Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research.

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.

Postpartum dietary intake, depression and the concentration of docosahexaenoic acid in mature breast milk in Wuhan, China.

Background: Docosahexaenoic acid (DHA, C22:6) is an important fatty acid in breast milk and is essential for infantile growth and cognitive development. However, the factors that affect the DHA concentration in breast milk have not been completely clarified. Objective: This study aimed to characterize the composition of breast milk fatty acids and to identify maternal factors associated with breast milk DHA concentration in postpartum women in Wuhan, China. Methods: In this cross-sectional study, we analyzed milk fatty acids in 115 lactating women at 30-120 days postpartum using GC-MS. Maternal sociodemographic, health and other information were collected using a self-reported questionnaire. Maternal dietary intake information was collected through a 24-hour dietary recall method. Postpartum depression status was identified using the Edinburgh Postnatal Depression Scale (EPDS). Results: The mean DHA proportion in breast milk was 0.49%. The multivariate regression model showed that the milk DHA proportion was positively associated with maternal aquatic product intake (ß = 0.183, 95%CI: 0.052, 0.314) and DHA supplement use (ß = 0.146, 95%CI: 0.108, 0.185), and negatively associated with postpartum depression status (ß = -0.122, 95%CI: -0.243, -0.002) after adjustment for several maternal and infant factors. Conclusion: Increasing maternal aquatic product intake and DHA supplement use and improving postpartum depression status may increase DHA concentration in breast milk in lactating women.

Pregnancy thiamine and riboflavin intake and the risk of gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Thiamine and riboflavin deficiencies exist to varying degrees worldwide, especially in developing countries. Evidence regarding the association between thiamine and riboflavin intake and gestational diabetes mellitus (GDM) is scarce. OBJECTIVES: We aimed to evaluate the association of thiamine and riboflavin intake during pregnancy, including dietary source and supplementation, with GDM risk in a prospective cohort study. METHODS: We included 3036 pregnant women (923 in the first trimester and 2113 in the second trimester) from the Tongji Birth Cohort. A validated semi-quantitative food frequency questionnaire and a lifestyle questionnaire were used to assess thiamine and riboflavin intake from dietary source and supplementation, respectively. GDM was diagnosed using the 75 g 2-h oral glucose tolerance test at 24-28 weeks of gestation. A modified Poisson regression or logistic regression model was used to evaluate the association between thiamine and riboflavin intake and GDM risk. RESULTS: Dietary intake of thiamine and riboflavin was at low levels during pregnancy. In the fully adjusted model, compared with participants in quartile 1 (Q1), those who had more total thiamine and riboflavin intake had a lower risk of GDM during the first trimester [thiamine: Q2: RR: 0.58 (95% CI: 0.34, 0.98); Q3: RR: 0.45 (95% CI: 0.24, 0.84); Q4: RR: 0.35 (95% CI: 0.17, 0.72), P for trend = 0.002; riboflavin: Q2: RR: 0.63 (95% CI: 0.37, 1.09); Q3: RR: 0.45 (95% CI: 0.24, 0.87); Q4: RR: 0.39 (95% CI: 0.19, 0.79), P for trend = 0.006]. This association was also observed during the second trimester. Similar results were observed for the association between thiamine and riboflavin supplement use but not dietary intake and GDM risk. CONCLUSIONS: Higher intake of thiamine and riboflavin during pregnancy is associated with a lower incidence of GDM. This trial was registered at http://www.chictr.org.cn as ChiCTR1800016908.

The protective effect of zinc, selenium, and chromium on myocardial fibrosis in the offspring of rats with gestational diabetes mellitus.

