Vasaka
Jennifer Dysart
Used by Permission. Copyright Dr. Ajay Padmawar, Amruta Herbals Pvt. Ltd.
As the study of medicine propels itself through time, the scope of pharmocology has stretched between laboratory biosynthesis and drug isolation from natural resources. Natural medicine has a practical side; but it is often popularized in the race for cures . One can not help but be enticed by the thought that a simple backyard plant may hold the key to nature's miracles. In countries such as India, plant medicine has connected a large spiritual and cultural heritage, like Ayurveda (Sanskrit for "the science of life")[1], spanning millenia. A hardy shrub, commonly known as Vasaka, is a plant of wide medicinal value in several such cultures. Vasaka has been well studied and used for centuries as a multifunctional medication and resource[2].
Vasaka enjoys a plethora of names from many countries and in just as many tongues. This is in addition to the traditional botanical and medical naming systems. Vasaka belongs to the plant family Acanthaceae, its botanical/taxonomic name is Justicia adhatoda L. [3]Some of its synonyms are Adhatoda vasica and Adhatoda zeylanica(Medicus). Vasaka appears to be the most common name for this plant; but additional names, to name a few are: Malabarnut, Arusa, Vasa, Adhatodai,Basak, and Bansa. [4]Though the preceding names were not translated, just like in slang terminology, it is also common for localities to form their own names of plants, animals, etc. in a native language.
The Vasaka plant classifies as a perennial and evergreen plant, meaning that the plant lives for multiple seasons and retains its leaves throughout the year.[5] A shrub, the plant consists of abundant sprays of long green lanceolate (tapers from a rounded base) leaves typically 5-30cm long. Vasaka can grow quite tall, reportedly 1.2-6 meters in height. Vasaka bears a wide berth as it has multiple stems and leaves. Vasaka also produces white blossoms.The flowers are pink-veined (some pink spotting too) and bloom in bunches that cascade along the stem.[2] Vasaka produces its flowers and then prune-shaped fruits through the months of August to November. [6]
Vasaka has taken to several temperate and tropical regions in the East, native mainly throughout India. Vasaka also originates in Nepal, Pakistan, Sri Lanka, China, Vietnam, Indonesia, the Himalayas, and Malaysia. Vasaka is sometimes grown for asthetic purposes or for soil enrichment; but often the plant is simply harvested from the wild.[3] As supported by its wide dispersment, Vasaka is not too picky about its soil. It is content to inhabit even wastelands or higher altitudes, up to 1300 m. [2] Like many plants, Vasaka prefers loamy soil,[7] which is a soil that has an "equal amounts of sand, silt, and clay" for a balance of ventilation and moisture.[8]
This plant has a handful of medicinal uses, to name a few, mainly antispasmodic,fever reducer, anti-inflammatory,anti-bleeding,brochodilating (opens the breathing passages), antidiabetic, disinfectant, anti- jaundice, assistance in uterine contractions, and expectorant(promotes easier flow of mucous). Most of these attributes fall mainly into the repiratory therapy category for colds, asthma, bronchitis, tuberculosis, etc. The antispasmodic and antiinflammatory properties apply to diarrhea, arthritis, vomiting, and gingivitis. The leaves are a source of Vitamin C as well. The entire plant has been put to some use, either in parts or in its entirety. The plant is administered orally, locally, or inhaled in various bitter-tasting forms such as oils, alcohols, cigarrettes, paste, or juice. The roots, or leaves and stems are often ground up into a powder as the leaves are vert brittle when dry. Oral concoctions are commonly derived from boiling the leaves, stems, roots, or any combination desired; sometimes with a bit of salt or honey to dilute the bitter taste.Most sources claim no side effects known, but common sense dictates that an individual should refrain from copius overdoses, and pregnant women should avoid the drug as large doses can cause termination of the preganancy.[9],[10],[11],[12],[13]. Recommended dosages vary, but some directions call for: 3 boiled leaves in 1 cup of water, 1/2 cup 3 to 4 times dail; or 1/2 tsp of a more concentrated blend of leaves pulverized with a small amount of water, or 1 -2g diluted to 1-4 mL.[4],[11]
Used by Permission. Copyright Dr. Ajay Padmawar, Amruta Herbals Pvt. Ltd.
