Advertisement

Pharmaceutical perspective on bioactives from Alstonia scholaris: ethnomedicinal knowledge, phytochemistry, clinical status, patent space, and future directions

  • Komal Pandey
  • Chaitrali Shevkar
  • Khemraj Bairwa
  • Abhijeet S. KateEmail author
Article
  • 2 Downloads

Abstract

Alstonia scholaris (L.) R. Br (Apocynaceae), a tropical tree native to Indian subcontinent, Australasia, and Malay Peninsula is well documented in Traditional Chinese Medicine and Ayurveda to cure fever, pain, inflammation, cancer, respiratory, and skin disorders. Nearly 169 alkaloids have been reported along with iridoids, coumarins, flavonoids and steroids from this plant. The highlights of current review are demonstrated in six tables encompassing ethnomedicinal values, pharmacological activities, phytochemistry, clinical significances, and patents associated with A. scholaris. The data analysis of these tables revealed the requirements to convert existed knowledge into finished products. For example, strictamine isolated from this plant has shown an equipotent antiviral activity to that of acyclovir. However, the discovery of such new potent antiviral indole alkaloids will require structure activity relationship studies with natural analogues of this scaffold. In conclusion, despite of over 100 patents and numerous pharmacological activities of A. scholaris, only one product has reached the market. The report stipulates the gap between the existing knowledge and the requisites for commercialization of A. scholaris derived products.

