Mechanism of Dried Fruiting Bodies of Fomes officinalis Against Alzheimer's Disease： Based on Network Pharmacology and In Vitro Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of dried fruiting bodies of Fomes officinalis （FOA） against Alzheimer's disease （AD） based on network pharmacology and experimental verification. MethodThe effective components of FOA were retrieved from a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and previous reports. The targets of the components were searched from PharmMapper and TargetNet， and the targets related to AD from Gene Expression Omnibus （GEO）， DrugBank， among other databases. Thereby， the common targets of FOA and AD were obtained， and the protein-protein interaction （PPI） network and component-target network were established based on STRING and Cytoscape 3.7.1， followed by the topology analysis of the networks， and Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis of the common targets. The results were verified by the molecular docking and the in vitro cell experiment. ResultA total of 24 candidate components and 242 predicted targets of FOA， and 96 common targets of FOA and AD were screened out. The key components included ［2-（1-carboxyhexadecylamino）-2-aminosuccinic acid］， 3-keto-dehydrosulfurenic acid， and eburicoic acid， and the active targets were albumin （ALB）， acetylcholinesterase （AChE）， estrogen receptor 1 （ESR1）， cysteine aspartate-specific protease-3 （Caspase-3）， and beta-secretase1 （BACE1）. The common targets were involved in 392 GO terms， and the key terms were the β-amyloid metabolic process and cholinesterase activity. A total of 77 KEGG pathways were obtained， which mainly included estrogen signaling pathway， cholinergic synapse， and AD. The results of molecular docking showed that 7 components of FOA had high binding affinity to amyloid precursor protein （APP）， BACE1， AChE， and Caspase-3. The cell survival rate rose （P<0.01） and the mRNA and protein expression of APP， BACE1， AChE， and Caspase-3 reduced in FOA groups in a dose-dependent manner compared with those in the model group （P<0.05）. ConclusionThis study reveals for the first time that FOA has multi-component， multi-target， and multi-pathway characteristics in the treatment of AD， which serves as a reference for further explaining the mechanism of FOA against AD.

Calcium Supplementation Alleviates High-Fat Diet-Induced Estrous Cycle Irregularity and Subfertility Associated with Concomitantly Enhanced Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue.

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.

N-acetylcysteine alleviated bisphenol A-induced testicular DNA hypermethylation of rare minnow (Gobiocypris rarus) by increasing cysteine contents.

Ubiquitous BPA exposure resulted in DNA methylation errors and oxidative stress. Numerous studies have demonstrated that oxidative stress can lead to changes in DNA methylation levels and supplementation with antioxidants, including N-acetylcysteine (NAC), was able to restore these changes. Our previous study supposed that BPA-induced de novo synthesis of glutathione (GSH) promoted DNA methylation process in Gobiocypris rarus testes. To validate this conjecture and explore the protective effects of NAC on BPA toxicity, the present study was carried out. Adult male G. rarus was treated with 225 µg L-1 BPA and/or NAC for 7 days. The sperm motility and DNA integrity of G. rarus were determined. Meanwhile, the levels of 5-methylcytosine (5mC), GSH, hydrogen peroxide (H2O2), DNA methyltransferase proteins (DNMTs), γ-glutamyl cysteine synthetase (GCS), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine (HCY), nicotinamide adenine dinucleotide phosphate (NADPH) and cysteine in the testes were detected. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Results indicated that NAC addition resulted in increase of cysteine contents and partially inhibited the BPA-induced DNA hypermethylation of G. rarus testes. In addition, the changes in DNA methylation levels in the testes after BPA and/or NAC treatment might be controlled by DNA methylation process that mediated by DNMTs. Moreover, BPA exposure caused oxidative stress in the testes and the elimination of H2O2 might be mainly accomplished by CAT while it changed to mainly through GPx after NAC supplement. Finally, the positive response of testicular antioxidant enzyme system and the antioxidant activity of NAC itself protected sperm motility and DNA integrity from oxidative damage in each group.

Author Correction: Establishment of the most comprehensive ITS2 barcode database to date of the traditional medicinal plant Rhodiola (Crassulaceae).

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Phytol stimulates the browning of white adipocytes through the activation of AMP-activated protein kinase (AMPK) α in mice fed high-fat diet.

Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 µM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.

Nutritional status affects the microRNA profile of the hypothalamus of female sheep.

