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Objective: To investigate the value of 68 Ga-PSMA-11 positron emission tomography/computerized tomography (PET/CT) in evaluating lacrimal and salivary glands function. Methods: Ten patients with pSS and 18 healthy volunteers were recruited in this study. All participants underwent 68 Ga-PSMA-11 PET/CT, and the patients with pSS performed salivary gland scintigraphy the next day. The maximum standardized uptake value (SUVmax), average of the standard uptake value (SUVavg), the average CT value (CTavg), and volume (V) in the region of interest (ROI) of each lacrimal and salivary gland were analyzed in68Ga-PSMA-11 PET/CT. The uptake ratio (UR) of the bilateral parotid gland and submandibular gland was calculated in salivary gland scintigraphy (SGS). Statistical analysis was processed by the SPSS software and the MedCalc software. A p-value of < 0.05 was considered as statistically significant. Results: Almost all the parameters of pSS were significantly lower than those of the control group (p < 0.05). The left parotid gland (PG) UR was positive correlation with left PG SUVmax (r = 0.758, p = 0.011) and left PG SUVavg (r = 0.770, p = 0.009); the right PGUR was positive correlation with right PG SUVmax (r = 0.721, p = 0.019) and right PG SUVavg (r = 0.721, p = 0.019). The SUVmax and SUVavg of both sides of acrimal and salivary glands had area under the receiver operating curve values greater than 0.5. Conclusions: 68 Ga-PSMA-11 PET/CT can simultaneously enable the visualization of lacrimal glands and salivary glands and be used to evaluate the lacrimal and salivary glands function. Key Points • We have firstly investigated the value of 68 Ga-PSMA-11 PET/CT in evaluating lacrimal and salivary glands function in patients with pSS 68 Ga-PSMA-11 PET/CT can simultaneously allow the visualization of lacrimal glands and salivary glands. • The results of the present study imply that 68 Ga-PSMA-11 PET/CT can be used to evaluate the lacrimal and salivary glands function in patients with pSS meanwhile. [ABSTRACT FROM AUTHOR]

Abstract: The antiosteoporotic effect of a herbal formula, Er-Xian Decoction (EXD), in ovariectomized (OVX) rats model of osteoporosis was investigated. The rats were divided into Sham and OVX groups. The OVX rats were further sub-divided into four groups administered orally with water, nylestriol (1mg/kg, weekly) or EXD (300, 600mg/kg, daily) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by EXD treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with EXD and nylestriol. In addition, EXD completely corrected the decreased concentration of calcium, phosphorus, and estradiol in serum observed in OVX rats. EXD also significantly increased biomechanical strength comparable to the Sham group. This was also confirmed by histological results that showed its protective action. The findings assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters strongly suggested that EXD had a definite antiosteoporotic effect, which is similar to estrogen. [Copyright &y& Elsevier]

Inhibition of the human ether‐à‐go‐go‐related gene (hERG) ion channel may lead to prolonged QT interval and even fatal ventricular arrhythmia. Therefore, evaluating the hERG liability has become a mandatory requirement for drug development and drug safety process. However, standard experimental assays are complex, expensive and time‐consuming. Various in silico tools have been developed to identify potential hERG blockers and reduce in advance the risk of cardiotoxicity‐related attritions during the early drug discovery phase. In this review, we first outlined the structure and gating properties of the hERG channel briefly. Then analyzed the advantages of computational technology, and comprehensively summarized the in silico methods of hERG‐related cardiotoxicity, including ligand‐based and structure‐based methods. Additionally, the current predictive models in prediction of hERG blockage were emphatically reviewed. Finally, issues involved in the current computational methods, as well as the future direction for developing reliable models of hERG channel blockers, are discussed. [ABSTRACT FROM AUTHOR]

Recent studies have identified G protein‐coupled receptor 40 (GPR40) as a promising target for treating type 2 diabetes mellitus, and GPR40 agonists have several superior effects over other hypoglycemic drugs, including cardiovascular protection and suppression of glucagon levels. In this study, we constructed an up‐to‐date GPR40 ligand dataset for training models and performed a systematic optimization of the ensemble model, resulting in a powerful ensemble model (ROC AUC: 0.9496) for distinguishing GPR40 agonists and non‐agonists. The ensemble model is divided into three layers, and the optimization process is carried out in each layer. We believe that these results will prove helpful for both the development of GPR40 agonists and ensemble models. All the data and models are available on GitHub. (https://github.com/Jiamin‐Yang/ensemble_model) [ABSTRACT FROM AUTHOR]

Endophytic fungi play important roles in regulating plant growth and development and usually used as a promising strategy to enhance the biosynthesis of host valuable secondary metabolite, but the underlying growth-promoting mechanisms are only partly understood. In this study, the wild-type Arabidopsis thaliana seedlings co-cultured with fungal endophyte Epichloë bromicola showed auxin (IAA)-stimulated phenotypes, and the growth-promoting effects caused by E. bromicola were further verified by the experiments of spatially separated co-culture and fungal extract treatment. IAA was detected and identified in the extract of E. bromicola culture by LC-HRMS/MS, whereas 2,3-butanediol was confirmed to be the predominant volatile active compound in the diethyl ether and ethyl acetate extracts by GC–MS. Further study observed that IAA-related genes including synthesis key enzyme genes (CYP79B2, CYP79B3, NIT1, TAA1 and YUCCA1) and controlling polar transport genes (AUX1, BIG, EIR1, AXR3 and ARF1), were highly expressed at different periods after E. bromicola inoculation. More importantly, the introduction of fungal endophyte E. bromicola could effectively promote the growth and accumulation of coixol in Coix under soil conditions. Our study showed that endophytic fungus E. bromicola might be considered as a potential inoculant for improving medicinal plant growth. [ABSTRACT FROM AUTHOR]

The article discusses chemical composition of Arabidopsis thaliana. It is stated that study has become the model system for studying various aspects of plant biology and biochemistry. It is stated in 2009, wild herbs of A. thaliana were collected from Jiande, Zhejiang, China, and dried and powdered material was extracted with 95% EtOH at room temperature.

