Search

For centuries, Foeniculi fructus (F. fructus) has been used as a traditional herbal medicine in China and Europe and is widely used as a natural therapy for digestive disorders, including indigestion, flatulence, and bloating. The mechanism of F. fructus that alleviates functional dyspepsia was analyzed through network pharmacology, and its therapeutic effect on an animal model of functional dyspepsia were investigated. The traditional Chinese medicine systems pharmacology (TCMSP) database was used to investigate the compounds, targets, and associated diseases of F. fructus. Information on the target genes was classified using the UniProtdatabase. Using the Cytoscape 3.9.1 software, a network was constructed, and the Cytoscape string application was employed to examine genes associated with functional dyspepsia. The efficacy of F. fructus on functional dyspepsia was confirmed by treatment with its extract in a mouse model of loperamide-induced functional dyspepsia. Seven compounds targeted twelve functional dyspepsia-associated genes. When compared to the control group, F. fructus exhibited significant suppression of symptoms in a mouse model of functional dyspepsia. The results of our animal studies indicated a close association between the mechanism of action of F. fructus and gastrointestinal motility. Based on animal experimental results, the results showed that F. fructus provided a potential means to treat functional dyspepsia, suggesting that its medical mechanism for functional dyspepsia could be described by the relationship between seven key compounds of F. fructus, including oleic acid, β-sitosterol, and 12 functional dyspepsia-related genes.

For centuries, Foeniculi fructus (F. fructus) has been used as a traditional herbal medicine in China and Europe and is widely used as a natural therapy for digestive disorders, including indigestion, flatulence, and bloating. The mechanism by which F. fructus alleviates functional dyspepsia was analyzed through network pharmacology, and its therapeutic effect on an animal model of functional dyspepsia was investigated. The compounds, targets, and related diseases of F. fructus were studied utilizing the traditional Chinese medicine systems pharmacology (TCMSP) database. Information on the target genes was classified using the UniProt database. A network was built using Cytoscape 3.9.1, and functional dyspepsia-related genes were checked using the Cytoscape string application. The efficacy of F. fructus on functional dyspepsia, including gastroparesis and gastrointestinal motility, was confirmed by treatment with its extract in a mouse model of loperamide-induced functional dyspepsia. Seven compounds targeted twelve functional dyspepsia-associated genes. In a functional dyspepsia mouse model, F. fructus significantly suppressed the symptoms when compared to that in the control group. Our animal studies showed that the mechanism of action of F. fructus is closely related to gastrointestinal motility. Based on animal experimental results, the results showed that F. fructus provides a potential means to treat functional dyspepsia, suggesting that its medical mechanism for functional dyspepsia can be described by the relationship between seven key compounds of F. fructus, including oleic acid and β-sitosterol, and 12 functional dyspepsia-related genes.

Herbal medicines have traditionally been used as an effective digestive medicine. However, compared to the effectiveness of Herbal medicines, the treatment mechanism has not been fully identified. To solve this problem, a system-level treatment mechanism of Jakyakgamcho-Tang (JGT), which is used for the treatment of functional dyspepsia (FD), was identified through a network pharmacology study. The two components, paeoniae radix alba and licorice constituting JGT were analyzed based on broad information on chemical and pharmacological properties, confirming 84 active chemical compounds and 84 FD-related targets. The JGT target confirmed the relationship with the regulation of various biological movements as follows: cellular behaviors of muscle and cytokine, calcium ion concentration and homeostasis, calcium- and cytokine-mediated signalings, drug, inflammatory response, neuronal cells, oxidative stress and response to chemical. And the target is enriched in variety FD-related signaling as follows: MAPK, Toll-like receptor, NOD-like receptor, PI3K-Akt, Apoptosis and TNF signaling pathway. These data give a new approach to identifying the molecular mechanisms underlying the digestive effect of JGT.

