作者机构：
[常小荣; 邓凯文] Department of Acupuncture and Moxibustion, the First Affiliated Hospital of Hunan University of CM, Changsha 410007, China;[唐闻汉; 周逸群; 贺福元; 杨岩涛; 陶叶琴; 石继连; 刘文龙] College of Pharmaceutics, Hunan University of CM, Changsha 410007, China;[唐闻汉; 周逸群; 贺福元; 杨岩涛; 陶叶琴; 石继连; 刘文龙] Hunan Provincial Key Laboratory of Druggability and Preparation Modification of TCM, Changsha 410007, China;[贺福元] Key laboratory of Property and pharmacodynamic of TCM, State Administration of TCM, Changsha 410007, China;[周逸群; 贺福元; 杨岩涛; 石继连; 刘文龙] Supramolecular Mechanism and Mathematic-Physics Characterization for Chinese Materia Medica, Hunan University of CM, Changsha 410007, China
摘要：
OBJECTIVE: To evaluate the pharmacokinetics and relative bioavailability of two allopurinol tablets in healthy Chinese volunteers. METHODS: A single-center, randomized, cross-over, two-period study design was conducted in healthy male subjects who were identified as not carrying the HLA-B*58:01 allele. Under fasting conditions, a single oral dose of 300 mg test or reference tablets was given with a 1-week washout period. The blood samples were collected for up to 12 hours after the administration and the plasma concentrations of allopurinol were determined by high performance liquid chromatography. Subject interviews and physical examinations were done over regular intervals to monitor the adverse events. RESULTS: 18 subjects were enrolled in the study, and none dropped out. The main pharmacokinetic parameters of allopurinol test and reference preparations were as follows: AUC<sub>0-tlast</sub> was 6,725.1 +/- 1,390.0 ngxhxmL<sup>-1</sup> and 6,425.6 +/- 1,257.6 ngxhxmL<sup>-1</sup>; AUC<sub>0-infinity</sub> was 7,069.1 +/- 1,503.2 ngxhxmL<sup>-1</sup> and 6,750.6 +/- 1,347.7 ngxhxmL<sup>-1</sup>; t<sub>max</sub> was 1.3 +/- 0.8 hours and 1.3 +/- 0.8 hours; C<sub>max</sub> was 2,203.7 +/- 557.4 ngxmL<sup>-1</sup> and 2,310.8 +/- 662.8 ngxmL<sup>-1</sup>; and T<sub>1/2</sub> was 2.0 +/- 1.6 hours and 1.7 +/- 0.7 hours. The relative bioavailability was 105.1 +/- 12.6%. The 90% confidence intervals for the geometric mean ratios (test/reference) of C<sub>max</sub>, AUC<sub>0-tlast</sub>, and AUC<sub>0-infinity</sub> of both preparations fell within the bioequivalence acceptance criteria (80 - 125%). No adverse events were found or reported during the study. CONCLUSION: The test allopurinol preparations and the reference preparations are bioequivalent and both are well tolerated..
摘要：
The seeds of Strychnos nux-vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnos nux-vomica. Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.
期刊：
International Immunopharmacology,2017年49(10):155-160 ISSN：1567-5769
通讯作者：
Yuan, Yu-he;Chen, Nai-hong
作者机构：
[Yang, Peng-fei; Shao, Qian-hang; Chen, Nai-hong; Zhang, Xiao-ling; Yuan, Yu-he] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China.;[Yang, Peng-fei; Shao, Qian-hang; Chen, Nai-hong; Zhang, Xiao-ling; Yuan, Yu-he] Chinese Acad Med Sci, Neurosci Ctr, Beijing 100050, Peoples R China.;[Yang, Peng-fei; Shao, Qian-hang; Chen, Nai-hong; Zhang, Xiao-ling; Yuan, Yu-he; Chen, NH] Peking Union Med Coll, I Xiannongtan St, Beijing 100050, Peoples R China.;[Chen, Nai-hong] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.;[Yuan, Yu-he; Chen, NH] Chinese Acad Med Sci, Inst Mat Med, Dept Pharmacol, I Xiannongtan St, Beijing 100050, Peoples R China.
