著者

Suzuki Hideo Kaneko Tsuyoshi Mizokami Yuji Narasaka Toshiaki Endo Shinji Matsui Hirofumi Yanaka Akinori Hirayama Aki Hyodo Ichinosuke

出版者

Baishideng Publishing Group Inc.

雑誌

World journal of gastroenterology (ISSN:10079327)

巻号頁・発行日

vol.19, no.17, pp.2718-2722, 2013-05

被引用文献数

59 2

---

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may become intractable when treated with conventional medications such as aminosalicylates, corticosteroids, and azathioprine. The herbal medicine Qing Dai has traditionally been used in Chinese medicine to treat UC patients, but there is a lack of published data on the efficacy of Qing Dai in UC treatment. We report several cases of patients with intractable UC who take Qing Dai in a retrospective observational study. Furthermore, we explore the mechanisms of action of Qing Dai. Nine patients with active UC who received conventional medications but wished to receive Qing Dai as an alternative medication were included in our analysis. The UC severity level was determined based on the clinical activity index (CAI). Additionally, 5 of the 9 patients were endoscopically evaluated according to the Matts grading system. Each patient received 2 g/d of Qing Dai orally and continued taking other medications for UC as prescribed. Electron spin resonance was applied to explore the mechanisms of action of Qing Dai. After 4 mo of treatment with Qing Dai, the CAI score decreased from 8.3 ± 2.4 to 2.4 ± 3.4 (mean ± SD; P < 0.001). Similarly, the endoscopic Matts grade decreased from 3.4 ± 0.5 to 2.2 ± 0.8 (P = 0.02). Six of 7 patients who were on prednisolone upon enrollment in the study were able to discontinue this corticosteroid. Electron spin resonance revealed that Qing Dai possesses strong hydroxyl radical scavenging activity. Qing Dai showed significant clinical and endoscopic efficacy in patients who failed to respond to conventional medications. Scavenging of hydroxyl radicals appears to be a potential mechanism through which Qing Dai acts, but the significance of the scavenging ability of Qing Dai with respect to the anti-inflammatory effect in UC patients warrants further investigation.

著者

Tamura Masato Matsui Hirofumi Kaneko Tsuyoshi Hyodo Ichinosuke

出版者

Society for Free Radical Research Japan

雑誌

Journal of clinical biochemistry and nutrition (ISSN:09120009)

巻号頁・発行日

vol.53, no.2, pp.75-80, 2013-08

被引用文献数

45 4

---

Alcohol/ethanol has been reported to derived necrosis and apoptosis with an oxidative stress in gastric mucosal cells. However the clear evidence for reactive oxygen species (ROS) generation by alcohol in gastric cells in vitro is none. In this study, we elucidated ethanol is an oxidative stress inducer on rat gastric epithelial cells by electron paramagnetic resonance measurement in living cells. We also confirmed whether ethanol-induced cellular ROS was derived from mitochondria or not. The results of cellular ROS determination showed that an increment of cellular ROS was shown for 15 min from exposing 1% (v/v) ethanol. Lipid peroxidation in cellular membrane also induced by 1% ethanol and the tendency is same in the results of cellular ROS determination. JC-1 stained showed the decrement of mitochondrial membrane potential. Additionally the localization of cellular ROS coincided with mitochondria. These results indicated that ethanol is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer via injured mitochondria.

著者

Sha Sha Vong Long Binh Chonpathompikunlert Pennapa Yoshitomi Toru Matsui Hirofumi Nagasaki Yukio

出版者

Elsevier

雑誌

Biomaterials (ISSN:01429612)

巻号頁・発行日

vol.34, no.33, pp.8393-8400, 2013-11

被引用文献数

46 5

---

Patients regularly taking non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) have a risk of small intestinal injuries. In this study, we have developed an oral nanotherapeutics by using a redox nanoparticle (RNPO), which is prepared by self-assembly of an amphiphilic block copolymer that possesses nitroxide radicals as side chains of hydrophobic segment via ether linkage, to reduce inflammation in mice with IND-induced small intestinal injury. The localization and accumulation of RNPO in the small intestine were determined using fluorescent-labeled RNPO and electron spin resonance. After oral administration, the accumulation of RNPO in both the jejunum and ileum tissues was about 40 times higher than those of low-molecular-weight nitroxide radical compounds, and RNPO was not absorbed into the bloodstream via the mesentery, thereby avoiding the adverse effects of nitroxide radicals in the entire body. RNPO remarkably suppressed inflammatory mediators such as myeloperoxidase, superoxide anion, and malondialdehyde in the small intestines of IND-treated mice. Compared to low-molecular-weight nitroxide radical compounds, RNPO also significantly increased the survival rate of mice treated daily with IND. On the basis of these results, RNPO is promising as a nanotherapeutics for treatment of inflammation in the small intestine of patients receiving NSAIDs.

著者

Vong Long Binh Tomita Tsutomu Yoshitomi Toru Matsui Hirofumi Nagasaki Yukio

出版者

Elsevier

雑誌

Gastroenterology (ISSN:00165085)

巻号頁・発行日

vol.143, no.4, pp.1027-1036.e3, 2012-10

被引用文献数

153 22

---

Background & AimsDrugs used to treat patients with ulcerative colitis are not always effective because of nonspecific distribution, metabolism in the gastrointestinal tract, and side effects. We designed a nitroxide radical-containing nanoparticle (RNPO) that accumulates specifically in the colon to suppress inflammation and reduce the undesirable side effects of nitroxide radicals.MethodsRNPO was synthesized by assembly of an amphiphilic block copolymer that contains stable nitroxide radicals in an ether-linked hydrophobic side chain. Biodistribution of RNPO in mice was determined from radioisotope and electron spin resonance measurements. The effects of RNPO were determined in mice with dextran sodium sulfate (DSS)-induced colitis and compared with those of low-molecular-weight drugs (4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl [TEMPOL] or mesalamine).ResultsRNPO, with a diameter of 40 nm and a shell of poly(ethylene glycol), had a significantly greater level of accumulation in the colonic mucosa than low-molecular-weight TEMPOL or polystyrene latex particles. RNPO was not absorbed into the bloodstream through the intestinal wall, despite its long-term retention in the colon, which prevented its distribution to other parts of the body. Mice with DSS-induced colitis had significantly lower disease activity index and less inflammation following 7 days of oral administration of RNPO compared with mice with DSS-induced colitis or mice given low-molecular-weight TEMPOL or mesalamine.ConclusionsWe designed an orally administered RNPO that accumulates specifically in the colons of mice with colitis and is more effective in reducing inflammation than low-molecular-weight TEMPOL or mesalamine. RNPO might be developed for treatment of patients with ulcerative colitis.