Vasaka contains several active ingredients, the main one of which is the alkaloid vasicine, which is responsible for much of the bronchodilating effect of Vasaka. Vasicine is mainly derives from the leaves of the plant, along with an essentail oil as well. Vasicine concentration reportedly varies throughout the year, seeming to peak during the flowering and fruit season ofJune-September. [4] Vasicine also goes by another name, peganine. Vasicine's systematic name is 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-ol, however the name Vasicine is used almost exclusively in the popular and scientific sectors.[14] Vasicine and vasicinone are also subject to the effects of chirality and reportedly preferred by nature in the l-forms as opposed to a racemic mix. [4] Other important active ingredients contained in the stems and roots include vasicinol and the alkaloid vasicinone. Some other, less active chemicals present in the roots are quinazoline, anisotine, vasicol, vasicinolone, and adhatodine.[4],[13]
Left Image: ACDLabs ChemSketch derived 2D structures of vasicine stereoisomers, Far Right: 3D rendering of (-)-vasicine, Middle: (+)-vasicine
The major active ingredient of Vasaka is vasicine, as previously mentioned, the (-) (3S- or l-) stereoisomer appears to be the active form isolated from the Vasaka plant. The (+) form is peganine and is isolated from a different plant species. However, in lab synthesis both forms tend to be produced. The structure of vasicine,C11H12N2 O, was a combined effort of several scientists, namely Spath, etal. ; Morris, etal.; and Hanford, etal. The resulting structure deduced as in the above figures. [15],[16],[17]The final stereochemistry of the chiral carbon was finally deduced with x-ray chrystallography by Joshi[18]
Isolations of vasicine from the plant follows a procedure concerned with separating the alkaloid components from the plant extract, and then separating vasicine from that fraction. The process begins with pulverizing the dry plant leaves into a powder. The powder is refluxed in alcohol (90%), and then elaborately separated from the rest of the plant mass. The alkaloids in the leaves (vasicine and vasicinone) are painstakingly filtered and washed repeatedly in hot water, and then chloroform. The extract is subjected to a series of filtrations and extractions involving distilled water, chloroform, base (caustic soda), and acid (HCl) to achieve the desired separation of alkaloids. The resulting extract is further separated by partition chromatography, eluting with chloroform. The crude vasicine is purified by dissolving in chloroform and passing through an alumina column. Other extraction techniques included similar methods, but some with further separations phases and recrystallizations without column chromatography. [19],[20].
Spath performed the earliest mentioned syntheses in 1934-1935, and several research groups have modified and optimized the synthesis to date.Spath's original journal article proves incredibly difficult to find, and is in German; but other synthesis journal articles cite and discuss his work extensively. [16]Subsequent modifications have been performed in efforts to derive new compounds with desired properties, such as halogenation or oxidation via hydrogen peroxide. [15] [21] Spath's first synthesis involved reacting α-hydroxy-γ-aminobutyrate with o-nitrobenzyl chloride, which produced l-(o-nitrobenzyl)-3-hydroxy-2-oxopyrrolidine. That compound was then mixed with "stannous chloride in HCl, which reduced the nitro and spontaneous cyclization with dehydration to give 35% yield of dl-vasicine." [16] A more recent synthesis was performed by Wasserman and Parr, whom have worked on novel syntheses involving intramolecular reactions of vinyl tricarbonyls and amines; such as o-aminobenzylamine with a tricabonyl vinyl compound, tert-butyl 2,3-dioxopent-4-enoate,in the presence of CHCl3 at 20° C for 2 hrs. In this reaction, the "primary amino group behaved as a dinucleophilic agent." This is followed by a series of intramolecular reactions and electron rearrangements when each intermediate was treated with SiO2, then NaBH4, then TFA (40° C), to yield the tricyclic Vasicine product in its racemic form. [22].
