Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/50772
標題: Contents of pseudohypericin and hypercin in five Hypericum species in Taiwan and the in vitro and in vivo antioxidant activities and the effects of crude extract of Hypercium samsponii on acetaminophen-induced acute toxicities in rats.
五種台灣金絲桃屬植物之 pseudohypericin 和 hypericin 含量分析與元寶草粗萃物之體內外抗氧化性以及對acetaminophen所誘發之大鼠急性肝、腎毒性之影響
作者: 王昭君
Wang, Zhao-Jun
關鍵字: Key words: pseudohypericin
關鍵詞:pseudohypericin
hypericin
Hypericum in Taiwan
H. sampsonii
antioxidative property
acetaminophen
hepatotoxicity
nephrotoxicity
hypericin
台灣金絲桃屬植物
元寶草
抗氧化性
acetaminophen
肝毒性
腎毒性。
出版社: 食品科學系
摘要: 近年來,外國流行一種由金絲桃草花葉萃取物(St John’s Wort)做成的天然抗憂鬱藥,其大多標示每粒錠劑含有900 μg hypericin之抗憂鬱有效成份,但有關於市售錠劑產品及台灣金絲桃屬植物中抗憂鬱成份之實際含量的報導甚少。因此,本研究目的在於:(1) 分析市售錠劑及台灣本土產金絲桃屬植物之抗憂鬱成份pseudohypericin及hypericin之含量,評估開發抗憂鬱茶包之可行性。(2)以台灣金絲桃屬植物中抗憂鬱成份含量最高者為研究對象,探討單一服用之安全性及在活體外(in vitro)和活體內(in vivo)試驗系統中的抗氧化活性。此外,在研究以毒性劑量之acetaminophen (APAP, 1.2 g/kg b.w.)誘發大鼠肝及/或腎毒性之實驗模式,探討其臨床上之醫藥作用性。 五種不同品牌之市售金絲桃草錠劑之分析結果顯示:發現pseudohypericin的含量多高出hypericin 1.48至3.1倍,而兩種成份相加之總含量,以品牌Source Naturals (pseudohypericin:465 ± 28 和hypericin:150 ± 9.4 μg/錠劑;總含量:615 ± 37 μg/錠劑)為最高。在台灣本土之元寶草、地耳草、金絲梅、金線海棠、玉山金絲桃等五種台灣金絲桃屬植物之甲醇粗萃物方面,分析結果顯示此五種粗萃物中均含有pseudohypericin及hypericin,其中又以元寶草含pseudohypericin:121  18.8 和 hypericin:62.4  9.6 g/g 粉末 為最高。 因此,本研究選用元寶草粗萃物為下述研究之對象。小鼠之急毒性試驗顯示服用高達10.0 g/kg b.w.之劑量時,也不會造成小鼠急毒性死亡。此外,以0.5、 1.0、 2.0 g元寶草粗萃物/kg b.w. 三種劑量管餵大鼠,其肝腎組織病理切片圖及血清GOT和GPT活性、BUN和CRE含量均未顯著地受到影響,顯示出元寶草粗萃物為一極低毒性的草藥。 元寶草粗萃物在活體外具有抗脂質過氧化、清除DPPH自由基、螯合亞鐵離子、類SOD活性、還原力等作用,以及抑制由Fe3+-EDTA/H2O2/ ascorbic acid 所誘發之去氧核糖傷害,並比mannitol清除羥自由基的反應速率大五倍。因此,在活體外(in vitro)的試驗中元寶草粗萃物具有廣泛的抗氧化性質。 然而,在管餵一次元寶草粗萃物之情況下,活體內(in vivo)的試驗並不能明顯地表現出抗氧化作用。管餵劑量0.5、1.0及2.0 g 元寶草粗萃物/kg b.w.對於大鼠體內之脂質過氧化、蛋白質羰基含量、抗氧化防禦系統(包括:抗氧化酵素:SOD、catalase、GSH peroxidase,總硫醇基及GSH含量,GSH相關酵素活性)皆無顯著之影響(p>0.05)。 APAP 加上管餵0.5 g元寶草粗萃物/kg b.w. 使sGPT 活性比APAP組增加2.19 倍 (p<0.05);加上2.0 g 元寶草粗萃物/kg b.w. 之處理組,sGOT 活性則增加3.84 倍 (p<0.05)。觀察肝組織病理切片圖時,亦發現同時管餵元寶草粗萃物會造成中央靜脈區的壞死面積增廣。 腹腔注射APAP不會顯著地影響血清BUN、CRE含量(p>0.05),但APAP 加上管餵2.0 g/kg b.w.元寶草粗萃物的處理時,則會使BUN和CRE比控制組各增加4.76倍(p<0.05)及2.51倍(p<0.05)。這些結果意謂著APAP 加上元寶草粗萃物時,可能造成腎損傷。此外,同時管餵元寶草粗萃物會增加血清APAP濃度,且呈正比劑量的關係。因此,元寶草對APAP之肝腎傷害模式除無保護作用之外,尚可能干擾APAP之生理代謝,發生交互作用,反可能會加強其毒性。 APAP 加上管餵元寶草粗萃物的處理時,肝腎之脂質過氧化、總硫醇基和蛋白質羰基含量並未顯著地改變( p>0.05)。不過,APAP會造成肝中抗氧化酵素和GSH含量顯著性下降( p<0.05),腎則不受影響。APAP加上管餵2.0 g 元寶草粗萃物/kg b.w.會使肝GSH含量減低61% (p<0.05),增加腎中2.41倍(p<0.05)的GSH含量與1.64倍 (p<0.05)的GSH reductase活性 (p<0.05),干擾GSH的代謝。這些結果暗示元寶草粗萃物經由促進體內氧化壓力,而增強了肝腎毒性的可能性較低。 綜合而論,本研究之結果發現:(1) 市售金絲桃草錠劑中同時含有抗憂鬱成份pseudohypericin和hypericin,且兩化合物之實際加總量也多低於標示量,(2)元寶草為五種台灣金絲桃屬植物中最適合開發成為抗憂鬱茶包者,(3)元寶草粗萃物雖然在活體外的試驗中表現出廣泛的抗氧化性質,但管餵一次的前提下,並不能在活體內發揮相類似的效果,(4)同時將元寶草粗萃物和APAP一起服用時,可能增強APAP的毒性,故一般民眾在併用中西藥時,應儘量避免同時服用這兩種藥物為佳。
Recently, extracts of Hypericum perforatum (popularly called St John's Wort) have been used as an effective treatment for depression, and most tablets are claimed to contain about 900 μg hypericins. However, there are few papers about the actual contents of hypericin in commercial products and in the plants of Hypericum in Taiwan. The purposes of this study were: (1) to determine the contents of pseudohypericin and hypericin in five different commercial products and in plants of Hypericum in Taiwan, and (2) to investigate antioxidative properties and toxicity extracts of Hypericum species in Taiwan which contained the highest level of hypericin. Furthermore, we investigated the effect of the extracts on acetaminophen (APAP)-induced acute hepato-toxicity and/or nephrotoxicity in rats. The contents of pseudohypericin in five commercial products were 1.48 to 3.1 times higher than those of hypericin. The total contents of both compounds were highest in “Source Naturals” product, which contained 150 ± 9.4 μg hypericin /tablet and 465 ± 28 μg pseudohypericin /tablet. The contents of pseudohypericin and hypericin in methanolic extracts