€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DISS ABSTR INT (SCI)***** Adams SM THE ANTINEOPLASTIC EFFECTS OF PRUNUS ARMENIACA AND PEGANUM HARMALA IN MURINE P388 AND L1210 LEUKEMIA MODELS In: Diss Abstr Int (Sci) (1983) 44(4):1052-B 1983 This study was conducted to, one, establish a program to study by in vitro and/or in vivo techniques, the antineoplastic activity of natural plant products and two, to utilize these techniques to study the extracts of two plants, Prunus armeniaca (PA) and Peganum harmala (PH). Three in vitro procedures, (a) The growth inhibition of murine P388 leukemia cells in culture, (b) the assay of cytotoxicity utilizing Cr51 labeled P388 cells and (c) the assay of P388 colony forming units (CFU) in soft agar were employed and compared with in vivo studies conducted in CD2F1 mice implanted with P388 or L1210 leukemia cells. Water soluble extracts of the seeds of PA were prepared, dialyzed against distilled H2O (12,000 MW cutoff) and lyophilyzed. The seeds of PH were extracted into 70% ethanol and then either extracted into chloroform (Phase I) or ultracentrifuged and fractionated (Phase II) into three fractions: (a) crude (b) less than 300,000 MW ('300M') and (c) less than 100,000 MW ('100M'). Experiments measuring the antineoplastic effects of PA by measurement of the growth inhibition of P388 cells in culture showed a maximum of 65% inhibition with a concentration of 500 ug/ml. PA was cytotoxic to Cr51 labeled P388 cells but only slightly so (1 mg/ml giving an estimated cytotoxicity of 18%). There was no indication from these in vitro studies that followup in vivo studies would show any appreciable increases in lifespan (ILS). However, in vivo studies of PA showed markedly increased lifespans [T/C x 100(%) 100% where T = lifespan of treated mice and C = lifespan of untreated controls] of 25.7% (total dose = 300 mg/kg) in P388 inoculated mice and 15.5% in L1210 inoculated mice. When assayed for inhibition of P388 colony forming units (CFU) in soft agar, PH Phase II '300M' showed a marked decrease in CFU with a greater than 98% reduction of CFU at a concentration of 5 ug/ml. This method was more indicative of followup in vivo studies in that it measures both direct cytotoxicity and inhibition of replication. Phase I extracts of PH showed marked increases in lifespan (ILS) of CD2F1 mice bearing p388 tumors (ILS of 36% at a total dose of 300 mg/kg) and L1210 tumors (ILS of 33% at a total dose of 300 mg/kg). Testing of the fractionated Phase II extract of PH gave evidence to show that the active ingredient is less than 300,000 MW and!/reater than 100,000 MW as evidenced by the following data. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL JOURNAL OF DERMATOLOGY***** El-Saad El-Rifaie M Peganum harmala: its use in certain dermatoses. In: Int J Dermatol (1980 May) 19(4):221-2 ISSN: 0011-9059 The extract of Peganum harmala (Rutaceae) was used topically to treat certain dermatoses of inflammatory nature. Results were encouraging and proved the antibacterial, antifungal, antipruritic and probably antiprotozoal effects of the extract. Registry Numbers: 304-21-2 (Harmaline) 442-51-3 (Harmine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Shapira Z Terkel J Egozi Y Nyska A Friedman J Abortifacient potential for the epigeal parts of Peganum harmala. In: J Ethnopharmacol (1989 Dec) 27(3):319-25 ISSN: 0378-8741 The effect of methanol and acetone extracts of the epigeal parts of Peganum harmala, a common medicinal plant among Bedouins in Israel, was studied on several parameters of reproduction in female rats. The methanol extract at a dose of 2.5 g/kg/day, offered in food or in drinking suspension for 30 days, significantly prolonged diestrus by 1.0 day. The