The anti-cancer effects of [6]-gingerol ([6]-GIN), the main active polyphenol of ginger (

Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI) tract. The present study investigated the effects of grape seed powder (GSP) on ICC properties and GI motility. GSP depolarized the pacemaker potentials of ICCs in a dose‑dependent manner. Y25130 or SB269970 slightly inhibited GSP‑induced effects. However, Y25130 and SB269970 together completely blocked GSP-induced effects. In the presence of inhibitors of protein kinase C, protein kinase A, or mitogen-activated protein kinase, GSP‑induced ICC depolarization was inhibited. GSP increased the intestinal transit rate in normal mice and in mice with acetic acid-induced GI motility disorder. In addition, the levels of motilin and substance P were elevated after GSP dosing. These results demonstrate that GSP can regulate GI motility, and therefore, it is a potential therapeutic agent for treating GI motility disorders.

The levels of eIF2α phosphorylation in the livers of adult mice after 5 weeks of HFrD. Western blot analysis of liver lysates from 4-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 5 wks. The * indicates non-specific bands in the Western blot. (PDF 325 kb)

Hepatocyte death and fibrosis in 13 month-old A/A Hep mice fed a regular diet (RD) or a 60% high fructose diet (HFrD) for 5 wks (a) Hematoxylin and eosin (H&E)-stained images of liver tissue sections from 13-month-old Cont. (A/A-fTg) (n = 5) and A/A Hep mice (n = 8) fed an RD. Representative images are shown. (b) TUNEL and (c) Cleaved caspase-3-stained images of liver tissue sections from 13-month-old Cont. (A/A-fTg or S/A-fTg) and A/A Hep mice fed an RD (n = 5 ~ 8 mice per group) or an HFrD (n = 7 mice per group) for 5 wks. The arrowheads indicate positive cells. Representative images are shown. (d) Sirius red-stained and (e) Masson’s trichrome-stained images of liver tissue sections from 13-month-old Cont. (A/A-fTg) (n = 5) and A/A Hep mice (n = 8) fed an RD. Representative images are shown. (PDF 5270 kb)

eIF2α phosphorylation in adult mice prevents hepatocyte death induced by a long-term HFrD. (a) Hematoxylin and eosin (H&E)-stained images of paraffin-embedded liver sections from 7-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 16 wks. Inset shows a magnified view of the area outlined in the black dotted box. The image reveals a necrotic hepatocyte surrounded by leukocytes. (b) Hematoxylin and eosin (H&E)-stained images of liver tissue sections from 7-month-old A/A Liv mice fed an HFrD for 16 wks. Dashed lines delineate the area consisting of ruptured dead cells (asterisks) and dying hepatocytes with fragmented nuclei (red arrow) and atypic nuclei (arrow head). (c) Hematoxylin and eosin (H&E)-stained images of OCT-embedded liver sections from 7-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 16 wks. To prepare frozen blocks, tissue was embedded in Tissue-Tek OCT compound (Sakura Finetek). OCT-embedded sections (7 μm) of frozen livers were stained with haematoxylin and eosin (H&E). Inset shows a magnified view of the area outlined in the black dotted box. The image reveals a necrotic hepatocyte surrounded by leukocytes. (d) Masson’s trichrome-stained images of liver tissue sections from 7-month-old Cont. and A/A Hep mice fed an RD for 16 wks. Representative images are shown (n = 6 mice per group). (e) TUNEL analysis and (f) Immunohistochemical staining of cleaved caspase3 of liver tissue sections from 7-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 16 wks. The arrowheads indicate positive cells. Representative images are shown (n = 6 mice per group). (PDF 6082 kb)

The severity of HFrD-mediated damage is higher in middle-aged A/A Hep mice. (a) The data (serum ALT level, necrotic cell #, TUNEL positive cell #, and cleaved caspase 3 positive cell # of RD-fed adult A/A Hep mice from Fig. 3a–d and RD-fed middle-aged A/A Hep mice from Fig. 2b–e) were reused to generate the graphs. The data were statistically analyzed to evaluate the difference of measured values. Data are means ± SEM (n = 6 mice for RD-fed adult A/A Hep mice and n = 8 mice for RD-fed middle-aged A/A Hep mice). ns stands for no significant. (b) The data (serum ALT level, necrotic cell #, TUNEL positive cell #, and cleaved caspase 3 positive cell # of 16 wks HFrD-fed adult A/A Hep mice from Fig. 3a–d and 5 wks HFrD-fed middle-aged A/A Hep mice from Fig. 2b–e) were reused to generate the graphs. The data were statistically analyzed to evaluate the difference of measured values. Data are means ± SEM (n = 6 mice for 16 wks HFrD-fed adult A/A Hep mice and n = 7 mice for 5 wks HFrD-fed middle-aged A/A Hep mice); # p

