Active fraction combination from Liuwei Dihuang decoction improves adult hippocampal neurogenesis and neurogenic microenvironmentin cranially irradiated mice / 中国药理学与毒理学杂志

OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however, the conse?quent cognitive and emotional dysfunctions seriously impair the life quality of patients. LW-AFC, an active fraction combi?nation extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction, can improve cogni?tive and emotional dysfunctions in many animal models;however, the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported. Recent studies indicate that impairment of adult hippocampal neurogenesis (AHN) and alterations of the neurogenic microenvironment in the hippocampus constitute crit?ical factors in cognitive and emotional dysfunctions following cranial irradiation. Here, our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dys?functions in mice. METHODS LW-AFC (1.6 g·kg-1) was intragastrically administered to mice for 14 d before cranial irra?diation (7 Gyγ-ray). AHN was examined by quantifying the number of proliferative neural stem cells and immature neu?rons in the dorsal and ventral hippocampus. The contextual fear conditioning test, open field test, and tail suspension test were used to assess cognitive and emotional functions in mice. To detect the change of the neurogenic microenvi?ronment, colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress, neurotrophic and growth factors, and inflammation in the hippocampus. RESULTS LW-AFC exerted beneficial effects on the contex?tual fear memory, anxiety behavior, and depression behavior in irradiated mice. Moreover, LW-AFC increased the num?ber of proliferative neural stem cells and immature neurons in the dorsal hippocampus, displaying a regional specificity of neurogenic response. For the neurogenic microenvironment, LW-AFC significantly increased the contents of superox?ide dismutase, glutathione peroxidase, glutathione, and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice, accompanied by the increase in brain-derived neurotrophic factor, insulin-like growth factor-1, and interleukin-4 content. Together, LW-AFC improved cognitive and emotional dysfunctions, promoted AHN preferentially in the dorsal hippocampus, and ameliorated disturbance in the neurogenic microenvironment in irradiated mice. CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions, and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic micro?environment. LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology / 中国天然药物

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine / 中国药理学与毒理学杂志

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Research progresses in pharmacological effects of rhynchophylline and its isomers on nervous system / 药学学报

Uncaria rhynchophylla is one of the frequently used herbs in China, it is mainly used for heat-clearance, suppression of hyperactive liver, calming endogenous wind and arresting convulsion in traditional Chinese medicine (TCM). Alkaloids are the main active materials in Uncaria rhynchophylla, pharmacological studies have shown that Uncaria rhynchophylla and its alkaloids have comprehensive biological effects on the nervous system. Rhynchophylline is one of the most abundant alkaloids in Uncaria rhynchophylla. The recent studies demonstrate that rhynchophylline and its isomers (isorhynchophylline, corynoxine, corynoxine B) may be good drug candidates for treatment of Alzheimer's disease, Parkinson's disease, epilepsy, etc. Although the structures of the 4 alkaloids are very similar, they have different effects on nervous system. For example, corynoxine and corynoxine B exhibit better sedative effects than isorhynchophylline. Rhynchophylline and isorhynchophylline have been extensively studied. For development and utilization of rhynchophylline for nervous system disease, more studies are needed to unveil the structure-function relationship and the underlying mechanisms. Here, we summarizes the progresses the effects of rhynchophylline and its isomers on the nervous system.

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Ideas of systems biology on study of traditional Chinese medicine / 中国中药杂志

Traditional Chinese medicine (TCM) is the scientific therapeutics derived from the traditional Chinese physician's considerable clinical practice during the long history, with the characteristic of significant clinical therapeutic effects. The therapeutic philosophy of TCM is integrative medicine and pattern differentiation. The ideas of systems biology on the study of TCM were formed after the micro-and macro-outcome of systems biology being used into the practice of study on TCM. It is very important for the inheritance and development of TCM to disclose the basic mechanism of the clinical therapeutic effects of TCM and find new drugs, from the herbal preparation, pharmacology and pharmacokinetic to drug development using modern science technologies based on the theory of TCM.

A new monoterpene glycoside from active fraction (DSS-A-N-30) of Danggui Shaoyao San / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of an active fraction (DSS-A-N-30) from Danggui Shaoyao San.</p><p><b>METHOD</b>DSS-A-N30 was prepared by macroporous resin chromatography, the compound was isolated by column chromatography on silica gel and RPC-18, the structure was elucidated by spectroscopic methods.</p><p><b>RESULT</b>A new monoterpene glycoside was isolated and identified from DSS-A-N-30.</p><p><b>CONCLUSION</b>The new monoterpene glycoside was identified as 4"-hydroxyl-albiflorin.</p>

