Shen Yuan extract exerts a hypnotic effect via the tryptophan/5-hydroxytryptamine/melatonin pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.

Integrating metabolomics and network pharmacology to assess the effects of quercetin on lung inflammatory injury induced by human respiratory syncytial virus.

Quercetin (QR) has significant anti-respiratory syncytial virus (RSV) effects. However, its therapeutic mechanism has not been thoroughly explored. In this study, a lung inflammatory injury model caused by RSV was established in mice. Untargeted lung tissue metabolomics was used to identify differential metabolites and metabolic pathways. Network pharmacology was used to predict potential therapeutic targets of QR and analyze biological functions and pathways modulated by QR. By overlapping the results of the metabolomics and the network pharmacology analyses, the common targets of QR that were likely to be involved in the amelioration of RSV-induced lung inflammatory injury by QR were identified. Metabolomics analysis identified 52 differential metabolites and 244 corresponding targets, while network pharmacology analysis identified 126 potential targets of QR. By intersecting these 244 targets with the 126 targets, hypoxanthine-guanine phosphoribosyltransferase (HPRT1), thymidine phosphorylase (TYMP), lactoperoxidase (LPO), myeloperoxidase (MPO), and cytochrome P450 19A1 (CYP19A1) were identified as the common targets. The key targets, HPRT1, TYMP, LPO, and MPO, were components of purine metabolic pathways. The present study demonstrated that QR effectively ameliorated RSV-induced lung inflammatory injury in the established mouse model. Combining metabolomics and network pharmacology showed that the anti-RSV effect of QR was closely associated with purine metabolism pathways.

Protective effect of Gastrodia elata blume ameliorates simulated weightlessness-induced cognitive impairment in mice.

During the long-term orbital flight, exposure to microgravity negatively affects the astronauts' development of cognition, characterized by learning and memory decline. Gastrodia elata Blume (GEB) has a significant protective effect on cognitive impairment and has been used in Asia for centuries as a functional product. A previous study demonstrated that GEB could improve memory loss in mice caused by circadian rhythm disorders. However, the effects of GEB on cognitive dysfunction caused by weightless environments have not been investigated. In this study, mice received daily treatment with GEB (0.5, 1 g·kg-1d-1, i.g) and Huperzine A(Hup, 0.1 mg·kg-1d-1, i.g) orally until the end of the behavioral test (New object recognition test (NORT). Malondialdehyde (MDA) and nitric oxide (NO) levels were detected by kits, and expression of brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), phosphorylated Akt (P-AKT), synaptophysin (SYN) and postsynaptic density 95(PSD95) in hippocampus were detected by western blotting. The results show that administration of GEB (0.5, 1 g·kg-1d-1, i.g) and Hup (0.1 mg·kg-1d-1, i.g) remarkably reverse HLS-induced learning and behavioral memory disorders, which were associated with significant changes in MDA and NO levels. Additionally, the protein expressions of BDNF, P-AKT/AKT, SYN, and PSD95 were significantly increased in the hippocampus. In summary, our findings will improve the reference for developing GEB as a functional product that improves memory decline.

