Associations between acetylcholinesterase-1 mutations and chlorpyrifos resistance in beet armyworm, Spodoptera exigua.

Control of the beet armyworm, Spodoptera exigua depends heavily on chemical insecticides. Chlorpyrifos, an acetylcholinesterase (AChE) inhibitor, has been used in beet armyworm control for many years in China. Here we describe high level resistance to chlorpyrifos in a S. exigua strain, FX19-R, which was developed from a field-collected Chinese strain (FX) by selection with chlorpyrifos in the laboratory. FX19-R showed 1001-fold resistance to chlorpyrifos compared with the laboratory reference strain WH-S. The esterase inhibitor triphenyl phosphate (TPP) provided significant but small synergism (only 3.5-fold) for chlorpyrifos and neither of the glutathione s-transferase depletor diethyl maleate and the cytochrome P450s inhibitor piperonyl butoxide provided any detectable synergism, indicating that AChE insensitivity may play the major role in the resistance in FX19-R. Consistent with this, an amino acid substitution, F443Y (F331Y in standard Torpedo californica numbering) in AChE1 was identified in the FX19-R strain and shown to be tightly linked to chlorpyrifos resistance. Precisely homologous substitutions have been associated with organophosphate resistance in other pest species. A novel amino acid substitution, G311S (or G198S in standard numbering), was also identified in the reference strain WH-S. Recombinantly expressed AChE1 proteins carrying the G311S and F443Y substitutions were about 4.2-fold and 210-fold less sensitive to inhibition by chlorpyrifos oxon than wild-type AChE1, respectively. These results enhance our understanding of the mechanisms of chlorpyrifos resistance and provide a basis for resistance management based on monitoring the F443Y and G311S substitutions.

Historical Evolution and Clinical Application of Classical Prescription Xiao Xumingtang / 中国实验方剂学杂志

Xiao Xumingtang in The Catalogue of Famous Ancient Classics （The First Batch） issued by the National Administration of Traditional Chinese Medicine is derived from the Important Prescriptions Worth a Thousand Gold for Emergency （Bei Ji Qian Jin Yao Fang） written by SUN Si-miao in the Tang dynasty. The present study systematically explored the origin， development， historical evolution， and clinical application of Xiao Xumingtang. As revealed by the results， Xiao Xumingtang as well as its analogues are primary prescriptions indicated for apoplexy before the Tang and Song dynasties and serve as the benchmark for the treatment of apoplexy. After the Song dynasty， due to the changes in the understanding of the pathogenesis of apoplexy and the limitations of the understanding of Xiao Xumingtang， its clinical application to apoplexy gradually decreased. In modern times， it has been re-recognized and applied， during which its clinical applications have undergone great changes. Its clinical applications are extensive， involving a variety of diseases related to the brain and nervous systems， such as stroke and its sequelae， peripheral facial paralysis， rheumatoid arthritis， hypertension， and other diseases related to the motor nervous system. Its primary indications are stroke and its sequelae， followed by peripheral facial paralysis. Other new indications are gradually found. This study is expected to provide references for the clinical application of Xiao Xumingtang and the transformation of new drugs.

Anti-tumor Application and Pharmacological Mechanism of Xihuangwan： A Review / 中国实验方剂学杂志

Malignant tumors are currently seriously endangering human health and life， which has become one of the main causes of death in China. In modern Western medicine， they are mainly tackled by surgery， chemotherapy， and radiotherapy， but the death toll continues to rise year by year. At present， most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects， affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance， making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine （TCM）， it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore， the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors， and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan， a classic heat-clearing prescription， is composed of Calculus Bovis， Moschus， Olibanum， and Myrrh and has the effects of clearing away heat， removing toxin， eliminating edema， and dissipating mass， which is mainly used to treat carbuncle， pustule， scrofula， multiple abscess， and cancer caused by heat-toxin obstruction. In modern clinical practice， it has been employed in patients with lung cancer， breast cancer， gastric cancer， liver cancer， colorectal cancer， and other malignant tumors， especially during the advanced stage， as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids （such as masticinic acids）， volatile oils， steroids （like porcine deoxycholic acid）， and bilirubin， which have been proved effective in anti-tumor. This paper reviewed the prescription source， pharmaceutical research， clinical anti-tumor research， and pharmacological mechanisms of Xihuangwan， which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.

