Structural characterization of an inulin neoseries-type fructan from Ophiopogonis Radix and the therapeutic effect on liver fibrosis in vivo.

Ophiopogonis Radix is a well-known Traditional Chinese Medicine and functional food that is rich in polysaccharides and has fructan as a characteristic component. In this study, an inulin neoseries-type fructan designated as OJP-W2 was obtained and characterized from Ophiopogonis Radix, and its potential therapeutic effect on liver fibrosis in vivo were investigated. Structural studies revealed that OJP-W2 had a molecular weight of 5.76 kDa and was composed of glucose and fructose with a molar ratio of 1.00:30.87. Further analysis revealed OJP-W2 has a predominantly lineal (1-2)-linked ß-D-fructosyl units linked to the glucose moiety of the sucrose molecule with (2-6)-linked ß-D-fructosyl side chains. Pharmacological studies revealed that OJP-W2 exerted a marked hepatoprotective effect against liver fibrosis, the mechanism of action was involved in regulating collagen deposition (α-SMA, COL1A1 and liver Hyp contents) and TGF-ß/Smads signaling pathway, alleviating liver inflammation (IL-1ß, IL-6, CCL5 and F4/80) and MAPK signaling pathway, and inhibiting hepatic apoptosis (Bax, Bcl-2, ATF4 and Caspase 3). These data provide evidence for expanding Ophiopogonis Radix-acquired fructan types and advancing our understanding of the specific role of inulin neoseries-type fructan in liver fibrosis therapy.

Versatile functionalization of pectic conjugate: From design to biomedical applications.

Pectin exists extensively in nature and has attracted much attention in biological applications for its unique chemical and physical characteristics. Functionalized pectin, especially pectic conjugates, has given many possibilities for pectin to improve its properties and bioactivity as well as to deliver active molecules. To better exploit this strategy of pectic functionalization, this review presents in detail the structural modifications of pectin, different synthetic methods, and design strategies of pectic conjugates involving both traditional chemical and "green" approaches. Here, the research ideas and applications of pectic prodrugs as well as the development of preparation based on pectic conjugates are reviewed, with emphasis on crosslinking systems of functionalized pectin and nanosystems based on self-assembly techniques. We hope this review will provide comprehensive and valuable information for the functionalization and systematization of the pectic conjugate from synthesis to application.

Structure characterization of pectin from the pollen of Typha angustifolia L. and the inhibition activity of lipid accumulation in oleic acid induced L02 cells.

The pollen of Typha angustifolia L. decoction was clinically used to treat hyperlipidemia in China. A pectin polysaccharide (PTPS-2-2) was obtained from T. angustifolia pollen through water extraction, ion-exchange chromatography, and gel chromatography. Structural characterization showed that PTPS-2-2 had a molecular weight of 54 kDa and was composed of rhamnose, arabinose, xylose, galactose, and galacturonic acid with a molar ratio of 11.5: 36.5: 4.1: 36.7: 11.2. PTPS-2-2 consisted of rhamnogalacturonan I (RG-I) and arabinogalactan II (AG-II) domains. Its backbone was predominantly composed of →4-α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→, with branches of 1,3-Galp, 1,6-Galp, 1,3,6-Galp, T-Araf, 1.5-Araf and T-Xylp, connected to the 4-position of 1,2-Rhap and the 3-position of 1,4-GalpA. The inhibitory effect of PTPS-2-2 on lipid accumulation was studied in vitro, using L02 cells induced by oleic acid. This experiment shows that PTPS-2-2 treatment at 100-400 µg/mL dose-dependently reduce cellular triglycerides (TG), cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, while elevated superoxide dismutase (SOD) levels. This indicated that PTPS-2-2 potentially ameliorated oleic acid-induced hepatic steatosis by inhibiting lipid accumulation and oxidative stress.

The impact of the methyl esters of homogalacturonan on cellular uptake dependent hypoglycemic activity in IR-HepG2 cells.