Traditional uses, phytochemistry, pharmacology, toxicology, and quality control of Rhododendron dauricum L. leaves: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron dauricum L. is a traditional herb mainly distributed in the northeast China, Mongolia, Korea Peninsula, and Russia Far East. The dried leaves of Rhododendron dauricum L. (LRD), generally known "Man Shan Hong" have been traditionally applied as folk medicines to treat fever, copious phlegm, asthma, acute and chronic bronchitis, sore throat, dysentery, diabetes mellitus, cancer, and hypertension. To date, no comprehensive review on R. dauricum leaves has been published. AIM OF THE STUDY: Recent progresses in traditional use, phytochemistry, pharmacology, toxicology, and quality control of R. dauricum leaves are systematically presented and critically evaluated in order to provide scientifical basis for its reasonable utilization and further study. MATERIALS AND METHODS: All information about R. dauricum leaves were retrieved from internet scientific databases including Sci-Finder, Web of Science, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, SpringerLink, and the Chinese Pharmacopoeia between 1970 and 2022. Plant names were validated by "The Plant List" (http://www.theplantlist.org/). RESULTS: So far, 114 structurally diverse compounds have been isolated and identified from LRD, mainly including flavonoids, diterpenoids, triterpenoids, meroterpenoids, phenols, and 54 volatile components were identified from the essential oils of LRD. Among these, flavonoids are considered as characteristic components and major bioactive phytochemicals. The crude extracts and compounds from LRD have been reported to possess broad pharmacological effects including antitussive and expectorant, anti-inflammatory, anti-HIV, antibacterial, and cytotoxic effects, etc. CONCLUSIONS: As a traditional herb medicine, LRD have been used popularly. On the one hand, traditional uses of LRD provide valuable directions for current research; on the other hand, modern phytochemical and pharmacological studies verify the traditional uses to make its reasonable utilization. However, several defects such as active components determination, in vivo and clinical pharmacological evaluation, toxicology assessment, and quality control of LRD need further study.

Application progress on anti-skin aging effect of traditional Chinese medicine / 药学学报

With the aging of population intensifies and the level of population health have improved, thus much attention has been directed to how to delaying or preventing skin aging. Skin aging is associated with age, ultraviolet and lifestyle, mainly characterized as skin sagging, wrinkles, pigmentation, so it is urgent to seek traditional Chinese medicine and related cosmetics to solve the problem of skin aging. Traditional Chinese medicine has the functions of anti-oxidation, enhancing human immunity, promoting body metabolism and regulating endocrine, therefore, it has become a research focus in anti-skin aging. This article reviews the skin aging mechanism and the research advances of traditional Chinese medicine anti-skin aging, in order to provide a reference for future research and development of anti-aging traditional Chinese medicine.

Effect of Radix Polygalae extract on the colonic dysfunction in rats induced by chronic restraint stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Polygalae, a commonly used traditional Chinese herb, has conventionally functioned in tranquilization and sedation, where anti-inflammation may be the underlying mechanism. AIM OF THE STUDY: Chronic restraint stress (CRS), a risk factor for the etiology of intestinal disorders, was used in the present study to examine whether Radix Polygalae extract (RPE) could modulate colonic dysfunction in CRS rats. MATERIALS AND METHODS: Wistar rats were exposed to 28-day CRS (6 h daily), and RPE (135 mg/kg and 270 mg/kg) was intragastrically administered 1 h before CRS. Subsequently, the gut microbiota was determined using metagenomic sequencing. Colonic proinflammatory interleukin-1ß, -6, and -18 were assayed using qRT-PCR and ELISA. Tight junction proteins were quantified by qRT-PCR and western blotting (WB), and tryptophan metabolic enzymes and metabolites were determined using qRT-PCR and UFLC-QTRAP-5500/MS. Moreover, protein expression of colonic tight junction proteins, NF-κB-NLRP3 signaling involved in the underlying mechanism of RPE were detected by WB. RESULTS: RPE significantly decreased proinflammatory cytokines and reshaped the gut microbiota, especially the probiotics, including Lactobacillus and Bacteroides. Moreover, RPE could modulate the metabolite contents and enzyme expression associated with colonic tryptophan-kynurenine (TRP-KYN) metabolism and could increase tight junction protein expression in CRS rats. Furthermore, RPE inhibited the activation of NF-κB-NLRP3 signaling in the colon of CRS rats. CONCLUSION: RPE could modulate colonic inflammation, colonic microbiota, tight junction, TRP-KYN metabolism and NF-κB-NLRP3 signaling to reach a colonic balance of CRS rats. The present study helped us to better understand and appreciate the various beneficial effects of RPE.

Phytochemical Characterizations of Maranthes polyandra (Benth.) Prance.

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.

Diterpenoids from the whole plants of Croton yunnanensis and their bioactivities.

