dinoprost and gingerol

The mechanism of potentiation of prostaglandin (PG) F2alpha-induced contraction of mouse mesenteric veins by (+/-)-[6-gingerol was investigated in vitro. (+/-)-[6]-Gingerol (0.3mM) potentiated the maximal contraction response elicited by PGF2alpha (0.28 mm) in the presence of intact vascular endothelium, but not in its absence (de-endothelialized preparations). The potentiating effect was completely inhibited by cyclooxygenase inhibitors (0.2 mm aspirin and 0.2 mm indomethacin) and partly by calcium antagonists (2 microM verapamil, 8 nM nitrendipine and 1 microM ryanodine), but not inhibited by nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor and ONO-3708, a thromboxane (TX) A2 antagonist. The potentiation by (+/-)-[6]-gingerol is also observed in mesenteric veins of streptozotocin-diabetic mice where the enhancement of PGF2alpha-induced contraction is caused mainly by activation of lipoxygenase. The potentiation of PGF2alpha-induced contraction by (+/-)-[6]-gingerol may be caused by a cyclooxygenase-dependent release of vasoconstrictors, other than PGF2alpha and TXA2, or by inhibiting vasorelaxants released from endothelial cells of mouse mesenteric veins.

Topics: Animals; Catechols; Diabetes Mellitus, Experimental; Dinoprost; Drug Synergism; Endothelium, Vascular; Fatty Alcohols; Lipoxygenase; Male; Mesenteric Veins; Mice; Prostaglandin-Endoperoxide Synthases; Streptozocin; Vasoconstriction

The effects of the active principles of crude ginger (a traditional Sino-Japanese medicine), the gingerols, on the contractile responses to eicosanoids were compared using isolated mouse and rat blood vessels. Leukotrienes (LT) C4 and D4, a thromboxane (TX) A2 derivative (U-46619), prostaglandins (PG) F2 alpha, PGI2-Na, PGE2, the stable PGI2 derivative TRK-100, and PGD2 induced contraction in longitudinal segments of mouse mesenteric veins in that order of potency. Exogenous arachidonic acid and PGE1 did not cause contraction. The mesenteric veins also contracted in response to noradrenaline (NA) and phenylephrine (PhE), but not to clonidine. The gingerols alone relaxed the muscle transiently and then augmented the response to PGF2 alpha, PGE2, PGI2-Na, and TRK-100, but suppressed the response to PGD2, U-46619, LTC4, LTD4, NA and PhE. (+/-)-[6]-Gingerol also potentiated the PGF2 alpha-induced contraction in longitudinal segments of rat mesenteric vein and vena cava, but inhibited it in circular segments of rat aorta and longitudinal segments of mouse mesenteric arteries. These results showed that (+/-)-[6]- and (+/-)-[8]-gingerols potentiated the contraction induced by prostanoids (except PGD2) and inhibited that produced by PGD2, TXA2, and LT, suggesting the modulation of eicosanoids-induced responses by (+/-)-[6]- or (+/-)-[8]-gingerol.

Topics: Animals; Catechols; Dinoprost; Drug Interactions; Fatty Alcohols; In Vitro Techniques; Leukotrienes; Male; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Phenylephrine; Prostaglandins; Rats; Rats, Inbred Strains; Splanchnic Circulation

The effects of crude and processed ginger extracts and pungent components, S-(+)-[6]-gingerol and [6]-shogaol, on noradrenaline (NA)- and prostaglandin (PG) F2 alpha-induced contraction were investigated using mouse mesenteric veins. Both spicy constituents inhibited the contractile responses to NA. Crude ginger extract and S-(+)-[6]-gingerol potentiated the PGF2 alpha-induced contraction, whereas processed ginger extract and [6]-shogaol inhibited the contraction.

Topics: Animals; Catechols; Dinoprost; Fatty Alcohols; In Vitro Techniques; Male; Mesenteric Veins; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Plant Extracts; Stereoisomerism

We have previously reported that (+/-)-[6]- and (+/-)-[8]-gingerols potentiate prostaglandin (PG) F2 alpha-induced muscle contraction, and that other gingerol-related derivatives do not necessarily produce the same effect. The moiety necessary for potentiation was therefore investigated. 1) (+/-)-[8]-Gingerol potentiated PGF2 alpha-induced contraction to a greater extent than (+/-)-[6]-gingerol and (+/-)-hexahydrocurcumine (HHC), but [6]-shogaol produced inhibition; 2) Noradrenaline (NA)-induced contraction was inhibited in the following order: [6]-shogaol greater than (+/-)-[8]-gingerol greater than [6]-gingerdione greater than (+/-)-[6]-gingerol greater than S-(+)-[6]-gingerdiacetate (GDA) greater than [6]-dehydrogingerdione (DHG), whereas (+/-)-HHC had no significant inhibitory action; 3) [6]-gingerdione had different effects on PGF2 alpha-induced contraction, indicating inhibition just after preparation of the solution, no effect apparent after 2 h, and potentiation after 5 h; 4) [6]-gingerdione showed a change in its chemical structure after 5 h as measured by the FeCl3 reaction, and ultraviolet and 1H nuclear magnetic resonance spectra. It was concluded that the aliphatic hydroxyl group present in gingerol derivatives is necessary for potentiation of PGF2 alpha- and the keto group for inhibition of NA-induced contraction.

Topics: Animals; Catechols; Chemical Phenomena; Chemistry; Dinoprost; Drug Synergism; Fatty Alcohols; In Vitro Techniques; Male; Mesenteric Veins; Mice; Mice, Inbred Strains; Muscle Contraction; Plants, Medicinal; Structure-Activity Relationship