Background: Ophiopogon japonicus, mainly planted in Sichuan (CMD) and Zhejiang (ZMD) province in China, has a lengthy cultivation history. During the long period of domestication, the genetic diversity of cultivated O. japonicus has substantially declined, which will affect the population continuity and evolutionary potential of this species. Therefore, it is necessary to clarify the phylogeography of cultivated O. japonicus to establish a theoretical basis for the utilization and conservation of the genetic resources of O. japonicus. Result: The genetic diversity and population structure of 266 O. japonicus individual plants from 23 sampling sites were analyzed based on 4 chloroplast DNA sequences (atpB-rbcL, rpl16, psbA-trnH and rpl20-5'rps12) to identify the effects of domestication on genetic diversity of cultivars and determine their geographic origins. The results showed that cultivated O. japonicus and wild O. japonicus had 4 and 15 haplotypes respectively. The genetic diversity of two cultivars (Hd = 0.35700, π = 0.06667) was much lower than that of the wild populations (Hd = 0.76200, π = 0.20378), and the level of genetic diversity in CMD (Hd = 0.01900, π = 0.00125) was lower than that in ZMD (Hd = 0.06900, π = 0.01096). There was significant difference in genetic differentiation between the cultivated and the wild (FST = 0.82044), especially between the two cultivars (FST = 0.98254). This species showed a pronounced phylogeographical structure (NST > GST, P < 0.05). The phylogenetic tree showed that the genetic difference between CMD and ZMD was not enough to distinguish the cultivars between the two producing areas by using O. amblyphyllus Wang et Dai as an outgroup. In addition, both CMD and ZMD have a closer relationship with wild populations in Sichuan than that in Zhejiang. The results of the TCS network and species distribution model suggested that the wild population TQ located in Sichuan province could serve as the ancestor of cultivated O. japonicus, which was supported by RASP analysis. Conclusion: These results suggest that cultivated O. japonicus has experienced dramatic loss of genetic diversity under anthropogenic influence. The genetic differentiation between CMD and ZMD is likely to be influenced by founder effect and strong artificial selection for plant traits. It appears that wild populations in Sichuan area are involved in the origin of not only CMD but also ZMD. In addition, we also raise some suggestions for planning scientific strategies for resource conservation of O. japonicus based on its genetic diversity and population structure. [ABSTRACT FROM AUTHOR]

Background & objectives: The nature of adaptable change of B-cell lymphoma-2 (BCL-2) and/or Bcl2-associated X protein (BAX) gene expression in the human peripheral blood mononuclear cells (PBMCs) irradiated by radioiodine in thyroid diseases therapy is not fully understood. In this study, the alternation of apoptotic gene expression was evaluated while the PBMCs collected from healthy volunteers were irradiated by the radioiodine-131 (131I). Methods: Fasting blood samples were obtained from healthy volunteers. PBMCs from group 0 to 6 were incubated and exposed to different doses of 131I in cell suspension for 6, 12, 24 and 48 h. The apoptosis rates and expression of BCL-2 and BAX genes of PBMCs were examined. Results: The apoptosis rate in the human PBMCs was gradually enhanced after six hour irradiation. The values of BCL-2 and BAX gene expression in groups 1-6 were higher than in group 0 within 6 h of irradiation, and then, these were decreased gradually from 6 to 12 h. BCL-2 gene expression increased in groups 1-3 after 12 h irradiation, but there was no difference in groups 4-6. The ratio of BCL-2/BAX gene expression among groups 4-6 gradually decreased during the period from 6 to 12 h, and it was significantly lower than in the group 0 at 12, 24 and 48 h. Interpretation & conclusions: The expression of BCL-2 and BAX genes was initially upregulated following irradiation. Later, the balance of BCL-2/BAX genes expression was adjusted, and then, PBMCs underwent apoptosis at higher doses of radiation. [ABSTRACT FROM AUTHOR]

[Display omitted] Janus kinases (JAKs), a kind of non-receptor tyrosine kinases, the function has been implicated in the regulation of cell proliferation, differentiation and apoptosis, immune, inflammatory response and malignancies. Among them, JAK1 represents an essential target for modulating cytokines involved in inflammation and immune function. Rheumatoid arthritis, atopic dermatitis, ulcerative colitis and psoriatic arthritis are areas where approved JAK1 drugs have been applied for the treatment. In the review, we provided a brief introduction to JAK1 inhibitors in market and clinical trials. The structures of high active JAK1 compounds (IC 50 ≤ 0.1 nM) were highlighted, with primary focus on structure–activity relationship and selectivity. Moreover, the druggability processes of approved drugs and high active compounds were analyzed. In addition, the issues involved in JAK1 compounds clinical application as well as strategies to surmount these challenges, were discussed. [ABSTRACT FROM AUTHOR]

Dendrobium officinale Kimura et Migo (D. officinale) is used as herbal medicine and new food resource in China, which is nontoxic and harmless, and can be used as common food. Polysaccharide as one of the main bioactive components in D. officinale , mainly composed of glucose and mannose (Man p : Glc p = 2.01:1.00-8.82:1.00), along with galactose, xylose, arabinose, and rhamnose in different molar ratios and types of glycosidic bonds. Polysaccharides of D. officinale exhibit a variety of biological effects, including immunomodulatory, anti-tumor, gastro-protective, hypoglycemic, anti-inflammatory, hepatoprotective, and vasodilating effects. This paper presents the extraction, purification, structural characteristics, bioactivities, structure-activity relationships and analyzes gaps in the current research on D. officinale polysaccharides. In addition, based on in vitro and in vivo experiments, the possible mechanisms of bioactivities of D. officinale polysaccharides were summarized. We hope that this work may provide helpful references and promising directions for further study and development of D. officinale polysaccharides. • D. officinale polysaccharides are purified by anion exchange and gel permeation chromatography. • D. officinale polysaccharides possess diverse structures and configurations. • D. officinale polysaccharides exhibit diverse biological activities. • Structure-activity relationship of D. officinale polysaccharides should be addressed in future studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Relieve resource shortages of Paris polyphylla and improve resource utilization. • DES-UAE can remarkably improve the extraction efficiency of Polyphyllins. • The perspectives and future development direction of DES-UAE are presented. • The study provides proof for using P. polyphylla resources and saponins extraction. As a rare and valuable Chinese herb, Paris polyphylla var chinensis has good pharmacological effects, among which Polyphyllins (PNs) are widely studied as the main active ingredients. Recently, alternative solvents namely, ionic liquids and deep eutectic solvents (DESs) have been used to extract active ingredients with remarkable efficiency. Compared to ionic liquids, deep eutectic solvents (DESs) were found to be effective with the added advantages of ease of production, economy and environment-protecting solvents to substitute common organic ones and have gradually become the research focus of green chemistry. In the present research, twelve varieties of DESs were tailored and PNs were successfully extracted by ultrasound assistance. Among them, combined with single-factor experiments and optimized using response surface methodology (RSM) and artificial neural network (ANN), a liquid–solid ratio of 41.72 mL/g, extraction temperature of 55.97 °C, extraction time of 30.21 min were the optimum extraction method with the overall PNs extraction yield of 52.56 mg/g. Moreover, DESs displayed superior extraction performance in PNs extraction than those traditional solvents. Overall, this study implied that DESs were more conducive to the full utilization and development of the resources of Paris polyphylla, which also confirmed the ability of DESs to effectively extract biologically active ingredients for next step adhibition. [ABSTRACT FROM AUTHOR]