In determining vasicine's characterization data, some properties were well-reported, while others proved difficult or impossible to find through journal searches. Properties such as the melting point is common as it is used extensively for identification in separation and synthesis procedures. The melting point of purified l-vasicine has typically been reported at 195-196°C and 197-198°C.[19][23] Data such as refractive index, boiling point, and IR spectra of pure vasciine were absent in the available journal literature. The absence of boiling point and refractive index data were likely due to the fact that much of the work with vasicine is done with the solid form and some work suggests vasicine decomposes upon melting; which would imply no real boiling point. [16]
1HNMR of l-vasicine showed signals for 1 l-vasicine: δ6.8-7.3 for the four aromatic protons, a triplet(1 H) at δ4.80, two proton multiplets (2H's, C-1 and C-2)at δ2.80 and δ3.50 and a singlet (2H's at C-9)at δ4.62. 13C NMR displayed shifts for the following positions: 1=δ48.1, 2=δ28.8, 3=δ70.2, 3a-δ163.9, 4a=δ142.3, 5=δ123.6, 6=δ128.3, 7=δ124.0, 8=δ125.7, 8a=δ119.0, 9=δ47.0. Position number refer to numbering beginning at the uppermost right Carbon position on the 5 membered ring, numbering clockwise from that position about the tricyclic compound.[20] IR spectra obtained through journal literature search, but not for the pure form of vasicine. One study of the Hydrogen chloride complexed-peganine ((+)-vasicine), which should be very similar in basic major peaks to (-)-vasicine, depicts the expected characteristic peaks: strong broad maximum at 3448 cm-1 for the hydroxyl group, and some peaking for the N-H+ bond at 2883-2989 cm -1. However, the presence of the complex and not the pure compound will add some extra peaks and shift the spectrum. [24] The Mass spec. (m/z) data from literature sources indicate an M+ peak at 188.[23]Other Interesting Facts
Vasaka has more than just medicinal purposes, some people use it as an herbicide. The resin in the leaves deters crop insects. As a testament to the diversity of this single plant, the demand for Vasaka in India is a reported whopping 500 tons a year.[4],[9]
Bibliography
[1] Sanatan Society:What is Ayurveda? Retrieved March 6, 2008, from http://www.sanatansociety.org/ayurveda_home_remedies/what_is_ayurveda.htm
[2] International Centre for Science and High Technology:Adhatoda zeylanica Medic.Retrieved October 6, 2008, from http://www.ics.trieste.it/MAPs/MedicinalPlants_Plant.aspx?id=572.
[3] USDA/Germplasm Resources Information Network:Justicia adhatoda information from NPGS/GRIN. Retrieved October 1, 2008, from http://www.ars-grin.gov/cgi-bin/npgs/html/taxon.pl?20895
[4]Herbalnet: Adhatoda zeylanica. Retrieved September 29, 2008, from http://www.herbalnet.org/leaf/adhatoda%20zeylanica.htm
[5]Master Gardener,Ohio State University Extension:Botany. Retreived October 6, 2008, from http://www.hcs.ohio-state.edu/mg/manual/botany4.htm
[6]Department of Botany: Floristic Survey of the Institute of Science Campus, Mumbai, Maharashtra State. Retrieved October 4, 2008, from http://iscmumbai.maharashtra.gov.in/floristic%20survey.html
[7] Foundation for Revitalisation of Local Health Status of Commercially Important Medicinal Plant Species of the Project Area of Andhra Pradesh Community Forest Management Project. Retrieved october 4, 2008, from http://forest.ap.nic.in/JFM%20CFM/CFM/Special%20Reports/FRLHT/Reports/06.%20APCFProp.pdf
[8]Purdue University Consumer Horticulture: What is Loam? Retrieved October 6, 2008, from http://www.hort.purdue.edu/ext/loam.html