通讯机构：
[Yuan, YH; Chen, NH] P;[Yuan, YH; Chen, NH] C;Peking Union Med Coll, I Xiannongtan St, Beijing 100050, Peoples R China.;Chinese Acad Med Sci, Inst Mat Med, Dept Pharmacol, I Xiannongtan St, Beijing 100050, Peoples R China.
摘要：
Neuroinflammation has been shown as an essential factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and Multiple Sclerosis. Furthermore, activated microglia and increased pro-inflammatory cytokines are the major hallmarks in neurodegenerative diseases. A multimolecular complex named as inflammasome is involved in the process of inflammatory response, which can activate inflammatory caspases, leading to the cleavage and secretion of inflammatory cytokines, and finally generates a potent inflammatory response. In neurodegenerative diseases, it has been widely assumed that some types of amyloid proteins might be the triggers to activate the NLRP3 inflammasome. In this review, we summarize the current researches about the role of NLRP3 inflammasome, by reviewing the main studies in vitro and in vivo experiments and discuss the potential for new therapeutic interventions in neurodegenerative diseases.
作者：
Seo, Yun-Soo;Lee, Seok-Jeon;Li, Zhi;Kang, Ok-Hwa;Kong, Ryong;...
期刊：
Molecular Medicine Reports,2017年16(1):857-864 ISSN：1791-2997
通讯作者：
Kwon, Dong-Yeul;Liu, Xiangqian
作者机构：
[Zhou, Tian; Kong, Ryong; Kim, Sang-A; Kang, Ok-Hwa; Kwon, Dong-Yeul; Seo, Yun-Soo] Wonkwang Univ, Wonkwang Oriental Medicines Res Inst, Coll Pharm, Dept Oriental Pharm, 460 Iksandae Ro, Iksan 570749, Jeollabuk, South Korea.;[Lee, Seok-Jeon] Wonkwang Univ, Dept Med 3, Profess Grad Sch Oriental Med, Iksan 570749, Jeollabuk, South Korea.;[Liu, Xiangqian; Li, Zhi] Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Kwon, Dong-Yeul] W;[Liu, Xiangqian] H;Wonkwang Univ, Wonkwang Oriental Medicines Res Inst, Coll Pharm, Dept Oriental Pharm, 460 Iksandae Ro, Iksan 570749, Jeollabuk, South Korea.;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
araliasaponin II;anti-inflammatory;Toll-like receptor 4;nuclear factor-kappa B
摘要：
Araliasaponin II (AS II) is a bioactive compound isolated from Acanthopanax henryi (Oliv.) Harms, a plant widely used in traditional oriental medicine. The present study investigated the anti-inflammatory effects of AS II using murine macrophages. The effects of AS II on inflammatory mediator and cytokine production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was evaluated. Nitric oxide (NO) and cytokine production were determined using the Griess reagent and an ELISA kit. The expression levels of cytokines, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA were examined by reverse transcription-quantitative polymerase chain reaction. The expression levels of iNOS, COX-2 and toll-like receptor (TLR)-4 protein were examined by western blotting. Translocation of nuclear factor-kappa B (NF-kappa B) and TLR-4 expression were visualized by immunofluorescence staining. AS II markedly inhibited the production of NO and prostaglandin E2, and reduced iNOS and COX-2 expression at the transcriptional and translational levels. AS II downregulated the expression of interleukin-6 and tumor necrosis factor-alpha at the protein and mRNA levels. Furthermore, pre-treatment with AS II significantly suppressed the TLR-4-NF-kappa B signaling pathway; this effect may be cause by AS II competing with LPS for binding to TLR-4 and subsequently inhibiting translocation of the NF-kappa B/p65 protein to the nucleus. The results suggested that the anti-inflammatory properties of AS II may result from inhibiting pro-inflammatory mediators by suppressing the initiation of the inflammatory response and inhibiting TLR-4-NF-kappa B signaling pathways.