Acute EPA-induced learning and memory impairment in mice is prevented by DHA.

Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid (DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice. Similar deficits are duplicated by endogenously elevating EPA in the hippocampus in the transgenic fat-1 mouse. Furthermore, the damaging effects of EPA are mediated through enhancing GABAergic transmission via the 5-HT6R. Interestingly, DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR. We conclude that EPA exhibits an unexpected detrimental impact on cognitive functions, suggesting that caution must be exercised in omega-3 fatty acid supplementation and the combination of EPA and DHA at a natural ratio is critical for learning and memory and synaptic plasticity.

Analysis on Medication Rules of National Medical Masters in Treatment of Stomachache / 中国实验方剂学杂志

Objective: To analyze medication rules of national medical masters in the treatment of stomachache by data mining. Method: Prescriptions were collected from 9 works as well as the first batch of national medical masters' medical cases and prescriptions for stomachache recorded in CNKI. Then, Microsoft Excel 2016 was adopted for analyzing the frequencies, properties, flavors and meridian tropisms of herbs, the Apriori algorithm provided by SPSS Clementine 12.0 software was used to analyze association rules of the herbs, and factor analysis was conducted by SPSS 19.0 software. Result: A total of 175 prescriptions containing 230 herbs were selected. The top five herbs used in frequency ranking were Glycyrrhizae Radix et Rhizoma, Paeoniae Radix Alba, Pinelliae Rhizoma, Atractylodis Macrocephalae Rhizoma, Poria. The medical properties with high usage frequency were warm, mild and slight cold. The flavors were sweet, bitter and pungent. Meridian tropisms were spleen, stomach and lung. Herbs for regulating Qi, tonifying Qi and promoting digestion ranked top three according to the classification of efficacy. The association rules analysis showed that the highest confidence and support of the related drugs was Atractylodis Macrocephalae Rhizoma→Codonopsis Radix-Poria, which reflected treatment characteristics of national medical masters with Sijunzitang as the basic prescription for tonifying Qi. A total of 12 strongly association rules of 2-drug pairs were obtained by association rules, and the most commonly used of which was Paeoniae Radix Alba-Glycyrrhizae Radix et Rhizoma. Nine common factors were respectively extracted by factor analysis. Conclusion: Herbs used in the prescriptions of national medical masters for treatment of stomachache are often with the actions of regulating Qi, invigorating deficiency and benefiting Qi, in addition, Shaoyao Gancaotang is often used to generate Yin and relieve pain.

Generalized science of Chinese material medica-from preventive treatment of disease to Chinese medicine health industry / 中国中药杂志

Based on the systematic summary of the results of the fourth general survey of traditional Chinese medicine resources, the cultivation of large varieties of Chinese material medica and the latest research on health industrial development, the novel concepts and scientific connotations of generalized science of Chinese material medica are put forward, and the basic ideas and methods of a new Chinese medicine academic system, the cultivation system of large varieties of Chinese medicinal materials and the application system of the large health industry are constructed. This kind of generalized science of Chinese material medica, rooted in the traditional Chinese culture and the theory of "preventive treatment of disease", can avoid the narrow prospect induced by the increasing specialization and refinement of knowledge of science of Chinese material medica. It will play an important role in the modernization, industrialization, internationalization of traditional Chinese medicine.

Receptor and transporter binding and activity profiles of albiflorin extracted from Radix paeoniae Alba.

Albiflorin, a traditional Chinese herb, is a main component of Radix paeoniae Alba, which has been used for the treatment of depressive disorders since ancient times. However, the mechanism of the antidepressant effect of albiflorin is poorly understood. Thus, we explored the binding profile of albiflorin at neurotransmitter receptors and transporters. We also characterised the in vivo effect of albiflorin on monoaminergic systems by using microanalysis to determine the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the hypothalamus of freely moving rats administered albiflorin. We found that albiflorin inhibited the uptake of 5-HT and NE and displayed robust binding affinities for the transporters of both neurotransmitters. By contrast, albiflorin (10 µM) showed no significant affinity to a wide array of central nervous system receptors. The results of our in vivo microdialysis studies showed that administration of albiflorin (3.5, 7.0, 14.0 mg/kg) significantly increased extracellular concentrations of 5-HT and NE in the hypothalamus of freely moving rats. Overall, the current study showed that albiflorin is a novel 5-HT and NE reuptake inhibitor with high selectivity.