Graphic abstract

Keywords

Alstonia scholaris Anticancer Antiviral Monoterpenoid alkaloids Strictamine 

Abbreviations

5-HTP

5-Hydroxy tryptophan

ACP

Acid phosphates

ALP

Alkaline phosphatase

CAs

Chromosomal aberrations

CFDA

China Food and Drug Administration

COX

Cyclooxygenase

CSIR

Council of Scientific and Industrial Research

DCM

Dichloromethane

IPR

Intellectual property rights

LOX

Lipoxygenase

LRP

Luciferase reporter phage

MEP

Methyl erythritol 4-phosphate

MIAs

Monoterpenoid indole alkaloids

MMS

Methyl methane sulfonate

NSCLC

Non small cell lung carcinoma

RI

Replication Index

SCE

Sister chromatid exchange

SDL

Step down latency

SGOT

Serum glutamic oxaloacetic transaminase

SGPT

Serum glutamic pyruvic transaminase

TB

Total bilirubin

TL

Transfer latency

WCSP

World Checklist of Selected Plant Families

WIPO

World Intellectual Property Organization

Notes

Acknowledgements

We acknowledge the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India and the Director, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad for providing the required facilities and support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Abdillah S, Tambunan RM, Farida Y et al (2015) Phytochemical screening and antimalarial activity of some plants traditionally used in Indonesia. Asian Pac J Trop Dis 5(6):454–457CrossRefGoogle Scholar
  2. Abe F, Chen RF, Yamauchi T et al (1989) Alschomine and iscoalschomine, new alkaloids from the leaves of Alstonia scholaris. Chem Pharm Bull 37:887–890CrossRefGoogle Scholar
  3. Abe F, Yamauchi T, Shibuya H et al (1998) Indole alkaloids from the leaves of Alstonia villosain Sunbawa. Chem Pharm Bull 46:1235–1238CrossRefGoogle Scholar
  4. Adams GL, Carroll PJ, Smith AB III et al (2012) Access to the Akuammiline family of alkaloids: total synthesis of (+)-scholaricine. A J Am Chem Soc 135(1):519–528PubMedCrossRefGoogle Scholar
  5. Ahmad FB, Holdsworth DK (2003) Medicinal plants of Sabah, East Malaysia—part I. Pharm Biol 41(5):340–346CrossRefGoogle Scholar
  6. Ahmad Y, Fatima K, Occolowitz JL et al (1977) Structure and absolute configuration of strictamine and strictalamine from Rhazya stricta. Stereochemistry of the picralima alkaloids. J Am Chem Soc 99(6):1943–1946CrossRefGoogle Scholar
  7. Ahmad Y, Fatima K, Le Quesne PW et al (1983) Further alkaloidal constituents of the leaves of Rhazya stricta. Phytochemistry 22(4):1017–1019CrossRefGoogle Scholar
  8. Alex B, Stephen R (2016a) Composition exfoliante pour la peau. WO2016183634A1. 24 Nov 2016Google Scholar
  9. Alex B, Stephen R (2016b) Skin cleansing composition. WO2016183633A1. 24 Nov 2016Google Scholar
  10. Almeida JRGS, de Lima JT, de Oliveira HR et al (2011) Antinociceptive activity of discretamine isolated from Duguetia moricandiana. Nat Prod Res 25:1908–1915PubMedCrossRefGoogle Scholar
  11. Anonymous (1985) The Wealth of India. Publications and information Directorate, Council of Scientific and Industrial Research, New Delhi, pp 201–204Google Scholar
  12. Anonymous (2001) The ayurvedic pharmacopoeia of India. Part-I, Volume-I. Government of India Ministry of Health and Family Welfare Department of Ayush, New Delhi, pp 97–98Google Scholar
  13. Antonty M, Shekhar MC, Thankamani V (2014) Antibacterial activity of plant extracts of Alstonia scholaris. Int J Pharmacogn Phytochem Res 5:285–291Google Scholar
  14. Antony M, James J, Misra CS et al (2012) Anti mycobacterial activity of the plant extracts of Alstonia scholaris. Int J Curr Pharm Res 4:40–42Google Scholar
  15. Anurakkun NJ, Bhandari MR, Kawabata J (2007) α-Glucosidase inhibitors from Devil tree (Alstonia scholaris). Food Chem 103:1319–1323CrossRefGoogle Scholar
  16. Anusha I, Samba Naik A, Jagadish Naik M (2016) Anti hyperglycemic activity of ethanolic leaf extract of Alstonia scholaris (L.) in induced diabetic rats. J Glob Biosci 5:4535–4540Google Scholar
  17. Arora A, Rai Y (2015) A review: phytochemistry, ethanobotanical and pharmacological activities of Alstonia scholaris R. Br (Apocynaceae). Int J Adv Res 3:584–590Google Scholar
  18. Arulmozhi S, Mazumder PM, Sathiyanar L et al (2012) Analgesic, anti-inflammatory and anti-ulcerogenic activities of fractions from Alstonia scholaris. Pharmacologia 3:132–137CrossRefGoogle Scholar
  19. Atta-ur-Rahman, Alvi KA (1987) Indole alkaloids from Alstonia scholaris. Phytochemistry 26:2139–2142CrossRefGoogle Scholar
  20. Atta-ur-Rahman, Asif AM, Ghazala M et al (1985) Scholaricine, an alkaloid from Alstonia scholaris. Phytochemistry 24:2771–2773CrossRefGoogle Scholar
  21. Atta-ur-Rahman, Alvi KA, Muzaffar A (1986) Isolation and 1H/13C-NMR studies on 19,20-dihydrocondylocarpine: an alkaloid from the leaves of Ervatamia coronaria and Alstonia scholaris. Planta Med 52:325–326CrossRefGoogle Scholar
  22. Atta-ur-Rahman, Alvi KA, Abbas SA et al (1987) Isolation of 19, 20-Z-vallesamine and 19, 20-E-vallesamine from Alstonia scholaris. Heterocycles 26(2):413–419CrossRefGoogle Scholar
  23. Ayers S, Zink DL, Mohn K et al (2007) Anthelmintic activity of aporphine alkaloids from Cissampelos capensis. Planta Med 73(3):296–297PubMedCrossRefGoogle Scholar
  24. Ayusawa M, Mohammad NH, Yamashita R et al (2008) External preparation for skin for ameliorating cytotoxicity of active oxygen species. JP2008184439A. 14 Aug 2008Google Scholar
  25. Ayyanar M, Ignacimuthu S (2005) Traditional knowledge of kani tribals in Kouthalai of Tirunelveli hills, Tamil Nadu, India. J Ethnopharmacol 102(2):246–255PubMedCrossRefGoogle Scholar
  26. Bairwa K, Jachak SM (2015a) Anti-inflammatory potential of a lipid-based formulation of a rotenoid-rich fraction prepared from Boerhavia diffusa. Pharm Biol 53:1231–1238PubMedCrossRefGoogle Scholar
  27. Bairwa K, Jachak SM (2015b) Development and optimisation of 3-acetyl-11-keto-β-boswellic acid loaded poly-lactic-co-glycolic acid-nanoparticles with enhanced oral bioavailability and in vivo anti-inflammatory activity in rats. J Pharm Pharmacol 67:1188–1197PubMedCrossRefGoogle Scholar
  28. Baliga MS (2012) Review of the phytochemical, pharmacological and toxicological properties of Alstonia scholaris. Chin J Integr Med.  https://doi.org/10.1007/s11655-011-0947-0 CrossRefPubMedGoogle Scholar
  29. Baliga MS, Jagetia GC, Ulloor JN et al (2004) The evaluation of the acute toxicity and long-term safety of hydroalcoholic extract of Sapthaparna (Alstonia scholaris) in mice and rats. Toxicol Lett 15:317–326CrossRefGoogle Scholar
  30. Bandaru N, Ramu A, Vidyadhara S et al (2016) Evaluation of in vivo anti-diarrheal and cytotoxic activity of ethanolic extract of Alsotinia scholaris leaves. Int J Pharm Sci Rev Res 1:38–42Google Scholar
