作者机构：
[Jia, Yan-Zhe; Wang, Wei; Peng, Cai-Yun; Jian, Yu-Qing; Peng, CY; Li, Bin; Xie, Qing-Ling; Yang, Yu-Pei; Wang, Meng-Yun] Hunan Univ Chinese Med, Sch Pharm, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab, Changsha 410208, Peoples R China.;[Cheng, Shao-Wu] Hunan Univ Chinese Med, Key Lab Coll & Univ Hunan Prov Cytobiol & Mol Bio, Key Lab Hunan Prov Integrated Tradit Chinese & We, Changsha 410208, Hunan, Peoples R China.;[Liu, Bin] Hunan Univ, Coll Biol, Changsha 410082, Hunan, Peoples R China.;[Cao, Liang] Hunan Acad Agr Sci, Inst Agr Environm & Agroecol, Changsha 410125, Peoples R China.
通讯机构：
[Peng, CY; Wang, W ] H;Hunan Univ Chinese Med, Sch Pharm, Innovat Mat Med Res Inst, TCM & Ethnomed Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
关键词：
Kadsura coccinea (Lem.) A. C. Sm.;Schisandraceae;Heilaohu;Phytochemical;Lignans;Hepatoprotective activity;Fruit
摘要：
Phytochemical investigations on the fresh fruits of Kadsura coccinea (Lem.) A. C. Sm. have led to the isolation of fourteen undescribed 2,2'-cyclolignans named heilaohuguosus A-N, four undescribed aryltetrahydronaphthalene lignans, heilaohuguosus O-R and one tetrahydrofuran lignan, heilaohuguosu 5, with twenty-seven previously described lignan analogues. Their structures and absolute configurations of heilaohuguosus A S were established by spectroscopic methods including 1D and 2D-NMR techniques and CD experiments. All isolated compounds were evaluated for their hepatoprotective activity against APAP-induced toxicity in HepG 2 cells, four 2,2'-cyclolignans, heilaohuguosus A and L, tiegusanin I and kadsuphilol I showed good hepatopmtective activities against APAP toxicity in HepG 2 cells with cell survival rates of 53.5 +/- 1.7%, 55.2 +/- 1.2%, 52.5 +/- 2.4%, and 54.0 +/- 2.2% (positive control bicyclol, 52.1 +/- 1.3%) at 10 mu M, respectively.
作者机构：
[江建锋; 游柏稳; 白强] Department of Geriatrics, The Second Hospital of Hunan University of Chinese Medicine, Changsha, 410005, China;[成绍武; 贺春香; 宋祯彦] Hunan Key Laboratory of Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构：
[You, B.-W.] D;Department of Geriatrics, China
作者机构：
[Zhu, Xing; Sun, Yanyan; Ouyang, Zhicui; Tang, Zhen] Cent South Univ, Xiangya Hosp 3, Dept Pediat, Changsha 410013, Hunan, Peoples R China.;[Cheng, Shaowu] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & We, Changsha 410208, Hunan, Peoples R China.;[Zhang, Yunqiao] Kunming Med Univ, Affiliated Hosp 6, Neuropsychol Ctr, Kunming 653100, Yunnan, Peoples R China.;[Wang, Bo; Hei, Mingyan; Hei, MY; Xiang, Xiying] Capital Med Univ, Beijing Childrens Hosp, Neonatal Ctr, Nanlishi Rd 56, Beijing 100045, Peoples R China.
通讯机构：
[Hei, MY ] C;Capital Med Univ, Beijing Childrens Hosp, Neonatal Ctr, Nanlishi Rd 56, Beijing 100045, Peoples R China.
关键词：
Hypoxia-ischemia(HI);Neuroprotection;Brain injuries;Hippocampus;Toll-like receptor 4;Rat model
摘要：
Neonatal hypoxic-ischemic brain damage (HIBD) survivors present with long-term neurological disorders affecting their quality of life, and there remains a lack of effective treatment. Toll-like receptor 4 (TLR4) is widely distributed in nerve cells and its inhibition has a neuroprotective effect against brain injury. The present study aimed to evaluate the long-term neuroprotective effects of early inhibition of TLR4 during HIBD. Seven-day-old rat pups were subjected to left carotid artery ligation followed by 2 h of hypoxia (8.0% O-2). A single dose of TAK-242 (0.5 mg/kg), a TLR4-specific antagonist, was intraperitoneally injected half an hour prior to hypoxic ischemia (HI). The long-term effects of TAK-242 inhibition on the induced hippocampal injury were investigated by assessing behaviour at P28, and then using a variety of methods to exploring the mechanism, including immunofluorescence, Golgi silver staining, Western blotting and real-time polymerase chain reaction (RT-PCR). TAK-242 treatment significantly reduced the expression levels of TLR4 and its downstream signalling molecules in the ipsilateral lesion of the hippocampus 24 h after HIBD. The Morris water maze (MWM) test demonstrated that TAK-242 treatment reduced the loss of HI-induced learning and memory functions. Immunofluorescence experiments showed that TAK-242 administration attenuated HI-induced loss of neurons, prevented the activation of microglia and astrocytes, and increased the expression of the glutamate receptor subtype, N-methyl D-aspartate 2A (NR2A) in the ipsilateral hippocampus region. Golgi silver staining revealed that TAK-242 prevented an HI-induced decline in spine density in the ipsilateral hippocampus. Western blot and RT-PCR results indicated that the expression of NR2A protein and mRNA in the ipsilateral hippocampi of adolescent rats decreased after neonatal HIBD; early TAK-242 administration may reverse these effects. In conclusion, our findings indicate that early inhibition of TLR4 signalling may improve the long-term prognosis of neonatal HIBD. The mechanisms contributing to this improvement involve reductions in neuronal loss, a decrease in glial cell activation, and an improvement in synaptic plasticity.
作者机构：
[Eckert G.P.] Institute of Nutritional Sciences, Laboratory for Nutrition in Prevention and Therapy, Justus-Liebig-University of Giessen, Biomedical Research Center Seltersberg (BFS), Giessen, 35390, Germany;[Shao-Wu C.; Zhen-Yan S.] The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
通讯机构：
[Gunter P. Eckert] I;Institute of Nutritional Sciences, Laboratory for Nutrition in Prevention and Therapy, Justus-Liebig-University of Giessen, Biomedical Research Center Seltersberg (BFS), Giessen, 35390, Germany