Scrophularia ningpoensis Hemsl. (known as Xuanshen) has been used in China for centuries as a traditional medicinal plant to treat numerous diseases including inflammation, hypertension, cancer, and diabetes. In this review, we provide an update on the botany, pharmacology, phytochemistry, pharmacokinetics, traditional uses, and safety of S. ningpoensis to highlight future research needs and potential uses of this plant. All information on S. ningpoensis was obtained from scientific databases including ScienceDirect, Springer, PubMed, Sci Finder, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar, and Baidu Scholar. Additional information was collected from Chinese herbal medicine books, Ph.D. dissertations, and M.Sc. Theses. Plant taxonomy was verified by "The Plant List" database (http://www.theplantlist.org). S. ningpoensis displays fever reducing, detoxifying, and nourishing 'Yin' effects in traditional Chinese medicine (TCM). More than 162 compounds have been identified and isolated from S. ningpoensis , including iridoids and iridoid glycosides, phenylpropanoid glycosides, organic acids, volatile oils, terpenoids, saccharides, flavonoids, sterols, and saponins. These compounds possess a diverse variety of pharmacological properties that affect the cardiovascular, hepatic, and nervous systems, and protect the body against inflammation, oxidation, and carcinogenesis. Modern pharmacological studies have confirmed that S. ningpoensis is a valuable Chinese medicinal herb with many pharmacological uses in the treatment of cardiovascular, diabetic, and liver diseases. Most of the S. ningpoensis activity may be attributed to iridoid glycosides and phenylpropanoid glycosides; however, detailed information on the molecular mechanisms, metabolic activity, toxicology, and structure-function relationships of active components is limited. Further comprehensive research to evaluate the medicinal properties of S. ningpoensis is needed. Image 1 [ABSTRACT FROM AUTHOR]

Abstract Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption. Highlights • Rubiadin-1-methyl ether (RBM) inhibits osteoclastogenesis at early stage. • RBM inhibits bone resorption by reducing expression of osteoclastic c-Fos and NFATc1. • RBM is involved in RANKL-induced NF-κB signaling pathway in osteoclasts. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Atractylodes macrocephala Koidz. (called Baizhu in China) is a medicinal plant that has long been used as a tonic agent in various ethno-medical systems in East Asia, especially in China, for the treatment of gastrointestinal dysfunction, cancer, osteoporosis, obesity, and fetal irritability. Aim of the review This review aims to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of A. macrocephala to explore the future therapeutic potential and scientific potential of this plant. Materials and methods A literature search was performed on A. macrocephala using scientific databases including Web of Science, Google Scholar, Baidu Scholar, Springer, PubMed, SciFinder, and ScienceDirect. Information was also collected from classic books of Chinese herbal medicine, Ph.D. and M.Sc. dissertations, unpublished materials, and local conference papers on toxicology. Plant taxonomy was confirmed to the database “The Plant List” ( www.theplantlist.org ). Results More than 79 chemical compounds have been isolated from A. macrocephala , including sesquiterpenoids, triterpenoids, polyacetylenes, coumarins, phenylpropanoids, flavonoids and flavonoid glycosides, steroids, benzoquinones, and polysaccharides. Crude extracts and pure compounds of A. macrocephala are used to treat gastrointestinal hypofunction, cancer, arthritis, osteoporosis, splenic asthenia, abnormal fetal movement, Alzheimer disease, and obesity. These extracts have various pharmacological effects, including anti-tumor activity, anti-inflammatory activity, anti-aging activity, anti-oxidative activity, anti-osteoporotic activity, neuroprotective activity, and immunomodulatory activity, as well as improving gastrointestinal function and gonadal hormone regulation. Conclusions A. macrocephala is a valuable traditional Chinese medicinal herb with multiple pharmacological activities. Pharmacological investigations support the traditional use of A. macrocephala , and may validate the folk medicinal use of A. macrocephala to treat many chronic diseases. The available literature shows that much of the activity of A. macrocephala can be attributed to sesquiterpenoids, polysaccharides and polyacetylenes. However, there is a need to further understand the molecular mechanisms and the structure-function relationship of these constituents, as well as their potential synergistic and antagonistic effects. Further research on the comprehensive evaluation of medicinal quality, the understanding of multi-target network pharmacology of A. macrocephala , as well as its long-term in vivo toxicity and clinical efficacy is recommended. [ABSTRACT FROM AUTHOR]

Estrogen deficiency and inflammation are known to play important roles in bone metabolism and occurrence of osteoporosis. Monotropein as an iridoid glycoside is reported to decrease estrogen deficiency-induced bone loss and inhibit inflammatory response in LPS-induced RAW 264.7 macrophages. However, the effect of monotropein on bone loss in chronic inflammatory conditions remains unclear. It was found in the present study that monotropein significantly inhibited bone mass reduction and improved bone micro-architectures by enhancing bone formation and blocking increased secretion of inflammatory cytokines in osteoporotic mice induced by combined ovariectomy and LPS. Our in vitro experiment further demonstrated that monotropein was able to increase the proliferation and activity of alkaline phosphatase (ALP), bone matrix mineralization and the expression of bone matrix protein osteopontin (OPN) in osteoblastic MC3T3-E1 cells injured by LPS. In addition, monotropein significantly decreased the production of IL-6 and IL-1β, inhibited the nuclear translocation of p65 and NF-κB P50, and down-regulated the phosphorylation of NF-κB p65 and IKK, indicating that monotropein could attenuate inflammatory impairment to MC3T3-E1 cells by suppressing the activation of NF-κB pathway. All these results suggest that monotropein may prove to be a promising candidate for the prevention and treatment of inflammatory bone loss. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The medicinal plant Morinda officinalis How. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis. Aim of the review This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant. Methods A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines. Results The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000 mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases. Conclusion MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. Materials and methods In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic–pituitary–adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. Results The results showed that PS extracts (100, 200 mg/kg) and PSY (12.5, 25, 50 mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20 mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. Conclusions These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. [ABSTRACT FROM AUTHOR]

A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants. [ABSTRACT FROM AUTHOR]

ContextLitsea cubeba(Lour.) Pers. (Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) for the treatment of rheumatic diseases. Previous studies from our laboratory indicated thatL. cubebaextract showed anti-arthritic activity in rats. ObjectiveTo studyL. cubebachemically and biologically and to find the potential constituents responsible for its anti-arthritic effect. Materials and methodsThe compounds were isolated from the root ofL. cubebaby column chromatography which eluted with PE:EtOAc gradient system, and the structures were elucidated by detailed spectroscopic data analysis; the anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide (LPS)-induced RAW 264.7 cells and the TNF-α and NO level were measured by ELISA (commercial kit); The iNOS and COX-2 mRNA expression were measured by RT-PCR and the phosphorylation of IκBα, IKKβ, P38 and Akt were determined by western blots. ResultsA novel 9-fluorenone, 1-ethoxy-3,7-dihydroxy-4,6-dimethoxy-9-fluorenone (1), together with 4 known compounds, namely pinoresinol (2), syringaresinol (3), 9,9′-O-di-(E)-feruloyl-meso-5,5′-dimethoxysecoisolariciresinol (4) and lyoniresinol (5) were isolated from the root ofL. cubebafor the first time. The IC50for NO inhibition on compounds1and4were 56.1 ± 1.2 and 32.8 ± 2.3 μM, respectively. The IC50for TNF-α inhibition were 28.2 ± 0.9 and 15.0 ± 1.0 μM, respectively. Both1and4suppress mRNA expression of iNOS, COX-2 and protein phosphorylation of IκBα, IKKβ in LPS-induced RAW 264.7 cells. Discussion and conclusionCompounds1and4isolated fromL. cubebaexhibited potent anti-inflammatory activity through the NF-κB signal pathway. [ABSTRACT FROM PUBLISHER]

