Antiinflammatory and antinociceptive activities of gossypin and procumbentin – cyclooxygenase‐2 (COX‐2) inhibition studies

In the present study the antiinflammatory and antinociceptive activities of a few selected flavonoids were investigated. Procumbentin, gossypin, chrysin and methylhespiridin were studied for antiinflammatory and antinociceptive activities using in vitro enzymatic assays and in animal models utilizing acetic acid‐induced writhing in mice and hind paw edema in rats. In vitro studies were performed using TMPD (NNN′N′‐tetramethyl‐p‐phenylene diamine) and oxygraphic methods for COX‐1 (cyclooxygenase‐1), COX‐2, 5‐LOX (5‐lipoxygenase) and 15‐LOX. Gossypin and procumbentin showed COX‐2 inhibitory activity and exhibited IC₅₀ (COX‐2/COX‐1) ratios of 0.14 and 0.11, respectively. None of the flavonoids tested in this study showed LOX inhibitory activity. Four groups were studied for each test compound following intraperitoneal (i.p.) administration of doses of 10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin‐induced rat hind paw edema model and antinociceptive activity by acetic acid‐induced writhing. Procumbentin and gossypin showed antinociceptive activity at the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30, 100 mg/kg. Procumbentin and gossypin exhibited COX‐2 inhibitory activity when tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and gossypin showed antiinflammatory, activities. Copyright © 2008 John Wiley & Sons, Ltd.     

牙疾宁的药理学及毒理学研究

牙疾宁给小鼠口服０．２５ｇ·ｋｇ－１和０．１６ｇ·ｋｇ－１能减少醋酸所引起的扭体反应次数（Ｐ＜０．０１）。牙疾宁小鼠耳朵外涂０．０３ｍｌ（浓度为１００ｇ·Ｌ－１）能抑制二甲苯引起的水肿（Ｐ＜０．０１），其对金黄色葡萄球菌、白色葡萄球菌和绿脓杆菌的最小抑菌浓度为１．２５ｇ·Ｌ－１，对溶血性链球菌和白色念珠菌的最小抑菌浓度为２．５ｇ·Ｌ－１．牙疾宁小鼠口服ＬＤ５０为１１２９ｍｇ·ｋｇ－１。     

二苯噁丙酸的抗炎作用及其机理

以多种炎症模型观察了二苯丙酸的抗炎作用。给动物灌服二苯丙酸，能抑制角叉莱胶致足跖肿胀和棉球致内芽组织增生，对大鼠佐剂性关节炎也有明显的抑制作用。该药的抗炎作用强度与阿司匹林相似，但作用时间明显延长。探讨其作用机理表明，二苯丙酸能降低毛细血管通透性，抑制白细胞游走反应，但对血浆皮质醇的含量无明显影响。     

Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release

The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05–0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca²⁺ concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflamatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1–1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K⁺ current and Ca²⁺-activated K⁺ current in a concentration-dependent manner. Niflumic acid (0.1–1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na⁺ current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K⁺ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca²⁺ with each impulse.     

Correlation of antiinflammatory and hormonal activity of derivatives of the 8,16-diazasteroid series

Antiinflammatory activity and mechanism of action are studied for seven compounds of the 8,16-diazasteroid series. It is established that the antiinflammatory activity of the compounds is increased on the whole due to the reduced ketofunction in the 12 position of 8,16-diazasteroid as well as for the introduction of methoxy groups in the 2 and 3 position or phenol substitute in the 16 position. The activity of compounds VI and VII also depends on the inflammation model or on the pain reaction and differs significantly from the effectiveness of diclofenac sodium and prednisolone. Unlike the latter, the compounds under study are virtually devoid of hormonal activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 168–171, February, 1995 Presented by P. V. Sergeev, Member of the Russian Academy of Medical Sciences     

栀子的抗炎镇痛作用研究

用３．０和１．０ｇ浸膏／ｋｇ２个剂量进行试验,探讨单味桅子７５％甲醇提取物对炎症组织的影响,结果表明,桅子浸膏可显著抑制醋酸诱发血管通透性增加,高、低剂量的抑制率分别为４４．７％和２５．６％;显著抑制叉菜所致大鼠足肿胀作用,第６小时抑制率分别为３３．６％和２５．４％;显著抑制棉球肉芽组织增生,抑制率分别为５４．１％和３３．０％;对醋酸诱发的小鼠扭体反应有一定抑制作用,抑制率分别为２６．８％和１８．     

联合给药法治疗强直性脊柱炎

目的 采用氨甲喋呤（ＭＴＸ）、抑氮磺胺吡啶（ＳＡＳＰ） 非甾体类药（ＮＳＡＩＤｓ）“递减法”联合给药治疗７８例强直性脊柱炎（ＡＳ的临床疗效观察。方法 ＳＡＳＰ０．５ｇ,２次／日,服１周后改为０．７５ｇ,２次／日,第２周后改为１．０ｇ,２次／日,以后每周１．０ｇ,２次／日,疗程２年,ＭＴＳ５ｍｇ,１次／周,每周递增５ｍｇ,加量至１５～２０ｍｇ／周时维持０．５～１年,ＮＳＡＩＤｓ疗程为３个月左右减半量     

西红花总苷的药理学研究Ⅰ.对炎症及免疫功能的影响

西红花总苷ｉｇ明显抑制二甲苯所致小鼠急性耳廓肿胀、醋酸所致上鼠腹腔毛细血管通透性增高及蛋清、角叉菜胶所致大鼠足跖肿胀、且有一定的镇痛效应，对正常小鼠的免疫器官重量、非牧场划性免疫、特异性体液免疫功能无明显影响，但对迟发型变态反应有明显的抑制作用。