一條根萃取物及其活性成分Daidzin可透過抗氧化、抗纖維化、以及抗發炎來改善Cyclophosphamide誘發出血性膀胱炎與氧化壓力

吳宮頡¹、林威佑^1,2、宋依婷¹、吳威毅¹、鄭瑀萱¹、陳冬生¹、姜秉鈞^1,3、鄭劍廷¹

¹國立臺灣師範大學生命科學專業學院；²衛生福利部臺北醫院 泌尿科；³天主教耕莘醫療財團法人耕莘醫院 泌尿外科

Glycine tomentella Hayata Extract and its Ingredient Daidzin Ameliorate Cyclophosphamide‑Induced Hemorrhagic Cystitis and Oxidative Stress through the Action of Antioxidation, Anti‑Fibrosis, and Anti‑Inflammation

Kung‑Chieh Wu¹, Wei‑Yu Lin^1,2, Yi‑Ting Sung¹, Wei‑Yi Wu¹, Yu‑Hsiuan Cheng¹, Tung‑Sheng Chen¹, Bing‑Juin Chiang^1,3, Chiang‑Ting Chien¹

¹Department of Life Science, College of Science, National Taiwan Normal University, Taipei, Taiwan; ² Department of Urology, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan; ³Department of Urology, Cardinal Tien Hospital, New Taipei City, Taiwan

Purpose:

We explored the therapeutic potential of intragastric administration of traditional Chinese medicine Glycine tomentella Hayata (I‑Tiao‑Gung [ITG]) extract and its major component Daidzin on cyclophosphamide (CYP)‑induced cystitis, oxidative stress, fibrosis, inflammation, and bladder hyperactivity in rats.

Materials and Methods:

Female Wistar rats were divided into control, CYP (200 mg/kg), CYP+ITG (1.17 g/kg/day), and CYP+Daidzin (12.5 mg/kg/day) groups. We measured the voiding function by the transcystometrogram and evaluated the pathology with the hematoxylin and eosin and Masson stain. We determined the bladder reactive oxygen species (ROS) amount by an ultrasensitive chemiluminescence analyzer, the expression of 3‑nitrotyrosine (3‑NT) and NADPH oxidase 4 (NOX4) by Western blot and the expression of multiple cytokine profiles, including matrix metalloproteinase (MMP)‑8 and tissue inhibitor of metalloproteinase (TIMP)‑1 through a cytokine array.

Results:

ITG extract contains 1.07% of Daidzin through high‑performance liquid chromatography. The effect of ITG extract and Daidzin in scavenging hydrogen peroxide activity was more efficient than distilled water. CYP‑induced higher urination frequency, shorter intercontraction interval, and lower maximal voiding pressure in the bladders and these symptoms were significantly ameliorated in CYP+ITG and CYP+Daidzin groups. The amount of in vivo bladder ROS and the expression of 3‑NT and NOX4 expressions were significantly increased in CYP group but were efficiently decreased in the CYP+ITG and CYP+Daidzin groups.

Conclusions:

CYP‑induced fibrosis, hemorrhage, leukocyte infiltration, and edema in the bladders were significantly attenuated in the CYP+ITG and CYP+Daidzin groups. These results suggested that ITG extract and its active component Daidzin effectively improved CYP‑induced oxidative stress, inflammation, and fibrosis through inhibiting the MMP‑8, TIMP‑1, and oxidative stress.