The antidepressant-like pharmacological profile of Yuanzhi-1, a novel serotonin, norepinephrine and dopamine reuptake inhibitor.

Triple reuptake inhibitors that block dopamine transporters (DATs), norepinephrine transporters (NETs), and serotonin transporters (SERTs) are being developed as a new class of antidepressants that might have better efficacy and fewer side effects than traditional antidepressants. In this study, we performed in vitro binding and uptake assays as well as in vivo behavioural tests to assess the pharmacological properties and antidepressant-like efficacy of Yuanzhi-1. In vitro, Yuanzhi-1 had a high affinity for SERTs, NETs, and DATs prepared from rat brain tissue (Ki=3.95, 4.52 and 0.87nM, respectively) and recombinant cells (Ki=2.87, 6.86 and 1.03nM, respectively). Moreover, Yuanzhi-1 potently inhibited the uptake of serotonin (5-hydroxytryptamine; 5-HT), norepinephrine (NE) and dopamine (DA) into rat brain synaptosomes (Ki=2.12, 4.85 and 1.08nM, respectively) and recombinant cells (Ki=1.65, 5.32 and 0.68nM, respectively). In vivo, Yuanzhi-1 decreased immobility in a dose-dependent manner, which was shown among rats via the forced-swim test (FST) and mice via the tail-suspension test (TST). The results observed in the behavioural tests did not appear to result from the stimulation of locomotor activity. Repeated Yuanzhi-1 treatment (2.5, 5 or 10mg/kg) significantly reversed depression-like behaviours in chronically stressed rats, including reduced sucrose preference, decreased locomotor activity, and prolonged time to begin eating. Furthermore, in vivo microdialysis studies showed that 5- and 10-mg/kg administrations of Yuanzhi-1 significantly increased the extracellular concentrations of 5-HT, NE and DA in the frontal cortices of freely moving rats. Therefore, Yuanzhi-1 might represent a novel triple reuptake inhibitor and possess antidepressant-like activity.

The discovery of Yuanzhi-1, a triterpenoid saponin derived from the traditional Chinese medicine, has antidepressant-like activity.

Yuanzhi, the dried root of Polygala tenuifolia Willd., is a well-known traditional Chinese medicine used for its sedative, antipsychotic, cognitive improving, neuroprotective, and antidepressant effects. The present study was designed to screen and identify the antidepressant-like effect of six triterpenoid saponin components derived from Yuanzhi (Yuanzhi-1 to Yuanzhi-6) using in vitro radioligand receptor binding assays and in vivo behavioral tests. Yuanzhi-1, -3, -5 and -6 were shown to have antidepressant-like activity in the tail suspension test and forced swim test in mice, with no stimulant effect on locomotor activity. The minimal effective dose of Yuanzhi-1 (2.5 mg/kg) was lower than that of duloxetine (5mg/kg), a serotonin and norepinephrine reuptake inhibitor commonly used in the treatment of depression. Yuanzhi-1 (1 nM) had a high affinity for serotonin, norepinephrine and dopamine transporters. Acute toxicity tests indicated that the LD50 of Yuanzhi-1 (86.5mg/kg) was similar to that of duloxetine (73.2 mg/kg). These findings demonstrate that Yuanzhi-1 has a potential to be a novel triple monoamine reuptake inhibitor of antidepressant-like activity.

