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Some Dorema species are used in Persian traditional medicine. In the present study the total extract from the roots of Dorema hyrcanum Koso-Pol. was investigated for its in-vitro (pLDH assay) and in-vivo (Peters' 4-days suppressive test) antiplasmodial effects and assessed for cytotoxicity against the normal cell line MDBK (MTT test). The IC50 values for a chloroquine- sensitive (3D7) and a chloroquine- resistant (K1) strain of Plasmodium falciparum were 28.64 and 9.79 µg/mL, respectively. The inhibition percentage of the rodent parasite, Plasmodium berghei, on day 4 in mice was 77.9% and IC50 value on Madin-Darby bovine kidney cells (MDBK cells) was 59.84 µg/mL. The total extract was subjected to a bioassay-guided fractionation protocol based on the in-vivo model which resulted in the isolation of an acetophenon (compound 1), one new sesquiterpenoid; naghibione (compound 2) and two known sesquiterpenoid derivatives (compounds 3, 4). Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR experiments and ESI-MS. All compounds were evaluated for in-vivo antiplasmodial effect and the results revealed that naghibione showed good suppression activity, inhibiting 68.1 % of the parasite growth.

Im Verlauf der Untersuchungen von Agrostemma githago L. var. githago, eines bekannten giftigen Vertreters der Caryophyllaceae, verwendeten wir neben Agrostemmasaponin das Saponinum album aus Gypsophila paniculata L., ebenfalls mit Gypsogenin (3b-Hydroxy-Olean-12-en-23-al-28-Säure) als Aglykon. Eine Kombination dieser Saponinderivate (3 µg/ml) mit einer Formylfunktion an Position C4 des Aglykons in Kombination mit RIPs und anderen natürlichen Toxinen zeigte eine kooperative Toxizität an ECV 304-Zellen. Ribosomen-inaktivierende Proteine (RIPs; EC Nr. 3.2.2.22) sind eine heterogene Familie von strukturell und evolutionsbedingt ähnlichen Proteinen mit einer katalytischen Domäne, die einen spezifischen Adeninrest enzymatisch von einer definierten Position der rRNA prokaryotischer und eukaryotischer Ribosomen zu entfernen vermag. Die kombinierte Verabreichung von subtoxischen Konzentrationen eines RIP-Typ 1 und des Saponins zeigte in dieser Studie einen spezifischen und zum ersten Mal größeren zytotoxischen Effekt auf Tumorzellen im Vergleich mit natürlichem Diphtheriatoxin. Es wird ein analoger, synergistischer Wirkungsmechanismus zwischen der durch Gypsophilasaponin induzierten Toxizität von Agrostin aus Agrostemma githago L. und von Saporin aus Saponaria officinalis L. bzw. dem rekombinant hergestellten his-Saporin diskutiert. Offensichtlich nutzen diese aus den Samen der Caryophyllaceae isolierten Proteine einen ähnlichen Weg, um die Zellmembran zu passieren, was auf den Abwehrmechanismus dieser Pflanzen gegen pathogene Organismen schließen lässt., In the course of our investigation of Agrostemma githago L. var. githago, a well-known toxic member of the Caryophyllaceae family, we tested Saponinum album from Gypsophila paniculata L., both saponins with gypsogenin (3b-hydroxy-olean-12-en-23-al-28-oic acid) as aglycone. A combination of these particular saponin derivatives with a formyl function in triterpene position 4 (3 µg/ml) together with RIPs and other natural toxins revealed a co-operative toxicity against ECV 304-cells. Ribosome-inactivating proteins (RIPs; EC No. 3.2.2.22) are a heterogeneous family of structurally and evolutionary related plant proteins. They share a common functional domain capable of catalytically removing a specific adenine residue from a highly conserved, surface-exposed stem-loop structure in the large rRNA of prokaryotic and eukaryotic ribosomes. The combined administration of individually non-toxic concentrations of a RIP type 1 and a saponin presented in this study leads to a potent and for the first time greater specifically cytotoxic effect on tumor cells in comparison with natural diphtheria toxin. An analogy could be drawn between the observed induction of RIP-toxicity of Agrostin and of Saporin/ genetically engineered his-Saporin from Saponaria officinalis L. in combination with Gypsophilasaponin. Obviously these proteins, both obtained from the seeds of Caryophyllaceae species, use a similar mechanism to penetrate through the cell membrane in vitro suggesting a similar defence mechanism of these plants against pathogenic organisms.