Four new 19-nor-clerodane diterpenoids (1-4), one new 15,16-dinor-ent-pimarane diterpenoid (5) together with four known diterpenoids (6-9) were isolated from whole plants of Croton yunnanensis. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparing their NMR data with those of previously reported compounds. The experimental and calculated electronic circular dichroism data were used to define their absolute configurations. The 1H and 13C NMR spectra of 6 were completely assigned for the first time. All isolated compounds (1-9) were evaluated for their cytotoxic activities against five human cancer cell lines (including SMMC-7721, HL-60, A-549, MCF-7, and SW-480), and anti-inflammatory activities in LPS-induced RAW264.7 macrophages. Crotonyunnan E (5) exhibited selective cytotoxicities against three tumor cell lines, SMMC-7721 (human hepatoma cells, IC50 4.47 ± 0.39 µM), HL-60 (human premyelocytic leukemia, IC50 14.38 ± 1.19 µM), and A-549 (human lung cancer cells, IC50 27.42 ± 0.48 µM), while none of the compounds showed obviously anti-inflammatory activities at 50 µM level.

Anti-inflammatory effects of three withanolides isolated from Physalis angulata L. in LPS-activated RAW 264.7 cells through blocking NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L. is commonly used in many countries as popular medicine for the treatment of a variety of diseases such as malaria, hepatitis, dermatitis and rheumatism. But the anti-inflammatory active constituents of this medicinal plant and their molecular mechanism are still not elucidated clearly. AIM OF THE STUDY: The aim of the study is to isolate and identify a series of compounds from the ethanolic extract of Physalis angulata L., and to investigate the anti-inflammatory activities in vitro and the molecular mechanism of physagulin A, physagulin C, and physagulin H. MATERIALS AND METHODS: In order to further understand the anti-inflammatory mechanism of the three compounds, their potential anti-inflammatory activities were investigated in vitro in LPS-activated RAW 264.7 macrophage cells by Griess assay, ELISA, Western blot and immunofluorescence methods in the present study. RESULTS: Physagulin A, physagulin C, and physagulin H could not only inhibit the release of NO, PGE2, IL-6 and TNF-α, but also could down-regulate the expression of iNOS and COX-2 proteins. Furthermore, physagulin A, physagulin C, and physagulin H could remarkably block the degradation of IκB-α and the nuclear translocation of NF-κB/p65 in LPS-activated RAW 264.7 cells. However, none of them could inhibit the phosphorylation of MAPKs family proteins ERK, JNK and p38. Thus, the anti-inflammatory actions of physagulin A, physagulin C, and physagulin H were mainly due to the significant inhibition of NF-κB signaling pathway rather than MAPKs signaling pathway. CONCLUSIONS: All the results clearly showed that physagulin A, physagulin C, and physagulin H demonstrated potent anti-inflammatory activity and can be used as novel NF-κB inhibitors. They are potential to be developed as an alternative or complementary agents for inflammatory diseases.

The antidepressant-like effects of Shen Yuan: Dependence on hippocampal BDNF-TrkB signaling activation in chronic social defeat depression-like mice.

The Shen Yuan prescription (SY) comprises Panax ginseng (GT) and Polygala tenuifolia (YT), elicited superior antidepressant activity compared with that of GT or YT alone. The aim of this paper is to elucidate the effects of SY treatment on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism. Our results indicated that SY treatment reverses the depressive-like behaviors induced by CSDS as measured by the social interaction test, sucrose preference test, forced swim test, and tail suspension test. SY decreased the serum levels of CORT and increased hippocampal neurotransmitters (5-HT, DA, and NE) in CSDS mice. Meanwhile, SY upregulated the brain-derived neurotrophic factor (BDNF) signaling pathway and reversed the decreased hippocampal neurogenesis caused by CSDS. In addition, we found that the TrkB antagonist K252a fully blocked the SY effects on behavioral improvement and eliminated the promoting effects of SY on hippocampal neurogenesis and BDNF-TrkB signaling (including the downstream ERK and Akt pathways) activation, thus further demonstrating that BDNF-TrkB signaling was necessary for the SY effects. In conclusion, our study showed that SY acted as an antidepressant in mice exhibiting CSDS-induced depression-like symptoms, and its effect was facilitated by promoting hippocampal neurogenesis and BDNF signaling pathway activation.