作者机构：
[胡超; 刘文龙; 贺福元; 范诗琪; 朱俊平; 肖小芹; 杨姣; 李森; 刘金玲] School of Pharmacy, Hunan University of Traditional Chinese Medicine, Changsha 410208, China;[刘文龙; 贺福元] Hunan Key Laboratory of Druggability and Preparation Modification of Traditional Chinese Medicine, Changsha 410208, China;[刘文龙; 贺福元] Supramolecular Mechanism and Mathematics-Physics Characterization Laboratory for Chinese Materia Medica, Hunan University of Traditional Chinese Medicine, Changsha 410208, China
作者机构：
[Gu, Hong-Feng; Tang, Xiao-Qing; Tang, Ya-Ling] Univ South China, Dept Physiol, Hengyang, Peoples R China.;[Gu, Hong-Feng; Tang, Xiao-Qing; Tang, Ya-Ling] Univ South China, Inst Neurosci, Hengyang, Peoples R China.;[Li, Hai-Zhe; Nie, Ya-Xiong] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang, Peoples R China.;[Xie, Xue-Jiao; Liao, Duan-Fang] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha, Hunan, Peoples R China.
通讯机构：
[Nie, Ya-Xiong] U;[Liao, Duan-Fang] H;Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang, Peoples R China.;Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha, Hunan, Peoples R China.
作者机构：
[Liu, Jianghua; Zu, Xuyu] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Yan, Ruilan; Cao, Yu; Ma, Jun; Zu, Xuyu; Zhong, Linlin; Cao, Deliang] Southern Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Simmons Canc Inst, 913 N Rutledge St, Springfield, IL 62794 USA.;[Chung, Fung-Lung; Pan, Jishen] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.;[Cao, Deliang; Huang, Dan; Liao, Duan-Fang; Cai, Chuan] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
通讯机构：
[Zu, Xuyu] U;[Cao, Deliang] S;Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.;Southern Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Simmons Canc Inst, 913 N Rutledge St, Springfield, IL 62794 USA.
关键词：
AKR1B10;electrophilic carbonyl compounds;DNA damage;acrolein-deoxyguanosine adducts;colorectal cancer
摘要：
Electrophilic carbonyl compounds are highly cytotoxic and genotoxic. Aldo-keto reductase 1B10 (AKR1B10) is an enzyme catalyzing reduction of carbonyl compounds to less toxic alcoholic forms. This study presents novel evidence that AKR1B10 protects colon cells from DNA damage induced by electrophilic carbonyl compounds. AKR1B10 is specifically expressed in epithelial cells of the human colon, but this study found that AKR1B10 expression was lost or markedly diminished in colorectal cancer, precancerous tissues, and a notable portion of normal adjacent tissues (NAT). SiRNA-mediated silencing of AKR1B10 in colon cancer cells HCT-8 enhanced cytotoxicity of acrolein and HNE, whereas ectopic expression of AKR1B10 in colon cancer cells RKO prevented the host cells against carbonyl cytotoxicity. Furthermore, siRNA-mediated AKR1B10 silencing led to DNA breaks and activation of -H2AX protein, a marker of DNA double strand breaks, particularly in the exposure of HNE (10M). In the AKR1B10 silenced HCT-8 cells, hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequency increased by 26.8 times at basal level and by 33.5 times in the presence of 10M HNE when compared to vector control cells. In these cells, the cyclic acrolein-deoxyguanosine adducts levels were increased by over 10 times. These findings were confirmed by pharmacological inhibition of AKR1B10 activity by Epalrestat. Taken together, these data suggest that AKR1B10 is a critical protein that protects host cells from DNA damage induced by electrophilic carbonyl compounds. AKR1B10 deficiency in the colon may be an important pathogenic factor in disease progression and carcinogenesis. (c) 2016 Wiley Periodicals, Inc.
