植物藥已經被作為中草藥的來源，從過去到現在持續的作為許多藥物的使用依據。本論文的研究主題，是研究丹參酚酸鎂鹽B (MLB) 活血化瘀與樟芝酸A (antcin A) 抗發炎的分子機制。過去的研究顯示，丹參酚酸鎂鹽B能夠抑制鈉鉀幫浦；本實驗結果顯示，丹參酚酸鎂鹽B與哇巴因 (ouabain, 強心配醣體) 相同，都能夠使神經細胞內的鈣離子增加；而鈣離子的來源是藉由鈉鈣交換蛋白，將細胞外的鈣離子送入細胞內，以及內質網膜上的IP3通道，將鈣離子釋放至細胞質中；利用分子模擬分析顯示，丹參酚酸鎂鹽B與哇巴因，均可與鈉鉀幫浦形成五個氫鍵；丹參酚酸鎂鹽B並不會使細胞的形態有所改變，綜合上述結果，丹參酚酸鎂鹽B與哇巴因相同，皆具有抑制鈉鉀幫浦的能力並啟動下游相同的機制，因此，丹參酚酸鎂鹽B具有潛力，開發作為心臟疾病的治療用藥。
牛樟芝是臺灣特有的藥用真菌，其良好的抗發炎效果已經有文獻報導，同時該療效也被使用者所認同；由本論文結果顯示，樟芝酸A的結構與醣皮質激素中的cortisone結構相似；並且與醣皮質激素相同，皆能夠使醣皮質激素受體進入細胞核內，但樟芝酸A所需要的有效濃度高於醣皮質激素，才能驅使醣皮質激素受體進入細胞核內；分子模擬結果顯示，樟芝酸A所形成的氫鍵數少於醣皮質激素中的dexamethasone；綜合上述實驗結果，顯示樟芝酸A對於牛樟芝的抗發炎效果是有所貢獻的，它模擬醣皮質激素啟動了受體進入細胞核，經由基因的調控抑制發炎。

Botanical remedies have been used as a source of traditional Chinese medicines throughout history and continue to serve as the basis for many pharmaceuticals used today. This study focused on the molecular mechanism of magnesium lithospermate B (MLB) and antcin A in the promotion of blood circulation and anti-inflammation. Previous studies have indicated that the MLB extract from the Danshen (Salvia miltiorrhiza Bunge) inhibits the activity of Na+/K+-ATPase. The results of Chapter 1 demonstrate that the increase in intracellular free Ca2+ levels follows similar patterns when MLB and ouabain were used to treat neuroblastoma cells. Intracellular free Ca2+ is obtained from outside the cell via the Na+/Ca2+ exchanger and IP3 channel of the ER membrane. Both MLB and ouabain are equivalent, forming 5 hydrogen bonds in the Na+/K+-ATPase cavity. There was a change in dendrite morphology under ouabain treatment, but not under MLB. Comparable to ouabain, MLB triggered the same mechanism by inhibiting Na+/K+-ATPase, and it possesses more potential as a botanical medicine for cardiac disease.
Niuchangchih (Antrodia camphorata, syn. Taiwanofungus camphoratus) is a unique medicinal fungus found in Taiwan. Its anti-inflammatory effect has been reported, and consumer experience attests to this. The results in Chapter 2 demonstrate that the structure of antcin A, extracted from the fruiting bodies of Niuchangchih, is similar to that of the glucocorticoid cortisone. Examination of the nuclear migration of the glucocorticoid receptor (GR) effect demonstrated that antcin A and glucocorticoids both migrate into the nucleus and the minimal effective concentration of antcin A exceeds that of glucocorticoids. Molecular modeling indicated that antcin A forms hydrogen bonds less than the glucocorticoid dexamethasone. In the study, the anti-inflammatory effect of Niuchangchih should be partly attributed to antcin A, which mimics glucocorticoids and triggers translocation of the GR into the nucleus to initiate suppression of inflammation via gene regulation.

TABLE OF CONTENTS

ABSTRACT IN CHINESE………………………………………..... i
ABSTRACT IN ENGLISH...……………………………………….. ii
TABLE OF CONTENTS……………………………………………... iv
LIST OF FIGURE………………………………………………….. v
RESEARCH BACKGROUND……………………………………....... 1
REFERENCES……………………………………………………….. 11
FIGURES.…………………………………………………………… 21

CHAPTER 1 Magnesium lithospermate B extracted from Salvia miltiorrhiza elevates intracellular Ca2+ level in SH-SY5Y cells

ABSTRACT………………………………………....... 32
INTRODUCTION…………………………………....... 34
MATERIALS AND METHODS………………….......... 36
RESULTS…………………………………………...... 41
DISCUSSION………………………………………..... 44
REFERENCES……………………………………....... 47
FIGURES…………………………………………...... 52

CHAPTER 2 Antcin A, by mimicking glucocorticoids, triggers the mechanism putatively responsible for the anti-inflammatory effect of Antrodia camphorata

ABSTRACT………………………………………....... 58
INTRODUCTION…………………………………....... 60
MATERIALS AND METHODS………………….......... 62
RESULTS…………………………………………...... 67
DISCUSSION………………………………………..... 71
REFERENCES……………………………………....... 74
FIGURES…………………………………………...... 78

CONCLUSION……………………………………………………… 85
REFERENCES……………………………………………………… 87

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