Molecular Mechanism of Modified Guizhi Fulingwan Intervention on Uterine Fibroids in Rats Based on micRNA Expression Profiling / 中国实验方剂学杂志

Objective:To explore the molecular mechanism of modified Guizhi Fulingwan in rats with uterine fibroids. Method:Seventy-two female adult SD rats of SPF grade were randomly divided into a model group， a normal group， and a preventive administration group. The model group and preventive administration group were established by estrogen and progestin loading method. After successful modeling， the rats in the model group were randomly divided into a western medicine group （mifepristone）， the high-dose traditional Chinese medicine（TCM） group， and a low-dose TCM group. All the rats were dosing as required once a day for 28 consecutive days. Hematoxylin-eosin（HE）staining was used to observe the morphological changes of the uterus. The micRNA gene chip was used to detect the expression profile of uterine micRNA gene. Differential expressions of micRNA were screened by bioinformatics methods. Gene function enrichment was used to predict the possible signaling pathways in rats with uterine fibroids by modified Guizhi Fulingwan. Result:Compared with the normal group， microRNA of the model group was 1 up-regulated and 9 down-regulated. Compared with the model group， microRNA of the high-dose group of TCM group was 2 up-regulated and 1 down-regulated， in the preventive administration group， 9 was up-regulated and 2 was down-regulated. Gene function enrichment analysis indicated that four signaling pathways were closely related to uterine fibroids. They were mitogen-activated protein kinase （MAPK） signaling pathway， Wnt signaling pathway， mammalian rapamycin target protein （mTOR） signaling pathway and vascular endothelial cell growth factor （VEGF） signaling pathway. Conclusion:Modified Guizhi Fulingwan affected the expression profile of micRNA in rat model of uterine fibroids induced by estrogen and progesterone， suggesting that modified Guizhi Fulingwan may involve in a variety of biological processes such as signal transduction and gene regulation in the treatment of uterine fibroids.

The role of Chinese medicine in COVID-19 pneumonia: A systematic review and meta-analysis.

INTRODUCTION: Chinese medicine (CM) has been used to treat Novel Coronavirus 2019 (COVID-19) pneumonia in China. This meta-analysis was conducted to evaluate the clinical efficacy and safety of CM in the treatment of COVID-19 pneumonia. METHODS: Randomized controlled trials (RCTs) involving CM in the treatment of COVID-19 pneumonia were identified from Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Database and VIP Information Database. The methodological quality of trials was evaluated with Cochrane Hanadbook criteria, and the Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 7 valid studies involving 681 patients were included. The meta-analysis exhibited in comparison to conventional treatment, CM combined with conventional treatment significantly improved clinical efficacy (RR = 1.21, 95% CI [1.08,1.36]), and significantly increased viral nucleic acid negative conversion rate (RR = 1.49, 95% CI [1.13,1.97]). CM also prominently reduced pulmonary inflammation (RR = 1.27, 95% CI [1.12,1.44]), and improved host immune function (WBC, MD = 0.92, 95% CI [0.07,1.76]; LYM, MD = 0.33, 95% CI [0.08,0.57]; LYM%, MD = 2.90, 95% CI [2.09,3.71]; CRP, MD = -12.66, 95% CI [-24.40, -0.92]). Meanwhile, CM did not increase the incidence of adverse reactions (RR = 1.17, 95% CI [0.39,3.52]). CONCLUSION: According to the allocated data, CM has demonstrated clinical efficacy and safety on COVID-19 pneumonia, which need to be confirmed by high quality, multiple-center, large sample randomized controlled trials.

miR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation.