  31. Bandaru N, Ramu A, Vijetha P et al (2017) Evaluation of ex vivo anticataract activity of ethanolic extract of Alstonia scholaris leaves on dexamethasone-induced cataract by using isolated goat lens. Asian J Pharm Clin Res 10:8–11CrossRefGoogle Scholar
  32. Bandawane D, Juvekar AR, Juvekar M (2011) Antidiabetic and antihyperlipidemic effect of Alstonia scholaris Linn bark in streptozotocin induced diabetic rats. Ind J Pharm Educ Res 45:114–120Google Scholar
  33. Banerji A, Banerji J (1977) Isolation of pseudoakuammigine from the leaves of Alstonia scholaris R. Br. Indian J Chem Sect B Org Chem Incl Med Chem 15B(4):390–391Google Scholar
  34. Banerji A, Siddhanta AK (1981) Scholarine: an indole alkaloid of Alstonia scholaris. Phytochemistry 20:540–542CrossRefGoogle Scholar
  35. Banerji J, Mustafi R, Roy DJ et al (1984) (−)-scholarine and (+)-lochneridine constituents of Alstonia-scholaris R. BR. (apocynaceae). Indian J Chem Sect B Org Chem Incl Med Chem 23(5):455Google Scholar
  36. Bello I, Bakkouri AS, Tabana YM et al (2016) Acute and sub-acute toxicity evaluation of the methanolic extract of Alstonia scholaris stem bark. Med Sci (Basel) 4:1–14Google Scholar
  37. Benayad S, Ahamada K, Lewin G et al (2016) Preakuammicine: a long-awaited missing link in the biosynthesis of monoterpene indole alkaloids. Eur J Org Chem 8:1494–1499CrossRefGoogle Scholar
  38. Bernard D, Mahe Y (2007) Administration of 8-hexadecene-1,16-dicarboxylic acid for promoting cohesion of the epidermal horny layer. US20070059269A1. 15 Mar 2007Google Scholar
  39. Bhandary MJ, Chandrashekar KR, Kaveriappa KM (1995) Medical ethnobotany of the siddis of Uttara Kannada district, Karnataka, India. J Ethnopharmacol 47(3):149–158PubMedCrossRefGoogle Scholar
  40. Bharati KA, Sharma BL (2010) Some ethnoveterinary plant records for Sikkim Himalaya. Indian J Tradit Knowl 9(2):344–346Google Scholar
  41. Bhardwaj S, Gakhar SK (2005) Ethnomedicinal plants used by the tribals of Mizoram to cure cuts & wounds. Indian J Tradit Knowl 4(1):75–80Google Scholar
  42. Bhogayata K, Sharma PP, Patel BR (2009) A clinical evaluation of Saptaparna (Alstonia scholaris L, R. Br.) on essential hypertension. Ayu 30:318–322Google Scholar
  43. Bianco A, de Luca A, Mazzei RA et al (1994) Iridoids of Rauwolfia grandiflora. Phytochemistry 35(6):1485–1487CrossRefGoogle Scholar
  44. Biswas GK, Saharia GS (1978) A new alkaloidal glycoside from Alstonia scholaris. Indian J Chem 1(1):66–67Google Scholar
  45. Boonchuay W, Court WE (1976a) Alkaloids of Alstonia scholaris from Thailand. Planta Med 29:380–390PubMedCrossRefGoogle Scholar
  46. Boonchuay W, Court WE (1976b) Minor alkaloids of Alstonia scholaris root. Phytochemistry 15(5):821CrossRefGoogle Scholar
  47. Bosch J, Bonjoch J, Amat M et al (1996) The strychnos alkaloids. In: Cordell GA (ed) The alkaloids: chemistry and pharmacology, vol 48. Academic Press, New York, pp 75–189Google Scholar
  48. British Pharmaceutical Codex (1949) Council of the Pharmaceutical Society of Great Britain. The Pharmaceutical Press, London, p 1441Google Scholar
  49. Buckingham J, Baggaley KH, Roberts AD, Szabo LF et al (2010) Dictionary of alkaloids with CD-ROM. CRC Press, Boca RatonCrossRefGoogle Scholar
  50. Burkill HM (1985) The useful plants of west tropical Africa, vol 1. Royal Botanic Gardens, KewGoogle Scholar
  51. Cai XH, Du ZZ, Luo XD (2007) Unique monoterpenoid indole alkaloids from Alstonia scholaris. Org Lett 9:1817–1820PubMedCrossRefGoogle Scholar
  52. Cai XH, Liu YP, Feng T et al (2008a) Picrinine-type alkaloids from the leaves of Alstonia scholaris. Chin J Nat Med 6:20–22CrossRefGoogle Scholar
  53. Cai XH, Tan QG, Liu YP et al (2008b) A cage-monoterpene indole alkaloid from Alstonia scholaris. Org Lett 10(4):577–580PubMedCrossRefGoogle Scholar
  54. Cai XH, Shang JH, Feng T et al (2010) Novel alkaloids from Alstonia scholaris. Z Naturforsch 65b:1164–1168CrossRefGoogle Scholar
  55. Cao J, Shen HM, Wang Q et al (2016) Characterization of chemical constituents and rats metabolites of an alkaloidal extract of Alstonia scholaris leaves by liquid chromatography coupled with mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1026:1–13CrossRefGoogle Scholar
  56. Chakravarti RN, Chakravarti D, Sur R (1968) A simplified method for isolation of echitamine. Bull Calcutta Sch Trop Med 16(3):81PubMedGoogle Scholar
  57. Channa S, Dar A, Ahmed S et al (2005) Evaluation of Alstonia scholaris leaves for broncho-vasodilatory activity. J Ethnopharmacol 97:469–476PubMedCrossRefGoogle Scholar
  58. Chatterjee A, Ghosal S (1961) Echitamidine. Kurze Originalmitteilungen 48:328Google Scholar
  59. Chatterjee A, Mukherjee B, Ray AB et al (1965) The alkaloid of the leaves of Alstonia scholaris R. Br. Tetrahedron Lett 6:2–6Google Scholar
  60. Chatterjee A, Mukheqee B, Ghosal S et al (1969) Occurrence of rhazine in Alstonia scholaris R. Br.: biogenetic and chemotaxonomic significance of co-occurrence of several indole alkaloids having a common structural pattern. J Indian Chem Soc 46:635Google Scholar
  61. Chen YY, Yang J, Yang XW, Yang XW et al (2016) Alstorisine A, a nor-monoterpenoid indole alkaloid from cecidogenous leaves of Alstonia scholaris. Tetrahedron Lett 57(16):1754–1757CrossRefGoogle Scholar
  62. Chopra RN, Chopra IC (1933) Indigenous drugs of India. Academic Publishers, Calcutta, pp 276–278Google Scholar
  63. Choudhary M, Rani S, Sharma P (2017) Anti-fertility and abortifacient potential of hydroalcoholic leaves extract of Alstonia scholaris in female rats: an ethnomedicine used by Papua women in New Guinea. Bull Fac Pharm Cairo Univ 55:123–127CrossRefGoogle Scholar
  64. Compiling Group of Yunnan Traditional Chinese Medicine (1977) Yunnan traditional Chinese medicinal plant. Yunnan People’s Press, KunmingGoogle Scholar
  65. Costa EV, Sampaio MFC, Salvador MJ et al (2015) Chemical constituents from the stem bark of Annona pickelii (Annonaceae). Quím 38:769–776Google Scholar
  66. Crawford AD, Liekens S, Kamuhabwa AR et al (2011) Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants. PLoS ONE 6:1–9CrossRefGoogle Scholar
  67. Da Silva TMS, Da Silva BA, Mukherjee R (1999) The monoterpene alkaloid cantleyine from Strychnos trinervis root and its spasmolytic properties. Phytomedicine 6:169–176PubMedCrossRefGoogle Scholar
  68. Dash GK, Murthy PN (2011) The wound healing effects of a new polyherbal formulation. Der Pharm Lett 3:342–349Google Scholar
  69. Datta HM, Chandrakantbhai MA (2016) Foot care compositions. WO2016110872A1. 14 July 2016Google Scholar
