhibition as well as suitability of drug supplement for the treatment or prevention of diabetes. [16]

Toxicity

The ethanolic extract of the leaves of Alstonia scholaris (30, 300, 1000 and 2000 mg/kg body weight) intraperitoneally did not elicit any changes in the behavior and autonomic responses of mice compared to controls.  None of the mice treated with the up to 2 g/kg of the extract died during the 48 hour observation period following the administration of the extract. [14]

The hydroalcoholic extract of the stem bark of A. scholaris showed acute toxic effects that were dependent of the season of collection, the bark collected in the summer was most toxic (LD50of 900 mg/kg), followed by collection in the winter (LD50 of 1075 mg/kg) while the monsoon season extract yielded the least toxic extract (LD50of 1200 mg/kg). Toxicity was dependent on the mice strain, the most susceptible was Swiss albino mice (all animals died at 1100 mg/kg) followed by DBA (all died at 1200 mg/kg) and C57BL mice (all died at 1300 mg/kg) while crossbred mice were resistant. Administration of the extract by the oral route was less toxic than the intraperitoneal (i.p.) route as the oral LD50 values for the oral route in all mice strains were higher than the i.p. LD50 value of 850 mg/kg body weight. Orally administered extract was non-toxic up to 2000 mg/kg body weight. A dose of 1100mg/kg given by the intraperitoneal route led to the maximum number of dead animals. [9]

Subacute toxicity tests were carried out in rats with daily doses of 120 and 240 mg/kg (corresponding to 1/10th and 1/5th of the LD50 dose) for 30 days. No changes were seen in general behaviour, physiological activities, or final body weights of the rats receiving the lower dose and none of these rats died.  The higher dose caused lethargy in the rats.  It was also more toxic, causing 30% mortality, a significant reduction in the final body weight and deformity in the various organs. Males were more susceptible than females to the higher dose of A. scholaris extractHigh doses of A. scholaris elicit marked damage to all major organs of the body thus, usage of high doses for prolonged periods should be undertaken with caution. [9]

Teratogenic effects

The hydroalcoholic extract of Alstonia scholaris extract produced teratogenic effects in mice at doses greater than 240 mg/kg (>20% of the LD50) when exposure occurred at day 11 of gestation. The extract at doses of 60, 120, 180, and 240 mg/kg did not cause mortality, congenital malformations, or alter the normal growth patterns.  Doses of 360 or 480 mg/kg caused a dose-dependent increase in mortality, growth retardation and congenital malformations, characterized mainly by bent tails and syndatyly. These doses also significantly delayed fur development, eye opening, pinna detachment and vaginal opening. Doses of 240-480 mg/kg also delayed incisor eruption and testes decent. [17]

Clinical Data

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

 

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Figure 1: The line drawing of A. scholaris [2]

References

  1. The Plant List. Ver1.1. Alstonia scholaris (L.) R. Br. [homepage on the Internet]. c2013 [updated 2012 Apr 18; cited 2016 May 27]. Available from: http://www.theplantlist.org/tpl1.1/record/tro-50185720
  2. Teo SP. Alstonia scholaris (L.) R.Br. In: van Valkenburg JLCH, Bunyapraphatsara N, editors. Plant Resources of South-East Asia No. 12(2): Medicinal and poisonous plants 2. Leiden, Netherlands: Backhuys Publishers, 2001; p. 67-68.
  3. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume I A-B. Boca Raton, Florida: CRC Press, 2012; p. 210-211.
  4. Cai XH, Liu YP, Feng T, Luo XD. Picrinine-type alkaloids from the leaves of Alstonia scholaris. Chin J Nat Med. 2008;1(6):20-22.
  5. Xu Y, Feng T, Cai XH, Luo XD. A New C13-Norisoprenoid from leaves of Alstonia scholaris. Chin J Nat Med. 2009;1(7):21-23.
  6. Wang F, Ren FC, Liu JK. Alstonic acids A and B, unusual 2,3-secofernane triterpenoids from Alstonia scholaris. Phytochemistry. 2009;5(70):650-654.
  7. Yamauchi T, Abe F, Chen RF, Nonaka GI, Santisuki T, Padolina WG. Alkaloids from the leaves of Alstonia scholaris in Taiwan, Thailand, Indonesia and Philippines. Phytochemistry. 1990;29(11):3321-3325.
  8. Yamauchi T, Abe F, Padilina WG, Dayrit FM. Alkaloids from leaves and bark of Alstonia scholaris in the Philippines. Phytochemistry . 1990;29(10):3321-3325.
  9. Baliga MS, Jagetia GC, Ulloor JN, et al. The evaluation of the acute toxicity and long term safety of hydroalcoholic extract of Sapthatparna (Alstonia scholaris) in mice and rats. Toxicol Lett. 2004;151(2):317-326.
  10. Jagetia GC, Baliga MS, Venkatesh P. Effect of Sapthaparna (Alstonia scholaris Linn) in modulating the benzo(a)pyrene-induced forestomach carcinogenesis in mice. Toxicol Lett. 2003;144(2):183-193.
  11. Banerji A, Siddhanta AK. Scholarine: An indole alkaloid of Alstonia scholaris. Phytochemistry. 1981;20(3):540-542.
  12. Jagetia GC, Baliga MS. The effect of seasonal variation on the antineoplastic activity of Alstonia scholaris R. Br. in HeLa cells. J Ethnopharmacol. 2005;96(1-2):37-42.
  13. Kritikar KR, Basu BD, Blatter E. Indian medicinal plants Vol II. 2nd ed. New Delhi: Dehra Dun, 1975; p. 1565-1567.
  14. Channa S, Dar A, Ahmed S, Atta-Ur-Rahman. Evaluation of Alstonia scholaris leaves for broncho-vasodilatory activity . J Ethnopharmacol. 2005;97(3):469-476.
  15. Gupta RS, Sharma R, Sharma A, et al. Effect of Alstonia scholaris bark extract on testicular function of Wistar rats. Asian J Androl. 2002;4(3):175-178.
  16. Nilubon Jong-Anurakkun, Megh Raj Bhandari, Jun Kawabata.  α-Glucosidase inhibitors from Devil tree (Alstonia scholaris). Food Chemistry. 2007;4(103):1319-1323.
  17. Jagetia GC and Baliga MS. Induction of developmental toxicity in mice treated with Alstonia scholaris (Sapthaparna) in utero. Repro Toxicol. 2003;68(6):472-478.