Ibrahim A. Al-Meshal

An evaluation of the male reproductive toxicity of cathinone.

(-)-Cathinone is the major psychoactive component of khat plant (Catha edulis Forssk.). Khat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of khat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydigs cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers.

On the possible role of qinghao acid in the biosynthesis of artemisinin

Abstract Artemisinin (qinghaosu), a seco -sesquiterpene peroxide, is the clinically established antimalarial principle isolated from the leaves of the Chinese medicinal herb, Artemisia annua . Recent studies have suggested that arteannuin B, another metabolite of this plant, could serve as a precursor for artemisinin. In the present study, qinghao acid, the major sesquiterpene constituent of A . annua , was converted to arteannuin B by singlet oxygen ( 1 O 2 ) generated by sensitized photo-oxygenation. The formation of this compound was monitored by high-pressure liquid chromatographic analysis, and the identity of the isolated material was established by direct comparison. Since 1 O 2 is known to play a role in biogenetic reactions, it appears that qinghao acid can serve as a biogenetic precursor for artemisinin.

Clastogenic evaluation of cathinone and amphetamine in somatic cells of mice.

Clastogenic effects of cathinone, the active principle from khat (Catha edulis) and amphetamine, a compound having similar chemical structure and pharmacological activity, have been studied on the somatic cells of mice. Both of them produced marked clastogenic activity and affected the cell proliferation in the bone marrow of mice. They induced a significant increase in the frequency of micronucleated polychromatic erythrocytes at higher doses. These results substantiate our earlier observations on the clastogenic and mitodepressive activity of cathinone on the meristematic region of Allium cepa, and indicate that cathinone may be responsible for the mutagenic effect of khat reported by other workers. The clastogenic effects of amphetamine are being reported for the first time. Further studies are required to substantiate these findings and to study whether cathinone and amphetamine produce a direct clastogenic effect or whether they act as spindle poisons.

Cytological Effects of Khat (Catha Edulis) in Somatic and Male Germ Cells of Mice

Cytological effects of khat (Catha edulis), a popular drug of abuse from Southern Arabia and Eastern Africa, have been studied in Swiss albino mice. The studies on the somatic system involved the use of micronucleus test and the cytological analysis of the mitotic index in the femoral cells of mice. In the micronucleus test, the mice were treated with different doses of khat extract (125, 250 and 500 mg/kg, p.o.) 30 and 6 hours before sacrificing the animals. The polychromatic erythrocytes were screened for the induction of micronuclei. For the analysis of bone marrow cytotoxicity, the mice were treated with the dose of 125, 250 and 500 mg/kg, body weight, p.o. daily for 5 consecutive days. The animals were sacrificed and the femoral cells were microscopically examined for the mitoses. Following the same schedule of treatment, studies on the cytogenetic analysis of meiotic chromosomal aberrations and the sperm head abnormality were undertaken. Khat extract significantly increased the frequency of micronucleated polychromatic erythrocytes, induced bone marrow depression and reduced the mitotic index of the somatic cells. It induced significant chromosomal aberrations viz., aneuploids, autosomal univalents, univalents of the sex chromosomes and polyploids. The frequency of abnormal sperms was also increased.

Comparative study of cathinone and amphetamine on brown adipose thermogenesis

The effect of cathinone and amphetamine on brown adipose tissue thermogenesis and its modification with propranolol and timolol has been studied in rats. Both cathinone and amphetamine produced significant dose dependent increases in intracapsular brown adipose tissue (IBAT) and rectal temperatures. Amphetamine was found to be three times more potent as compared to cathinone, on a dose basis. Pretreatment of animals with propranolol and timolol individually inhibited cathinone and amphetamine induced hyperthermia. These findings suggest the involvement of beta adrenergic receptors in cathinone and amphetamine induced thermogenesis.

Anti-inflammatory activity of the flavonoid fraction of khat (Catha edulis Forsk)

The administration of the flavonid fraction, isolated from Khat (Catha edulis Forsk), in a dose of 200 mg/kg orally, produced a significant anti-inflammatory activity against the carrageenan induced paw oedema and cotton pellet granuloma in albino rats. The results were comparable with the standard anti-inflammatory drug oxyphenbutazone.

The induction of dominant lethal mutations upon chronic administration of khat (Catha edulis) in albino mice

The mutagenicity of a methanolic extract of khat has been evaluated on male germ cells using the dominant lethal test in albino mice. An aqueous solution of khat extract was administered orally in doses of 50, 100 and 200 mg/kg body wt., respectively, to 3 different groups of male mice for a period of 6 weeks. At the end of treatment each male mouse was allowed to mate with 2 different groups of 3 females each, on 2 consecutive weeks. These females were necropsied on the 13th day of their presumptive mating, and the number of implants in each female and the ratio of live and dead embryos were determined. The results of this study showed that the treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in the rate of fertility in the first week after mating, which was irreversible in the second week at the highest dose (200 mg/kg). Khat extract also induced post-implantation loss during the first week following treatment. However, a comparison of the results of the first and second weeks showed a reversible pattern of dominant lethality.

A flavone and diterpene from Psiadia arabica

Abstract The aerial parts of Psiadia arabica yielded two new constituents: a flavone, 5,7,3′-trihydroxy-2′,4′,5′-trimethoxyflavone, the structure of which was derived from spectral data and chemical derivatization, and a kaurane diterpene named psiadian, which was characterized unambiguously from its chemical and spectral data in conjunction with X-ray crystallography.

(+)-Dihydroperfamine: An Alkaloid from Haplophyllum tuberculatum

AbstractDihydroperfamine (I), partially enriched by its dextrorotatory enantiomer, has been isolated from a Saudi Arabian variant of Haplophyllum tuberculatum. Its structure was deduced from its physical and spectral data, and by direct comparison with the (-)-antipode. The profile of the other isolated constituents, justicidin A, justicidin B, 3-dimethyaUyl-4-dimethylallyloxy-2-quinolone and (+)-tuberine has been compared to those reported in other variants.

Aromatic Plants of Saudi Arabia - Part 8 -* GC/MS Analysis of Essential Oils of Pulicaria arabica and P. undulata

AbstractThe composition of the steam distilled oils of the fresh aerial parts of Pulicaria arabica (L.) Cass, and P. undulata (L.) Kostel was investigated by coupled GC-MS. Based on comparing the resultant mass spectra with available standards as well as with those delivered by the electronic data system attached to the apparatus and with reported data, many volatile components of the two species could be identified and compared. The oil of P. arabica is characterized by the presence of high percentage of sesquiterpene hydrocarbons and alcohols while that of P. undulata is rich in phenolic compounds and monoterpene hydrocarbons and comparatively low in sesquiterpene hydrocarbons.