A homogalacturonan (HG) FPLP obtained from Ficus pumila L. was reported to have anti-diabetic activity but how this is influenced by degree of methyl-esterification (DM) of HG is unknown. To comprehensively analyze the role of DM in hypoglycemic activity in insulin-resistant HepG2 cells, HG derivatives (0 < DM < 100) were prepared from FPLP (DM25) by alkali or methanol acidified with acetyl chloride. Interestingly, a quadratic curve relationship revealed that hypoglycemic effect increased and then decreased with DM, and which was the most pronounced with DM54. DM might regulate activity by altering the intracellular drug concentration through cellular uptake. Furthermore, HG-DMn (0 < n < 100) were dependent on macropinocytosis, while HG-DMn (30 < n < 100) were also dependent on caveolae-mediated endocytosis. For HG, higher lipophilicity, smaller particle size, and more endocytosis mechanisms involved were favorable for cellular uptake, thereby increasing the intracellular drug concentration and enhancing the hypoglycemic activity. This work provides ideas for future investigations on structure-activity relationships.

A lymphatic route for a hyperbranched heteroglycan from Radix Astragali to trigger immune responses after oral dosing.

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiota-independent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.

Quality Markers of Dendrobium officinale by "Oligosaccharide-Spectrum-Effect" Relationships.

Dendrobium officinale Kimura et Migo has been used as a traditional Chinese medicine (TCM) and a functional food for thousands of years. Carbohydrate is one of the most important effective substances and indicative components in D. officinale. However, since the qualitative and quantitative analysis of polysaccharides in D. officinale remains a challenge and limitation, herein, an oligosaccharide-quality marker approach was newly developed for quality assessment of D. officinale by spectrum-effect relationships between high performance liquid chromatographic (HPLC) fingerprints and anti-inflammatory effects. The HPLC fingerprints of 48 batches of oligosaccharides from D. officinale (DOOS) were developed and analyzed with similarity analysis (SA) and hierarchical cluster analysis (HCA), and eight common peaks were identified. In vitro screening experiment indicated that DOOS potentially inhibited nitric oxide (NO) production and effectively reduced the release of inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß in RAW 264.7 cells, thereby reducing the inflammatory response of cells. Finally, the HPLC fingerprint of different batches of DOOS was combined with in vitro anti-inflammatory activity to assess the spectrum-effect relationships of DOOS by gray correlation analysis (GCA), in addition, the purified oligosaccharide components were identified and validated for NO inhibitory activity. Our results showed four DOOS (maltotetraose, maltopentaose, maltohexaose, and mannohexaose) were relevant to anti-inflammatory effects and could be as quality markers for the quality control of D. officinale. It suggests that the "oligosaccharide-spectrum-effect" relationships approach is a simple and reliable method for the quality control of herb medicines or nutritious foods.

Rubus chingii Hu. unripe fruits extract ameliorates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance.

BACKGROUND: The unripe fruits of Rubus chingii Hu. ("Fu-peng-zi" in Chinese) is a well-known herbal tonic in traditional Chinese medicine (TCM) for tonifying liver and kidney. However, little is known regarding its therapeutic efficacy against liver fibrosis and the underlying mechanism. METHODS: The current research aims to explore the potential of Rubus chingii Hu. unripe fruits extract (RF) in the treatment of liver fibrosis and explore the underlying mechanism. RF was administered (450 and 900 mg·kg- 1 of body weight per day) orally to male C57BL/6 mice with CCl4-induced liver fibrosis for 3 weeks. The histopathological changes and fibrosis stage in liver tissue were assessed using hematoxylin and eosin (H&E) and Sirius red staining. The distribution of α-SMA and Col1A1 in the liver was analyzed to determine the hepatic stellate cells (HSCs) activation using immunohistochemistry and immunofluorescent analysis. Various biochemical markers in serum (ALT, AST) and liver (Hyp, IL1-ß, IL6, TNF-α and MCP-1) were observed to assess the liver's injury, fibrosis, and inflammation. In liver tissue, fibrosis-associated proteins including α-SMA, TGF-ß1, Smad2/3, p-Smad2/3, and Smad4 were detected through a Western blot assay. Pyrosequencing-based analysis of bacterial 16 S ribosomal RNA from variable regions V3-V4 of fecal samples characterized the gut microbiota. Spearman's rank correlation analysis was performed for the association between altered bacterial genera by RF and pharmacodynamics parameters. RESULTS: Three weeks of RF treatment can significantly lower liver inflammatory levels, pathological abnormalities, and collagen fibrous deposition in mice with CCl4-induced liver fibrosis. The expressions of α-SMA and Col1A1 were lowered by RF, while the expression levels of TGF-ß/Smads signaling pathway-related proteins, including TGF-ß1, p-Smad2/3, and Smad4, were dramatically decreased by RF. The RF treatment significantly increased or reduced 18 different bacterial species, restoring the CCl4-induced gut microbiota imbalance to the normal group's levels. According to correlation analysis, the bacterial genera Bifidobacterium and Turicibacter were the most significant in restoring CCl4-induced liver fibrosis. CONCLUSIONS: RF can reduce liver damage and delay the onset of liver fibrosis through modulating TGF-ß/Smads signaling pathway. Furthermore, RF's anti-liver fibrosis effect was related to balancing the gut microbial community, partly attained by increasing Bifidobacterium and Turicibacter in liver fibrosis.

Inhibition of the intestinal postprandial glucose transport by gallic acid and gallic acid derivatives.

Inhibition of glucose uptake in the intestine through sodium-dependent glucose transporter 1 (SGLT1) or glucose transporter 2 (GLUT2) may be beneficial in controlling postprandial blood glucose levels. Gallic acid and ten of its derivatives were identified in the active fractions of Terminalia chebula Retz. fructus immaturus, a popular edible plant fruit which has previously been associated with the inhibition of glucose uptake. Gallic acid derivatives (methyl gallate, ethyl gallate, pentyl gallate, 3,4,6-tri-O-galloyl-ß-d-glucose, and corilagin) showed good glucose transport inhibition with inhibitory rates of 72.1 ± 1.6%, 71.5 ± 1.4%, 79.9 ± 1.2%, 44.7 ± 1.2%, and 75.0 ± 0.7% at 5 mM d-glucose and/or 56.3 ± 2.3, 52.1 ± 3.2%, 70.2 ± 1.7%, 15.6 ± 1.6%, and 37.1 ± 0.8% at 25 mM d-glucose. However, only 3,4,6-tri-O-galloyl-ß-d-glucose and corilagin were confirmed GLUT2-specific inhibitors. Whilst some tea flavonoids demonstrated minimal glucose transport inhibition, their gallic acid derivatives strongly inhibited transport effect with GLUT2 specificity. This suggests that gallic acid structures are crucial for glucose transport inhibition. Plants, such as T. chebula, which contain high levels of gallic acid and its derivatives, show promise as natural functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.

Polysaccharide-rich extract from Polygonatum sibiricum protects hematopoiesis in bone marrow suppressed by triple negative breast cancer.

Polysaccharide is one of main components in Polygonatum sibiricum (PS), which is an herbal medicine widely used in East Asia. Polysaccharides from Polygonatum sibiricum has been shown to exhibit multiple biological activities, such as anti-diabetes, anti-inflammation, antioxidant, immunity modulation, and anticancer. Since hematopoietic system is one of determinant factors in cancer control, we here explored the effect of polysaccharide-rich extract from Polygonatum sibiricum (PREPS) on hematopoiesis in the mice bearing triple negative breast cancer (TNBC). We found that the 4T1 TNBC tumor significantly increased myeloid cells in peripheral blood, bone marrow and spleen, while decreasing bone marrow hematopoietic stem and progenitor cells (HSPCs), indicative of an inhibition of medullary hematopoiesis. When 4T1 TNBC tumor-bearing mice were treated with PREPS, the percentage of myeloid cells within tumor-infiltrating immune cells was reduced. In addition, PREPS also inhibited hematopoietic cell expansion in the spleen, which was induced by TNBC tumors. Importantly, PREPS markedly increased HSPCs and common lymphoid progenitors in the bone marrow that had been suppressed by TNBC tumors. These findings suggest that PREPS protect hematopoiesis inhibited by TNBC tumors in the bone marrow. Although PREPS alone did not achieve statistical significance in the suppression of TNBC tumor growth, it may have a long-lasting anti-tumor effect to assist TNBC therapies by sustaining hematopoiesis and lymphoid regeneration in bone marrow.

