Yu S M, Ko F N, Wu T S, Lee J Y, Teng C M
Department of Pharmacology, Chang Gung Medical College, Taiwan.
Eur J Pharmacol. 1994 Apr 11;256(1):85-91. doi: 10.1016/0014-2999(94)90620-3.
The pharmacological activity of cinnamophilin ((8R,8'S)-4,4'-dihydroxy-3,3'-dimethoxy-7-oxo-8,8'-neolignan), isolated from Cinnamomum philippinense, was studied in isolated rat aorta, guinea-pig trachea and rabbit platelets. Cinnamophilin was found to be a thromboxane A2 receptor blocking agent in these tissues as revealed by its competitive antagonism of the U-46619 (9,11-dideoxymethanoepoxy-9 alpha,11 alpha-prostaglandin F2 alpha)-induced contraction of rat aorta and guinea-pig trachea and aggregation of rabbit platelets with pA2 values of 7.3 +/- 0.2, 5.2 +/- 0.1 and 6.3 +/- 0.3, respectively. Protection against the irreversible vasoconstriction of rat aorta caused by U-46619 (0.05 microM) was obtained by cinnamophilin (10 microM) but not by caffeine (25 mM). Cinnamophilin (1-15 microM) also possessed voltage-dependent Ca2+ channel blocking action, judging from its antagonism of the high K+ (60 mM)- and Bay K 8644 (0.1 microM)-induced contraction in rat thoracic aorta. Cinnamophilin (30 microM) produced a slight relaxation of noradrenaline (3 microM)-induced tonic contractions, and this relaxing effect was abolished in the presence of nifedipine (1 microM). Nifedipine (10 microM) sufficient to inhibit high K(+)-induced contractions failed to attenuate the contractile response to U-46619. A high concentration of cinnamophilin (100 microM) did not affect the aortic contraction induced by endothelin-1, angiotensin II, carbachol or serotonin. Neither cAMP nor cGMP in rat aorta was increased by cinnamophilin. These results indicate that cinnamophilin is a selective thromboxane A2 receptor antagonist especially in rat aorta, and also possesses voltage-dependent Ca2+ channel blocking properties.
从菲律宾樟（Cinnamomum philippinense）中分离得到的桂木素（(8R,8'S)-4,4'-二羟基-3,3'-二甲氧基-7-氧代-8,8'-新木脂素）的药理活性，在离体大鼠主动脉、豚鼠气管和兔血小板中进行了研究。结果发现，桂木素在这些组织中是一种血栓素A2受体阻断剂，这可通过其对U-46619（9,11-二脱氧甲撑环氧-9α,11α-前列腺素F2α）诱导的大鼠主动脉和豚鼠气管收缩以及兔血小板聚集的竞争性拮抗作用得以揭示，其pA2值分别为7.3±0.2、5.2±0.1和6.3±0.3。桂木素（10μM）可防止U-46619（0.05μM）引起的大鼠主动脉不可逆血管收缩，而咖啡因（25 mM）则无此作用。从桂木素（1 - 15μM）对高钾（60 mM）和Bay K 8644（0.1μM）诱导的大鼠胸主动脉收缩的拮抗作用判断，其还具有电压依赖性钙通道阻断作用。桂木素（30μM）可使去甲肾上腺素（3μM）诱导的强直性收缩略有松弛，且在硝苯地平（1μM）存在时这种松弛作用消失。足以抑制高钾诱导收缩的硝苯地平（10μM）未能减弱对U-46619的收缩反应。高浓度的桂木素（100μM）不影响内皮素-1、血管紧张素II、卡巴胆碱或5-羟色胺诱导的主动脉收缩。桂木素不会增加大鼠主动脉中的环磷酸腺苷（cAMP）或环磷酸鸟苷（cGMP）。这些结果表明，桂木素是一种选择性血栓素A2受体拮抗剂，尤其在大鼠主动脉中，并且还具有电压依赖性钙通道阻断特性。