The offspring of gestational diabetes mellitus (GDM) mothers are considered to be at the risk of cardiovascular diseases due to intrauterine hyperglycemia exposure. Our previous study showed that zinc, selenium, and chromium dramatically alleviated glucose intolerance in GDM rats and their offspring (P < 0.05). However, the effects of these elements on the damage of the cardiac myocytes of GDM offspring and the underlying mechanisms have not been demonstrated. Here, we investigated the beneficial effects of zinc (10 mg per kg bw), selenium (20 µg per kg bw), and chromium (20 µg per kg bw) supplementation on myocardial fibrosis in the offspring of GDM rats induced by a high-fat and sucrose (HFS) diet. The results showed that maternal GDM induced glucose intolerance, oxidative stress, cardiac inflammation and myocardial fibrosis in offspring rats during different ages (3 days, 3 weeks, and adulthood), which were ameliorated by zinc, selenium and chromium supplementation (P < 0.05). The activity of cardiac damage markers such as creatine kinase-myocardial band isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) decreased by 40-60% in element-supplemented offspring compared to that in non-supplemented offspring of GDM dams (P < 0.05). Moreover, maternal GDM-induced expression of fibrosis-related proteins and the transforming growth factor-beta 1 (TGF-ß1)/small mothers against decapentaplegic homolog 3 (Smad3) signaling pathway in the heart tissue of offspring was down-regulated by zinc, selenium, and chromium supplementation (P < 0.05). In conclusion, zinc, selenium, and chromium may play a protective role in maternal GDM-induced myocardial fibrosis in offspring from birth to adulthood by inactivating the TGF-ß1/Smad3 pathway.

Transgenerational effects of zinc, selenium and chromium supplementation on glucose homeostasis in female offspring of gestational diabetes rats.

Clinical studies have demonstrated that maternal gestational diabetes mellitus (GDM) increases the offspring's risk of developing glucose intolerance. Our previous study reported that co-supplementation with zinc, selenium, and chromium improved insulin resistance in diet-induced GDM rats. Here, Transgenerational effects of supplementation with zinc (10 mg/kg.bw), selenium (20 µg/kg.bw), and chromium (20 µg/kg.bw) in F1 female offspring of both zinc, selenium and chromium (ZnSeCr)-treated, and untreated GDM rats daily by gavage from weaning to the postpartum were investigated in the present study. Glucose homeostasis in the F1 female offspring of GDM at different stages were evaluated. Maternal GDM did increase the birth mass of newborn F1 female offspring, as well as the serum glucose and insulin levels. Zinc, selenium and chromium supplementation attenuated the GDM-induced mass gain, increased serum glucose and insulin levels in the female neonates. The high fat and sucrose (HFS) diet-fed GDM-F1 offspring developed GDM, with glucose intolerance, hyperglycemia and insulin resistance during pregnancy. Moreover, endoplasmic reticulum (ER) stress-related protein levels were increased and the activation of insulin signaling pathways were reduced in the liver of HFS-fed GDM-F1 offspring. Whereas glucose homeostasis in parallel with insulin sensitivity was normalized in the female offspring of GDM by supplementation both F0 dams and F1 offspring with zinc, selenium and chromium, not in those either F0 or F1 elements supplemented offspring. Therefore, we speculate that zinc, selenium and chromium supplementation may have a potential beneficial transgenerational effect on the glucose homeostasis in the female offspring of GDM.

A strategy for the rapid discovery and validation of active diterpenoids as quality markers in different habitats of Langdu using ultrahigh-performance liquid chromatography-tandem mass spectrometry with multivariate statistical analysis.

Langdu, known as a traditional Chinese medicine, was identified as the roots of species of Euphorbia ebracteolata Hayata and Euphorbia fischeriana Steud, displaying anti-tuberculosis activity. To clarify the potent quality markers of Langdu, this research first developed a fast and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry method for the quantification of 13 diterpenoids in Langdu. The developed method was further applied in the analyses of 12 authentic E. ebracteolata and E. fischeriana samples collected in northern and southeastern China. Then, the anti-tuberculosis evaluation of 12 batches of Langdu samples was performed in vitro. Finally, partial least squares discrimination analysis was used in the discrimination of E. ebracteolata and E. fischeriana from different origins and processing methods. Jolkinolide A (1), jolkinolide E (3), yuexiandajisu D (6), and ebractenone A (11) were identified as key, potent diterpenoids for the quality control of E. ebracteolata Hayata and E. fischeriana Steud. The present study established a qualitative chemical analysis method for Langdu (E. ebracteolata and E. fischeriana) and suggested the key bioactive components that will improve qualitative control methodology for this important medicine.

