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| 題名: | 藥用植物叢立孔雀椰子,印度崖豆,和哈哼花的生物活性成分
Bioactive constituents from medicinal plants: Caryota mitis Lour., Millettia pulchra Kurz, and Staurogyne concinnula (Hance) Kuntze |
| 作者: | Hoa, Vo Thanh |
| 貢獻者: | 中草藥臨床藥物研發博士學位學程
郭曜豪
李慶國 |
| 關鍵詞: | 活 性 成 分;孔雀椰子;印度崖豆;哈 哼 花
Bioactive constituents;Caryota mitis;Millettia pulchra;Staurogyne concinnula、Isolation、Quantification、Optimization |
| 日期: | 2021-07-09 |
| 上傳時間: | 2021-12-29 15:23:55 (UTC+8) |
| 摘要: | 三種藥用植物的生物活性和植物化學成分，包括兩種越南 Caryota mitis Lour。和Millettia pulchra Kurz，以及台灣Staurogyne concinnula (Hance) Kuntze 的一名博士生進行了研究。論文。
為了從自然資源中開發抗炎和抗免疫抑製劑，我們發現 M. pulchra radix 提取物對 LPS 刺激的 RAW264.7 細胞中的 NO 產生具有潛在抑製作用。通過柱層析和製備型 HPLC 進一步純化，五種未描述的黃酮類衍生物 (1-5)、三種未描述的齊墩果型皂苷 (33-35)、四種未描述的環肽 (36-39) 以及 28 種已知的成功隔離。化合物 1-13 的生物學評價表明，化合物 1、4、pongamol (7) 和 2'',2''-二甲基吡喃-[5'',6'':7,8]-黃酮 (8) 顯示顯著抑制炎性細胞因子 IL-6 的產生和 8 還表明 RAW264.7 鼠巨噬細胞中 TNF-α 的產生受到抑制。此外，EtOAc層的主要成分化合物4和8在BV2小膠質細胞中具有顯著的抗NO產生活性。而化合物 33 具有預防百草枯誘導的細胞毒性的前景。
在抗血管生成活性測定後，進行了從 Staurogyne concinnula 的乙醇提取物中分離的潛在正丁醇層。通過 Diaion HP20 柱和反相製備型 HPLC 色譜進一步純化，從正丁醇中分離並表徵了四種未描述的三萜皂苷衍生物 (41-43, 45)、已知的 baptisiasaponin I (44) 以及五種已知的苯丙醇苷層。生物學評估顯示 baptisiasaponin I 具有顯著的抗血管生成作用 (IC50 4.0 ± 0.2 µM)。還介紹了 baptisiasaponin I 通過抑制整聯蛋白/FAK/樁蛋白信號通路及其下游效應物如 MMP2 和 MMP9 的進一步作用機制。
基於來自 Caryota mitis 的正丁醇層的神經保護作用，進一步分離了八種已知化合物，包括兩種肽、兩種黃酮類化合物和四種咖啡酸衍生物。然而，只有化合物 57（一種肽）具有防止百草枯引起的神經毒性的溫和能力。
此外，由於最具潛在的生物效應，M. pulchra 和 S. concinnula 被研究以量化主要成分並優化提取過程。因此，根據國際協調會議 (ICH) 指南，開發並驗證了一種簡單而準確的高效液相色譜 - 光電二極管陣列 (HPLC-PDA) 方法，具有顯著的統計影響。此外，響應面方法 (RSM)、人工神經網絡 (ANN) 模型用於預測性能和提取過程優化。 RSM 和 ANN 建模都證明了出色的預測質量。然而，人工神經網絡模型提供了較高的決定係數值和較低的均方根誤差值，表明人工神經網絡模型可以有效地預測反應。因此，本研究提出了一種有效的定量方法和最佳提取條件，這將有助於這些物種藥物開發中的質量控制。
The biological activities and phytochemical constituents of three medicinal plants including two Vietnamese Caryota mitis Lour. and Millettia pulchra Kurz, and one Taiwanese Staurogyne concinnula (Hance) Kuntze were investigated in the Ph.D. thesis.
In order to develop the anti-inflammatory and anti-immunosuppressive agents from natural resources, we found that the extract of M. pulchra radix possesses the potential inhibition of NO production in the LPS-stimulated RAW264.7 cell. Further purification by column chromatography and preparative HPLC, five undescribed flavonoid derivatives (1-5), three undescribed oleanane-type saponins (33-35), four undescribed cyclic peptides (36-39), along with twenty-eight known ones, were isolated successfully. Biological evaluation of compounds 1-13 revealed that compounds 1, 4, pongamol (7), and 2′′,2′′-dimethylpyrano-[5′′,6′′:7,8]-flavone (8) showed the significant suppression of inflammatory cytokine IL-6 production and 8 also showed the suppression of TNF-α production in RAW264.7 murine macrophage cells. Moreover, the major components of the EtOAc layer, compounds 4 and 8, possessed significant anti-NO production activities in BV2 microglia cells. Whereas compound 33 possessed the promising prevention of paraquat-induced cytotoxicity.
After anti-angiogenic activity assay, the potential n-butanol layer partitioned from the ethanol extract of Staurogyne concinnula was conducted. Further purification by Diaion HP20 column and reversed-phase preparative HPLC chromatography, four undescribed triterpenoid saponin derivatives (41-43, 45), the known baptisiasaponin I (44), and along with five known phenylpropanoid glycosides were isolated and characterized from n-butanol layer. Biological evaluation revealed that baptisiasaponin I possessed significant anti-angiogenic effects (IC50 4.0 ± 0.2 µM). Further mechanism of action of baptisiasaponin I by inhibition of integrin/FAK/paxillin signaling pathway and its downstream effectors as MMP2 and MMP9 are also presented.
Based on the neuroprotective effect of n-butanol layer from Caryota mitis, eight know compounds, including two peptides, two flavonoids, and four caffeic acid derivatives were further isolated. However, only compound 57, a peptide, had the gentle ability to prevent paraquat-induced neurotoxicity.
In addition, M. pulchra and S. concinnula were studied to quantify the major components and optimize the extraction process, due to the most potential biological effects. As a result, a simple and accurate high-performance liquid chromatography–photodiode array (HPLC–PDA) method has been developed and validated with significantly statistical impacts, according to International Conference on Harmonization (ICH) guidelines. Furthermore, the Response Surface Methodology (RSM), Artificial Neural Network (ANN) models were employed for predictive performance and the extraction process optimization. Both RSM and ANN modellings proved an excellent predictive quality. However, the ANN model provided the higher coefficient of determination values, and lower root means square error values, indicating that the ANN model can effectively predict responses. Thus, this research suggests an effective quantitative method and an optimal extraction condition, which will be helpful for quality control in the pharmaceutical development of these species. |
| 描述: | 博士
指導教授：郭曜豪
指導教授：李慶國
委員：陳日榮 |
| 資料類型: | thesis |
| 顯示於類別: | [中草藥臨床藥物研發博士學位學程] 博碩士論文
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