[9]C. Kameswara Rao: Adhatoda zeylanica. Retrieved September 29, 2008, from
[10]U Kyaw Tun, U Pe Than, and staff of TIL:Myanmar Medicinal Plant Database. Retrieved October 3, 2008, from http://www.tuninst.net/MyanMedPlants/TIL/famA/Acanthaceae.htm#Adhatoda-vasica
[11]Sakthi Foundation:Adhatoda. Retrieved October 2, 2008, from http://herbs.sakthifoundation.org/Adhatoda.htm
[12]Indus Herbal Extracts:Adhatoda Vasica. Retrieved October 6, 2008, from http://www.indusextracts.com/adhatoda-vasica.htm
[13]Center of Excellence for Medicinal Plants in Sri Lanka: Adhatoda vasica (Nees). Retrieved October 6, 2008, from http://www.agri.ruh.ac.lk/medicinalplants/medicinal_plants/families/acanthaceae/plants/ada_thoda.html
[14]Chemspider.com:http://www.google.com/search?q=InChI=1/C11H12N2O/c14-10-5-6-13-7-8-3-1-2-4-9(8)12-11(10)13/h1-4,10,14H,5-7H2. Retrieved October 6, 2008, from http://www.chemspider.com/InChIKey=YIICVSCAKJMMDJ-UHFFFAOYAL
[15]Morris, R.C, P., Hanford, W.E., and Adams, R. J. Am. Chem. Soc., 1935, 57, 5."Structure of Vasicine. III. Position of the Hydroxyl Group".http://mutex.gmu.edu:2314/cgi-bin/archive.cgi/jacsat/1935/57/i05/pdf/ja01308a052.pdf;DOI: 10.1021/ja01308a052
[16]Southwick, P.L. and Casanova, J. J. Am. Chem. Soc., 1958, 80, 5."A New Synthesis of dl-Vasicine and a Methoxy Analog'".http: //mutex.gmu.edu:2314/cgi-bin/archive.cgi/jacsat/1958/80/i05/pdf/ja01538a039.pdf;DOI: 10.1021/ja01538a039
[17] Hanford, W.E., Liang, P., and Adams, R. J. Am. Chem. Soc., 1934, 56, 12."The Constitution of Vasicine".http://mutex.gmu.edu:2314/cgi-bin/archive.cgi/jacsat/1934/56/i12/pdf/ja01327a078.pdf;DOI: 10.1021/ja01327a078
[18]Joshi, B.S., Newton, M.G., Lee, and D.W. Tetrahedron: Asymmetry, 1996, 7, 1."Reversal of Absolute Stereochemistry of the Pyrrolo[2,1-b]quinazoline Alkaloids Vasicine,Vasicinone, Vasicinol and Vasicinolone".http://mutex.gmu.edu:2096/sc ience?_ob=MImg&_imagekey=B6THT-4106DF6-1C-F&_cdi=5291&_user=650615&_orig=search&_coverDate= 12%2F31%2F1996&_sk=999929998&view=c&wchp=dGLzVzz-zSkWA&_valck=1&md5=5b11dabdd8ac01d3a1a4134 64eb666a4&ie=/sdarticle.pdf;DOI:10.1016/0957-4166(95)00412-2
[19] Mehta, D.R., Naravane, J.S., and Desai, R.M. J. Org. Chem., 1963, 28, 2."Vasicinone. A Bronchodilator Principle from Adhatoda Vasica Nees (N. O. Acanthaceae)".http://mutex.gmu.edu:2314/cgi-bin/archive.cgi/joceah/1963/28/i02/pdf/jo01037a041.pdf;DOI: 10.1021/jo01037a041
[20]Joshi, B.,Mohindar, P., Dubose, K., and Pelletier, S.W. Journal of Natural Products, 1994, 57, 7."'H- and 13C-NMR Assignments for some Pyrrolo[2,lb]- Quinazoline Alkaloids of Adhatoda Vasica".http://mutex.gmu.edu:2314/cgi-bin/archive.cgi/jnprdf/1994/57/i07/pdf/np50109a012.pdf;DOI: 10.1021/np50109a012
[21]Southwick, P.L. and Cremer, S.E. J. Org. Chem., 1959, 57, 4."Synthesis of a Chloro Derivative of DL-Vasicine".http: //mutex.gmu.edu:2314/cgi-bin/archive.cgi/joceah/1959/24/i06/pdf/jo01088a006.pdf;DOI: 10.1021/jo01088a006
[22] Wasserman, H.H. and Parr, J. J. Acc. Chem. Res., 2004, 37, 9."The Chemistry of Vicinal Tricarbonyls and Related Systems".h ttp://mutex.gmu.edu:2314/cgi-bin/article.cgi/achre4/2004/37/i09/pdf/ar0300221.pdf; DOI: 10.1021/ar0300221
[23]Das, C., Rajlakshmi, P., and Chowdhury, A. Phytochem. Anal., 1935, 57, 5."HPTLC determination of vasicine and vasicinone in Adhatoda vasica".http://mutex.gmu.edu:2155/cgi-bin/fulltext/110477913/PDFSTART;DOI:10.1002.pca.817
[24] Kristallovich, E.L.and etal. Chemistry of Natural Compounds, 1997, 33, 6."IR Spectroscopy of 2,3-Polymethylene-3,4- Dihydroquinazolines and their Complexes".h ttp://springer.metapress.com/content/78p7384ljp81j5n4/fulltext.pdf; DOI: 10.1007/BF02249637