Recent studies on the seasonal regulation of the oestrous cycle in sheep have focussed mainly on the responses to photoperiod. However, the brain systems that control reproductive activity also respond to nutritional inputs, although the molecular mechanisms involved are not completely understood. One possibility is that small, non-coding RNAs, such as micro-RNAs (miRNAs), have significant influence. In the present study, the amounts and characteristics of miRNAs in hypothalamus from oestrous and anestrous ewes, fed low- or high-nutrient diets, were compared using Illumina HiSeq sequencing technology. In total, 398 miRNAs, including 261 novel miRNAs, were identified in ewes with an enhanced nutritional status (HEN), whereas 384 miRNAs, including 247 novel miRNAs, were identified in the ewes with a lesser nutritional status (HAN). There were eight conserved and 140 novel miRNAs expressed differentially between the two libraries. Based on quantitative real-time polymerase chain reaction, six miRNAs were assessed to verify the accuracy of the library database. Moreover, the correlation between the miRNA target and several upstream and downstream genes in the oestrus-related pathways were also verified in hypothalamus nerve cells. According to the results, nutritional status plays an important role in oestrous regulation in sheep, and the hypothalamic processes and pathways induced by nutritional signals (folic acid and tyrosine) are different from those induced by photoperiodic regulation of oestrus. We have expanded the repertoire of sheep miRNAs that could contribute to the molecular mechanisms that regulate the initiation of oestrous cycles in anestrous ewes in response to the influence of nutritional status.

Establishment of the most comprehensive ITS2 barcode database to date of the traditional medicinal plant Rhodiola (Crassulacaee).

The roots and rhizomes of Rhodiola crenulata and R. rosea have been used worldwide as adaptogens for hundreds of years. However, rapid growth in demand has resulted in merchants using other species of Rhodiola as adulterants. Here, we surveyed 518 individuals representing 47 of the 55 species in the genus, including 253 R. crenulata individuals from 16 populations and 98 R. rosea individuals from 11 populations, to evaluate the utility of the internal transcribed spacer 2 (ITS2) barcode for identification of Rhodiola species. We detected six haplotypes in R. crenulata and only one haplotype in R. rosea. An obvious overlap between intra- and inter-specific distance was detected, and the authentication efficacy of ITS2, which was assessed by BLAST1, a nearest distance method, and a tree test, was much lower than in other groups. However, R. crenulata and R. rosea could be exactly identified. Analysis showed that the secondary structure of ITS2 differs in R. crenulata and its closest relatives. Our results demonstrated that both a mini barcode from ITS2 and the structure of ITS2 are effective markers for the identification of R. crenulata and R. rosea. This study represents the most comprehensive database of ITS2 barcodes in Rhodiola to date and will be useful in Rhodiola species identification.

Stearic acid suppresses mammary gland development by inhibiting PI3K/Akt signaling pathway through GPR120 in pubertal mice.

It has been demonstrated that dietary high fat diet negatively affects the pubertal mammary gland development. The aim of the present study was to investigate the effects of stearic acid (SA), an 18-carbon chain saturated fatty acid, on mammary gland development in pubertal mice and to explore the underlying mechanism. Our results demonstrated that dietary supplementation of 2% SA suppressed mammary duct development, with significant reduction of terminal end bud (TEB) number and ductal branch. In accord, the expression of proliferative marker Cyclin D1 was markedly decreased by dietary SA. Furthermore, dietary SA led to increase of G protein-coupled receptor 120 (GPR120) expression and inhibition of PI3K/Akt signaling pathway in mammary gland of pubertal mice. In good agreement with the in vivo findings, the in vitro results showed that 40 µM SA significantly suppressed proliferation of mouse mammary epithelial cell HC11 by regulating mRNA and/or protein expression of proliferative markers such as Cyclin D1/3, p21, and PCNA. Meanwhile, SA activated GPR120 and inhibited PI3K/Akt signaling pathway in a GPR120-dependent manner. In addition, SA-induced inhibition of PI3K/Akt signaling pathway, suppression of HC11 proliferation, and alteration of proliferative markers expression were abolished by knockdown of GPR120 with siRNA. Collectively, these findings showed that SA suppressed mammary gland development of pubertal mice, which was coincident with the SA-inhibited HC11 proliferation, and was associated with inhibition of PI3K/Akt signaling pathway through activation of GPR120. These data provided new insights into the regulation of mammary gland development by dietary fatty acids.

