傳統中醫藥對於發炎性疾病的治療潛力

Therapeutic Potential of Traditional Chinese Medicine on Inflammatory Diseases

蔡文興(Tsai Wen-Hsin)

指導教授 ： 吳忠信 ； 鄭劍廷

國立臺灣師範大學/理學院/生命科學系/博士(2016年)

https://doi.org/10.6345/NTNU202204403

摘要

氧化壓力的增加，誘發多個組織/器官的發炎，導致細胞死亡和長期傷害。傳統的中醫學（TCM）具有抗氧化，抗發炎，抗凋亡和自噬調控功能已被廣泛地用在現代醫學中的預防或治療策略。氧化壓力和發炎已經被廣泛報導有關於臨床上所見P物質介導的神經源性膀胱過動。
為了改善膀胱過動症，我們探討潛在的藥物和神經源性膀胱機制。 P物質（SP）會藉由興奮膀胱的感覺傳入神經和細胞間粘附分子-1（ICAM-1）介導白血球粘附和活性氧族（ROS）產物的增加引起的膀胱過動。八味地黃丸（BWDHW）是一種傳統的中草藥複方，一直使用來治療罹患下尿路症狀的患者，但作用機轉並不清楚。我們在本研究探討其中的活性成分及BWDHW對於SP誘發膀胱活動過度的影響。結果顯示，BWDHW是經由loganin抑制SP /神經激肽-1(NK-1)受體信號傳導，降低NF-κB/ ICAM-1介導白血球粘附和浸潤和ROS水平，因而改善膀胱過動症狀。
我們也探討L-茶氨酸對於P物質誘導的促炎信號PKC / ERK / NF-κB/ ICAM-1 / IL-33，白血球浸潤和粘附，活性氧（ROS）產物，自噬和凋亡對膀胱過動的療效。總之，口服L-茶氨酸確定能藉由抑制促炎信號，氧化壓力，膀胱神經活性，細胞凋亡和自噬，改善P物質誘導的膀胱過動。

關鍵字

細胞凋亡 ； 細胞自噬 ； 發炎 ； 氧化壓力 ； 傳統中醫學 ； 膀胱過動症 ； P物質 ； 八味地黃丸 ； 茶氨酸

並列摘要

Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to substance P–mediated neurogenic hyperactive bladder based on clinical findings.
To improve hyperactive bladder, we explored potential drugs and mechanism on neurogenic bladder. Substance P (SP) induced hyperactive bladder via the enhancement of bladder afferent signaling and intercellular adhesion molecule-1 (ICAM-1) mediated leukocyte adhesion and ROS production. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese herbal mixture, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We investigated the active components and effects of BWDHW on SP-induced bladder hyperactivity. Our results indicate that BWDHW via loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1 receptor signaling and depressing NF-κB/ICAM-1 mediated leukocyte adhesion and infiltration and ROS levels.
We explored the effect of L-theanine treatment on SP-induced proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, leukocyte infiltration and adhesion, ROS production, autophagy and apoptosis in the bladder. In summary, oral intake L-theanine ameliorates substance P-induced bladder hyperactivity via the inhibition of proinflammatory signaling, oxidative stress, exaggerated bladder nerve activity, apoptosis and autophagy.

並列關鍵字

Apoptosis ； Autophagy ； Inflammation ； Oxidative stress ； Traditional Chinese Medicine ； Overactive bladder ； Substance P ； BWDHW ； Theanine

參考文獻

Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. (2002). The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn, 21(2):167-78.

Barr J, Sharma CS, Sarkar S, Wise K, Dong L, Periyakaruppan A, et al. (2007). Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells. Mol Cell Biochem, 297:93-9.

Bauer, V., R. Sotnikova, J. Machova, S. MatyasS, V. Pucovsky and M. Stefek. (1999). Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants. Life Sci. 65: 1909–1917.

Chen WC, Hayakawa S, Shimizu K, Chien CT, Lai MK. (2004). Catechins prevents substance P-induced hyperactive bladder in rats via the downregulation of ICAM and ROS. Neurosci Lett, 367:213-7.

Chen WC, Shih CC, Lu WA, Li PC, Chen CJ, Hayakawa S, et al. ( 2006). Combination of Wu Lin San and Shan Zha ameliorates substance P-induced hyperactive bladder via the inhibition of neutrophil NADPH oxidase activity. Neurosci Lett, 402:7-11.