oxepins and grandiflorenic-acid

Montanoa tomentosa (zoapatle) is a Mexican plant popularly used for antifertility purposes and with promising characteristics for the development of a new oral contraceptive agent with uteroevacuant properties. In a previous pharmacological report we established the ambivalent myometrial response to zoapatle leaves aqueous extract (ZACE) depending on the animal species used and on the existence or absence of pregnancy. This fact could be useful in determining an appropriate medical use of zoapatle and suggests an interesting possible hormonal dependence in its mechanism of action. To elucidate the ZACE effect upon the pattern of uterine contractility in different hormonal stages, the rat uterus in vitro during oestrus cycle was studied. The aqueous crude extract of Montanoa tomentosa leaves produced different (or even opposite), effects on uterine motility during the distinct phases of the oestrus cycle in the rat. Furthermore, pure grandiflorenic acid (GA), obtained from the phytochemical work up of this plant reproduced the uterine responses induced by ZACE. The action of zoapatle is discussed in relation to hormonal stage and to a probable adrenergic mechanism involved.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Animals; Diterpenes; Estrus; Female; In Vitro Techniques; Montanoa; Oxepins; Potassium; Pregnancy; Rats; Rats, Inbred Strains; Uterine Contraction

Kauradienoic acid was obtained from the hexanic extract of M. tomentosa (Cerv) leaves by chromatographic separation. This substance influenced the in vitro contractility of the rat, dog and guinea pig uterine strips. It also induced strong contractions of the guinea pig uterus in vivo when administered intravenously, without changes on arterial blood pressure. The effects produced by the plant infusion, the hexanic extract and pure species were compared. The hexanic of other utero-active compounds in M. tomentosa in addition to those already described is discussed.. The investigation of uterotonic effects of the hexanic extract (HE) of M. tomentosa leaves, as well as that (-)-kaura-9(11), 16-dien-19-oic acid, henceforth referred to as kauradienoic acid (KA) is described. Pregnant and nonpregnant female Wistar rats, guinea pigs, and dogs were used in this study. Strips obtained from 5 animals had spontaneous rhythmical contractions constant in amplitude and frequency. Muscular tone and frequency of contractions were notably increased by addition of 20 ul/ml of zoapatle aqueous crude extract (ZACE). The preparation returned to the original spontaneous contractility pattern after washing with a modified Ringer solution. Strips obtained from 5 gravid guinea pigs showed scarce spontaneous contractility which was strongly augmented by addition of ZACE. Regular spontaneous contractions were observed in over 30 assays of uterine strips obtained from 5 nongravid rats. The addition of ZACE drastically inhibited the spontaneous contractility. Constant and reproducible results were obtained in gravid rats by addition of ZACE. A gradual decrease in amplitude of contractions was observed. The addition of ZACE depressed the uterine contractility (UC) of 8 uterine strips from 2 animals. The addition of ZACE in gravid dogs in 8 uterine strips was accompanied by an increase of muscular tonus and frequency. A gradual decrease in the amplitude of the rat spontaneous UC was an effect produced by the HE. Addition of water suspension of HE elicited an immediate increase of guinea pig's uterine motility. Results were similar with those observed with ZACE. KA inhibited the "in vitro" rat UC and increased the "in vitro" guinea pig contractions of uterine musculature in a similar fashion as observed with ZACE and HE.

Topics: Animals; Diterpenes; Dogs; Female; Guinea Pigs; Montanoa; Oxepins; Plant Extracts; Plants, Medicinal; Pregnancy; Rats; Rats, Inbred Strains; Uterine Contraction