Isolation and in vitro permeation of phenylpropylamino alkaloids from Khat (Catha edulis) across oral and intestinal mucosal tissues.
BACKGROUND
Khat, the leaves of Catha edulis, is used as a "natural amphetamine-like" stimulant in eastern and southern Africa, as well as in the Arabian Peninsula. Leaves are masticated to elicit a state of euphoria. Although the psychostimulatory effects of the leaves are attributed to the presence of phenylpropylamino alkaloids (i.e. cathinone, cathine and norephedrine), the extent of permeation of these alkaloids across the oral and intestinal mucosa has not been established.


METHODS
Cathinone was isolated in the form of the oxalate salt from young buds, following acid-base extraction. High performance countercurrent chromatography (HPCCC) was used to isolate cathine and norephedrine, following borohydride reduction of a mixture of the three alkaloids. The in vitro permeability of these three alkaloids in their pure form, as well as in a crude extract, was evaluated across Caco-2 cell monolayers and across excised porcine intestinal, sublingual and buccal tissues.


RESULTS
The purities of the isolated cathine and norephedrine were in excess of 90%, thereby proving that HPCCC can be applied for efficient separation of these alkaloids from extracts of Khat. The apparent permeability (Papp) coefficients for the Khat alkaloids in their pure form were all above 1.0×10-6cm/s, indicating that the transport of the three alkaloids across the selected biological membranes is comparable to that of the highly permeable reference compound, caffeine. Although readily transported across the various membranes, the alkaloids were transported to a lesser extent when present in a leaf extract, suggesting that other phytochemicals present in the extract influence their permeation.


CONCLUSIONS
These results provide evidence that chewing of Khat contributes to the buccal and sublingual absorption of the psychoactive alkaloids in the bloodstream directly across the oral mucosal membranes. In addition, it confirms that these metabolites will be readily absorbed from the gastrointestinal tract when swallowed.
Department of Chemistry, Tshwane University of Technology, Pretoria 0001, South Africa; Department of Chemistry, Bahir Dar University, P.O. Box 79, Ethiopia. Electronic address: atminale2004@gmail.com.
Minaleshewa
M
Atlabachew
Department of Pharmaceutical Sciences, Tshwane University of Technology, Pretoria 0001, South Africa; SAMRC Herbal Drugs Research Unit, Tshwane University of Technology, Pretoria 0001, South Africa. Electronic address: combrincks@tut.ac.za.
Sandra
S
Combrinck
Department of Pharmaceutical Sciences, Tshwane University of Technology, Pretoria 0001, South Africa; SAMRC Herbal Drugs Research Unit, Tshwane University of Technology, Pretoria 0001, South Africa. Electronic address: viljoenam@tut.ac.za.
Alvaro M
AM
Viljoen
Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: sias.hamman@nwu.ac.za.
Josias H
JH
Hamman
Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: chrisna.gouws@nwu.ac.za.
Chrisna
C
Gouws
D000470:Alkaloids / Q000302:isolation & purification* / Q000493:pharmacokinetics; D000818:Animals; D018938:Caco-2 Cells; D003377:Countercurrent Distribution; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D057230:Limit of Detection; D009061:Mouth Mucosa / Q000378:metabolism*; D010539:Permeability; D013552:Swine
D000470:Alkaloids
Caco-2 cell monolayer; Catha edulis; Countercurrent chromatography; Khat; Porcine buccal tissue; Porcine sublingual tissue