Synergistic Effects of NSAIDs with Natural Products on Inflammatory Responses

• Main Authors: Sung-Hui Tseng, 曾頌惠
• Other Authors: Ling-Ling Yang
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/07694329025406041313

碩士 === 台北醫學院 === 生藥學研究所 === 90 === Combine therapy of different classes of drugs in treatment of those diseases which are difficult to gain good clinical result, such as cancer, hypertension, rheumatoid arthritis, has gained more popularity due to better result and less side effects in the past decade. In the field of inflammation, many natural compounds have been found to possess anti-inflammatory property. Therefore, we investigated the effects of Chinese herbs in the absence or presence of NSAIDs on antiinflammatory responses. We first sorted out 23 most frequently used herbs for treating arthritis. These 23 herbs were than extracted with 50 % ethanol. The anti-inflammatory effects of these extracts were examined on LPS-induced NO and PGE2 production and expression of iNOS and COX-2 proteins in RAW 264.7 murine macrophage. Eucommia Cortex, Scrutelleriae Radix, and Phellodendri Cortex showed significant inhibition on NO production by LPS-activated Raw 264.7 cells. Angelicae Laxiflorae Radix, Carthami Flos, Angelicae Sinensis Radix, Aconiti Tuber, Rhei Rhizoma, Eucommia Cortex, Ephedra Herba, Scrutellariae Radix, and Phellodendri Cortex, 9 out of the 23 crude extracts, showed significant inhibition on PGE2 production . Combined treatment of the 23 herbs with indomethacin increased 15 herbs’ inhibition on NO production . However, when celebrex ( COX-2 inhibitor) was used to combined with the 23 herbs, the inhibitory effect of most of the herbs on NO production by LPS-activated RAW 264.7 cells were antagonized. We then determined whether combined treatment in vivo produces better anti-inflammatory effect. Carrageenin induced pleurisy in rats is a well established model of acute inflammation, and NSAIDs have been reported to inhibit a variety of inflammatory parameter. Adult male Wistar rats were used in the experiment. Drugs including NO inhibitor(L-NAME), indomethacin, or both, crude extract of Linderae Radix or with indomethacin were given 30min i.p. before the induction of pleurisy by 1% carrageenin. The group of rat treated with Linderae Radix or Linderae Radix with indomethacin showed less exudates than the rats treated with indomethacin or L-NAME. In the second part , we investigated the effects of anti-inflammatory compounds from Atractylodes Rhizoma(atractylenolide I), Scrutellariae Radix(wogonin, baicalein, baicalin, oroxylin A) and Rhei Rhizoma (emdin, rhein)on LPS-stimulated NO and PGE2 production in RAW 264.7 cells. The inhibitory effects when the compounds were combined with COX inhibitors were also investigated. The results indicated that both COX inhibitors could increase the inhibitory effect of atractylenolide I on NO production by LPS-induced RAW 264.7 cells. Only indomethacin could enhance the inhibitory effect of emodin and rhein on NO production by LPS-induced RAW 264.7 cells. The inhibitory effects on NO production of wogonin, baicalein, and oroxylin A did not increase after combined with NSAIDs. From the above results, we thus suggested the following: 1, Nonselective COX inhibitors can enhance the anti-inflammatory effect of natural compounds more significantly than selective COX inhibitors; 2, NSAIDs could antagonized the anti-inflammatory effect of Scrutellariae Radix and Rhei Rhizoma and was most likely due to NSAIDs could antagonize the anti-inflammatory effect of wogonin, baicalein, and oroxylin A; 3, the models used in the experiments could provide useful informations for future research on the combined treatment of medicine and Chinese herbs.