Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependently relaxed histamine (30 microM), carbachol (0.2 microM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine-induced precontraction, the potency order was quercetin 3,3',4,'5,7-pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.

The selective antianginal effect without changing blood pressure of butylidenephthalide in conscious rats.

Synthetic butylidenephthalide (Bdph), 60 mg/kg per os (p.o.) given 3 h prior to injection of pituitrin (4 U/kg, i.v.), significantly prevented T-wave lowering on lead II electrocardiograph in unanesthetized rats. The effective dose, 60 mg/kg, was about 1/56th of the median lethal dose (LD50, p.o.) in rats. However, Bdph (60 mg/kg, p.o.) did not affect systolic pressure and heart rate in unanesthetized rats. Therefore, Bdph, found in the rhizome of Ligusticum chuaxiong Hort. (L. wallichii Franch., Umbelliferae), appears to have selective antianginal effect without changing blood pressure and heart rate.

Effect of butylidenephthalide on calcium mobilization in isolated rat aorta.

Butylidenephthalide (Bdph), an antispasmodic compound originally isolated from the rhizome of Ligusticum chuaxiong, has a selective anti-anginal effect without changing blood pressure. Experiments have been performed to determine the mechanism of this action. Synthetic Z-butylidenephthalide concentration-dependently relaxed phenylephrine (1 microM)- or KCl (60 mM)-induced precontractions of intact and denuded rat aorta rings. The relaxation induced by Bdph was endothelium-independent. Bdph (30-300 microM) concentration-dependently reduced cumulative phenylephrine- and KCl-induced contractions of intact rat aortic rings and non-competitively inhibited their log concentration-response curves. The pD2' values of Bdph for phenylephrine- and KCl-induced contraction were 3.66+/-0.13 (n = 8) and 3.71+/-0.07 (n = 8), respectively, which were not significantly different from each other. Bdph also concentration-dependently reduced cumulative Ca2+-induced contractions of intact rat aortic rings in high-KCl (60 mM) Ca2+-free physiological salt solution and non-competitively inhibited its log concentration-response curve. The pD2' value of Bdph for the Ca2+-induced contractions was 3.21+/-0.01 (n = 7) which was significantly different from the pD2' value obtained from the cumulative KCl-induced contractions. These results suggest that Bdph inhibits calcium release from calcium stores more selectively than calcium influx from extracellular space via voltage-dependent calcium channels. The inhibition by Bdph of calcium release from KCl-sensitive calcium stores might be similar to its inhibition of calcium release from phenylephrine-sensitive calcium stores. However, because phenylephrine generates inositol-1,4,5-trisphosphate (IP3) whereas KCl does not, the inhibitory effect of Bdph might not be related to IP3 production.

Stereoselectivity of butylidenephthalide on voltage-dependent calcium channels in guinea-pig isolated ileum.

Two geometric isomers, the Z- and the E- forms, can be separated from synthetic mixtures of butylidenephthalide (Bdph). Z-Bdph (50-100 microM) non-competitively inhibited Ca(2+)-induced contractions in depolarized (K+, 60 mM) guinea-pig ileum longitudinal smooth muscle, with a pD2' value of 3.88 +/- 0.20 (n = 5). However, E-Bdph (20-100 microM) competitively inhibited these contractions with a pA2 value of 4.56 +/- 0.18 (n = 5) which was significantly (P < 0.05) greater than the pD2' value of Z-Bdph. In contrast, the two isomers had no stereoselective inhibitory action on Ca2+ influx through pre- or post-junctional membranes of cholinergic nerve endings from which the transmitter acetylcholine is released or on Ca2+ release from intracellular stores. Therefore, the trans-Z and cis-E forms of Bdph might have geometric stereoselectivity for voltage-dependent calcium channels (VDC) in guinea-pig longitudinal smooth muscle. Both isomers might inhibit more selectively the contractile twitch responses evoked by electrical stimulation than by cumulative acetylcholine- or carbachol-induced transient contractions in guinea-pig ileum longitudinal smooth muscle.

Inhibition of platelet aggregation by some flavonoids.

The inhibitory effects of five flavonoids on the aggregation and secretion of platelets were studied. These flavonoids inhibited markedly platelet aggregation and ATP release of rabbit platelets induced by arachidonic acid or collagen, and slightly those by platelet-activating factor. ADP-induced platelet aggregation was also suppressed by myricetin, fisetin and quercetin. The IC50 on arachidonic acid-induced platelet aggregation was: fisetin, 22 microM; kaempferol, 20 microM; quercetin, 13 microM; morin, 150 microM less than IC50 less than 300 microM. The thromboxane B2 formations were also inhibited by flavonoids in platelets challenged with arachidonic acid. Fisetin, kaempferol, morin and quercetin antagonized the aggregation of washed platelets induced by U46619, a thromboxane A2/prostaglandin endoperoxides mimetic receptor agonist. In human platelet-rich plasma, quercetin prevented the secondary aggregation and blocked ATP release from platelets induced by epinephrine or ADP. These results demonstrate that the major antiplatelet effect of flavonoids tested may be due to both the inhibition of thromboxane formation and thromboxane receptor antagonism.

[Imported case of malaria in Taiwan: analysis of 11 cases].

The "eradication of malaria" in Taiwan was announced by WHO in 1965. From 1966 to 1989, 919 malaria cases were detected in Taiwan. Of these cases, 803 were classified as imported malaria. During 1977 to 1989, our hospital collected 11 cases of imported malaria, 6 of Plasmodium falciparum (PF), including 1 suspicious case, 2 of Plasmodium vivax (PV), 1 of mixed infection (PF plus PV), and 2 unclassified. Most of the patients presented clinically with fever and chills. Hepatosplenomegaly was the most common abnormal finding during the physical examination. Jaundice and anemia occurred in the more severe cases. No cases had lymphadenopathy which is helpful in making a differential diagnosis. Six cases had thrombocytopenia which may be considered as an indirect sign in the diagnosis. The MCV levels were within normal limits in all of the cases. This may indirectly imply a potential protective effect against malaria infection in cases of congenital hemoglobinopathy such as thalassemia or G6PD deficiency. Initially, 10 cases were given "standard treatment", which consisted of chloroquine 450 mg qd for 2 days then 300 mg qd for 2 days and primaquine 15 mg qd for 2 weeks. Four cases of chloroquine resistance were encountered, all in cases with PF infection. Two cases were grade I delayed type resistance and were successfully treated with Fansidar, tetracycline and quinine. Two cases were grade II resistance and presented clinically as cerebral malaria. Intravenous quinine was given plus Fansidar and tetracycline. The cases were resolved without sequele or recurrence. None of the cases, except for 2, received chemoprophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)