A high fructose diet increases expression of proapoptotic genes in liver tissues of A/A Hep mice. (a) Quantitative real-time PCR analysis to assess the expression of selected genes (anti/proapoptotic genes) in liver tissues from 7-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 16 wks. Data are means ± SEM (n = 5 ~ 6 mice per group); *p

eIF2α phosphorylation in hepatocytes is dispensable for survival of adult mice. (a) Diagram depicting the four genotypes of mice used in these experiments. S/A and A/A represent heterozygous and homozygous eIF2α Ser51Ala (*) mutation(s) in exon 2 of one eIF2α allele and both eIF2α alleles, respectively. fTg/0 represents the floxed wild type (WT) eIF2α transgene driven by the CMV enhancer and chicken β-actin promoter (Enh-Pro). The loxP sequences (black arrowheads) allow excision of the WT eIF2α floxed transgene (fTg) and expression of EGFP, an indicator of recombination. CRE Hep /0 represents the Cre recombinase transgene driven by the promoter (Alfp) of Alb1 (encoding albumin) and the enhancer of Afp (encoding alpha-fetoprotein). (b) Efficiency of deletion of the fTg in liver tissues. Results from quantitative RT-PCR analyses of transgenic and total eIF2α mRNAs are shown. Data are means ± SEM (n = 4 ~ 5 mice per group); ### p

Comparison of hepatic and serum triglyceride levels in RD and HFrD-fed mice. (a) Weight gain of Cont. and A/A Hep mice on an RD or an HFrD for 13 wks. Data are means ± SEM (n = 6 mice per group); *p

The aspects of cellular metabolism controlled by phosphatidylinositol phosphates (PtdInsPs) have been broadly expanded, and these phospholipids have drawn tremendous attention as pleiotropic signaling molecules. PtdInsPs analysis using LC/MS/MS has remained challenging due to the strong hydrophilicity of these lipids. Multiple reaction monitoring (MRM) or a neutral loss scan has been performed to quantitatively measure PtdInsPs after chemical derivatization on the phosphate groups of inositol moieties. Only predefined PtdInsPs can be measured in MRM mode, and fatty acyl compositions of sn-1 and sn-2 positions of PtdInsPs cannot be obtained from a neutral loss scan. In our present study, we developed a simple LC/MS/MS method for structural identification of sn-1 and sn-2 fatty acids of PtdInsPs and their relative quantitation. Precursor ion scans of sn-1 monoacylglycerols (MAGs) of PtdInsPs provided structural information about the lipids, and ammonium adduction enhanced signal intensities of PtdInsPs. The relative amount of observed PtdInsPs in biological samples could be compared using chromatographic peak areas from the neutral loss scans. Using precursor ion scans of sn-1 MAG and neutral loss scans of headgroups, major PtdInsPs in cells and tissues were successfully identified with structural information of sn-1 and sn-2 fatty acids, and their relative amounts in different samples were compared.

Transmission electron microscopy of hepatocytes in fructose-fed mice. Transmission electron microscopy (TEM) was performed on liver sections of 7-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 16 wks. The arrowheads indicate the ER compartments. Representative images are shown (n = 3 mice per group). (PDF 1049 kb)

Transmission electron microscopy of hepatocytes in fructose-fed mice. Transmission electron microscopy (TEM) was performed on liver sections of 7-month-old Cont. and A/A Hep mice fed an RD or an HFrD for 16 wks. The arrowheads indicate the ER compartments. Representative images are shown (n = 3 mice per group). (PDF 1049 kb)