CRINUM; AN ENDLESS SOURCE OF BIOACTIVE PRINCIPLES: A REVIEW. PART IV: NON-ALKALOIDAL CONSTITUENTS

CRINUM; AN ENDLESS SOURCE OF BIOACTIVE PRINCIPLES: A REVIEW. PART IV: NON-ALKALOIDAL CONSTITUENTS

John Refaat*¹, Mohamed S. Kamel ¹, Mahmoud A. Ramadan ² and Ahmed A. Ali ²

Pharmacognosy Department, Faculty of Pharmacy, Minia University ¹, 61519 Minia, Egypt

Pharmacognosy Department, Faculty of Pharmacy, Assiut University ², 71515 Assiut, Egypt

ABSTRACT: Crinum is an important and fascinating genus of the large and equally captivating Amaryllidaceae family. Owing to the valuable biological effects and therapeutic potentials of its chemical constituents, many Crinum species have a worldwide folkloric reputation. Additionally, Crinum species have been subjected to extensive chemical, cytological and pharmacological investigations. The present part of our comprehensive review work on the phytochemical and biological studies conducted on Crinum plants reviews the non-alkaloidal principles isolated up till now in addition to their distribution in different Crinum species.

Amaryllidaceae, Crinum, Non-Alkaloidal Constituents

INTRODUCTION: Crinums are herbaceous plants with large tunicated bulbs which produce a neck or a pseudostem made up of the sheathing bases of the old leaves ¹. There are about 130 species of Crinum worldwide, occurring in America, Africa, southern Asia and Australia. This genus is related to a group of mostly southern African endemic genera, constituting the tribe Amaryllideae and about twenty-two species at present are recognized in southern Africa ². Larger in stature than most other Amaryllidaceae species, most Crinums are suitable as landscape plants. Furthermore, Crinum species have been used traditionally to cure ailments and diseases throughout the world and some of the most noted effects are analgesic, anticholinergic, antitumour and antiviral ³.

Recently, galanthamine has been registered as an acetylcholinesterase inhibitor, which is an important approach in treating Alzheimer's disease ⁴. Since about 1950s, Crinums have been subjected to extensive chemical and biological investigations due to their richness in pharmacologically active principles, especially alkaloids whereas the non-alkaloidal constituents received much less attention ⁵. Therefore, in continuation of our comprehensive review work regarding both the alkaloidal and non-alkaloidal principles of Crinums as well as their biological activities, the present part of our work concentrates on the non-alkaloidal constituents (Table 1 and Figure 1) isolated so far together with their structural and stereochemical differences. Additionally, their distribution in various species is also completely considered.

Volatile Constituents of Crinum: In addition to the non-alkaloidal compounds mentioned in Table 1, the volatile constituents of some Crinum plants were analyzed using GC/MS technique and several compounds belonging to different structural types were identified as follows:

The volatiles of C. latifolium L. leaves were found to contain n-hexadecane, n-heptadecane, n-octadecane, 2-methyl hexadecane, tetramethyl pentadecane, tetramethyl hexadecane, decylbenzene, phenanthrene, phytol, phenol, cyanophenol, o-cresol, p-cresol, acetal- dehyde, nonanal, benzaldehyde, hexahydro farnesyl acetone, acetic acid, 2,2-dimethyl propanoic acid, nonanoic acid, benzoic acid, formamide, N-methyl-N-phenyl-formamide, N,N-diphenyl-formamide and N-propyl benzamine ⁶.

Similarly, the volatile constituents of C. asiaticum L. leaves were found to contain 2,2-diethoxy ethyl benzene, glycerin, phytol, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, 3-octyn-1-ol, octahydro-azocine, n-hexadecanoic acid, dodecanoic acid, (Z, Z)-9,12-octadecadienoic acid, (Z, Z, Z)-9,12,15-octadecatrienoic acid, (+)-2-piperidinecaboxylic acid, n-hexadecanoic acid ethyl ester, 9,12-octadecadienoic acid ethyl ester, 5-hydroxymethyl-2-furancarboxaldehyde, 4H-pyran-4-one-2, 3-dihydro-3, 5-dihydroxy-6-methyl, 1-mono linoleoyl glycerol trimethylsilyl ether, 2-amino-9,10-anthracenedione, 1H-azonine octahydr-1-nitroso, 2-methyl-N-1-butanamine, β-D-glucopyranose and farnesyl-β-D-mannofuranoside ⁷.

