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Antihypertensive effects of Hsian-taso in spontaneously hypertensive rats
|關鍵字:||仙草;Hsian-tsao;咖啡酸;自發性高血壓鼠;降血壓;氧化壓力;總抗氧化力;血管收縮素轉換酶;分子機制;caffeic acid;spontaneously hypertensive rats;antihypertension;oxidative stress;antioxidant capacity;angiotensin converting enzyme;molecular mechanism||出版社:||食品暨應用生物科技學系||摘要:||
The aims of this study were to investigate the antihypertensive effects of Hsian-tsao (Mesona procumbens Hemsl.) and its active compound in spontaneously hypertensive rats (SHR). The results showed that the oral administration of the water extracts of Hsian-tsao (WEHT, 1.0 g/kg) or caffeic acid (CA, 0.1 g/kg) for 6 weeks significantly decreased the systolic blood pressure, diastolic pressure, heart rate and the angiotensin converting enzyme (ACE) activity of plasma in SHR. WEHT and CA supplementation led to significant prevention against ACE-induced hypertension. Oxidative stress is key evidence associated with hypertension. It was observed that increased expression of NAD(P)H oxidase p47phox in kidney, lipid peroxidation products in plasma and liver, and decreased total glutathione (GSH) content in liver of SHR compared to the WKY control. Furthermore, treatment with WEHT or CA both significantly increased the GSH content in liver and significantly reduced the formation of lipid peroxidation products in plasma and liver. Administration of WEHT or CA could promote the antioxidant capacity in liver and kidney, and the activities of GPx, GRd, CAT and SOD in liver and kidney and the mRNA levels of CuZnSOD, GPx, CAT and HO-1 in kidney. The results showed WEHT or CA significantly decreased oxidative stress, improvement of the antioxidant defences, reduced systolic blood pressure in SHR. Induction of such antioxidant genes by Nrf2 occurs through their recruitment to the antioxidant response element (ARE) in their gene promoters. The signaling pathway was determined by western blot. The results showed that WEHT or CA increased the nuclear levels of Nrf2 in kidney through promoting it translocated from cytoplasma to nucleus and promoted the expression of antioxidant genes. When investigating the signaling pathways responsible for Nrf2 activation in SHR, we observed that WEHT or CA activated the MAPK pathways. The results showed that the expression of antioxidant gene induced by WEHT or CA was through JNK1/2 and p38 kinases to stimulate Nrf2 to translocate into nucleus and activate ARE. In the bioavailability study, the concentration of CA in the plasma reached the maximum concentration of 0.9 μmol/L 1 h after administration of CA. In conclusion, the results of this study suggest that WEHT and CA possess an anti-hypertensive effect, this possibly due to amelioration of the oxidative damage and elevated the antioxidant capacity.
本研究乃是探討仙草水萃取物及其活性成分咖啡酸對自發性高血壓鼠 (SHR) 降血壓之作用。結果顯示餵食仙草水萃取物 (WEHT, 1.0 g/kg) 及咖啡酸 (CA, 0.1 g/kg) 六週可顯著降低 (p < 0.05) SHR之收縮壓、舒張壓、心跳及抑制血漿中血管收縮素轉換酶 (ACE) 之活性，顯示WEHT及CA具有良好降血壓之效果。高血壓與氧化壓力具有顯著的關連性。因此，進一步分析SHR體內氧化壓力相關之指標，由研究結果顯示，SHR相較於WKY正常組有較高之氧化壓力，導致腎臟中NAD(P)H oxidase p47phox及血漿、肝臟之脂質過氧化作用皆有顯著增加之趨勢，並且降低肝臟中GSH含量。餵食WEHT及CA則可顯著提高SHR肝臟中GSH含量，抑制血漿及肝臟中脂質過氧化作用 (p < 0.05); 並提升其肝、腎中總抗氧化能力、抗氧化酵素GPx、GRd、CAT及SOD之活性及腎臟中CuZnSOD、GPx、CAT及HO-1抗氧化基因之表現。以上結果顯示WEHT及CA具有降低SHR體內之氧化壓力及提升總抗氧化之能力，進而達到降血壓之效果。Nrf2與誘發antioxidant response element (ARE) 相關之抗氧化基因表現有關。因此進一步利用西方墨點法來分析WEHT及CA對轉錄因子Nrf2之表現。由結果證實WEHT及CA可活化腎臟中Nrf2的蛋白質表現，並使得細胞質中Nrf2轉位進入細胞核中，進而促進抗氧化基因之表現。接著探討WEHT及CA對調控Nrf2蛋白質表現之可能訊息傳導路徑之變化。結果顯示WEHT及CA可活化p38 及JNK1/2 MAP kinase 訊息傳遞路徑。因此推測WEHT及CA可透由JNK1/2及p38 MAP kinase之訊息傳遞使得Nrf2進入核內，進而啟動抗氧化基因之表現。藉由生物利用率之結果顯示，餵食SHR咖啡酸 (0.1 g/kg) 一小時後，於血漿中可偵測到游離狀態咖啡酸存在，其含量約為0.9μmol/L，表示CA能有效被吸收代謝並且與提升SHR體內抗氧化力有密切相關性。綜合以上結果，推測WEHT及CA具有降血壓之效果以及提高體內的抗氧化力，降低氧化傷害之保護作用。
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