of five plants of Hypericum (H.) in Taiwan, including H. sampsonii, H. japonicum, H. patutum, H. monogynum and H. nagasawai were determined by reverse-phase high-performance liquid chromatographic (HPLC) method. The results showed that all of these extracts contained both compounds and the extracts of H. sampsonii extracts (HSE) contained highest level (pseudohypericin = 121 ± 18.8 and hypericin = 62.4 ± 9.6 μg/g dry powders). Thus, we selected the HSE for the following experiments. Oral treatment of mice with HSE up to 10.0 g/kg b.w. resulted in death of mice. The effects of HSE were then studied in Wistar rats after a single oral dose of 0.5, 1.0 and 2.0 g HSE/kg b.w. The histopathology of the liver and kidney and the serum activities of sGOT, sGPT, BUN and CRE were not significantly affected. These results indicate that HSE has very low toxicity. HSE showed anti-lipid peroxidative activity, scavenging effects on DPPH radical , chelating effect on iron (Ⅱ), SOD-like activity and reducing power. Furthermore, HSE inhibited the damage of deoxyribose induce by Fe3+-EDTA/H2O2/ascorbic acid, and the reaction rate constant with hydroxyl radicals was 5 times higher than that of manntiol. These results indicate that HSE has extensive antioxidative properties in vitro. By contrast, a single oral dose of HSE showed no antioxidative activities in vivo. Lipid peroxidation, protein carbonyl contents, antioxidative enzyme activities, total sulfhydryl groups (TSH), glutathione (GSH) contents and GSH-related enzyme activities were not significantly affected by single oral treatment of 0.5, 1.0 and 2.0 g HSE/kg b.w. In rats first injected with APAP, oral treatment with 0.5 g HSE /kg b.w. significantly increased sGPT by 2.19-fold (p<0.05) while APAP treatment with 2.0 g HSE /kg b.w. increased sGOT by 3.84-fold over the APAP controls. Histopathological profiles showed that APAP combined with HSE treatments markedly increased the extent of liver necrosis. The serum BUN and CRE contents were not significantly affected by APAP injection. However, APAP combined with 2.0 g HSE /kg b.w. increased BUN by 4.76-fold (p<0.05) and CRE by 2.51-fold (p<0.05) over the controls. The results imply that combined treatment of APAP with HSE causes renal injury. In addition, HSE treatment significantly increased serum APAP concentrations, and the effect of HSE was dose-dependent. These results suggest that HSE treatment interferes with the metabolism of APAP and increases damage to the liver and kidney by APAP. There were no significant changes in lipid peroxidation, TSH and protein carbonyl contents in liver or kidney after combined treatment of rats with APAP and HSE. However, treatment with APAP (i.p.) led to significantly decreased antioxidant enzyme activities (p<0.05) and lowered NPSH contents (p<0.05) in the liver, but not in the kidney. Furthermore, APAP combined with 2.0 g HSE/ kg b.w. resulted in 61 % (p<0.05) decrease in hepatic GSH contents but 2.41-fold (p<0.05) increase in renal GSH contents and 2.14-fold increase in renal GSH reductase activity. These results imply that the increase in APAP hepatotoxicity by oral administration of HSE is attributed to the increased oxidative stress. In summary, this study showed that: (1) the commercial products contain both pseudohypericin and hypericin and the actual contents in the tablets are showed less than those shown on the label, (2) H. sampsonii is more suitable for development of antidepressant tea bag among the five Taiwanese Hypericum species tested, (3) HSE has extensive antioxidative properties in vitro but not in vivo in a single oral administration, and (4) HSE in combination with APAP may lead to herb-drug interactions. People should be advised to avoid taking H. sampsonii and acetaminophen together.
URI: http://hdl.handle.net/11455/50772
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