Ethnopharmacological relevance Osteoporosis is a chronic epidemic which can leads to enhanced bone fragility and consequent an increase in fracture risk. Traditional Chinese medicine (TCM) formulas have a long history of use in the prevention and treatment of osteoporosis. Antiosteoporotic TCM formulas have conspicuous advantage over single drugs. Systematic data mining of the existing antiosteoporotic TCM formulas database can certainly help the drug discovery processes and help the identification of safe candidates with synergistic formulations. In this review, the authors summarize the clinical use and animal experiments of TCM formulas and their mechanism of action, and discuss the potential antiosteoporotic activity and the active constituents of commonly used herbs in TCM formulas for the therapy of osteoporosis. Materials and methods The literature was searched from Medline, Pubmed, ScienceDirect, Spring Link, Web of Science, CNKI and VIP database from 1989 to 2015, and also collected from Chinese traditional books and Chinese Pharmacopoeia with key words such as osteoporosis, osteoblast, osteoclast, traditional Chinese medicine formulas to identify studies on the antiosteoporotic effects of TCM formulas, herbs and chemical constituents, and also their possible mechanisms. Results Thirty-three TCM formulas were commonly used to treat osteoporosis, and showed significant antiosteoporotic effects in human and animal. The herb medicines and their chemical constituents in TCM formulas were summarized, the pharmacological effects and chemical constituents of commonly used herbs in TCM formulas were described in detail. The action mechanisms of TCM formulas and their chemical constituents were described. Finally, the implication for the discovery of antiosteoporotic leads and combinatory ingredients from TCM formulas were prospectively discussed. Conclusions Clinical practice and animal experiments indicate that TCM formulas provide a definite therapeutic effect on osteoporosis. The active constituents in TCM formulas are diverse in chemical structure, and include flavonoids, lignans, saponins and iridoid glycosides. Antiosteoporotic mechanism of TCM formulas and herbs involves multi regulatory pathways, such as Wnt/β-catenin, BMP/Smad, MAPK pathway and RANKL/OPG system. Phytochemicals from TCM formulas and their compositional herb medicines offer great potential for the development of novel antiosteoporotic drugs. The active ingredients in TCM formulas can be developed in combination as potent drugs, which may exhibit better antiosteoporotic effects compared to the individual compound. [ABSTRACT FROM AUTHOR]

The article investigates iridoids and noridoprenoid content of Paederia scandens variety tomentosa, a climbing plant belonging to the genus Paederia that is widely distributed in China, Japan, India, and Malaysia. One norisoprenoid and six iridoids were isolated from the plant, with compounds 1-3 from the genus Paederia and compound 1 from the family Rubiaceae. 80% ethanol was used to extract the dried whole plants of P. scandens variety tomentosa, which were evaporated under vacuum.

Ethnopharmacological significance Icariin (I), ferulic acid (F) and timosaponin B II (T) derived respectively from the leaf of Epimedium brevicornu Maxim (EBM, Berberidaceae), rhizome of Anemarrhena asphodeloides Bunge (AAB, Liliaceae) and root of Angelica sinensis (Oliv.) Diels (ASD, Umbelliferae) are included in several traditional Chinese medicine (TCM) formulas for the treatment of osteoporosis. In addition, the medicinal materials and chemical constituents in many traditional Chinese formulas have been shown to have potential synergistic, additive and antagonistic effects. Aim of study To explore the action mechanism and interactions between I, T and F as bone anabolic ingredients on osteoblasts, and fully understand their action mechanism and rationality of the formula design. Materials and methods An osteoporotic model was established in bilaterally ovariectomized mice. Bone mineral density (BMD), bone mineral content (BMC) and serum biochemical parameters including alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), osteoprotegerin (OPG) and deoxypyridinoline cross-links (DPD) were measured to evaluate the effects of I, T or F alone and their combinations on osteoporotic mice. UMR-106 osteoblastic cells and primary osteoblasts in neonatal rat calvarias were used to evaluate the osteogenesis effect. The immunohistochemical method and Western-blot analysis were used to detect the expression of critical proteins in the process of proliferation and differentiation of osteoblasts. Results IFT combinations enhanced the therapeutic effect without increasing the adverse effects on osteoporotic mice, synergistically increased the osteoblast proliferation, ALP activity and mineralized nodule formation, and promoted the expression of bone matrix by regulating BMP and Wnt/β-catenin signaling pathways in osteoblasts. Conclusion IFT combinations reinforced the therapeutic effect on osteoporosis by modulating multi-signaling pathways and action targets. [ABSTRACT FROM AUTHOR]

Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds. [ABSTRACT FROM AUTHOR]

The development of plant tissue (including organ and cell) cultures for the production of secondary metabolites has been underway for more than three decades. Plant cell cultures with the production of high-value secondary metabolites are promising potential alternative sources for the production of pharmaceutical agents of industrial importance. Medicinal plant cell suspension cultures (MPCSC), which are characterized with the feature of fermentation with plant cell totipotency, could be a promising alternative “chemical factory”. However, low productivity becomes an inevitable obstacle limiting further commercialization of MPCSC and the application to large-scale production is still limited to a few processes. This review generalizes and analyzes the recent progress of this bioproduction platform for the provision of medicinal chemicals and outlines a range of trials taken or underway to increase product yields from MPCSC. The scale-up of MPCSC, which could lead to an unlimited supply of pharmaceuticals, including strategies to overcome and solution of the associated challenges, is discussed. [ABSTRACT FROM PUBLISHER]

Ethnopharmacological relevance Currently, human liver is susceptible to injury caused by alcohol and virus infiltration, resulting in hepatitis, cirrhosis, and even hepatocellular carcinoma. Paederia scandens (Lour.) Merr. var. tomentosa (Rubiaceae) has been used as traditional medicine in Asian countries to treat jaundice, dysentery, and abdominal mass. Furthermore, the abundance of iridoid glycosides in Paederia species indicates their notable hepatoprotective potential. Materials and methods Total iridoid glycosides (TG) was prepared, and constituents of TG were analyzed by HPLC. TG and silymarin (positive) were orally administered for 15 days. Then, acute liver injury rats was induced by intraperitoneally injection (i.p.) of 10% CCl 4 (0.12%, v/v, dissolved in olive oil, 10 mL/kg, body weight). Rats were sacrificed at 16 h after CCl 4 injection. Liver tissues and blood were collected. Serum samples were prepared to determine the activities of alanine transaminase (ALT) and aspartate transaminase (AST), whereas liver tissue sections were prepared for the purpose of examining possible liver histopathological changes. In addition, antioxidant enzyme activities in liver tissues were also evaluated. Results Our results demonstrated that TG significantly decreased the levels of AST and ALT, compared with those in control rats. In addition, pre-treatment of the rats with TG clearly alleviated their liver tissue injuries. What’s more, the activities of GSH, GAT and SOD in the groups of TG-treated rats were significantly increased compared with those of rats in the control group, whereas the levels of MDA were decreased. Conclusions Our present research indicated that TG possessed notable hepatoprotective activity via decreasing oxidative stress level in liver tissues. [ABSTRACT FROM AUTHOR]