Antidiabetic Effects of Tea.

Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed.

Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting reactive oxygen species-activated extracellular signal-regulated kinase 1/2 in H9c2 cardiac myocytes.

Doxorubicin (DOX) is a potent and available antitumor therapeutic agent; however, its clinical application is limited due to its cardiotoxicity. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX­induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether the extracellular signal­regulated kinase (ERK) 1/2 signaling pathway is involved in the cardioprotection of H2S against DOX­induced cardiotoxicity. The present study demonstrated that pretreatment with sodium hydrosulfide (NaHS; a donor of H2S) prior to DOX exposure attenuated the decreased cell viability, the increased apoptosis rate and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cardiac myocytes. Exposure of H9c2 cardiac myocytes to DOX upregulated the expression levels of phosphorylated ERK1/2, which had been reduced by pretreatment with NaHS or N­acetyl­L­cysteine, a ROS scavenger. In addition, H2S upregulated the anti­apoptotic protein, Bcl­2 and downregulated the pro­apoptotic protein, Bax. Notably, U0126, a selective inhibitor of ERK1/2, was observed to mimic the above­mentioned cytoprotective activity of H2S. In conclusion, these findings indicate that H2S attenuates DOX­induced cardiotoxicity by inhibiting ROS-mediated activation of ERK1/2 in H9c2 cardiac myocytes.

Comparison on chemical components and hypoglycemic activities between two closely-related Chinese materia medica / 中草药

Potentillae Discoloris cum Radice Herba and Agrimoniae Herba are closely-related medicinal plants in Rosaceae with specific hypoglycemic activities and applied as Chinese materia medica in clinical practice for the treatment of diabetes. Based upon pharmaphylogeny theories, the biosynthetic pathways of the principal active components of the above two Chinese herbs were summarized, and the commonness and differences of the active components were compared further and the correlation between material basis and curative effects was summarized as well. The results indicated that the common biosynthetic pathways of the two Chinese herbs accounted for 60%; The common components of tiliroside and quercetin, etc. as well as the differentiated components of potengriffioside A and rosolic acid, etc. are also the active components; The differences of the characteristic components and their contents may lead to the differences of functions and modes of action between the two Chinese herbs.

Therapeutic value of sesame oil in the treatment of adhesive small bowel obstruction.

BACKGROUND: The optimal treatment of partial adhesive small bowel obstruction (SBO) is still controversial. The purpose of this study was to determine the effects of oral administration of sesame oil to the standard of conservative treatment in this disease. METHODS: Sixty-four cases of partial adhesive SBO were retrospectively allocated into either the control group or the intervention group (with sesame oil added), and clinical results were compared. RESULTS: Of the 64 patients, 33 were in the control group and 31 in the intervention group. Significantly fewer patients required surgical intervention in the intervention group than in the control group (4/31 vs 16/33, P = .0029). Less SBO resolution time (24 hour vs 30 hour, P = .0019) and a shorter hospital stay (6 days vs 10 days, P = .0235) were observed in the interventional group. CONCLUSIONS: Our study showed that sesame oil was a safe and effective adjunct to the standard treatment of partial adhesive SBO.

Study on needling depth of Fengfu (GV 16) with CT / 中国针灸

<p><b>OBJECTIVE</b>To study on needling safe depth of Fengfu (GV 16) with CT, so as to provide reference for safe needling depth of Fengfu (GV 16) in clinical acupuncture treatment.</p><p><b>METHODS</b>Forty-one adult volunteers were divided into 3 groups, a thin person group, a moderate person group and a fat person group according to Luo's indexes, and computer-aided tomography (CT) was used to measure the needling depth of Fengfu (GV 16).</p><p><b>RESULTS</b>The safe depths of perpendicular needling of Fengfu (GV 16) were different for persons of different somatotypes. The safe needling depth was (27.73 +/- 3.45) mm for the thin person group, (30.78 +/- 2.90) mm for the moderate person group, and (33.39 +/- 4.27) mm for the fat person group.</p><p><b>CONCLUSION</b>The safe needling depth < or = the dangerous depth x 75% can be used for reference for the safe needling depth of Fengfu (GV 16) for different somatotypes persons.</p>