  70. De Luca V (2011) Monoterpenoid indole alkaloid biosynthesis, plant metabolism and biotechnology, 1st edn. Wiley, Hoboken, pp 263–291. ISBN 978-0-470-74703-2CrossRefGoogle Scholar
  71. Deepa S, Suseela PM, Krishnan C (2014) GC-MS analysis of ethanolic bark extract of Alstonia scholaris and evaluation of its pharmacological studies. Int J Pharm Sci Rev Res 28(51):284–287Google Scholar
  72. DeFilipps RA, Krupnick GA (2018) The medicinal plants of Myanmar. PhytoKeys 102:1–341CrossRefGoogle Scholar
  73. Dhar BDN, Suri SC, Dwivedi P (1977) Chemical examination of the flowers of Alstonia scholaris. Planta Med 31:6–7CrossRefGoogle Scholar
  74. Dixon C, Fyson GF, Pasiecznik N (2013) The CABI encyclopaedia of forest trees. Technology & engineering. CABI Publishing, Wallingford, pp 67–68Google Scholar
  75. Eckermann R, Gaich T (2013) The akuammiline alkaloids; origin and synthesis. Synthesis 45(20):2813–2823CrossRefGoogle Scholar
  76. El-Askary HI, El-Olemy MM, Salama MM et al (2012) Bioguided isolation of pentacyclic triterpenes from the leaves of Alstonia scholaris (Linn.) R. Br. growing in Egypt. Nat Prod Res 26(18):1755–1758PubMedCrossRefGoogle Scholar
  77. Feng T, Cai XH, Du ZZ et al (2008) Iridoids from the bark of Alstonia scholaris. Helv Chim Acta 91:2247–2251CrossRefGoogle Scholar
  78. Feng T, Cai X, Zhao P et al (2009) Monoterpenoid indole alkaloids from the bark of Alstonia scholaris. Planta Med 75:1537–1541PubMedCrossRefGoogle Scholar
  79. Feng L, Chen Y, Yuan L et al (2013) A combination of alkaloids and triterpenes of Alstonia scholaris (Linn.) R. Br. leaves enhances immunomodulatory activity in C57BL/6 mice and induces apoptosis in the A549 cell line. Molecules 18:13920–13939PubMedPubMedCentralCrossRefGoogle Scholar
  80. Furtado JC, Niege A, Pirson L et al (2017) Pentacyclic triterpene bioavailability: an overview of in vitro and in vivo studies. Molecules 22(3):400–424CrossRefGoogle Scholar
  81. Gandhi M, Vinayak VK (1990) Preliminary evaluation of extracts of Alstonia scholaris bark for in vivo antimalarial activity in mice. J Ethnopharmacol 29:51–57PubMedCrossRefGoogle Scholar
  82. Garcez WS, Garcez FR, da Silva LM et al (2009) Larvicidal activity against Aedes aegypti of some plants native to the West-Central region of Brazil. Bioresour Technol 100(24):6647–6650PubMedCrossRefGoogle Scholar
  83. Gardner S, Sidisunthorn P, Anusarnsunthorn V (2000) A field guide to forest trees of Northern Thailand. Kobfai Publishing Project, BangkokGoogle Scholar
  84. George L, Highland H (2016) Hydroalcoholic extract of Alstonia scholaris arrests invasion of Plasmodium falciparum by effective RBC membrane stabilization. J Adv Med Pharma Sci 9:1–9Google Scholar
  85. Godugu C, Patel AR, Doddapaneni R et al (2014) Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid. PLoS ONE 9(3):1–15CrossRefGoogle Scholar
  86. Goh SH, Ali ARM, Wong WH (1989) Alkaloids of Leuconotis griffithii and L. Eugenifolia (Apocynaceae). Tetrahedron 45:7899–7920CrossRefGoogle Scholar
  87. Goodson JA, Henry TA, Macfie JWS (1930) The action of the cinchona and certain other alkaloids in bird malaria. Biochem J 24(4):874–890PubMedPubMedCentralCrossRefGoogle Scholar
  88. Gosai KR (2017) A clinical trial to evaluate efficacy of Saptaparna (Alstonia scholaris Linn.) twak churna in vicharchika (eczema). J Ayurvedic Integr Med Sci 2:54–57Google Scholar
  89. Goun E, Cunningham G, Chu D et al (2003) Antibacterial and antifungal activity of Indonesian ethnomedical plants. Fitoterapia 74(6):592–596PubMedCrossRefGoogle Scholar
  90. Gupta U, Agrawal NK (2013) Prevention of radiation induced hematological alterations in mice by Alstonia scholaris extract. Int J Pharm Sci Res 4(4):1453–1459Google Scholar
  91. Gupta BD, Siddons LB, Chakravarti H (1944) Quinine and Alstonia scholaris (Chhatim) in malaria: a study of possible synergy. Indian Med Gaz 79(9):408–414Google Scholar
  92. Gupta RS, Bhatnager AK, Joshi YC et al (2005) Induction of antifertility with lupeol acetate in male Albino rats. Pharmacology 75:57–62PubMedCrossRefPubMedCentralGoogle Scholar
  93. Harsha VH, Shripathi V, Hegde GR (2005) Ethnoveterinary practices in Uttara Kannada district of Karnataka. Indian J Tradit Knowl 4(3):253–258Google Scholar
  94. Hirasawa Y, Miyama S, Kawahara N et al (2009) Indole alkaloids from the leaves of Alstonia scholaris. Heterocycles 79(1):1107–1112CrossRefGoogle Scholar
  95. Hou Y, Cao X, Wang L et al (2012) Microfractionation bioactivity-based ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in an alkaloidal extract of the folk herb Alstonia scholaris. J Chromatogr B Anal Technol Biomed Life Sci 908:98–104CrossRefGoogle Scholar
  96. Hu J, Mao X, Shi X, Jin N, Shi J et al (2018) Monoterpenoid indole alkaloids from the leaves of Alstonia scholaris. Chem Nat Compd 54(5):934–937CrossRefGoogle Scholar
  97. Huang RL, Chen CC, Huang YL et al (1998) Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla. Planta Med 64(3):212–215PubMedCrossRefPubMedCentralGoogle Scholar
  98. Hugel G, Royer D, Le Men-Olivier L et al (1997) Flow thermolysis rearrangements in the indole alkaloid series: strictamine and akuammicine derivatives. The absolute configurations of ngouniensine and epi-ngouniensine. J Org Chem 62(3):578–583PubMedCrossRefPubMedCentralGoogle Scholar
  99. Hui T, Sun Y, Zhu L et al (2009) Flavonoids in leaves of Alstonia scholaris. China J Chin Mater Med 34(9):1111–1113Google Scholar
  100. Ideta T, Ifuku O, Kojima M et al (1998) Composition for head. JPH10316541A. 02 Dec 1998Google Scholar
  101. Ingkaninan K, Ijzerman AP, Taesotikult T et al (1999) Isolation of opioid-active compounds from Tabernaemontana pachysiphon leaves. J Pharm Pharmacol 51(12):1441–1446PubMedCrossRefGoogle Scholar
  102. Intayoung P, Limtrakul P, Yodkeeree S et al (2016) Antiinflammatory activities of crebanine by inhibition of NF-κB and AP-1 activation through suppressing MAPKs and Akt signaling in LPS-induced RAW 264.7 macrophages. Biol Pharm Bull 39:54–61PubMedCrossRefGoogle Scholar
  103. Islam F, Miah SMA (2013) Essential oil composition from the flowers of Alstonia scholaris of Bangladesh. Int Food Res J 20:3185–3188Google Scholar
  104. Jagetia GC, Baliga MS (2003) Induction of developmental toxicity in mice treated with Alstonia scholaris (Sapthaparna) in Utero. Birth Defects Res Part B Dev Reprod Toxicol 478:472–478CrossRefGoogle Scholar
  105. Jagetia GC, Baliga MS (2006) Evaluation of anticancer activity of the alkaloid fraction of Alstonia scholaris (Sapthaparna) in vitro and in vivo. Phytother Res 109:103–109CrossRefGoogle Scholar