methanol extracts at doses of 2.0, 2.5 and 3.5 g/kg/day appeared to produce a dose-dependent significant decrease in litter size. No change in the physical and nutritional status of the animals and no adverse toxicological effects were observed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACOLOGY, BIOCHEMISTRY AND BEHAVIOR***** Abdel-Fattah AF Matsumoto K Gammaz HA Watanabe H Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism. In: Pharmacol Biochem Behav (1995 Oct) 52(2):421-6 ISSN: 0091-3057 The effect of total alkaloid extracted from Peganum harmala seeds collected in Egypt on body temperature was studied in rats. Intraperitoneal administration of the Peganum harmala extract produced significant and dose-dependent hypothermia. Similarly, harmine and harmaline, major constituents of the harmala alkaloid, lowered the body temperature. Pretreatment with p-chlorophenylalanine (100 mg/kg/day for 3 days), a 5-HT synthesis inhibitor, significantly attenuated the hypothermic effect of the total alkaloid and harmine, while it tended to block the hypothermic action of harmaline. Methysergide (2 mg/kg), a 5-HT antagonist, significantly attenuated the hypothermia induced by harmala alkaloids. Pindolol (0.05-2 mg/kg), a 5-HT1A receptor and beta-adrenoceptor antagonist, partly blocked the hypothermic effect of the harmala alkaloids in a dose- dependent manner, whereas propranolol (10 mg/kg), a beta-adrenoceptor antagonist, failed to alter it, suggesting that beta-adrenoceptor is not involved in the hypothermia caused by the alkaloids. Pretreatment with a dopamine receptor antagonist haloperidol (5 mg/kg, s.c. and 2 mg/kg, i.p. 24 and 2 h before the experiment, respectively) significantly attenuated the hypothermic effect of harmala alkaloids. Moreover, in haloperidol pretreated rats, methysergide (2 mg/kg, i.p.) and pindolol (0.05 and 2 mg/kg) completely attenuated the hypothermic effect of the alkaloids. These data suggest that harmala alkaloids produce hypothermic effect mainly through endogenous 5-HT stimulation of 5-HT1A receptor. Registry Numbers: 304-21-2 (Harmaline) 442-51-3 (Harmine) 50-67-9 (Serotonin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHYTOCHEMISTRY***** Sharaf M el-Ansari MA Matlin SA Saleh NA Four flavonoid glycosides from Peganum harmala. In: Phytochemistry (1997 Feb) 44(3):533-6 ISSN: 0031-9422 The aerial parts of Peganum harmala yielded four new flavonoids: acacetin 7-O-rhamnoside, 7-O-[6"-O-glucosyl-2"-O-(3'''- acetylrhamnosyl)glucoside and 7-O-(2'''-O-rhamnosyl-2"-O- glucosylglucoside), and the glycoflavone 2'''-O-rhamnosyl-2"-O- glucosylcytisoside. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]***** Li GW Liang PG Pan GY [Radioprotective effect of gamma-harmine and its carboline analogues] In: Yao Hsueh Hsueh Pao (1995) 30(9):715-7 ISSN: 0513-4870 (Published in Chinese) gamma-Harmine (I), harmine (II) and harmaline (III) were isolated from Peganum harmala L. (Zygophylaceae). Tests were conducted with mice to detect whether gamma-harmine (a new compound), harmine, harmol (IV) and harmalol (V) are effective radioprotective compounds against gamma-ray irradiation. Intraperitoneal injection of the hydrochlorides of the four alkaloids 50-80 mg.kg-1 X 1 in NIH male mice 30-45 minutes before 8.6-9.7 Gy whole body 60Co irradiation significantly increased the survival effects (1.33-2.61) and 30-day survival survival rate in comparison with control mice. The results indicate that gamma-harmine exhibited relatively good radioprotective effect. gamma-harmine is the first alkaloid isolated from a plant having protective effects against whole-body lethal irradiation in mice. Registry Numbers: 442-51-3 (Harmine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€