Cnidium monnieri (L.) Cuss., an annual plant of the Umbelliferae species is one of the most widely used traditional herbal medicines and its fruits have been used to treat a variety of diseases in China, Vietnam, and Japan. The aim of this review is to provide an up-to-date and comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity and contraindication of Cnidium monnieri (L.) Cuss. and to provide future directions of research on this plant. To date, 350 compounds have been isolated and identified from Cnidium monnieri (L.) Cuss., including the main active constituent, coumarins. In vitro and in vivo studies suggest that osthole and other coumarin compounds possess wide range of pharmacological properties for the treatment of female genitals, male impotence, frigidity, skin-related diseases, and exhibit strong antipruritic, anti-allergic, antidermatophytic, antibacterial, antifungal, anti-osteoporotic effects. Although coumarins have been identified as the main active constituents responsible for the observed pharmacological effects, the molecular mechanisms of their actions are still unknown. Therefore, further studies are still required to reveal the structure-activity relationship of these active constituents. In addition, toxicological and clinical studies are also required to provide further data for pharmaceutical use. [ABSTRACT FROM AUTHOR]

Curculigoside has an extensive pharmacological activity, including estrogen-like, improving sexual behavior, antiosteoporotic, antioxidant, immunomodulatory and neuroprotective effects. However, few investigations have been conducted about the pharmacokinetics and tissue distribution of curculigoside to better understand its behavior and action mechanism in vivo. Thus, a sensitive and reliable liquid chromatography with mass spectrometry (HPLC–MS) method was established and validated for the quantification of curculigoside in rat plasma and tissue samples. Biological samples were processed with methanol precipitation, and naringin was used as the internal standard. Chromatographic separation was performed on an Agilent XDB-C 18 chromatography column (3.0 mm × 50 mm, 1.8 μm) with a mobile phase consisting of acetonitrile and 0.1% formic acid. Quantification was performed by selected ion monitoring with m/z 511.1 [M + HCO 2 ] − for curculigoside and m/z 579.1 [M − H] − for the internal standard. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of curculigoside in rats. Non-compartmental pharmacokinetic parameters indicated that curculigoside had rapid distribution, extensive tissue uptake, and poor absorption into systemic circulation. The values of absolute bioavailability were 0.38%, 0.22% and 0.27% for oral doses of 100, 200 and 400 mg/kg, respectively. The results of the tissue distribution study suggested that curculigoside was distributed into the heart, lung, spleen, intestine, stomach, kidney, thymus, liver, brain, testis, and bone marrow after oral administration of 150 mg/kg. In conclusion, the present study may provide a material basis for study of the pharmacological action of curculigoside, and meaningful insights into further study on clinical application. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Red sage ( Salvia miltiorrhiza Bunge), also known as Danshen in Chinese, has been used historically and is currently exploited in combination with other herbs to treat skeletal diseases in traditional Chinese medicine (TCM). With the advance of modern analytical technology, a multitude of bone-targeting, pharmaceutically active, compounds has been isolated and characterized from various sources of TCM including those produced in Salvia miltiorrhiza root. The aim of the review is to provide a comprehensive overview about the historical TCM interpretation of the action of Salvia miltiorrhiza in osteoporosis, its use clinical trials, its main phytochemical constituents, and its action on bone-resorptive and bone formation-stimulating mechanisms in in vitro and in vivo studies. Materials and methods Literature sources used were Pubmed, CNKI.net, Cqvip.com, PubChem, and the Web of Science. For the inquiry, keywords such as Salvia, danshen, osteoporosis, bone, osteoclast and osteoblast were used in various combinations. About 130 research papers and reviews were consulted. Results In TCM, the anti-osteopororotic effect of Salvia miltiorrhiza is ascribed to its action on liver and blood stasis as main therapeutic targets defining osteoporosis. 36 clinical trials were identified which used Salvia miltiorrhiza in combination with other herbs and components to treat post-menopausal, senile, and secondary osteoporosis. On average the trials were characterized by high efficacy (>80%) and low toxicity problems. However, various limitations such as small patient samples, short treatment duration, frequent lack of detailed numerical data, and no clear endpoints must be taken into consideration. To date, more than 100 individual compounds have been isolated from this plant and tested in various animal models and biochemical assays. Compounds display anti-resorptive and bone formation-stimulating features targeting different pathways in the bone remodeling cycle. Pathways affected include the activation of osteoblasts, the modulation of osteoclastogenesis, and the inhibition of collagen degradation by cathepsin K. Conclusions The inclusion of Salvia miltiorrhiza in more than 30% of all herbal clinical trials successfully targeting osteoporosis has stimulated significant interest in the identification and characterization of individual constituents of this herb. The review highlights the anti-osteoporotic potential of Salvia miltiorrhiza in clinical applications and the potential of the herb to provide potent compounds targeting specific pathways in bone resorption and bone formation. [ABSTRACT FROM AUTHOR]

In this study, the isolation of an endophytic fungus from the leaves of the medicinal herb adlay ( Coix lacryma- jobi L. var. ma- yuen Stapf) is reported for the first time. The fungus produced Triolein (trioleoylglycerol), a major constituent of triacylglycerols (TAGs) of adlay, in rice medium under shake-flask and bench-scale fermentation conditions. The fungus was identified as Gibberella moniliformis ( Fusarium verticillioides) by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Triolein was identified by HPLC-ELSD coupled with APCI-MS and confirmed through comparison with authentic standard. The concentration of triolein produced by G. moniliformis AH13 reached 2.536 ± 0.006 mg/g dry weight of mycelium. Moreover, the EtOAc extract of G. moniliformis AH13 showed strong antitumor activity against four types of tumor cells (A549, HCT116, MDA-MB-231, and SW1990). These results suggest that G. moniliformis AH13 in adlay has significant scientific and industrial potential to meet the pharmaceutical demands and sustainable energy requirements for TAGs in a cost-effective, easily accessible, and reproducible way and is also a potential novel source of natural antitumor bioactive agents. [ABSTRACT FROM AUTHOR]

As cannabinoid CB2 receptors (CB2R) possess various pharmacological effects—including anti-epilepsy, analgesia, anti-inflammation, anti-fibrosis, and regulation of bone metabolism—without the psychoactive side effects induced by cannabinoid CB1R activation, they have become the focus of research and development of new target drugs in recent years. The present study was intended to (1) establish a double luciferase screening system for a CB2R modulator; (2) validate the agonistic activities of the screened compounds on CB2R by determining cAMP accumulation using HEK293 cells that are stably expressing CB2R; (3) predict the binding affinity between ligands and CB2 receptors and characterize the binding modes using molecular docking; (4) analyze the CB2 receptors–ligand complex stability, conformational behavior, and interaction using molecular dynamics; and (5) evaluate the regulatory effects of the screened compounds on bone metabolism in osteoblasts and osteoclasts. The results demonstrated that the screening system had good stability and was able to screen cannabinoid CB2R modulators from botanical compounds. Altogether, nine CB2R agonists were identified by screening from 69 botanical compounds, and these CB2R agonists exhibited remarkable inhibitory effects on cAMP accumulation and good affinity to CB2R, as evidenced by the molecular docking and molecular dynamics. Five of the nine CB2R agonists could stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. All these findings may provide useful clues for the development of novel anti-osteoporotic drugs and help elucidate the mechanism underlying the biological activities of CB2R agonists identified from the botanical materials. [ABSTRACT FROM AUTHOR]