  106. Jagetia GC, Baliga MS (2016) Preclinical evaluation of the anticancer activity of hydroalcoholic stem bark extract of Alstonia scholaris in ehrlich ascites carcinoma transplanted in the Swiss albino mice. J Altern Med Res 2:1–12CrossRefGoogle Scholar
  107. Jagetia GC, Baliga MS et al (2005) Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in vitro and in tumour-bearing mice. J Pharm Pharmcol 57:1213–1219CrossRefGoogle Scholar
  108. Jain L, Pandey MB, Singh S et al (2009) A new indole alkaloid from Alstonia scholaris. Nat Prod Res 23:1599–1602PubMedCrossRefGoogle Scholar
  109. Jain L, Pandey MB, Singh S et al (2014) A new indole alkaloid from Alstonia scholaris. Nat Prod Res 23:37–41Google Scholar
  110. Jaipuriar MK (2007) Herbs of Tribal Land Jharkhand, India. Scientific Publishers, Jodhpur, pp 24–25Google Scholar
  111. Jianhua L (2015) Cough relieving spray and preparation method thereof. CN104258333A. 07 Jan 2015Google Scholar
  112. Jinhua L, Yufeng Y, Yuming T et al (2015) Alstonia scholaris propagation method with big tree trunks cut. CN103598060B. 07 Jan 2015Google Scholar
  113. Joule JA (1983) Chemistry of heterocyclic compounds: Indoles- the monoterpenoid indole alkaloids. In: Saxton JE (ed) The uleine—ellipticine-vallesamine group. Wiley, New YorkCrossRefGoogle Scholar
  114. Kam TS, Nyeoh KT, Sim KM et al (1997) Alkaloids from Alstonia scholaris. Phytochemistry 45:1303–1305CrossRefGoogle Scholar
  115. Kamarajan P, Sekar N, Mathuram V et al (1991) Antitumor effect of echitamine chloride on methylcholonthrene induced fibrosarcoma in rats. Biochem Int 25(3):491–498PubMedGoogle Scholar
  116. Kanyanga RC, Lumpu SN, Ehata MT et al (2019) In vitro and in vivo antiplasmodial activity of extracts and isolated constituents of Alstonia congensis root bark. J Ethnopharmacol 242:1–6Google Scholar
  117. Keawpradub N, Kirby GC, Steele JC et al (1999) Antiplasmodial activity of extracts and alkaloids of three Alstonia species from Thailand. Planta Med 65(08):690–694PubMedCrossRefGoogle Scholar
  118. Khanum S (2014) Pharmacological investigation of the chloroform extracts of Alstonia scholaris (L.) R. Br. J Pharm Sci Innov 3(1):14–19CrossRefGoogle Scholar
  119. Khare CP (2007) Indian medicinal plants: an illustrated dictionary. Springer, Heidelberg, pp 38–39CrossRefGoogle Scholar
  120. Khyade MS, Vaikos NP (2014) Phytochemical and antibacterial activity of leaves of Alstonia scholaris R. Br. Afr J Biotechnol 8:6434–6436CrossRefGoogle Scholar
  121. Khyade MS, Kasote DM, Vaikos NP (2014) Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. Ex G. Don: a comparative review on traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 153:1–18PubMedCrossRefGoogle Scholar
  122. Kirtikar KR, Basu BD (1918) In: Sudhindra Nath Basu MB (ed) Indian medicinal plants, vol II. Indian Press, Allahabad, pp 786–790CrossRefGoogle Scholar
  123. Konkimalla VB, Efferth T (2010) Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine. Biochem Pharmacol 79(8):1092–1099PubMedCrossRefGoogle Scholar
  124. Krishnan P, Lee FK, Chong KW et al (2018) Alstoscholactine and alstolaxepine, monoterpenoid indole alkaloids with γ-lactone-bridged cycloheptane and oxepane Moieties from Alstonia scholaris. Org Lett 20:8014–8018PubMedCrossRefGoogle Scholar
  125. Krishnan P, Mai CW, Yong KT et al (2019) Alstobrogaline, an unusual pentacyclic monoterpenoid indole alkaloid with aldimine and aldimine-N-oxide moieties from Alstonia scholaris. Tetrahedron Lett 60(11):789–791CrossRefGoogle Scholar
  126. Kuehne ME, Xu F, Brook CS et al (1994) Syntheses of strychnos- and aspidospermatan-type alkaloids. 6. Total syntheses of (±)-echitamidine, (±)-alstogustine, (±)-19-epi-alstogustine, and (±)-akuammicine. J Org Chem 59(25):7803–7806CrossRefGoogle Scholar
  127. Kulkarni MP, Juvekar AR (2008) Effect of Alstonia scholaris (Linn.) R. Br. on stress and cognition in mice. Indian J Exp Biol 47:47–52Google Scholar
  128. Kuok CF, Zhang J, Fan CL et al (2017) Meloslines A and B, two novel indole alkaloids from Alstonia scholaris. Tetrahedron Lett 58:2740–2742CrossRefGoogle Scholar
  129. Kyung J, Kim K, Kyung E et al (2009) Cosmetic composition containing natural medicinal plant extract for alleviating skin inflammation. KR20090085844A. 10 Aug 2009Google Scholar
  130. Lavaud C, Massiot G, Vercauteren J et al (1982) Alkaloids of Hunteria zeylanica. Phytochemistry 21:445–447CrossRefGoogle Scholar
  131. Le PM, Srivastava V, Nguyen TT et al (2017) Stephanine from Stephania venosa (Blume) Spreng showed effective antiplasmodial and anticancer activities, the latter by inducing apoptosis through the reverse of mitotic exit. Phytother Res 31:1357–1368PubMedCrossRefGoogle Scholar
  132. Lecomte H (1907a) Flore Générale de l’Indo-Chine, vol 3 (8–9). Muséum National d’Histoire Naturelle, Laboratoire de Phanérogamie, ParisGoogle Scholar
  133. Lecomte H (1907b) Flore Générale de l’Indo-Chine, vol 7 (1). Muséum National d’Histoire Naturelle, Laboratoire de Phanérogamie, ParisGoogle Scholar
  134. Lee SJ, Cho SA, An S et al (2012) Alstonia scholaris R. Br. significantly inhibits retinoid-induced skin irritation in vitro and in vivo. Evid Based Complement Altern Med 1:1–11Google Scholar
  135. Lee JY, Kim KJ, Kim J et al (2016) Anti-osteoclastogenic effects of isoquinoline alkaloids from the rhizome extract of Sinomenium acutum. Arch Pharm Res 39(5):713–720PubMedCrossRefPubMedCentralGoogle Scholar
  136. Li R, Zi MJ, Gou ZP et al (2019) Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: a multiple doses phase I clinical trial. Phytomedicine 61:152828PubMedCrossRefPubMedCentralGoogle Scholar
  137. Lim SH, Low YY, Sinniah SK et al (2014) Macroline, akuammiline, sarpagine, and ajmaline alkaloids from Alstonia macrophylla. Phytochemistry 98:204–215PubMedCrossRefPubMedCentralGoogle Scholar
  138. Lim JL, Sim KS, Yong KT et al (2015) Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety. Phytochemistry 117:317–324PubMedCrossRefGoogle Scholar
  139. Lin HF, Huang HL, Liao JF et al (2015) Dicentrine analogue-induced G2/M arrest and apoptosis through inhibition of topoisomerase II activity in human cancer cells. Planta Med 81(10):830–837PubMedCrossRefPubMedCentralGoogle Scholar
  140. Liu L, Chen YY, Qin XJ et al (2015) Antibacterial monoterpenoid indole alkaloids from Alstonia scholaris cultivated in temperate zone. Fitoterapia 105:160–164PubMedCrossRefPubMedCentralGoogle Scholar
  141. Lounasmaa M, Jokela R, Hanhinen P et al (1995) The rhazimanine bhimberine enigma. J Nat Prod 58:131–133CrossRefGoogle Scholar