Lignans from Bupleurum marginatum and their antioxidant activity.

A new aryltetralin lignan, bupleroid A (1), along with ten known analogues (2-11) were isolated from Bupleurum marginatum. The structures of these isolates were determined by 1D and 2D NMR, HRESIMS, and ECD data analysis. In addition, the DPPH radical scavenging capacities of all compounds were evaluated. Compound 6 exhibited good DPPH radical scavenging activity at a concentration of 50 µM.[Formula: see text].

Neonatal Supplementation of Oleamide During Suckling Promotes Learning Ability and Memory in Adolescent Mice.

BACKGROUND: Fatty acid amides (FAMs) are present in breast milk. Oleamide (ODA), a member of the FAM family, has been reported to affect learning and memory-related abilities in animal experiments. OBJECTIVES: This study aimed to characterize the temporal changes of FAMs in human milk and sought to examine the effect of ODA supplementation during suckling on postweaning cognitive performance in mice. METHODS: FAMs were measured in human milk (postpartum 1-24 wk) by ultra-performance liquid chromatography-triple quadruple mass spectrometry (UPLC-TQ-MS) analysis. We supplemented neonatal C57BL/6J mice of both sexes with vehicle (control), 5 mg/(kg · day) ODA (L-ODA), or 25 mg/(kg · day) ODA (H-ODA) throughout suckling by oral gavage. After weaning, the Morris water maze test and novel object recognition test were performed. Neurogenesis, spinal morphogenesis in the dentate gyrus (DG) region, and hippocampal expression of synaptic markers were analyzed. Data were analyzed by ANOVA and repeated-measures ANOVA. RESULTS: ODA (0.566-1.31 mg/L) was the most abundant FAM in breast milk, followed by palmitamide (0.135-0.269 mg/L) and linoleamide (0.046-0.242 mg/L). Compared with the control group, the H-ODA group demonstrated shorter escape latency, shorter travel distance, 113% more platform crossing, and 48% greater discrimination index in behavioral tests (P < 0.05). Additionally, the H-ODA group showed a higher density of 5-ethynyl-2'-deoxyuridine (EdU)+ and EdU+& doublecortin (DCX)+ cells (62% and 53%, respectively), and 52% greater spine density in the DG region than the control group (P < 0.05). The synaptic markers, postsynaptic density protein 95 (PSD95) and synaptophysin (SYP), were upregulated in the H-ODA group compared with the control group (P < 0.05). The L-ODA group also showed shorter escape latency in behavioral tests and 27% greater spine density in the DG region than the control group (P < 0.05). CONCLUSIONS: ODA is the most common FAM in human milk. ODA supplementation during suckling promotes learning and memory-related abilities in adolescent mice by augmenting hippocampal neuronal proliferation and boosting synaptic plasticity.

Zinc, selenium and chromium co-supplementation improves insulin resistance by preventing hepatic endoplasmic reticulum stress in diet-induced gestational diabetes rats.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and results in adverse outcomes for pregnant women and their offspring. Endoplasmic reticulum (ER) stress is associated with insulin resistance and implicates in the development of GDM. Zinc, selenium and chromium have been shown to maintain glucose homeostasis via multiple mechanisms, but how these trace elements affect the insulin resistance and ER stress in GDM are largely unknown. To address this, a GDM rat model was induced by feeding female Sprague-Dawley rats a high-fat (45%) and sucrose diet, while zinc (10 mg/kg.bw), selenium (20 ug/kg.bw), chromium (20 ug/kg.bw) were daily supplemented alone or in combination from 6 weeks before mating to the end of lactation period. Maternal metabolic parameters, hepatic ER stress and insulin signaling were analyzed. The results showed that zinc, selenium and chromium co-supplementation dramatically alleviated high-fat and sucrose-induced glucose intolerance and oxidative stress during entire experiment period. Hepatic ER stress as well as the unfolded protein response was activated in GDM dams, characterized by the up-regulation of glucose-regulated protein 78, phosphorylated the protein kinase RNA-like endoplasmic reticulum kinase, and the inositol-requiring enzyme 1α. Zinc, selenium and chromium supplementation significantly prevented this activation, by which contributes to the promotion of the phosphorylated protein kinase B related insulin signaling and maintenance of glucose homeostasis. In conclusion, zinc, selenium and chromium supplementation may be a promising way to prevent the development of GDM by alleviating hepatic ER stress.

Triptolidenol, isolated from Tripterygium wilfordii, disrupted NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKß in clear cell renal cell carcinoma.

Triptolidenol (TPD) is an epoxy diterpene lactone from Tripterygium wilfordii, which has been used for chronic nephritis in China，and possessed various pharmacological properties, such as anti-inflammatory and anti-cancer activities. However, the precise molecular antitumor mechanism of TPD remains to be elucidated. In this study, we investigated the effects of TPD on human clear cell renal cell carcinoma (ccRCC) and investigated its precise anti-tumor mechanisms. It was showed that TPD significantly suppressed ccRCC cell proliferation, cell migration, and induced cell cycle arrest at S phase. Furthermore, TPD also induced apoptosis by activating the cytochrome c (cyt c)/caspase cascade signaling pathway. Moreover, using confocal immunofluorescence, a dual-luciferase reporter assay and molecular docking study, the results showed that TPD obviously reduced the expression of COX-2 by inhibiting the kinase activity of IKKß via targeting its ATP-binding domain, and then attenuating the transactivation of NF-κB. Collectively, our study demonstrated that TPD suppressed renal cell carcinoma growth through disrupting NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKß, and provided pharmacological evidence that TPD exhibits potential use in the treatment of COX-2-mediated diseases such as ccRCC.

Alkaloids from the nearly ripe fruits of Evodia rutaecarpa and their bioactivities.

Two novel quinolone alkaloids (1 and 2) and two novel indole alkaloids (5 and 8), together with eleven known analogues, were isolated from the nearly ripe fruits of Evodia rutaecarpa. Their structures were determined by extensive spectroscopic data, including NMR, HRESIMS, and ECD. Additionally, the anti-tumor, hypoglycemic, and anti-bacterial activities of the isolated alkaloids were evaluated in vitro. Compound 5 as a new alkaloid displayed moderate inhibitory effect against four human cancer cell lines (MCF-7 IC50 = 30.7 µM, Hepg-2 IC50 = 65.2 µM, A549 IC50 = 39.1 µM, and SHSY-5Y IC50 = 24.7 µM), α-glucosidase (IC50 = 23.9 µM) and PTP1B (IC50 = 75.8 µM). Compound 11 showed better inhibitory effect against PTP1B (IC50 = 16.2 µM) compared with that of the positive control. Compounds 5, 13, and 14 showed moderate inhibitory effects against Bacillus cereus with MIC values of 50, 25, and 10 µM, respectively.

[Catheter balloon dilation combined with acupuncture for cricopharyngeal achalasia after brain stem infarction: a randomized controlled trial].

OBJECTIVE: To screen the optimal acupuncture regimen for cricopharyngeal achalasia (CPA) after brain stem infarction and compare the therapeutic effect between the combined therapy of catheter balloon dilation and acupuncture and the simple application of catheter balloon dilation. METHODS: The patients suffering from neuropathic dysphagia in CPA after brain stem infarction were selected as the subjects. After confirmed in the diagnosis with video fluoroscopic swallowing study (VFSS), they were randomized into 6 groups, 15 cases in each one, named group A (routine treatment), group B (catheter balloon dilation), group C1 (treated with acupuncture in local area), group C2 (treated with acupuncture based on zangfu differentiation), group C3 (treated with acupuncture at the local area and the acupoints based on zangfu differentiation) and group D (catheter balloon dilation combined with the optimal acupuncture). Two phases were included in the study. In the first phase of study, the therapeutic effect was compared among the three acupuncture groups, named C1, C2 and C3 group, so as to screen the optimal acupuncture regimen. In the group C1, the main acupoints included Fengchi (GB 20), Wangu (GB 12), Yifeng (TE 17) and three-tongue points (Extra). In the group C2, the main acupoints were Neiguan (PC 6), Tongli (HT 5), Zusanli (ST 36) and Sanyinjiao (SP 6) as well as the supplementary acupoints in accordance with the syndrome differentiation. In the group C1 and group C2, after deqi, the electroacupuncture was used, with continuous dense wave, 5 to 8 Hz in frequency. The needles were retained for 30 min. Acupuncture was given once a day, 5 treatments a week. Before treatment, in 6 weeks of treatment or after removal of gastric tube, the rehabilitation was evaluated. In the group C3, the acupoints, manipulation and treating course were same as the group C1 and group C2. In the 2nd phase of study, theresults of rehabilitation treatment were compared among the group A, group B and group D. The treatment was given once a day, 5 times a week. Before treatment, after gastric tube removal or in 6 weeks of treatment, the evaluation was conducted. The feeding-swallowing function grade and VFSS were adopted in the evaluation among the above 6 groups. RESULTS: ① In the VFSS comparison at 1st phase of study after treatment, the food transporting ability at oral dysphagia, the results in the group C3 and group C1 were better obviously than the group C2 (both P<0.05). For the improvement in aspiration, the result in the group C3 was better obviously than the group C2 (P<0.05). In comparison of the three acupuncture groups with the group A, the difference was not significant statisticallys in the extubation rate among the four groups (P>0.05). The severity of dysphagia in the group C3 was milder than the group C2 and group A (both P<0.05). ② In the VFSS comparison at the 2nd phase of study, for the food transporting ability, the results in the group D and the group B were obviously better than the group A (both P<0.05). Regarding the function at the pharyngeal dysphagia and aspiration, the results in the group D were better than the group B and group A, those in the group B were better than the group A (all P<0.05). The difference in the extubation rate among the group A, group B and group D after treatment was significant statistically (P<0.01), of which, the extubation rate in the group D was the highest and the rate in the group A was the lowest. The dysphagia degree in the group D was milder than the group B and group A and that in the group B was milder than the group A (all P<0.05). CONCLUSION: In the study of the different acupuncture methods, the acupuncture at the local acupoints and the acupoints selected based on zangfu differentiation is the optimal acupuncture regimen for cricopharyngeal achalasia after brain stem infarction. The catheter balloon dilation combined with acupuncture present the synergistc effect on cricopharyngeal achalasia after brain stem infarction, obviously relieve dysphagia and reduce aspiration.

Yolk-Shell Structured Au Nanostar@Metal-Organic Framework for Synergistic Chemo-photothermal Therapy in the Second Near-Infrared Window.

Light-sensitive yolk-shell nanoparticles (YSNs) as remote-controlled and stimuli-responsive theranostic platforms provide an attractive method for synergistic cancer therapy. Herein, a kind of novel stimuli-responsive multifunctional YSNs has been successfully constructed by integrating star-shaped gold (Au star) nanoparticles as the second near-infrared (NIR-II) photothermal yolks and biodegradable crystalline zeolitic imidazolate framework-8 (ZIF-8) as the shells. In this platform, a chemotherapeutic drug (doxorubicin hydrochloride, DOX) was encapsulated into the cavity, which can show the behavior of controlled release due to the degradation process of ZIF-8 in the mildly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, gold nanostar@ZIF-8 (Au@MOF) nanoparticles exhibited outstanding synergistic anticancer effect based on their photothermal and promoted cargo release properties. Moreover, the strong NIR region absorbance endows the Au@MOF of NIR thermal imaging and photoacoustic (PA) imaging properties. This work contributes to design a stimuli-responsive "all-in-one" nanocarrier that realizes bimodal imaging diagnosis and chemo-photothermal synergistic therapy.

Enhanced photoconversion performance of NdVO4/Au nanocrystals for photothermal/photoacoustic imaging guided and near infrared light-triggered anticancer phototherapy.