Two new iridoids, jatamanvaltrates P and Q ( 1 and 2, resp.), together with three known iridoids, rupesin B ( 3), chlorovaltrate ( 4), and valtrate ( 5), were isolated from the root and rhizome of Valeriana jatamansi Jones. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D-NMR techniques. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF. Materials and methods: XSF extract was prepared and seven characteristic components were isolated and identified in XSF water extracts. We evaluated their hepatotoxicity effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and BRL liver cell line. An integrated metabonomics study using high-resolution 1H nuclear magnetic resonance (1H NMR) spectroscopy combined with multivariate statistical analysis was undertake to elucidate the hepatotoxicity mechanism induced in rats by XSF. The urine and serum metabolites were measured after treatment of rats with XSF (7.5, 15.0 and 30.0g/kg/day) for 5 days. Results: The results showed that atractyloside, carboxyatractyloside, 4'-desulphate-atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'-desulphate-atractyloside were the toxic components of XSF. When rats were treated with XSF at 30.0g/kg the hepatotoxicity was reflected in the changes observed in serum biochemical profiles and by the histopathological examination of the liver. The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum were increased in this group, while d-glucose, choline and valine were decreased. The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3-HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine, phenylalanine and tryptophan was observed in urine, in contrast a reduction in the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine-N-oxide (TMAO) was observed. Conclusions: The results demonstrate that the major hepatotoxicity constituents are atractyloside, carboxyatractyloside and 4'-desulphate-atractyloside, and the hepatotoxicity of XSF involves mitochondrial inability, fatty acid metabolism, and some amino acids metabolism. This integrated 1H NMR -based metabolic profiling approach has been able to capture and probe the metabolic alterations associated with the onset and progression of hepatotoxicity induced by XSF, and permits a comprehensive understanding of systemic toxicity for phytochemicals and other types of xenobiotic agents. [Copyright &y& Elsevier]

Abstract: Chemical investigation of Vitex negundo seeds afforded four new lignans, including a phenylindene-type lignan, vitexdoin F (1), and three phenylnaphthalene-type lignans, vitexdoins G, H and I (2–4). Their structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. All compounds were evaluated for their anti-inflammatory and anti-osteoporotic activities, employing RAW264.7 macrophages, osteoblast-like UMR106 and osteoclastic cells, respectively. Compound 1 showed significant inhibition on the nitric oxide (NO) production (IC50 4.17μg/mL) due to its down-regulation of the inducible nitric oxide synthase (iNOS) protein expression in LPS-stimulated RAW264.7 cells, which also exhibited potent stimulatory effects on the proliferation and ALP (alkaline phosphatase) activity of UMR106 cells, and significantly up-regulated the OPG/RANKL protein ratio. [Copyright &y& Elsevier]

Two strains of endophytic fungi, Penicillium melinii Yuan-25 and Penicillium janthinellum Yuan-27, with strong anti- Pyricularia oryzae activity, were obtained from the roots of Panax ginseng. Based on bioactivity-oriented isolation, a new benzaldehyde derivative, ginsenocin ( 1), together with six known compounds, methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate ( 2), 3,4,5-trimethyl-1,2-benzenediol ( 3), penicillic acid ( 4), mannitol ( 5), ergosterol ( 6), and ergosterol peroxide ( 7), were separated from the EtOAc extract of Yuan-25 culture, while brefeldin A ( 8) was isolated as the major constituent from the EtOAc extract of Yuan-27 culture. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1- 8 were evaluated for their cytotoxicity against six human cancer cell lines. Brefeldin A ( 8) was the most cytotoxic constituent against all the tested cell lines with IC values <0.12 μg/ml, while ginsenocin ( 1) and penicillic acid ( 4) also exhibited potent cytotoxicity with IC values ranging from 0.49 to 7.46 μg/ml. Our results suggest that endophytic fungi isolated from P. ginseng are a promising natural source of potential anticancer agents. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The dried root of Litsea cubeba (Lour.) Pers. (Family Lauraceae) has long been used as a folk remedy in Traditional Chinese Medicine (TCM) and Dai Ethnopharmacy for the treatment of rheumatic diseases in southwestern China. Aim of the study: This study investigated the preventive efficacy of Litsea cubeba root in treating rheumatoid arthritis using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model. Materials and methods: Arthritis was induced in male Wistar rats by immunization with CFA. Ethanol extract (EELC) and water extract (WELC) of Litsea cubeba root both at 50mg/kg and 200mg/kg were orally administered from a day after the induction of arthritis. Paw swelling, arthritic score, body weight growth rate, index of thymus and spleen were observed, and the production of TNF-α, IL-1β, IL-6 and IL-10 in serum were measured by enzyme-linked immunosorbent assay. The expression levels of inflammatory enzymes like cyclooxygenase and lipoxygenase were also measured by enzyme-linked immunosorbent assay. Moreover, histological changes in the ankle joint were analyzed in AA rats. Results: Both EELC and WELC significantly suppressed paw swelling and arthritic score, increased the loss in body weight and decreased the index of thymus. Histopathological improvement in joint architecture was also observed in EELC, WELC-treated AA rats. The expression levels of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) were decreased on treatment with EELC and WELC. Furthermore, the overproduction of TNF-α, IL-1β and IL-6 were remarkably attenuated in serum of all Litsea cubeba-treated rats, however, IL-10 was markedly increased at doses of 50mg/kg of EELC and WELC. Conclusions: These results indicate that extract of Litsea cubeba root significantly attenuates adjuvant arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing of IL-10 in serum as well as down-regulate the levels of inflammatory enzymes such as COX-2 and 5-LOX. This suggests that Litsea cubeba root might be used as a therapeutic agent for the treatment of human arthritis. [Copyright &y& Elsevier]

Two new bis-alkaloids, flavifloramides A ( 1) and B ( 2), as well as two known alkaloids, N- trans-feruloyltyramine ( 3) and paprazine ( 4), were isolated from the aerial part of Piper flaviflorum. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D-NMR techniques. [ABSTRACT FROM AUTHOR]