  142. Macabeo AP, Krohn K, Gehle D et al (2005) Indole alkaloids from the leaves of Philippine Alstonia scholaris. Phytochemistry 66:1158–1162PubMedCrossRefGoogle Scholar
  143. Maiden JH (1889) The useful native plants of Australia: (including Tasmania). Turner and Henderson. Library of New York Botanical Garden, Bronx, p 154CrossRefGoogle Scholar
  144. Makarasen A, Sirithana W, Mogkhuntod S et al (2011) Cytotoxic and antimicrobial activities of aporphine alkaloids isolated from Stephania venosa (Blume) Spreng. Planta Med 77:1519–1524PubMedCrossRefGoogle Scholar
  145. Maltese F, van der Kooy F, Verpoorte R (2009) Solvent derived artifacts in natural products chemistry. Nat Prod Commun 4(3):447–454PubMedGoogle Scholar
  146. Marini-Bettolo GB, Nicoletti M, Messana I (1983) Research on African medicinal plants—IV: Boonein, A new C-9 terpenoid lactone from Alstonia boonei: a possible precursor in the indole alkaloid biogenesis. Tetrahedron 39(2):323–329CrossRefGoogle Scholar
  147. Maurya A, Dwivedi GR, Darokar MP, Srivastava SK (2014) Preparative isolation of bioenhancer loganetin from by fast centrifugal partition chromatography. Sep Sci Technol 49(5):773–777CrossRefGoogle Scholar
  148. Mistry D, Pithawala M (2018) Protective effect of Alstonia scholaris Linn. R. Br. against bleomycin induced chromosomal damage in cultured human lymphocytes, in vitro. Drug Chem Toxicol 1:1–7Google Scholar
  149. Mollik MAH, Hossan MS, Paul AK et al (2010) A comparative analysis of medicinal plants used by folk medicinal healers in three districts of Bangladesh and inquiry as to mode of selection of medicinal plants. Ethnobot Res Appl 8:195–218CrossRefGoogle Scholar
  150. Morita Y, Hesse M, Schmid H et al (1977) Alstoniu scholaris: Struktur des Indoal kaloides Narelin. Helv Chim Acta 60:1419–1434PubMedCrossRefGoogle Scholar
  151. Morita H, Ichihara Y, Takeya K et al (1989) A new indole alkaloid glycoside from the leaves of Palicourea marcgravii. Planta Med 55:288–289PubMedCrossRefGoogle Scholar
  152. Mukerji B, Ghosh BK, Siddons LB (1942) Search for an antimalarial drug in the indigenous materia medica: part I—Alstonia scholaris, F. Br. Indian Med Gaz 77(12):723–725Google Scholar
  153. Mukherjee R, Rajesh MN (2009) Locality, history, memory: the making of the citizen in South Asia. Cambridge Scholars Publishing, Cambridge, p 232Google Scholar
  154. Nadkarni AK (1976) Indian materia medica, 3rd edn. Popular Press Ltd, Mumbai, pp 80–83Google Scholar
  155. Nakayama T, Sakamoto O, Suzuki Y et al (1997) Skin preparation for external use. JPH0987164A. 31 Mar 1997Google Scholar
  156. Opitz S, Nes WD, Gershenzon J et al (2014) Both methylerythritol phosphate and mevalonate pathways contribute to biosynthesis of each of the major isoprenoid classes in young cotton seedlings. Phytochemistry 98:110–119PubMedCrossRefGoogle Scholar
  157. Pan Q, Mustafa NR, Tang K et al (2015) Monoterpenoid indole alkaloids biosynthesis and its regulation in Catharanthus roseus: a literature review from genes to metabolites. Phytochem Rev 15(2):221–250CrossRefGoogle Scholar
  158. Pan Z, Qin XJ, Liu YP et al (2016) Alstoscholarisines H-J, indole alkaloids from Alstonia scholaris: structural evaluation and bioinspired synthesis of alstoscholarisine H. Org Lett 18:654–657PubMedCrossRefGoogle Scholar
  159. Pauli GF, Case RJ, Inui T et al (2005) New perspectives on natural products in TB drug research. Life Sci 78:485–494PubMedCrossRefGoogle Scholar
  160. Phillipson JD, Bisset NG (1972) Quaternisation and oxidation of strychnine and brucine during plant extraction. Phytochemistry 11(8):2547–2553CrossRefGoogle Scholar
  161. Pratap B, Chakraborthy GS, Mogha N (2013) Complete aspects of Alstonia scholaris. Int J Pharm Tech Res 5(1):17–26Google Scholar
  162. Prusti AB, Behera KK (2007) Ethnobotanical exploration of Malkangiri district of Orissa, India. Ethnobot Leafl 11:122–140Google Scholar
  163. Purkayastha J, Dutta M, Nath SC (2007) Ethnomedicinal plants from Dibru-Saikhowa biosphere reserve, Assam. Indian J Tradit Knowl 6(3):477–480Google Scholar
  164. Pushpangadan P, Rawat AK, Rao CV et al (2010) United States Patent, synergistic antipyretic formulation. US 7,658,954 B2. 09 Feb 2010Google Scholar
  165. Qin XJ, Zhao YL, Lunga PK (2015a) Indole alkaloids with antibacterial activity from aqueous fraction of Alstonia scholaris. Tetrahedron 71:1–5CrossRefGoogle Scholar
  166. Qin XJ, Zhao YL, Song CW et al (2015b) Monoterpenoid indole alkaloids from inadequately dried leaves of Alstonia scholaris. Nat Prod Bioprospect 5:185–193PubMedPubMedCentralCrossRefGoogle Scholar
  167. Quisumbing EA (1951) Medicinal plants of the Philippines. Department of Agriculture and Commerce, Philippine Islands Technical Bulletin. Katha Publishing Company, Quezon City, p 721Google Scholar
  168. Ragasa CY, Batarra TC, Tan MS et al (2016) Chemical constituents of Alstonia scholaris (L.) R. Br. Pharma Chem 8:193–196Google Scholar
  169. Rahmatullah M, Mollik MAH, Azam AA et al (2009) Ethnobotanical survey of the Santal tribe residing in Thakurgaon district, Bangladesh. Am Eurasian J Agric Environ Sci 3(4):889–899Google Scholar
  170. Rahmatullah M, Azam NK, Khatun Z et al (2012) Medicinal plants used for treatment of diabetes by the Marakh sect of the Garo tribe living in Mymensingh district, Bangladesh. Afr J Tradit Complement Altern Med 9(3):380–385PubMedPubMedCentralGoogle Scholar
  171. Raimo U, Mauri L (1981) 13 C NMR data of 3-isoajmalicine and 19-epiajmalicine. Planta Med 41:406–418CrossRefGoogle Scholar
  172. Rajakumar N, Shivanna MB (2010) Traditional herbal medicinal knowledge in Sagar taluk of Shimoga district, Karnataka, India. Indian J Nat Prod Resour 1(1):102–108Google Scholar
  173. Ramachandra YL, Sudeep HV, Rai PS et al (2012) Evaluation of wound healing activity of leaf extract of Alstonia scholaris. Int J Pharm Pharm Sci 4:390–393Google Scholar
  174. Ramirez A, García-Rubio S (2003) Current progress in the chemistry and pharmacology of akuammiline alkaloids. Curr Med Chem 10(18):1891–1915PubMedCrossRefGoogle Scholar
  175. Rastogi RC, Kapil RS (1970) Picralinal—a key alkaloid of picralima group from Alstonia scholaris R. Br. Experientia 26:1056PubMedCrossRefGoogle Scholar
  176. Reina M, Ruiz-Mesia L, Ruiz-Mesia W et al (2014) Antiparasitic indole alkaloids from Aspidosperma desmanthum and A. spruceanum from the Peruvian Amazonia. Nat Prod Commun 9:1075–1080PubMedGoogle Scholar
  177. Reisman SE (2011) New lead for pain treatment. Nature 473(7348):458–459PubMedCrossRefPubMedCentralGoogle Scholar
  178. Rosales PF, Gower A, Benitez MLR et al (2019) Extraction, isolation and in vitro evaluation of affinisine from Tabernaemontana catharinensis in human melanoma cells. Bioorg Chem 90:3–7Google Scholar
  179. Saikia B (2006) Ethnomedicinal plants from Gohpur of Sonitpur district, Assam. Indian J Tradit Knowl 5(4):529–530Google Scholar
  180. Salim V, De Luca V (2013) Towards complete elucidation of monoterpene indole alkaloid biosynthesis pathway: Catharanthus roseus as a pioneer system. Adv Bot Res 68:1–37CrossRefGoogle Scholar
  181. Salim AA, Garson MJ, Craik DJ (2004) New indole alkaloids from the bark of Alstonia scholaris. J Nat Prod 3:1591–1594CrossRefGoogle Scholar
  182. Saraswathi V, Ramamoorthy N, Subramaniam S et al (1998) Inhibition of glycolysis and respiration of sarcoma-180 cells by echitamine chloride. Chemotherapy 44:198–205PubMedCrossRefPubMedCentralGoogle Scholar
  183. Satoshi A, Arinori O (2004) IV type and VII type collagen production promoter and composition for caring skin basement membrane. JP2004018471A. 21 Jan 2004Google Scholar
  184. Satoshi KHA, Aoyama SY, Koga SY et al (2003) Skin vitalizing composition for external use anti-aging preparation. EP1281396A2. 05 Feb 2003Google Scholar
  185. Satoshi A, Toshio N, Keiko T (2004) Substances capable of potentiating laminin 5 productivity in epidermal cells and utilization thereof. EP1426030A1. 09 June 2004Google Scholar
  186. Saxton JE (1970) Alkaloids of Alstonia species. Alkaloids Chem Physiol 12:207–244Google Scholar
  187. Schnoes HK, Biemann K, Mokry J, Kompis I, Chatterjee A, Ganguli G (1966) Strictamine. J Organ Chem 31(5):1641–1642CrossRefGoogle Scholar
  188. Sen S, Chakraborty R, De B et al (2011) An ethnobotanical survey of medicinal plants used by ethnic people in West and South district of Tripura, India. J Forest Res 22(3):417–426CrossRefGoogle Scholar
  189. Shang JH, Cai XH, Feng T et al (2010a) Pharmacological evaluation of Alstonia scholaris: anti-inflammatory and analgesic effects. J Ethnopharmacol 129:174–181PubMedCrossRefPubMedCentralGoogle Scholar
  190. Shang JH, Cai XH, Zhao YL et al (2010b) Pharmacological evaluation of Alstonia scholaris: anti-tussive, anti-asthmatic and expectorant activities. J Ethnopharmacol 129:293–298PubMedCrossRefPubMedCentralGoogle Scholar
  191. Shankar R, Rawat MS, Deb S et al (2012) Jaundice and its traditional cure in Arunachal Pradesh. J Pharm Sci Innov 1(3):93–97Google Scholar
  192. Sharma H, Kumar A (2011) Ethnobotanical studies on medicinal plants of Rajasthan (India): a review. J Med Plants Res 5(7):1107–1112Google Scholar
  193. Shittu H, Gray A, Furman B et al (2010) Glucose uptake stimulatory effect of akuammicine from Picralima nitida (Apocynaceae). Phytochem Lett 3:53–55CrossRefGoogle Scholar
  194. Silva DF, Porto DL, Araújo IGA et al (2009) Endothelium-derived nitric oxide is involved in the hypotensive and vasorelaxant effects induced by discretamine in rats. Die Pharmazie Int J Pharm Sci 64:327–331Google Scholar
  195. Singh V, Jain AP (2003) Ethnobotany and medicinal plants of India and Nepal. Scientific Publishers, Jodhpur, p 138Google Scholar
  196. Singh MP, Panda H (2005) Medicinal herbs with their formulations. Daya Books, New DelhiGoogle Scholar
  197. Singh B, Sangwan P (2011) Taxonomy, ethnobotany and antimicrobial activity of Alstonia scholaris (L.) R. Br, Carissa carandas L. and Catharanthus roseus (L.) G. Don. Int J Biotechnol Biosci 1(1):102–112Google Scholar
  198. Singh VK, Govil JN, Hashmi S et al (2003) Recent progress in medicinal plants. Ethnomedicine and pharmacognosy II, vol 7. Studium Press, Texas, p 47Google Scholar
  199. Smith MW, Snyder SA (2013) A concise total synthesis of (+)-scholarisine A empowered by a unique C–H arylation. J Am Chem Soc 135(35):12964–12967PubMedCrossRefPubMedCentralGoogle Scholar
  200. Soares PR, de Oliveira PL, de Oliveira CM et al (2012) In vitro antiproliferative effects of the indole alkaloid vallesiachotamine on human melanoma cells. Arch Pharm Res 35(3):565–571PubMedCrossRefGoogle Scholar
  201. Sood SK, Thakur R (2015) Herbal resources of India and Nepal, vol 43. Scientific Publishers, Jodhpur, p 27Google Scholar
  202. Stephen R, Alex B (2016) Skin moisturizing composition. WO2016183630A1. 24 Nov 2016Google Scholar
  203. Stockigt J, Hofle G, Pfitzner A et al (1980) Mechanism of the biosynthetic conversion of geissoschizine to 19-epi-ajmalicine in Catharanthus roseus. Tetrahedron Lett 21(20):1925–1926CrossRefGoogle Scholar
  204. Stockigt J, Antonchick AP, Wu F et al (2011) The Pictet–Spengler reaction in nature and in organic chemistry. Angew Chem 50(37):8538–8564CrossRefGoogle Scholar
  205. Stowell CH, Stowell LR (1982) Microscopical diagnosis. Antic Hay Rare Books, Asbury ParkGoogle Scholar
  206. Su MJ, Nieh YC, Huang HW et al (1994) Dicentrine, an alpha-adrenoceptor antagonist with sodium and potassium channel blocking activities. Naunyn Schmiedebergs Arch Pharmacol 349(1):42–49PubMedGoogle Scholar
  207. Sultana N, Saleem M (2010) Phytochemical studies on Alstonia scholaris. Zeitschrift für Naturforschung B 65(2):203–210CrossRefGoogle Scholar
  208. Sultana N, Akhter M, Saify ZS et al (2013a) Isolation and structure determination of nematicidal iridoid sweroside from Alstonia scholaris. J Entamol Nematol 5:19–23CrossRefGoogle Scholar
  209. Sultana N, Saify ZS, Saleem M et al (2013b) Two new triterpenes from Alstonia scholaris flowers. Nat Prod Res 27:37–41CrossRefGoogle Scholar
  210. Tatsis EC, Carqueijeiro I, de Bernonville TD et al (2017) A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate. Nat Commun 8(1):316PubMedPubMedCentralCrossRefGoogle Scholar
  211. Teng CM, Yu SM, Ko FN et al (1991) Dicentrine, a natural vascular al-adrenoceptor antagonist, isolated from Lindera megaphylla. Br J Pharmacol 104:651–656PubMedPubMedCentralCrossRefGoogle Scholar
  212. Teotia UVS, Mishra AK, Kumar R et al (2014) Antiasthmatic potential of some medicinal plants. Asian Pac J Heal Sci 1(3):155–161CrossRefGoogle Scholar
  213. Thomas PS, Kanaujia A, Ghosh D et al (2008) Alstonoside, a secoiridoid glucoside from Alstonia scholaris. Ind J Chem Sect B 47:1298–1302Google Scholar
  214. Topcu G, Che CT, Cordell GA et al (1990) Iridolactones from Alyxia reinwardti. Phytochemistry 29(10):3197–3199CrossRefGoogle Scholar
  215. Uddin MZ, Hassan MA, Sultana M (2006) Ethnobotanical survey of medicinal plants in Phulbari Upazila of Dinajpur District, Bangladesh. Bangl J Plant Taxon 13(1):63–68CrossRefGoogle Scholar
  216. Vedavathy S, Sudhakar A, Mrdula V (1997) Tribal medicinal plants of Chittoor. Anc Sci Life 16(4):307–331PubMedPubMedCentralGoogle Scholar