BACKGROUND: In recent years, microRNAs (miRNAs) are reported to act as molecular biomarkers for cancer diagnosis, treatment, and prognosis (including liver cancer) and to be involved in the development and progression of cancer and other physiological and pathological changes. However, the role of miR-34a-5p in liver cancer is still largely unknown. METHODS: In our study, the expression of miR-34a-5p in liver cancer tissues and HCC cell lines was detected by qRT-PCR. The CCK-8, scratch wound-healing motility and Transwell assays were used to evaluate the effect on cell proliferation, migration and invasion. The expression of YY1, E-cadherin, N-cadherin and vimentin was analysed by western blotting. The dual luciferase assay was performed to confirm whether YY1 is a target of miR-34a-5p. The combination of YY1 and MYCT1 was detected by chromatin immunoprecipitation (ChIP) assay. RESULTS: The results showed that miR-34a-5p was downregulated in liver cancer tissues and HCC cell lines. Overexpression of miR-34a-5p inhibited the proliferation, migration and invasion of liver cancer cells. YY1 was a direct target of miR-34a-5p, and the expression of YY1 could reverse the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. YY1 inhibited MYCT1 expression by directly binding to its promoter region, and knockdown of MYCT1 reversed the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. CONCLUSION: Our results suggest that miR-34a-5p could inhibit the invasion and metastasis of hepatoma cells by targeting YY1-mediated MYCT1 transcriptional repression.

Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury.

Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

A Systematic Review on Secondary Metabolites of Paecilomyces Species: Chemical Diversity and Biological Activity.

Fungi are well known for their ability to synthesize secondary metabolites, which have proven to be a rich resource for exploring lead compounds with medicinal and/or agricultural importance. The genera Aspergillus, Penicillium, and Talaromyces are the most widely studied fungal groups, from which a plethora of bioactive metabolites have been characterized. However, relatively little attention has been paid to the genus Paecilomyces, which has been reported to possess great potential for its application as a biocontrol agent. Meanwhile, a wide structural array of metabolites with attractive bioactivities has been reported from this genus. This review attempts to provide a comprehensive overview of Paecilomyces species, with emphasis on the chemical diversity and relevant biological activities of these metabolic products. Herein, a total of 148 compounds and 80 references are cited in this review, which is expected to be beneficial for the development of medicines and agrochemicals in the near future.

Four new chemical constituents from Piper pleiocarpum.

Two new polyoxygenated cyclohexenes (1-2), one new benzoate derivative (3), and one new dineolignan (4) together with one known neolignan (5) were isolated from whole plants of Piper pleiocarpum. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. The 13C NMR spectra of the known compound 5 were completely assigned for the first time. All isolated compounds (1-5) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480), Only compound 4 showed inhibitory activity against MCF-7 cell line with IC50 value of 18.24 ± 0.69 µM.

Antidepressant-like effects of cajaninstilbene acid and its related mechanisms in mice.

Cajaninstilbene acid (CSA), a bioactive constituent isolated from pigeon pea leaves, exhibited neuroprotective activities in previous studies. The present study aims to evaluate the antidepressant effects of CSA by using behavioral despair models of tail suspension test (TST) and forced swimming test (FST), and a chronic unpredictable mild stress (CUMS) model. CSA (30 or 60 mg/kg), intragastrically administrated for 7 days, could significantly reduce the immobility time of mice in TST and FST. CSA treatment (15 or 30 mg/kg) significantly reversed the depressive-like behavioral changes of mice induced by 3 or 6 weeks CUMS that caused the decrease of sucrose preference, the increase of latency to feed in the novelty-suppressed feeding test, and the increase of immobility time in TST of mice. Furthermore, the related mechanisms of the effect were explored by accessing the metabolite levels of kynurenine pathway of tryptophan metabolism and the expression of some related proteins in cerebral cortex of CUMS mice. Our results showed that the kynurenine pathway was upregulated after CUMS, while the alteration could be significantly reversed by CSA. CSA also reversed the CUMS-induced decrease in the levels of BDNF, PSD-95, p-Akt/Akt and p-mTOR/mTOR. Therefore, the antidepressant-like effects of CSA might be achieved through regulating tryptophan metabolism, promoting BDNF and PSD-95 expression, and activating Akt/mTOR pathway in the cerebral cortex.