Based on bioactivity-oriented isolation, the EtOAc extract of a culture broth of the endophytic fungus Perenniporia tephropora Z41 from Taxus chinensis var. mairei, with strong anti- Pyricularia oryzae activity, afforded a new sesquiterpenoid, perenniporin A ( 1), together with three known compounds, ergosterol ( 2), rel-(+)-(2aR,5R,5aR,8S,8aS,8bR)-decahydro-2,2,5,8-tetramethyl-2H-naphtho[1,8-bc]genfuran-5-ol ( 3), and albicanol ( 4). Their structures were elucidated by means of spectroscopic methods. All the isolated compounds and the EtOAc extract of P. tephropora Z41 (EPT) were evaluated for their cytotoxic activity against three human cancer cell lines (HeLa, SMMC-7721, and PANC-1). EPT demonstrated significant cytotoxicity with IC values ranging from 2 to 15 μg/mL. Compound 2 was the most cytotoxic constituent against the tested cell lines with IC values of 1.16, 11.63, and 11.80 μg/mL, respectively, while compounds 1, 3, and 4 exhibited moderate cytotoxicity with IC values ranging from 6 to 58 μg/mL. We conclude that the endophytic fungus P. tephropora is a promising source of novel and cytotoxic metabolites. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Ligusticum chuanxiong Hort. (Umbelliferae) is a plant used as medicine and food in China. The essential oil (EO) extracted from its rhizomes possesses many pharmacological activities. However, there have been no scientific reports in the modern literature on the safety of EO. Aims of the study: The objective of this study was to conduct a chemical composition analysis and evaluate acute toxicity and skin sensitivity of EO from rhizomes of Ligusticum chuanxiong. Materials and methods: The chemical composition of hydrodistilled EO was analyzed by gas chromatography-mass spectrometry (GC–MS) and was evaluated in animals for acute toxicity, skin irritation and sensitization tests. Results: Dozens of compounds were detected and the major components of EO were ligustilide and butylidenephthalide with relative contents of 67.46 and 5.06%, respectively. The oral and intra-peritoneal lethal doses of 50% (LD50) in mice were 7.23g/kg (approximately 14,606 times of clinical dose used) and 2.25g/kg (approximately 5091 times of clinical dose used), respectively. The doses of 0.115 and 0.23g/kg EO (approximately 232.5 and 465 times of the respective clinical doses used) revealed slight irritation effects on rabbit skin, but 1g/kg EO (approximately 2020 times of clinical dose used) had no observable effect on guinea pig skin in the skin sensitization test. Conclusions: These experimental results indicate that short term application of EO is probably safe within the range of its clinical doses, but the dose should be controlled for external use due to its slight skin irritation. [Copyright &y& Elsevier]

Abstract: Six new acylphloroglucinol derivatives, sampsonols A-F (1–6), were isolated from the petroleum ether extract of the aerial parts of Hypericum sampsonii. The structures and relative configurations of sampsonols A-F were elucidated by extensive spectroscopic analyses. All these compounds were tested for their in vitro cytotoxic and anti-inflammatory activities. Sampsonols A and B (1 and 2) showed significant cytotoxicity against four human tumor cell lines with IC50 values in the range of 13–28μM, whereas sampsonols C and F (3 and 6) showed potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with IC50 values of 27.3 and 29.3μM, respectively. [Copyright &y& Elsevier]

Context: Sinomenium acutum (Thumb.) Rehd. et Wils. (Menispermaceae, SA) has been used as a traditional Chinese medicine in the treatment of various diseases for hundreds of years; it possesses favorable effects against autoimmune diseases, especially rheumatoid arthritis (RA). A great number of investigations have been done on SA in the last decade, but they are usually scattered across various publications. Objective: The purpose of this article is to summarize and review the published scientific information about the chemical constituents, pharmacological effects, pharmacokinetics, and clinic applications of this plant since 2000. Results: The information for 89 cases included in this review was compiled. The SA contains alkaloids, sterols, phospholipids, and some other components. A great deal of pharmacological and clinic research has been done on sinomenine, a main compound from SA, which mainly focuses on the immune system, cardiovascular system, and nervous system. Conclusion: Previous studies strongly support its potential as an effective adaptogenic herbal remedy. There is no doubt that SA is being widely used now and will have extraordinary potential for the future. [ABSTRACT FROM AUTHOR]

Two new clerodane-type diterpenes, solidagocanins A and B ( 1 and 2, resp.), as well as two known compounds, mellein ( 3) and physcion ( 4), were isolated from the aerial parts of Solidago canadensis. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D-NMR techniques. [ABSTRACT FROM AUTHOR]

Context: Vitex negundo Linn. (Verbenaceae) seeds are pepper substitute and occasionally used as a condiment for edible purposes. The seeds also find use for analgesia, sedation, rheumatism and joint inflammation in folk medicine. Objective: To isolate and characterize bioactive constituents from V. negundo seeds. Materials and methods: The ethanol extract of V. negundo seeds was subjected to repeated column chromatography. Chemical structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Several pathogenic fungi isolates were employed to evaluate the antifungal activity of the isolated compound. Results: Chemical investigations of the seed extract afforded a new labdane diterpenoid, named negundol ( 1a + 1b), as an inseparable mixture of two diastereoisomers in a 5:4 ratio. Their structures were identified as ( rel 3 S, 5 S, 8 R, 9 R, 10 S, 13 S, 16 S)-3-acetoxy-9, 13-epoxy-16-hydroxy-labda-15, 16-olide ( 1a), and ( rel 3 S, 5 S, 8 R, 9 R, 10 S, 13 S, 16 R)-3-acetoxy-9, 13-epoxy-16-hydroxy-labda-15, 16-olide ( 1b). Compound 1 was active as an antifungal agent with MIC80 values in the range of 16-64 μg/mL. Discussion and conclusion: The presence of compound 1 in V. negundo is of chemotaxonomic significance, since plants under the genus Vitex are chemically characterized with labdane diterpenoids. Compound 1 exhibited potential antifungal activity and may be considered a lead compound for promising antifungal agent. [ABSTRACT FROM AUTHOR]

Context: Endophytic fungi are microorganisms living within the tissues of host plants, and have proven to be rich sources of biologically active secondary metabolites and therefore have attracted increasing attention in recent years. Objective: To isolate and characterize bioactive constituents from the endophytic fungus cultures of Crocus sativus Linn. (Iridaceae). Materials and methods: Endophytes were isolated from the corm of C. sativus. Endophytic fungus cultures were subjected to repeated column chromatography. Chemical structure was elucidated based on extensive spectroscopic methods and X-ray diffraction analysis. Several pathogenic fungi isolates and tumor cell lines were employed to evaluate the antifungal and cytotoxic activities of the isolated compound. Results: An isolate of Penicillium vinaceum (strain no. X17) was obtained from the corm of C. sativus. Chemical investigations of the endophyte culture broth afforded an unique quinazoline alkaloid (1), identified as (-)-(1R,4R)- 1,4-(2,3)-indolmethane-1-methyl-2,4-dihydro-1H-pyrazino-[2,1-b]-quinazoline-3,6-dione, which showed cytotoxic (IC50 range 40.55–76.83μg/mL) and antifungal (MIC80 range 16–64μg/mL) activities. Discussion and conclusions: Endophytes in C. sativus can be a rich source of novel bioactive compounds, which prompts us to expand the medicinal resource of this valuable plant in another way. Compound 1 exhibited potential cytotoxic and antifungal activities and may be considered a lead compound for promising antifungal and anticariogenic agent. [ABSTRACT FROM AUTHOR]