期刊：
Journal of Pharmaceutical and Biomedical Analysis,2017年138:240-248 ISSN：0731-7085
通讯作者：
Tang, Qi;Zeng, Jian-Guo
作者机构：
[Tang, Q; Zeng, Jian-Guo; Zheng, Ya-Jie; Qing, Zhi-Xing; Tang, Qi; Liu, Xiu-Bin; Cheng, Pi; Yang, Xue-Yi; Huang, Peng] Hunan Agr Univ, Natl & Local Union Engn Res Ctr Vet Herbal Med Re, Changsha 410128, Hunan, Peoples R China.;[Tang, Q; Zeng, Jian-Guo; Zheng, Ya-Jie; Qing, Zhi-Xing; Tang, Qi; Liu, Xiu-Bin; Cheng, Pi; Yang, Xue-Yi; Huang, Peng] Hunan Agr Univ, Hunan Coinnovat Ctr Utilizat Bot Funct Ingredient, Changsha 410128, Hunan, Peoples R China.;[Qing, Zhi-Xing; Yang, Peng; Zeng, Jian-Guo] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.;[Zhao, Huan] China Acad Chinese Med Sci, Natl Resource Ctr Chinese Mat Med, State Key Lab Breeding Base Dao Di Herbs, Beijing 100700, Peoples R China.;[Mo, Chang-ming] Guangxi Bot Garden Med Plants, Nanning 530023, Peoples R China.
通讯机构：
[Tang, Q; Zeng, JG] H;Hunan Agr Univ, Natl & Local Union Engn Res Ctr Vet Herbal Med Re, Changsha 410128, Hunan, Peoples R China.;Hunan Agr Univ, Hunan Coinnovat Ctr Utilizat Bot Funct Ingredient, Changsha 410128, Hunan, Peoples R China.
摘要：
The fruits of Siraitia grosvenorii are considered to be health-promoting because of the diversity of their bioactive ingredients. In the present study, a screening method, using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening strategy, has been established. The technology was used to systematically screening the targeted metabolites, primarily from the complex matrix of S. grosvenorii. The compounds were then identified by their exact masses and characteristic fragment ions, in comparison with the fragmentation behaviors of 19 references. Finally, 122 compounds, including 53 flavonols and flavonol glycosides, 59 triterpene glycosides and 10 siraitic acid glycosides, were screened and identified in 10-, 50- and 80-day fruits, roots, stems and leaves of S. grosvenorii. 98 of them were reported for the first time. Additionally, the distribution of all identified components in different parts of the plant was determined and metabolic networks for flavonol and triterpene glycosides were proposed. (C) 2017 Published by Elsevier B.V.
摘要：
Oxidative stress is thought to be involved in the development of Parkinson's disease (PD). We previously reported that 20C, a bibenzyl compound isolated from Gastrodia elata, possesses antioxidative properties, but its in-depth molecular mechanisms against rotenone-induced neurotoxicity remains unknown. Recent studies indicate that without intact DJ-1, nuclear factor erythroid 2-related factor (Nrf2) protein becomes unstable, and the activity of Nrf2-mediated downstream antioxidant enzymes are thereby suppressed. In this study, we showed that 20C clearly protected PC12 and SH-SY5Y cells against rotenone-induced oxidative injury. Furthermore, 20C markedly up-regulated the levels of DJ-1, which in turn activated phosphoinositide-3-kinase (PI3K)/Akt signaling and inhibited glycogen synthase kinase 3 beta (GSK3 beta) activation, eventually promoted the nuclear translocation of Nrf2 and induced the expression of hemeoxygenase-1 (HO-1). The antioxidant effects of 20C could be partially blocked by ShRNA-mediated knockdown of DJ-1 and inhibition of the PI3K/Akt pathways with Akt1/2 kinase inhibitor, respectively. Conclusively, our findings confirm that DJ-1 is necessary for 20C-mediated protection against rotenone-induced oxidative damage, at least in part, by activating PI3K/Akt signaling, and subsequently enhancing the nuclear accumulation of Nrf2. The findings from our investigation suggest that 20C should be developed as a novel candidate for alleviating the consequences of PD in the future. (C) 2017 Elsevier B.V. All rights reserved.