Pleiocarpumlignan A, a new dineolignan from Piper pleiocarpum Chang ex Tseng.

The investigation of chemical constituents from the whole plants Piper pleiocarpum Chang ex Tseng resulted in the isolation of one new dineolignan, pleiocarpumlignan A (1), along with one known benzoate derivative, trans-2,3-diacetoxy-1-[(benzoy1oxy)methyl]-cyclohexa-4,6-diene (2), and two known neolignans (3-4) as (±)-trans-dehydrodiisoeugenol (3), (7R,8R,3'S)-△8'-3',6'-dihydro-3'-methoxy-3,4-methylenedioxy-6'-oxo-8,3',7,O,4'-lignan (4). Their structures were elucidated through extensive spectroscopic analyses including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. All compounds (1-4) were firstly isolated from Piper pleiocarpum Chang ex Tseng. The 13C NMR spectra of 2 were completely assigned for the first time. Cytotoxic activities of these isolated compounds against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480) were evaluated.

New Model of Traditional Chinese Medicine with Effect of Invigorating Kidney and Filling Sea of Marrow in Regulating Delay in Cortical Maturation of ADHD Based on Theory of Steady Yin and Vexed Yang / 中国实验方剂学杂志

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder among children. The theory of traditional Chinese medicine (TCM) does not have a special term of this disease, and classifies ADHD to the category of " forgetfulness" " dysphoria" " injudiciousness" according to its clinical manifestations. TCM theoretic and clinical systems for treating ADHD have been developed, but current pharmacodynamics studies of TCM on ADHD have mostly focused on neurotransmitter metabolic system and its receptor signaling pathway to reflect the advantages of multi-component and multi-target effect of TCM, but failed to demonstrate the scientific connotations of TCM theory, such as " coordination between kidney and brain" and " steady Yin and vexed Yang" , and ignored the delay in cortical maturation as the core neuropathology of ADHD. The symptoms relating to " restlessness of Yang" due to Yin deficiency that cannot inhibit hyperactivity of Yang, kidney-Yin deficiency and liver-Yang excess syndrome is the most common syndrome of ADHD, and TCMs with effect of invigorating kidney and filling sea of marrow are mostly used by TCM practitioners. According to anatomy basis of neuronal development disorder, the new theory of " energy metabolism dysfunction" , the pathogenesis hypothesis of sea of marrow development disorder and its relevant clinical practices and experimental studies, substantial basis studies of the therapy for " invigorating kidney and filling sea of marrow" , as well as pharmacodynamics study of <italic>Rehmannia glutinosa</italic> (Shudihuang) for treating ADHD, we put forward ADHD pathogenesis that " restlessness of Yang due to Yin deficiency" is related to the disorder of executive function due to the delay in cortical maturation, energy metabolism dysfunction and neurodevelopmental disorder, and regarded that TCMs with effect of invigorating kidney and filling sea of marrow are the most commonly used to treat ADHD, and improve delay in cortical maturation corresponding to sea of marrow insufficiency by regulating dysfunction of neurodevelopment and energy metabolism, so as to relieve the core symptoms of ADHD. The new treatment model of TCM with effect of invigorating kidney and filling sea of marrow for treating ADHD will provide a theoretical basis for improving the clinical efficacy of ADHD.

Antidepressant-like effects of 20(S)-protopanaxadiol in a mouse model of chronic social defeat stress and the related mechanisms.

20(S)-Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant-like effects on behaviour in the forced swimming test (FST) and tail suspension test (TST) and in rat olfactory bulbectomy depression models. However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression-like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5-HT and NE) in the hippocampus and serum corticosterone levels. Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p-TrkB/TrkB, p-Akt/Akt, and p-mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS-induced depression. Our results suggest that PPD exerts antidepressant-like effects in mice with CSDS-induced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway.