Effects of Chaihu Shugan San on Brain Functional Network Connectivity in the Hippocampus of a Perimenopausal Depression Rat Model.

In this study, we used Chaihu Shugan San (CSS), a traditional Chinese herbal formula, as a probe to investigate the involvement of brain functional network connectivity and hippocampus energy metabolism in perimenopausal depression. A network pharmacology approach was performed to discover the underlying mechanisms of CSS in improving perimenopausal depression, which were verified in perimenopausal depression rat models. Network pharmacology analysis indicated that complex mechanisms of energy metabolism, neurotransmitter metabolism, inflammation, and hormone metabolic processes were closely associated with the anti-depressive effects of CSS. Thus, the serum concentrations of estradiol (E2), glutamate (Glu), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The brain functional network connectivity between the hippocampus and adjacent brain regions was evaluated using resting-state functional magnetic resonance imaging (fMRI). A targeted metabolomic analysis of the hippocampal tricarboxylic acid cycle was also performed to measure the changes in hippocampal energy metabolism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CSS treatment significantly improved the behavioral performance, decreased the serum Glu levels, and increased the serum 5-HT levels of PMS + CUMS rats. The brain functional connectivity between the hippocampus and other brain regions was significantly changed by PMS + CUMS processes but improved by CSS treatment. Moreover, among the metabolites in the hippocampal tricarboxylic acid cycle, the concentrations of citrate and the upregulation of isocitrate and downregulation of guanosine triphosphate (GTP) in PMS + CUMS rats could be significantly improved by CSS treatment. A brain functional network connectivity mechanism may be involved in perimenopausal depression, wherein the hippocampal tricarboxylic acid cycle plays a vital role.

Genome-Wide Identification and Expression Analysis of the TCP Gene Family Related to Developmental and Abiotic Stress in Ginger.

Ginger (Zingiber officinale Roscoe), a widely consumed edible and medicinal plant, possesses significant nutritional and economic value. Abiotic stresses such as drought and low temperatures can impact the growth and development of ginger. The plant-specific transcription factor Teosinte branched1/cycloidea/proliferating cell factor (TCP) has progressively been identified in various plants for its role in regulating plant growth and development as well as conferring resistance to abiotic stresses. However, limited information on the TCP family is available in ginger. In this study, we identified 20 TCP members in the ginger genome, which were randomly distributed across 9 chromosomes. Based on phylogenetic analysis, these ginger TCP were classified into two subfamilies: Class I (PCF) and Class II (CIN, CYC/TB). The classification of the identified ginger TCPs was supported by a multi-species phylogenetic tree and motif structure analysis, suggesting that the amplification of the ginger TCP gene family occurred prior to the differentiation of angiosperms. The promoter region of ginger TCP genes was found to contain numerous cis-acting elements associated with plant growth, development, and abiotic stress response. Among these elements, the stress response element, anaerobic induction, and MYB binding site play a dominant role in drought responsiveness. Additionally, expression pattern analysis revealed variations in the expression of ginger TCP gene among different tissues and in response to diverse abiotic stresses (drought, low temperature, heat, and salt). Our research offers a thorough examination of TCP members within the ginger plant. This analysis greatly contributes to the understanding of how TCP genes regulate tissue development and response to stress, opening up new avenues for further exploration in this field.

A novel method for age identification of mountain-cultivated ginseng.

Panax ginseng, a slow-growing perennial herb, is the most praised and popular traditional medicinal herb. Mountain-cultivated ginseng (MCG) and cultivated ginseng (CG) both belong to Panax ginseng C. A. Meyer. The market price and medical effects of this popular health product are closely related to its age. It is widely acknowledged that CG is typically harvested after 4-6 years of growth, but MCG is often collected after 10 years. Until now, the age identification of MCG or mountain wild ginseng (MWG) has remained a major challenge. In this study, we established a novel and rapid method for staining xylem vessels with phloroglucinol and identifying the "annual growth rings" of ginseng by utilizing a stereoscope, which serves as a reliable indicator of the age of MCG. Statistical analysis of the ring radius and the ring density of MCG aged from 1 to 20 years shows that the secondary xylem of MCG increases rapidly in the first 3 years but then gradually slows down from 4 to 10 years, and minor fluctuation is observed in the next 10 years. Meanwhile, the space between the growth rings (ring density) becomes increasingly small with age. This straightforward staining approach can reveal the age of MCG with remarkable clarity and can distinguish MCG from CG. RESEARCH HIGHLIGHTS: A novel rapid staining method for Panax ginseng was established. The age of mountain-cultivated ginseng (MCG) can be identified by microscopic techniques. MCG and cultivated ginseng (CG) can be discriminated by microstructure characteristics.

Safety, Tolerability, and Pharmacokinetics of ß-Cryptoxanthin Supplementation in Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: ß-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation. METHODS: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral ß-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of ß-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated. RESULTS: ß-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma ß-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) (p < 0.03), and placebo (0.4 ± 0.1 µmol/L) (p < 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, ß-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition. CONCLUSIONS: Oral ß-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of ß-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women.

Study on the mechanism of American ginseng extract for treating type 2 diabetes mellitus based on metabolomics.

American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography-mass spectrometry-based (UHPLC-MS/MS-based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.

Untargeted metabolomics analysis of the anti-diabetic effect of Red ginseng extract in Type 2 diabetes Mellitus rats based on UHPLC-MS/MS.

Red ginseng is a traditional Chinese herbal medicine that has long been used to treat diabetes, and its blood sugar-lowering activity has been confirmed. However, the mechanism of action of red ginseng on type 2 diabetes mellitus (T2DM) at the metabolic level is still unclear. The purpose of this study is to investigate the effect of red ginseng extract in the treatment of T2DM rats based on untargeted metabolomics. The rat model of T2DM was induced by a high-fat diet (HFD) combined with streptozotocin (STZ), and serum samples were collected after four weeks of treatment. The ultra-high-performance liquid chromatography coupled with Q Exactive HF-X Mass Spectrometer was used to analyze the level of metabolites in serum to evaluate the differences in metabolic levels between different groups. The results of biochemical analysis showed that red ginseng extract intervention significantly improved the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), serum glucose (GLU), and fasting insulin (FINS) after four weeks. Orthogonal partial least squares discriminant analysis was used to study the overall changes of rat metabolomics. After the intervention of red ginseng extract, 50 biomarkers showed a callback trend. Metabolic pathway enrichment analysis showed that the regulated pathways were D-arginine and D-ornithine metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Generally, the results demonstrated that red ginseng extract had beneficial effects on T2DM, which could be mediated via ameliorating the metabolic disorders.

Plasma metabolomics-based reveals the treatment mechanism of ShenGui capsule for application to coronary heart disease in a rat model.

Shen Gui capsule (SGC) has been demonstrated to have a significant treatment effect for coronary heart disease (CHD). Nevertheless, the holistic therapeutic mechanism of SGC in vivo remain poorly interpreted. We aimed to systematically explore the preventive effect and mechanism of SGC on CHD rats using plasma metabolomics strategy. Rat CHD model was established by left anterior descending coronary artery ligation (LAD). Echocardiography, histological analyses of the myocardium and biochemical assays on serum were used to confirm the successful establishment of the CHD model and therapeutic effects of SGC. Then, UHPLC-MS/MS-based plasma metabolomics was combined with multivariate data analysis to screen potential pharmaco biomarkers associated with SGC treatment in the LAD-induced rat CHD model. After SGC treatment, 12 abnormal metabolites considered as potiential pharmaco biomarkers recovered to near normal levels. These biomarkers were involved in several metabolic pathways, including fat and protein metabolism, phenylalanine metabolism, neuroactive ligand-receptor interaction, androgen receptor signaling pathway, and estrone metabolism.These results suggested that SGC achieves therapeutic action on CHD via regulating various aspects of the body such as energy metabolism, neurological disturbances and inflammation, and thus plays a significant role in the treatment of CHD and its complications. The study is useful to systematically understand and analyze the mechanism of SGC's "multipie pathways, multiple levels, multiple targets" prevention and treatment of CHD.

Evaluation of the antibacterial effect of tea tree oil on Enterococcus faecalis and biofilm in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Tea tree essential oil (TTO) is extracted from the leaves of Melaleuca alternifolia by steam distillation. It is well known for its traditional medicinal uses, particularly for the treatment of bruises, insect bites, skin infections, vertigo, convulsions, toothache, and rheumatism. Earlier research has shown that TTO can effectively inhibit oral microorganisms in the root canals. Enterococcus faecalis (E. faecalis) has been considered to be associated with persistent root canal infections and root canal treatment failure. The biofilm of E. faecalis makes it more vigorous, toxic, and resistant to antibiotics. AIM OF THE STUDY: In this study, our aim was to evaluate the antimicrobial effects of TTO on planktonic E. faecalis and biofilms compared with 0.2% CHX. MATERIALS AND METHODS: We explored the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the bacteriostatic rate by MTT assay, the antimicrobial time by time-kill assay, and the effects on cell integrity, the biomass, and bacterial activity of E. faecalis biofilms. Finally, we investigated the microstructure changes of E. faecalis biofilms using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). RESULTS: The MIC and MBC values were 0.25% and 0.5%, the bacterial inhibition rate, time-kill was dosage dependent, and TTO can effectively destroy membrane integrity. SEM CLSM images revealed that TTO could reduce bacterial aggregation, biofilm thickness and inhibited biofilm formation. The effect of TTO was the same as that of 0.2% CHX at some specific concentrations. In summary, TTO has the potential to be effective against E. faecalis infections. CONCLUSIONS: TTO was able to inhibit E. faecalis by destroying cell membrane, inhibiting the formation of E. faecalis biofilms, and eliminating mature formed biofilms. In this study, TTO has the potential to be further developed as a novel antibacterial drug.

Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Knittable and Sewable Spandex Yarn with Nacre-Mimetic Composite Coating for Wearable Health Monitoring and Thermo- and Antibacterial Therapies.

The emerging personal healthcare has significantly propelled the development of advanced wearable electronics with novel functions of providing diagnostic information and point-of-care therapies for specific diseases. However, it is still challenging to simultaneously achieve high sensitivity for health biomonitoring and multifunction integration for point-of-care therapies in a one single flexible, lightweight yet robust fiber-based device. Here, a knittable and sewable spandex yarn with conductive nacre-mimetic composite coating has been developed through an alternant dip-coating method employing MXene nanosheets as the "brick" and polydopamine (PDA)/Ni2+ as the "mortar". The resultant spandex yarn coating with MXene/PDA/Ni2+ (MPNi@Spandex) can be assembled as a strain sensor with high sensitivity (up to 5.7 × 104 for the gauge factor), wide sensing range (∼61.2%), and low detection limit (0.11%) to monitor the biological activities of the human body. Furthermore, MPNi@Spandex displays great potential to give on-demand thermotherapy by virtue of the fast response to near-infrared irradiation, controllable surface temperature, and applicability even under sewing conditions. In addition, MPNi@Spandex knitted textiles demonstrate a strong antibacterial effect due to the sharp edges, anionic, and hydrophilic nature of MXene nanosheets. Remarkably, near-infrared irradiation further improves the bacteria-killing efficiency of an MPNi@Spandex knitted textile to more than 99.9%. This work paves the way for the design of multifunctional wearable electronics with an all-in-one theranostic platform for personal healthcare.

Hypoglycemic activity of extracts of Chamaecyparis obtusa var. formosana leaf in rats with hyperglycemia induced by high-fat diets and streptozotocin.

Chamaecyparis obtusa var. formosana is a species indigenous to Taiwan and has been used as a medicinal plant. It has been claimed that the hot water extracts of C. obtusa var. formosana leaves (CoLE) with flavonoids and proanthocyanidins have anti-oxidant and anti-hyperglycemic activities in vitro. This study further examines the anti-hyperglycemic activity of CoLE and its possible mechanisms in hyperglycemic rats. Hyperglycemia of rats was induced by streptozotocin (STZ) and high-fat diets (HFD). Hyperglycemic rats treated orally with 30 and 150 mg/kg CoLE were classified into LCO and HCO groups, respectively. After three-month treatment, both LCO and HCO groups showed improved glucose metabolism in oral glucose tolerance and postprandial blood glucose tests. Decrease in HOMA-IR, leptin and adiponectin levels of the HCO group revealed amelioration of insulin and leptin resistance. Obesity and accumulation of visceral fats induced by STZ and HFD could be alleviated in both HCO and LCO groups. These anti-diabetic effects might be contributed by inhibition of intestinal digested enzymes and protein tyrosine phosphatases (PTPases). Although other studies are necessary, these findings suggest that CoLE could be potentially used as a health complement for treating diabetes without significant toxicity.

Geniposide protects against ox-LDL-induced foam cell formation through inhibition of MAPKs and NF-kB signaling pathways.

Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in Gardenia jasminoides fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.

Effects of pulsed electromagnetic field therapy on pain, stiffness and physical function in patients with knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of classical pulsed electromagnetic field therapy on patients with knee osteoarthritis. METHODS: The databases PubMed, EMBASE, Web of Science and Cochrane Library were searched for relevant studies. Randomized controlled trials comparing classical pulsed electromagnetic field with placebo for patients with knee osteoarthritis were included. Data for primary outcomes, including pain, stiffness and physical function, were extracted. Data from 8 randomized controlled trials involving 421 patients were pooled. RESULTS: Pulsed electromagnetic field therapy had an effect on improving physical function (weighted mean difference; WMD = -5.28, 95% confidence interval; 95% CI -9.45 to -1.11, p = 0.01), but showed no advantage in the reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (WMD = -7.80, 95% CI -16.08 to 0.47, p = 0.06), WOMAC pain score (WMD = -1.06, 95% CI -2.30 to 0.17, p = 0.09), visual analogue scale pain score (WMD=-0.88, 95% CI -2.06 to 0.31, p = 0.15) or WOMAC stiffness score (WMD = -0.50, 95% CI -1.09 to 0.09, p = 0.1). CONCLUSION: Pulsed electromagnetic field therapy is beneficial for improving physical function despite having no advantage in treating pain and stiffness. Further randomized controlled trials are needed to confirm these findings and determine the optimal parameters and treatment regimen for pulsed electromagnetic field therapy.

Core-sheath micro/nano fiber membrane with antibacterial and osteogenic dual functions as biomimetic artificial periosteum for bone regeneration applications.

The traditional Chinese medicine icariin (ICA) and broad-spectrum antibacterial drug moxifloxacin hydrochloride (MOX) were introduced into a polycaprolactone core and gelatin shell, respectively, to develop osteogenic and antibacterial biomimetic periosteum by coaxial electrospinning. The physical properties, drug release, degradation, antibacterial property, in vitro and in vivo osteogenesis performances were investigated. Results demonstrated that stepwise and controlled drug release profiles were achieved based on the core-shell configuration and disparate degradation rate of PCL and gelatin. Only 20% ICA was released from this dual drug-loaded membrane after 1 month while the release of MOX was almost completed. Moreover, clear in vitro antibacterial effect and enhancement in osteogenic marker expressions including osteocalcin, type-I collagen expression, and calcium deposition were observed. Notably, the dual drug-loaded membrane displayed fascinating properties contributing to in vivo bone formation in terms of quality and quantity in a rabbit radius defect model.

An overview of energy and metabolic regulation.

The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identifying critical targets for treatment are important research goals. Therefore, the purpose of this article is to describe energy regulation by the central nervous system (CNS) and peripheral humoral pathway. Homeostasis and rewarding are the basis of CNS regulation. Anorexigenic or orexigenic effects reflect the activities of the POMC/CART or NPY/AgRP neurons within the hypothalamus. Neurotransmitters have roles in food intake, and responsive brain nuclei have different functions related to food intake, glucose monitoring, reward processing. Peripheral gut- or adipose-derived hormones are the major source of peripheral humoral regulation systems. Nutrients or metabolites and gut microbiota affect metabolism via a discrete pathway. We also review the role of peripheral organs, the liver, adipose tissue, and skeletal muscle in peripheral regulation. We discuss these topics and how the body regulates metabolism.

Antihyperglycemic activities of twig extract of indigenous cinnamon (Cinnamomum osmophloeum) on high-fat diet and streptozotocin-induced hyperglycemic rats.

BACKGROUND: Cinnamomum osmophloeum (indigenous cinnamon) is an endemic species in Taiwan and its twigs contain abundant A-type proanthocyanidins. C. osmophloeum twig extracts (CoTEs) were found to have α-glucosidase and α-amylase inhibitory activities in vitro. The aim of this study is to further investigate the antihyperglycemic activity of CoTEs in hyperglycemic rats. RESULTS: Hyperglycemic rats were divided into three groups and were treated orally with high-dosage CoTEs (HCO, 150 mg kg-1 ), low-dosage CoTEs (LCO, 30 mg kg-1 ) and positive control (PC, 30 mg kg-1 pioglitazone). The HCO group showed improved glucose tolerance in an oral glucose tolerance test after 1 month of treatment, contributed by the inhibition of intestinal disaccharidases, amylase, and lipase. Compared with the PC group, both the HCO and LCO groups had decreased weight of visceral fats and lower atherogenic index; while their low-density lipoprotein-cholesterol, food intake, feed efficiency, and biochemical parameters remained unchanged compared with the NC group. Furthermore, the HCO group had decreased weight gain and the LCO group had decreased serum leptin level. CONCLUSION: These results suggest that CoTE has potential antihyperglycemic activities for treating hyperglycemia without weight gain. © 2018 Society of Chemical Industry.

Corrosion inhibition of mild steel in sulfuric acid solution by loquat (Eriobotrya japonica Lindl.) leaves extract.

The inhibition performance and mechanism of loquat leaves extract (LLE) for the corrosion of mild steel in 0.5 M H2SO4 were investigated using weight loss method, electrochemical measurements and scanning electron microscope (SEM). The results revealed that LLE acted as a modest cathodic inhibitor, its inhibition efficiency increased with the concentration of LLE and reached a maximum value of 96% at the 100% V/V concentration, but decreased with incremental temperature. Besides, it was found that the adsorption of LLE on steel surface obeyed Langmuir adsorption isotherm, and then the thermodynamic and kinetic parameters were further determined accordingly. Furthermore, LLE was preliminarily separated by pH-gradient sedimentation and the synergistic inhibition between the isolates was investigated.

Icariin-loaded electrospun PCL/gelatin nanofiber membrane as potential artificial periosteum.

Due to the significant role of the periosteum in bone regeneration, we hypothesised that using a specially engineered artificial periosteum could lead to an enhancement in osteogenesis in bone grafts. Herein, we describe our work aimed at fabricating an electrospun fibrous membrane as an artificial periosteum that exhibits flexibility, permeability and osteoinduction. This membrane was designed to cover the complex surface of bone grafts to facilitate and accelerate bone regeneration. The traditional Chinese medicine icariin (ICA) was subsequently introduced into poly (ε-caprolactone) (PCL) /gelatin nanofibers to fabricate an artificial periosteum for the first time. The effects of ICA content on morphology, physical properties, drug release profile, in vitro degradability, biocompatibility and osteogenic differentiation properties were investigated. The ICA-loaded electrospun membranes showed significant improvement in hydrophilicity, high mechanical strength, appropriate degradation rates and excellent biocompatibility. Furthermore, clear enhancement in alkaline phosphatase (ALP) activity, as well as an increase in osteocalcin (OCN) and type collagen I (COL I) expression in MC3T3-E1 cells were detected. Furthermore, we observed clear calcium deposition content in MC3T3-E1 cells cultured on ICA-loaded fibrous matrix. The membrane loaded with 0.05 wt.% ICA displayed properties contributing to cell attachment, proliferation and differentiation. These results indicate the huge potential of this ICA-loaded PCL/gelatin electrospun membrane as a biomimetic artificial periosteum to accelerate bone regeneration.

Vitamin A bio-modulates apoptosis via the mitochondrial pathway after hypoxic-ischemic brain damage.

Our previous studies demonstrated that vitamin A deficiency (VAD) can impair the postnatal cognitive function of rats by damaging the hippocampus. The present study examined the effects of retinoic acid (RA) on apoptosis induced by hypoxic-ischemic damage in vivo and in vitro, and investigated the possible signaling pathway involved in the neuroprotective anti-apoptotic effects of RA. Flow cytometry, immunofluorescence staining and behavioral tests were used to evaluate the neuroprotective and anti-apoptotic effects of RA. The protein and mRNA levels of RARα, PI3K, Akt, Bad, caspase-3, caspase-8, Bcl-2, Bax, and Bid were measured with western blotting and real-time PCR, respectively. We found impairments in learning and spatial memory in VAD group compared with vitamin A normal (VAN) and vitamin A supplemented (VAS) group. Additionally, we showed that hippocampal apoptosis was weaker in the VAN group than that in VAD group. Relative to the VAD group, the VAN group also had increased mRNA and protein levels of RARα and PI3K, and upregulated phosphorylated Akt/Bad levels in vivo. In vitro, excessively low or high RA signaling promoted apoptosis. Furthermore, the effects on apoptosis involved the mitochondrial membrane potential (MMP). These data support the idea that sustained VAD following hypoxic-ischemic brain damage (HIBD) inhibits RARα, which downregulates the PI3K/Akt/Bad and Bcl-2/Bax pathways and upregulates the caspase-8/Bid pathway to influence the MMP, ultimately producing deficits in learning and spatial memory in adolescence. This suggests that clinical interventions for HIBD should include suitable doses of VA.

Characteristics of proanthocyanidins in leaves of Chamaecyparis obtusa var. formosana as strong α-glucosidase inhibitors.

BACKGROUND: In recent decades, there has been a growing demand for natural products with a view to using them as α-glucosidase inhibitors for reducing postprandial hyperglycemia. In this study, the hot water extract (HWE) from Chamaecyparis obtusa var. formosana (Hayata) Rehder (Cupressaceae) leaves and its soluble fractions were screened for α-glucosidase inhibition properties. The n-butanol-soluble fraction of HWE was further fractionated into 14 subfractions (B1-B14) using a Sephadex LH-20 column. The α-glucosidase-inhibitory activities and proanthocyanidin contents of all subfractions were determined. The structural characteristics of proanthocyanidins in proanthocyanidin-rich fractions were also elucidated. RESULTS: HWE produced a dose-dependent inhibition of α-glucosidase at low dose. Its IC50 value was 1.4 µg mL-1 , showing high inhibitory activity. Subfractions B7-B14 displayed powerful α-glucosidase-inhibitory activities with IC50 values ranging between 1 and 0.015 µg mL-1 and contained abundant proanthocyanidins exceeding 300 mg g-1 . The proanthocyanidins with higher mean degree of polymerization (mDP), higher proportions of procyanidin dimer (A1 or A2) and (epi)afzelechin of extension units and a lower proportion of epicatechin of terminal units displayed high α-glucosidase-inhibitory activities. CONCLUSION: Proanthocyanidins in HWE were viewed as potential natural α-glucosidase inhibitors for decreasing postprandial hyperglycemia. The results indicated that specific structural characteristics of proanthocyanidins would be required for α-glucosidase-inhibitory activity. © 2018 Society of Chemical Industry.