Abstract: Chemical investigation on the seeds of Vitex negundo has afforded a new furan-containing sesquiterpenoid, negunfurol (1), a new norlabdane-type diterpenoid, negundoal (2), and two new norursane-type triterpenoids, negundonorins A (3) and B (4), together with two know compounds, 3-formyl-4,5-dimethyl-8-oxo-5H-6,7-dihydronaphtho[2,3-b]furan (5) and 3-epi-corosolic acid (6). Their structures and configurations were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Compound 3 was strongly cytotoxic against ZR-75-30 cell line with IC50 value of 0.56±0.19μg/mL, whereas compound 1 was most active against HL-60 cell line with IC50 value of 0.94±0.26μg/mL. [Copyright &y& Elsevier]

Context: Ligusticum chuanxiong Hort (LC; Umbelliferae) is an effective medical plant, which has been extensively applied for many years to treat various diseases with other Chinese herbal medicines. Although a considerable amount of scientific research was reported on LC in the last decade, it is currently scattered across various publications. The present review comprises the chemical and pharmacological research on LC in the last decade. Objective: The objective of this review is to bring together most of the scientific research available on LC and evaluate its effects and mechanisms. Methods: The information for 82 cases included in this review was compiled using major databases such as Medline, Elsevier, Springer, Pubmed, and Scholar. Results: The compounds contained in LC can be divided into five kinds, essential oil (EO), alkaloids, phenolic acids, phthalide lactones, and other constituents. A great deal of pharmacological research has been done, which mainly focuses on cardiovascular and cerebrovascular effects, antioxidation, neuroprotection, antifibrosis, antinociception, antiinflammation, and antineoplastic activity. Conclusion: A large number of pharmacological and chemical studies during the last 10 years have demonstrated the vast medicinal potential of LC. It is still very clear that LC is a plant with widespread use now and also with extraordinary potential for the future. The documents strongly support the view that LC has beneficial therapeutic properties and indicates its potential as an effective adaptogenic herbal remedy. [ABSTRACT FROM AUTHOR]

Abstract: Two new sesquiterpenoids, identified as (rel 1S, 3R, 4R, 7R)-3-[5-hydroxy-4-methylpent-3-enyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (1) and (rel 1S, 3R, 4R, 7R)-3-[3, 4-dihydroxy-4-methylpentyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (2), were isolated from cultures of Trichoderma atroviride (strain no. S361), an endophytic fungal strain residing in the bark of Cephalotaxus fortunei. The structures of compounds 1 and 2 were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Both compounds 1 and 2 were potent inhibitors on NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 15.3 and 9.1μM, respectively. [Copyright &y& Elsevier]

Abstract: In order to effectively treat osteoporosis and other bone-loss disorders, small compounds that could induce bone formation are needed. The present study attempted to establish a screening system for detecting estrogenic activity of compounds, which probably have anti-osteoporosis effects. For this purpose, we established osteoblastic-like MG63 cells stably transfected with the PGL3 reporter gene driven by a promoter consisting of three estrogen response elements (EREs). Using this system, we screened numerous plant extracts, and found several which displayed bioactivity. We conclude that the MG63 cells with estrogen-specific reporter plasmids (MG63–pERE) are useful for high-throughput screening of estrogen receptor agonists from plants which may have favorable potency and could be developed into novel anti-osteoporosis drugs. [Copyright &y& Elsevier]

Context: Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of collagen and excessive deposition of extracellular matrix. Although the treatment with surgical excisions or steroid hormones can modify the symptoms, numerous treatment-related complications have also been established. Objective: To investigate the effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on hypertrophic scarring in a rabbit ear model. Materials and methods: A rabbit ear model of hypertrophic scarring was established. EO (5, 10, and 20%) was applied once daily to the scars for 22 days. After 28 days of post-wounding, excision of scars was respectively performed for both histological examination and assays of the levels of collagen I, collagen III, matrix metalloproteinase-1 (MMP-1), and transforming growth factor beta 1 (TGF-ββ1). The scar elevation index (SEI) was also determined. Results: After 22 days of treatment with indicated concentrations of EO, hypertrophic scarring was significantly inhibited in the rabbit ears. The levels of TGF-ββ1, collagen I, and collagen III evidently decreased and MMP-1 level markedly increased in the scar tissue. SEI was also significantly reduced. Immunohistochemical findings exhibited significant amelioration of the scar tissue. Discussion and conclusion: EO suppresses hypertrophic scarring in the rabbit ear model and is a probably effective cure for human hypertrophic scarring. [ABSTRACT FROM AUTHOR]

Context: Crocus sativus Linn. (Iridaceae), commonly known as saffron, becomes more and more popular due to its versatile biological and medicinal properties. At present, studies mainly focus on the traditional medicinal part, the saffron stigma, with less attention to the other parts of saffron, such as the perianth, the stamen, and the corm, which are high yield compared to the stigma and also possess various pharmacological effects. Objective: To determine the chemical compositions, antifungal, cytotoxic, and antioxidant activities of the ether fractions from the stamen, perianth, and stigma of saffron. Materials and methods: The chemical constituents of the ether fractions from different parts of saffron were investigated by gas chromatography/mass spectrometry. Several pathogenic fungi isolates and tumor cell lines were employed to evaluate the antifungal and cytotoxic activities of these three ether fractions. 1,1-Diphenyl-2-picrylhydrazyl assay was used to determine the free radical-scavenging activity. Results: The ether fractions composition of the three C. sativus parts are different from each other, but lauric acid, hexadecanoic acid, 4-hydroxydihydro-2(3H)-furanone, and stigmasterol were the common constituents shared by all the three fractions. The stamen ether fraction displayed the strongest antifungal and cytotoxic activities, whereas both of the saffron stamen and perianth ether fractions exhibited significant antioxidant activities. Discussion and conclusion: These findings demonstrate that the saffron stamen and perianth possess significant antifungal, cytotoxic, and antioxidant activities as well as the stigma, though not to the same extent, prompting us to expand the medicinal resource and make best use of this valuable plant. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The fruit of Illicium verum Hook. f. (Chinese star anise) has long been used in traditional Chinese medicine and food industry with the actions of dispelling cold, regulating the flow of Qi and relieving pain. Materials and methods: A bibliographic investigation was carried out by analyzing recognized books including Chinese herbal classic, and worldwide accepted scientific databases (Pubmed, SciFinder, Scopus and Web of Science) were searched for the available information on I. verum. Results: I. verum is an aromatic evergreen tree of the family Illiciaceae. It is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes. Traditional uses of I. verum are recorded throughout Asia and Northern America, where it has been used for more than 10 types of disorders. Numerous compounds including volatiles, seco-prezizaane-type sesquiterpenes, phenylpropanoids, lignans, flavonoids and other constituents have been identified from I. verum. Modern pharmacology studies demonstrated that its crude extracts and active compounds possess wide pharmacological actions, especially in antimicrobial, antioxidant, insecticidal, analgesic, sedative and convulsive activities. In addition, it is the major source of shikimic acid, a primary ingredient in the antiflu drug (Tamiflu). Aim of the review: This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of I. verum together with the toxicology, and discusses the possible trend and scope for future research of I. verum. [Copyright &y& Elsevier]