Moreover, the volatile oil of C. asiaticum L. flowers were found to contain n- pentacosanol, n-octacosanol, n-nonadecanol, n-nonacosanol, butylated hydroxy toluene, eugenol, isoeugenol and 1,2-benzene dicarboxylic acid dibutyl ester ⁸. In another study, the volatile oil of C. ornatum Ait. bulbs were found to contain 2,4-dimethyl hexane, nonacosane, eicosane, heneicosane, 2, 6, 10, 15-tetramethylheptanedecane, tetratriancontane, tetratetracontane, Cis-1,3-dimethyl cyclohexane, methyl benzene, Cis-decahydro naphthalene, trans-decahydronaphthalene, caryo phyllene, dodecanoic acid, n-hexanedecanoic acid, 9, 12-octadecadienoic acid, undecanoic acid ethyl ester, eicosanoic acid ethyl ester and 14-methylpentane decanoic acid methylester ⁹.

TABLE 1: A LIST OF NON-ALKALOIDAL COMPOUNDS ISOLATED FROM DIFFERENT CRINUM SPECIES

FIGURE 1: NON-ALKALOIDAL COMPOUNDS ISOLATED FROM DIFFERENT CRINUM SPECIES

CONCLUSION: During the last decade, Crinum specieshave widely attracted the attention of phytochemists. The extensive survey of literature demonstrated that the chemical analyses of Crinums have yielded a vast array of phytocompounds including about 180 bases belonging to different types of Amaryllidaceae alkaloids. The phytochemical studies were primarily concentrated on alkaloids, while the non-alkaloidal constituents were only touched limitedly. Crinine-, lycorine- and tazettine-types were found to be the most common groups among the isolated alkaloids.

On the other hand, despite being less considered in phytochemical investigations, about 100 non-alkaloidal compounds representing eleven different structural classes were isolated and identified. The non-alkaloidal constituents isolated so far were represented by a number of flavonoids, chromones, coumarins, terpenoids, steroids, simple glycosides, ionones, alcohols, aldehydes, ketones, acids, esters and long chain hydrocarbons. Phenolics prevail among the non-alkaloidal constituents identified. Moreover, analysis of the volatiles prepared from some Crinum species revealed their richness in various compounds belonging to different structural types.

That's why, Crinum plants seem to be an endless source of bioactive principles, especially Amaryllidaceae alkaloids.

REFERENCES:

1. Hutchinson J: The Genera of flowering plants. The claredon press, Oxford, Vol. I, 1964:43.
2. Snijman D and Linder HP: Phylogenetic relationships, seed characters, and dispersal system evolution in Amaryllideae (Amaryllidaceae). Annals of Missouri Botanical Garden 1996; 83:362–386.
3. Fennell CW and Van Staden J: Crinum species in traditional and modern medicine. Journal of Ethnopharmacology 2001; 78(1):15–26.
4. Jäger AK, Adsersen A and Fennell CW: Acetylcholinesterase inhibition of Crinum sp. South African Journal of Botany 2004; 70(2):323–325.
5. Wildman WC: The Alkaloids: Chemistry and Physiology. Edited by R.H.F. Manske, Academic Press, New York, London, Vol. VI, 1960.
6. Tram NT, Kamenarska Z, Handjieva N, Bankova V and Popov SS: Volatiles from Crinum latifolium. Journal of Essential Oil Research 2003; 15(3):195–197.
7. Ilavenil S, Kaleeswaran B and Ravikumar S: Evaluation of antibacterial activity and phytochemical analysis of Crinum asiaticum. International Journal of Current Research 2010; 1:35–40.
8. Refaat J, Mohamed SK, Ramadan MA and Ali AA: GC-MS studies of Crinum asiaticum L. Leaves and Flowers. Research Journal of Pharmacognosy and Phytochemistry 2011; 3(5): 232-235.
9. Oloyede KG, Oladosu IA and Shodia AF: Chemical composition and cytotoxicity of the essential oils of Crinum ornatum (Ait.) Bury. African Journal of Pure and Applied Chemistry 2010; 4(3):35–37.
10. Nam NH, Kim Y, You YJ, Hong DH, Kim HM and Ahn BZ: New constituents from Crinum latifolium with inhibitory effects against tube-like formation of human umbilical venous endothelial cells. Natural Products Research 2004; 18(6):485–491.
11. Ali AA, Sayed HM, Abdallah OM and Steglich W: Flavans from Crinum americanum. Pharmazie 1988; 43(4):295–296.
12. Mohamed SR: A pharmacognostical study of Crinum asiaticum L. cultivated in Egypt. A Thesis for Master Degree submitted to Assiut University, Egypt, 2000.
13. MinBS, Gao JJ, Nakamura N, Kim YH and Hattori M: Cytotoxic alkaloids and a flavan from the bulbs of Crinum asiaticum var. japonicum. Chemical PharmaceuticalBulletin (Tokyo) 2001; 49(9):1217–1219.
14. Ali AA, Ramadan MA and Abdel-Hafiz MA: Pyrrolophenanthridone alkaloids from Crinum augustum Rox. bulbs. Bulletin of Pharmaceutical Sciences (Assiut University) 1988; 11(2):273–280.
15. Ramadan MA: Phytochemical investigation of the minor alkaloids and phenolic compounds of Crinum bulbispermum Milne. and Crinum augustum Rox. cultivated in Egypt. A Thesis for Ph.D. Degree submitted to Assiut University, Egypt, 1986.
16. Kamel MS: Non-alkaloidal compounds from bulbs of Crinum moorei.Bulletin of Pharmaceutical Sciences (Assiut University) 1996; 19:63–65.
17. Kissling J, Ioset JR, Marston A and Hostettmann K: Bio-guided isolation of cholinesterase inhibitors from the bulbs of Crinum powellii. Phytotherapy Research 2005; 19(11):984–987.
18. Nam NH and Vung NT:  Isolation and structural elucidation of two flavonoids from Crinum latifolium. Tap Chi Duoc Hoc [Pharm J Hanoi] 2006; 7–9.
19. Ramadan MA, Kamel MS, Ohtani K, Kasai R and Yamasaki K: Minor phenolics from Crinum bulbispermum Miln. bulbs. Phytochemistry 2000; 54(8):891–896.
20. Abd El-Hafiz MA, Ramadan MA and Anton R: Minor phenolic constituents of Crinum augustum. Journal of Natural Products 1990; 53(5):1349–1352.
21. Khalifa AA: Non-alkaloidal constituents from Crinum bulbispermum bulbs. Bulletin of Pharmaceutical Sciences (Assiut University) 2001; 24(1):41–46.
22. Abou Donia AH, Abou-Ela MA, Hammoda HM and and Kashaba AA: Flavonol glucosides from the flowers of Crinum bulbispermum. Alexandria Journal of Pharmaceutical Science 2005; 19(2):153–157.
23. Ali AA, El-Moghazy, AM, Ross SA and El-Shanawany MA: Phytochemical studies on some Amaryllidaceae plants cultivated in Egypt. Fitoterapia 1981; 52(5): 209–212.
24. Nam N H and Jae YY: NF-κB Inhibitory activities of the methanol extracts and some constituents therein of some Vietnamese medicinal plants.Scientia Pharmaceutica 2009; 77:389–399.
25. Pousset JL and Poisson J: Vomifoliol, alcool terpenique isole des feuilles du Rauwolfia vomitoria afz. Tetrahedron Letters 10(15):1173–1174.
26. Tram NT, Titorenkova T, Bankova V, Handjieva N and Popov SS: Crinum L. Amaryllidaceae. Fitoterapia 2002; 73(3):183–208.
27. Refaat J: Phytochemical and biological studies of Crinum augustum Rox. and Crinum asiaticum L. family Amaryllidaceae cultivated in Egypt, A Thesis for Master Degree submitted to Minia University, Egypt, 2009.
28. Refaat J, Abdel-Lateff AA, Kamel MS, Ramadan MA, Okino T and Nogata Y: Antifouling alkaloids from Crinum augustum (Amaryllidaceae). Pharmacognosy Research 1(2):43–52.
29. Takagi S and Yamaki M: On the constituents of the bulbs of Crinum asiaticum var. japonicum Bak. On the neutral constituents. Yaku Zasshi 1977; 97(10):1155.
30. Abd El-Hafiz MA: Two keto alcohols from Crinum augustum. Phytochemistry 1990; 29 (12):3936–393.
31. Nkanwen ER, Gatsing D, Ngamga D, Fodouop SP and Tane P: Antibacterial agents from the leaves of Crinum purpurascens herb (Amaryllidaceae). African Health Sciences 2009; 9(4):264–269.
32. Ramadan MA: Investigation of petroleum ether extract of the bulbs of Crinum augustum Rox. Bulletin of Pharmaceutical Sciences (Assiut University) 1998; 21(2):97–102.
33. Likhitwitayawuid K, Ruangrungsi N and Cordell GA: Amabiloside, a new glycoside from Crinum amabile. Natural Products Letters 1993; 3(1):1–4.
34. Abdel-Halim OB, Marzouk A, Mothana R and Awadh N: A new tyrosinase inhibitor from Crinum yemense as potential treatment for hyperpigmentation. Pharmazie 2008; 63(5):405–407.
35. Watt J and Breyer-Brandwijk M: The medicinal and poisonous plants of southern and eastern Africa: Being an account of their medicinal and other uses, chemical composition, pharmacological effects and toxicology in man and animal. E. & S. Livingstone, 2^nd edition, 1962.
36. Abd El-Hafiz MA: Aliphatic hydroxy ketones from Crinum augustum. Phytochemistry 1991; 30(9):3127–3129.
37. Sun Q, Shen Y, Tian J, Tang J, Su J, Liu R, Li H, Xu X and Zhang W: Chemical constituents of Crinum asiaticum L. var. sinicum Baker and their cytotoxic activities. Chemistry and biodiversity 2009; 6(10):1751–1757.
38. Elgorashi EE, Drewes SE and Van Staden J: Alkaloids from Crinum macowanii. Biochemical Systematics and Ecology 2001; 29(7):749–750.
39. El-Moghazi AM and Ali AA: Investigation of the alkaloidal constituents of Crinum bulbispermum.Part II. Isolation andidentification of crinamine, and other three alkaloids.Planta Medica 1976; 29(2):156–159.
40. Tram NT, Mitova M, Bankova V, Handjieva N and Popov SS: GC-MS of Crinum latifolium L. Alkaloids. Zeitschrift für Naturforschung 2002; 57c:239–242.
41. Bordoloi M, Kotoky R, Mahanta JJ, Sarma TC and Kanjilal PB: Anti-genotoxic hydrazide from Crinum defixum. European Journal of Medicinal Chemistry 2008; 44(6):2754-2757.
42. Abd El-Hafiz MA and Mesbah AM: Investigation of mucilages and fatty acids of Crinum augustum Rox. and Crinum americanum L. Egypt Journal of Pharmaceutical Sciences 1984; 25(1–4):171–178.
43. Miyake T, Yamaoka R and Yahara T: Floral scents of hawkmoth-pollinated flowers in Japan. Journal of Plant Research 1998; 111:199–205.
44. Murav^'eva DA and Popova OI: Polysaccharides of Cochicum speciosum and Crinum amabile. Khimiko Farmatsevticheskii Zhurnal 1989; 23(5):619–620.
45. Yasuda H, Shitoh T, Yamano T, Itoh Y and Shimura S: Identification of neokestose produced from sucrose by an enzyme of Penicillium oxalicum. Agricultural Chemical Society of Japan (Tokyo) 1986; 50(3):777–778.
46. Tomoda M, Shimizu N, Shimada K and Suga M: Isolation and structural features of two glucans from the rhizomes of Crinum latifolium. Chemical Pharmaceutical Bulletin 33:16–21.
47. Ghosal S, Shanthy A, Das PK, Mukhopadhyay M and Sarkar M: Mast cell stabilizing effect of glucan A and phosphatidyllycorine isolated from Crinum latifolium. Phytotherapy Research 1988; 2(2): 76–79.
    

    ---

    How to cite this article:

    Refaat J, Kamel SM, Ramadan MA and Ali AA: Crinum; An Endless source of Bioactive principles: A Review. Part IV: Non-alkaloidal constituents. Int J Pharm Sci Res. 2013; 4(3); 941-948.

    ---