Effect of Huanglian Jiedutang on expression of hippocampus proteomics in senescence accelerated mouse / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Huanglian Jiedutang (HLJDT) on hippocampal protein expressions in senescence accelerated mouse-prone/8 (SAMP8).</p><p><b>METHOD</b>The 12-month-old senescence accelerated mice (SAM) were divided into three groups: SAM-resistance/1 (SAMR1), SAM-prone/8 (SAMP8) and SAMP8 treated with HLJDT. The effect of HLJDT on expressions of hippocampal proteins was analyzed by two dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS).</p><p><b>RESULT</b>Compared with same age SAMR1, there were 29 differential expressed hippocampal proteins in SAMP8. After treated with HLJDT, the expressions of 38 hippocampal proteins of SAMP8 were changed significantly. 12 reactive proteins of HLJDT were chosen to be identified by MALDI-TOF-MS and the results were searched in MASCOT database. Among 12 reactive proteins, the expressions of 4 hippocampal proteins which expressed differentially between SAMR1 and SAMP8 could be improved by HLJDT.</p><p><b>CONCLUSION</b>HLJDT may improve the aging of SAMP8 by regulating the expressions of proteins related with energy metabolism, signal transduction, cytoskeletal, amino acid metabolism and so on.</p>

Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse.

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of beta-endorphin (beta-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus-pituitary-ovary (HPO) axis of the SAMP8 strain as hypergonadotropic-hypogonad. The levels of beta-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in beta-EP and SP concentrations in the hypothalamus.

Inhibitory effect of active fraction of tiaoxin recipe on beta-amyloid protein induced long-term potentiation in CA1 area of rats' hippocampal slices / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of the active fraction of Tiaoxin recipe (TXR-A), in inhibiting long-term potentiation (LTP) induced by beta amyloid protein (beta-AP) in CA1 area of rats' hippocampal slices.</p><p><b>METHODS</b>The population spike (PS) in CA1 area of hippocampal slices incubated in different medium was recorded before and after LTP was evoked by a 100 Hz, 100 trains high frequency stimulation (HFS), using extracellular microelectrode recording techniques.</p><p><b>RESULTS</b>The amplitude of PS significantly decreased after HFS in hippocampal slices incubated in medium containing 0.2 micromol/L beta-AP for more than 1.5 hour, as compared with that incubated in normal cerebrospinal fluid, the difference was significant, suggesting that beta-AP could inhibit LTP in hippocampal slices. The average amplitude of PS in slices incubated in beta-AP containing medium could be significantly enhanced by adding high-concentration TXR-A or TXR into the medium, and TXR-A showed a better effect of enhancing than that of TXR, indicating that TXR-A could increase the amplitude of LTP.</p><p><b>CONCLUSION</b>TXR-A may be the chief ingredient extracted from TXR for improving beta-AP induced LTP in CA1 area of rats' hippocampus, to antagonise the inhibition of beta-AP on LTP is possibly one of the mechanisms for its intelligence benefiting action.</p>

Study on effect and mechanism of liuwei dihuang decoction in modulating hypothalamus-pituitary-ovary axis in senescence accelerated mice model / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the changes of hypothalamus-pituitary-ovary (HPO) axis of senescence accelerated mice (SAM) model in their aging process and the modulatory effect of Liuwei Dihuang decoction (LW) on the changes.</p><p><b>METHODS</b>Using vaginal smear to test the estrous cycle of animal; using radioimmunoassay to determine serum levels of estradiol (E2), and beta-endorphin (beta-EP) and substance P (SP) in hypothalamus; and the western bloting technique was adopted to quantify the level of luteinizing hormone (LH) in pituitary and estradiol receptor alpha (ER alpha) in pituitary and ovary.</p><p><b>RESULTS</b>The estrous cycle and diestrus were significantly prolonged as SAMP8 aged, the concentration of serum E2 was lower, pituitary LH was higher in the SAMP8 than those in SAMR1. Content of beta-Ep and SP in hypothalamus gradually lowered during aging, SP content lowered after a transient increasing, and ER alpha expression lowered significantly. LW could significantly shorten the diestrus, increase weight of ovary, elevate serum E2 level, significantly reduce the LH level in pituitary, increase beta-EP content in hypothalamus and ER alpha expression in ovary, but significantly lower SP content in hypothalamus. Oral administration of estrogen could increase serum E2, beta-EP and SP content in hypothalamus and ER alpha expression in pituitary, but lower LH level in pituitary, weight of ovary and ER alpha level in ovary.</p><p><b>CONCLUSION</b>SAMP8, in the aging process, develops a progressive HPO axis functional disturbance, it is closely related with the change of levels of peptide neuro-mediator in hypothalamus and change of ER alpha level in ovary. LW could improve or modulate the HPO axis functional disturbance in SAMP8.</p>