Although neodymium vanadate (NdVO4) has been investigated and applied in some fields owing to its intensive ultraviolet (UV) light absorption, weak absorption in visible (Vis) and near infrared (NIR) regions constrains its environmental remediation and biomedical applications. Herein, plasmonic precious metal Au as light trapping agent is deposited onto NdVO4 to form metal/semiconductor hybrid nanostructure for improving the Vis/NIR light absorption. NdVO4/Au heterojunction nanocrystals (NCs) were synthesized by NdVO4 nanorods (NRs) and plasmonic Au nanoparticles (NPs), followed by introducing polyvinylpyrrolidone (PVP) to enhance stability and biocompatibility, which exhibit elevated photocatalytic performance for organic dye degradation, photothermal conversion effect as high as 32.15% and cytotoxic reactive oxygen species (ROS) production ability. NdVO4/Au can be internalized efficiently via endocytosis and cause apparent phototoxicity on HeLa cells. In vivo experiments further show that NdVO4/Au can act as a high-efficiency NIR light-triggered anticancer agent with excellent tumor inhibition effect. In addition, based on outstanding light-to-heat conversion performance and thermal expansion effect under NIR irradiation, NdVO4/Au provides photothermal (PT) and photoacoustic (PA) dual-modal imaging platform for precise cancer diagnosis and treatment. STATEMENTS OF SIGNIFICANCE: It's the first report on integrating precious metal Au and rare earth orthovanadates semiconductor into NdVO4/Au heterojunction NCs. The as-prepared NdVO4/Au heterojunction NCs exhibits improved absorption in Vis/NIR region and increased generation efficiency of photo-induced electron/hole pairs due to the LSPR effect, which results in enhanced photothermal conversion efficiency and the production ability of cytotoxic O2- and OH in comparison with pristine NdVO4. For further clinical application, NdVO4/Au heterojunction NCs could be served as anticancer therapeutic agent for PA/PT dual-modal imaging guided and NIR-triggered photothermal/photodynamic synergistic anticancer treatment.

Chemical characteristics of the fungus Ganoderma lucidum and their inhibitory effects on acetylcholinesterase.

The chemical characteristic of a well-known folk medicine Ganoderma lucidum has been investigated by a series of chromatographic technologies, which displayed the presences of 45 lanostane type triterpenoids, including two new nor-lanostane triterpenoids (40, 41). Their structures were identified on the basis of spectroscopic data analysis (UV, IR, HRESIMS, 1D, and 2D NMR). Notably, some triterpenoids displayed moderate inhibitory effects against AChE (acetylcholinesterase) by an in vitro screened experiment. Triterpenoid 2 displayed the potent inhibitory effect with IC50 10.8 and Ki 14.95 µM (inhibition kinetic). The preliminary SAR has been discussed by the docking analyses between ganoderic acids (1, 2) and AChE.

Diterpenoids from the roots of Euphorbia fischeriana and their inhibitory effects on α-glucosidase.

Chemical investigation has been performed on the roots of Euphorbia fischeriana, a traditional Chinese medicine. Three diterpenoids were obtained using various chromatographic techniques, and their structures were determined by spectroscopic data including HRESIMS, 1D NMR, 2D NMR, ECD, and calculated ECD, which gave two new diterpenoids, daphnane type (1) and ent-pimarene type (3). Additionally, the isolated compounds (1-3) displayed moderate inhibitory effects against α-glucosidase in an in vitro bioassay.

Preventive and Therapeutic Effects of Thymol in a Lipopolysaccharide-Induced Acute Lung Injury Mice Model.