  217. Vikneshwaran D, Viji M, Lakshmi KR (2008) A survey of the ethnomedicinal flora of the Sirumalai Hills, Dindugul District, India. Ethnobot Leafl 12:948–953Google Scholar
  218. Wang F, Ren FC, Liu JK (2009) Alstonic acids A and B, unusual 2,3-secofernane triterpenoids from Alstonia scholaris. Phytochemistry 70:650–654PubMedCrossRefGoogle Scholar
  219. Wang CM, Chen HT, Wu ZY et al (2016a) Antibacterial and synergistic activity of pentacyclic triterpenoids isolated from Alstonia scholaris. Molecules 21(2):1–11Google Scholar
  220. Wang CM, Jhan YL, Tsai SJ et al (2016b) The pleiotropic antibacterial mechanisms of ursolic acid against methicillin-resistant Staphylococcus aureus (MRSA). Molecules 21(7):1–13Google Scholar
  221. Wang CM, Yeh KL, Tsai SJ et al (2017) Anti-proliferative activity of triterpenoids and sterols isolated from Alstonia scholaris against non-small-cell lung carcinoma cells. Molecules 22:1–13Google Scholar
  222. Wang B, Dai Z, Yang XW et al (2018) Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits of Alstonia scholaris. Phytomedicine 48:170–178PubMedCrossRefGoogle Scholar
  223. Waterman P, Zhong S (1982) Vallesiachotamine and isovallesiachotamine from the seeds of Strychnos tricalysioides. Planta Medica 45(05):28–30PubMedCrossRefGoogle Scholar
  224. Warrier PK, Nambiar VPK (1993) Indian medicinal plants: a compendium of 500 species, vol 1. Orient Blackswan, HyderabadGoogle Scholar
  225. Wei C, Huili T (2004) Dripping pills of folium Alstoniae scholaris and its preparation process. CN1989987A. 04 July 2004Google Scholar
  226. Wei X, Dai Z, Yang J et al (2018) Unprecedented sugar bridged bisindoles selective inhibiting glioma stem cells. Bioorg Med Chem 26:1776–1783PubMedCrossRefGoogle Scholar
  227. WIPO (2017) World Intelluctual Property. https://www.wipo.int/portal/en/index.html
  228. Wongseripipatana S, Chaisri L, Sritularak B et al (2004) Indole alkaloids from the fruits of Alstonia scholaris. Thai J Pharm Sci 28:173–180Google Scholar
  229. Wright CW, Allen D, Cai Y et al (1992) In vitro antiamoebic and antiplasmodial activities of alkaloids isolated from Alstonia angustifolia roots. Phytother Res 6(3):121–124CrossRefGoogle Scholar
  230. Wright CW, Allen D, Phillipson JD, Kirby GC, Warhurst DC, Massiot G, Le Men-Olivier L et al (1993) Alstonia species: are they effective in malaria treatment? J Ethnopharmacol 40(1):41–45PubMedCrossRefGoogle Scholar
  231. Xiaodong L, Jianhua S, Xiaojiang H et al (2011) Medicine for treating diseases concerned with respiratory and preparation method and application thereof. CN101084951B. 16 Mar 2011Google Scholar
  232. Xiaodong L, Yunli Z, Jianhua S et al (2017) Pharmaceutical composition for treating respiratory diseases. WO2017080485A1. 18 May 2017Google Scholar
  233. Xu Y, Feng T, Cai XH et al (2009) A new C13-norisoprenoid from leaves of Alstonia scholaris. Chin J Nat Med 7:21–23CrossRefGoogle Scholar
  234. Yamauchi T, Abe F, Chen RF et al (1990a) Alkaloids from the leaves of Alstonia scholaris in Taiwan, Thailand, Indonesia and the Philippines. Phytochemistry 29:3547–3552CrossRefGoogle Scholar
  235. Yamauchi T, Abe F, Padolina WG et al (1990b) Alkaloids from leaves and bark of Alstonia scholaris in the Philippines. Phytochemistry 29:3321–3325CrossRefGoogle Scholar
  236. Yang XW, Yang CP, Jiang LP et al (2014) Indole alkaloids with new skeleton activating neural stem cells. Org Lett 16:5808–5811PubMedCrossRefGoogle Scholar
  237. Yang XW, Luo XD, Lunga PK et al (2015) Scholarisines H-O, novel indole alkaloid derivatives from long-term stored Alstonia scholaris. Tetrahedron 71:3694–3698CrossRefGoogle Scholar
  238. Yang L, Yang C, Li C et al (2016a) Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants. Sci Bull 61:3–17CrossRefGoogle Scholar
  239. Yang Z, Sun L, Liang C et al (2016b) Simultaneous quantitation of the diastereoisomers of scholarisine and 19-epi-scholarisine, vallesamine, and picrinine in rat plasma by supercritical fluid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study. J Sep Sci 1:1–9Google Scholar
  240. Yang J, Fu J, Liu X et al (2018) Monoterpenoid indole alkaloids from the leaves of Alstonia scholaris and their NF-κB inhibitory activity. Fitoterapia 124:73–79PubMedCrossRefGoogle Scholar
  241. Yodkeeree S, Pompimon W, Limtrakul P (2014) Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products. Tumor Biol 35:8615–8624CrossRefGoogle Scholar
  242. Yodkeeree S, Ooppachai C, Pompimon W et al (2018) O-Methylbulbocapnine and dicentrine suppress LPS-induced inflammatory response by blocking NF-κB and AP-1 activation through inhibiting MAPKs and Akt signaling in RAW264.7 macrophages. Biol Pharm Bull 41(8):1219–1227PubMedCrossRefGoogle Scholar
  243. Yu HF, Huang WY, Ding CF et al (2018) Cage-like monoterpenoid indole alkaloids with antimicrobial activity from Alstonia scholaris. Tetrahedron Lett 59(31):2975–2978CrossRefGoogle Scholar
  244. Yusuf M, Wahab MA, Chowdhury JU et al (2006) Ethno-medico-botanical knowledge from Kaukhali proper and Betbunia of Rangamati District. Bangl J Plant Taxon 13(1):55–61CrossRefGoogle Scholar
  245. Zhang L, Zhang CJ, Zhang DB et al (2014) An unusual indole alkaloid with anti-adenovirus and anti-HSV activities from Alstonia scholaris. Tetrahedron Lett 55:1815–1817CrossRefGoogle Scholar
  246. Zhao YL, Yang ZF, Shang JH et al (2018) Effects of indole alkaloids from leaf of Alstonia scholaris on post-infectious cough in mice. J Ethnopharmacol 218:69–75PubMedCrossRefGoogle Scholar
  247. Zhou H, He HP, Luo XD et al (2005) Three new indole alkaloids from the leaves of Alstonia scholaris. Helv Chim Acta 88:2508–2512CrossRefGoogle Scholar
  248. Zhu WM, He HP, Fan LM et al (2005) Components of stem barks of Winchia calophylla A. DC. and their bronchodilator activities. J Integr Plant Biol 47:892–896CrossRefGoogle Scholar
  249. Zhu GY, Yao XJ, Liu L et al (2014a) Alistonitrine A, a caged monoterpene indole alkaloid from Alstonia scholaris. Org Lett 16(4):1080–1083PubMedCrossRefGoogle Scholar
  250. Zhu X, Zeng X, Sun C et al (2014b) Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus. Front Med 8(3):285–293PubMedCrossRefGoogle Scholar
  251. Zhu XX, Fan YY, Xu L et al (2019) Alstonlarsines A–D, four rearranged indole alkaloids from Alstonia scholaris. Org Lett 21(5):1471–1474PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2020

Authors and Affiliations

  1. 1.Department of Natural ProductsNational Institute of Pharmaceutical Education and Research-AhmedabadPalaj, GandhinagarIndia

Personalised recommendations