An establishment of theoretical structure of PRO questionnaire in treating chronic liver disease by Chinese medicine / 中国中西医结合杂志

By reviewing research contents of patient-reported outcome (PRO) and discussing Chinese medicine (CM) theories related to chronic liver disease (CLD), we have followed international PRO questionnaire development specification, combined CM theories such as uniformed spirit and body, correspondence between human and the universe, yin in property and yang in function of Gan, and seven emotions, and constructed theoretical structure of PRO questionnaire of treating CLD, including four major areas as physiology, psychology, independence, and society and nature. Of them, the physiological field contained six aspects such as blood deficiency, yin deficiency, bleeding, disorder of qi movement, improper transformation and transportation of Pi-Wei, and abnormal biliary excretion. The psychological field contained two aspects: Gan-related emotions and general disease related emotions. The independence field contained two aspects: daily life and study and work. The field of society and nature contains three aspects: social relations, social environment, and natural adaptability.

The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor.

Depression is a severe mood disorder with increasing morbidity and suicidality, while the current therapy is not satisfactory. Serotonin and noradrenaline reuptake inhibitors (SNRIs) have been reported to have higher efficacy and/or faster acting rate than commonly used antidepressants. The present study was designed to screen the potential SNRIs, using in vitro radioligand receptor binding assays and in vivo animal tests, and introduced the discovery of 071031B. In the tail suspension test and forced swimming test in mice, six compounds (071017S, 071026W, 071031A, 071031B, 080307A and 080307B) showed robust antidepressant activity, without stimulant effect on the locomotor activity or other side effects, and the minimal effective dose of 071017S, 071026W, 071031A and 071031B was less than that of duloxetine; in vitro binding tests indicated that 071031B had high affinity to both serotonin transporter and noradrenaline transporter with similar inhibitory rates to duloxetine at 1 and 100 nM; acute toxicity test indicated that the LD50 value of 071031B was similar to that of duloxetine. These findings demonstrated that this integrated system, combining high throughput screening technology and in vivo animal tests, is effective to screen potential monoamine reuptake inhibitors fast and accurately; 071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor for its robust antidepressant activity and transporter affinity.

Chromium level and intake from Chinese made tea.

Tea is a popular drink around the world. It is also one of the sources of metal intake. The objectives of this study were to assess chromium (Cr) intake from popular green, oolong, black and Pu-erh tea. In total, 128 Chinese made teas were analysed and concentration differences among four types of tea were explored. Black tea contained highest total Cr, which varied between 0.63 and 17.60 mg/kg. The lowest content was found in the green tea samples, between 0.26 and 1.30 mg/kg. Cr(III) and Cr(VI) in black tea were higher than in other types of tea. Cr(III), Cr(VI) and total Cr concentration in different tea infusions were also analysed. The results suggest that drinking tea is an effective way for Cr intake and the risk of adults and children being chronically intoxicated by tea infusions is low.

The extracts of Fructus Akebiae, a preparation containing 90% of the active ingredient hederagenin: serotonin, norepinephrine and dopamine reuptake inhibitor.

Fructus Akebiae is a traditional Chinese herbal extract that has been used for the treatment of depressive disorders in China. Previous studies demonstrated that Fructus Akebiae extracts (FAE) displayed a potent antidepressant-like activity in animal behavior tests and found that the specific active ingredient from the extracts of Fructus Akebiae is hederagenin. However, the underlying mechanism is unknown. Here we provide evidences that FAE enhances the signaling of central monoamines via inhibition of the reuptake of the extracellular monoamines including serotonin (5-HT), norepinephrine (NE) and dopamine (DA). In rat brain membrane preparations and HEK293 cells transfected with human serotonin transporter (SERT), NE transporter (NET) and DA transporter (DAT), we found that FAE displayed marked affinity to rat and cloned human monoamine transporters in ex vivo and in vitro experiments, using competitive radio ligand binding assay. In uptake assays using rat synaptosomes and transfected cells, FAE was found to significantly inhibit all three monoamine transporters in a dose- and time-dependent manner, with a comparable or better potency to their corresponding specific inhibitors. In contrast, FAE (10 µM), showed no significant affinity to a variety array of receptors tested from CNS. In support of our uptake data, in vivo microdialysis studies showed that administration of FAE (12.6, 25, 50 mg/kg) significantly increased extracellular concentrations of 5-HT, NE and DA in frontal cortex of freely moving rats. Taken together, our current study showed for the first time that FAE is a novel triple inhibitor of monoamine transporters, which may be one the mechanisms of its antidepressant activity.