Acute lung injury (ALI) is a life-threatening syndrome which causes a high mortality rate worldwide. In traditional medicine, lots of aromatic plants-such as some Thymus species-are used for treatment of various lung diseases including pertussis, bronchitis, and asthma. Thymol, one of the primary active constituent derived from Thymus vulgaris (thyme), has been reported to exhibit potent anti-microbial, anti-oxidant, and anti-inflammatory activities in vivo and in vitro. The present study aims to investigate the protective effects of thymol in lipopolysaccharide (LPS)-induced lung injury mice model. In LPS-challenged mice, treatment with thymol (100 mg/kg) before or after LPS challenge significantly improved pathological changes in lung tissues. Thymol also inhibited the LPS-induced inflammatory cells influx, TNF-α and IL-6 releases, and protein concentration in bronchoalveolar lavage fluid (BALF). Additionally, thymol markedly inhibited LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that thymol effectively inhibited the NF-κB activation in the lung. Taken together, these results suggested that thymol might be useful in the therapy of acute lung injury.

MANF regulates hypothalamic control of food intake and body weight.

The hypothalamus has a vital role in controlling food intake and energy homeostasis; its activity is modulated by neuropeptides and endocrine factors. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor that is also localized in the endoplasmic reticulum (ER) in neurons. Here we show that MANF is highly enriched in distinct nuclei of the mouse hypothalamus, and that MANF expression in the hypothalamus is upregulated in response to fasting. Increasing or decreasing hypothalamic MANF protein levels causes hyperphagia or hypophagia, respectively. Moreover, MANF triggers hypothalamic insulin resistance by enhancing the ER localization and activity of PIP4k2b, a kinase known to regulate insulin signaling. Our findings indicate that MANF influences food intake and body weight by modulating hypothalamic insulin signaling.MANF is a neurotrophic factor that is secreted but also mediates the unfolded protein response acting intracellularly. Here, the authors show that MANF expression in the brain is influenced by nutritional cues, and hypothalamic MANF influences food intake and systemic energy homeostasis.

Three new alkaloids from the seeds of Nigella glandulifera.

Three new alkaloids namely 8-(4-hydroxyphenyl)-6-methoxy-3,4-dihydroisoquinolin-1(2H)-one (1), 4-aminonigellidine (2), and N-[(4-hydroxy-2-isopropyl-5-methyl)]phenylurea (3), along with six known ones (4-9), were isolated from the seeds of Nigella glandulifera. The structures of 1-3 were determined through spectroscopic analyses (HRESIMS, 1D/2D NMR). Compound 1 was a rare isoquinolinone alkaloid with phenyl substituted at C-8.

Inhibition of melatonin metabolism in humans induced by chemical components from herbs and effective prediction of this risk using a computational model.

BACKGROUND AND PURPOSE: Herbs which are widely used as food and medicine, are involved in many physiopathological processes. Melatonin is a human hormone, synthesized and secreted by the pineal gland, with a range of biological functions. Here, we have evaluated the potential influences of components extracted from common herbs on melatonin metabolism in humans. EXPERIMENTAL APPROACH: An in vivo pharmacokinetic study involving 12 healthy subjects, in vitro incubations with human liver microsomes (HLMs) and recombinant human cytochrome P (CYP) isoenzymes and an in silico quantitative structure-activity relationship (QSAR) model analysis using comparative molecular field analysis and comparative molecular similarity indices analysis methods were employed to explore these interactions. KEY RESULTS: After systematic screening of 66 common herbs, Angelica dahurica exhibited the most potent inhibition of melatonin metabolism in vitro. The in vivo pharmacokinetic study indicated inhibition of melatonin metabolism, with approximately 12- and 4-fold increases in the AUC and Cmax of melatonin in human subjects. Coumarins from A. dahurica, including imperatorin, isoimperatorin, phellopterin, 5-methoxypsoralen and 8-methoxypsoralen, markedly inhibited melatonin metabolism with Ki values of 14.5 nM, 38.8 nM, 6.34 nM, 5.34 nM and 18 nM respectively, through inhibition of CYP 1A2, 1A1 and 1B1 in HLMs. A QSAR model was established and satisfactorily predicted the potential risk of coumarins for inhibition of melatonin metabolism in vivo. CONCLUSION AND IMPLICATIONS: Coumarins from A. dahurica inhibited melatonin metabolism in vivo and in vitro. Our findings provide vital guidance for the clinical use of melatonin.