A Combined Phytochemistry and Network Pharmacology Approach to Reveal the Effective Substances and Mechanisms of Wei-Fu-Chun Tablet in the Treatment of Precancerous Lesions of Gastric Cancer.

Wei-Fu-Chun (WFC) tablet is a commercial medicinal product approved by China Food and Drug Administration, which is made of Panax ginseng C.A.Mey., Citrus aurantium L., and Isodon amethystoides (Benth.). WFC has been popularly used for the treatment of precancerous lesions of gastric cancer (PLGC) in clinical practice. In this study, a UHPLC-ESI-Q-TOF/MS method in both positive and negative ion mode was employed to rapidly survey the major constituents of WFC. 178 compounds including diterpenoids, triterpenes, sesquiterpenes, flavonoids, saponins, phenylpropanoids, lignans, coumarins, organic acids, fatty acids, quinones, and sterols, were identified by comparing their retention times, accurate mass within 5 ppm error, and MS fragmentation ions. In addition, 77 absorbed parent molecules and nine metabolites in rat serum were rapidly characterized by UHPLC-ESI-Q-TOF/MS. The network pharmacology method was used to predict the active components, corresponding therapeutic targets, and related pathways of WFC in the treatment of PLGC. Based on the main compounds in WFC and their metabolites in rat plasma and existing databases, 13 active components, 48 therapeutic targets, and 61 pathways were found to treat PLGC. The results of PLGC experiment in rats showed that WFC could improve the weight of PLGC rats and the histopathological changes of gastric mucosa partly by inhibiting Mitogen-activated protein kinase (MAPK) signaling pathway to increase pepsin secretion. This study offers an applicable approach to identify chemical components, absorbed compounds, and metabolic compounds in WFC, and provides a method to explore bioactive ingredients and action mechanisms of WFC.

Roles of gut microbiota and metabolites in a homogalacturonan-type pectic polysaccharide from Ficus pumila Linn. fruits mediated amelioration of obesity.

In this study, the beneficial effects of a homogalacturonan(HG)-type pectic polysaccharide from Ficus pumila L. fruits (FPLP) in obese mice were investigated. The 17-week FPLP treatment effectively attenuated obesity, as mainly demonstrated by the reductions of body weight, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in high-fat diet (HFD)-induced obese mice. The decreased Firmicutes to Bacteroidetes abundance ratio, enriched Akkermansia, and reduced Blautia abundance suggested that FPLP ameliorated the HFD-induced gut dysbiosis. FPLP also influenced the levels of metabolites altered upon HFD feeding, including increases in myristoleic acid and pentadecanoic acid levels. The correlation studies indicated that FPLP ameliorated HFD-induced rise in TC and LDL-C levels through regulating gut microbial community and their associated metabolites. In conclusion, this study extends our understanding of the relationships among gut microbiota (Akkermansia and Blautia), metabolites (myristoleic acid and pentadecanoic acid), HG-type pectin and its TC- and LDL-C- lowering functions.

[Study on chemical constituents of Cinnamomi Ramulus].

The chemical constituents of Cinnamomi Ramulus were investigated in this study. Twenty-two compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC and their structures were identified by various spectral analyses as dihydrorosavin(1), rosavin(2), 1-phenyl-propane-1,2,3-triol(3), patchoulol(4), graphostromane B(5),(+)-lyoniresinol-3 a-O-ß-D-glucopyranoside(6),(-)-lyoniresinol-3 a-O-ß-D-glucopyranoside(7), cinnacaside(8), subaveniumin A(9), 3-phenyl-2-propenyl-6-O-L-arabinopyranosyl-ß-glucopyranoside(10), 2-phenylethyl-ß-vicianoside(11), cinnacasol(12), [(2R,3S,4S,5R,6R)-6-(benzyloxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl] methyl hydrogen sulfate(13), coniferyl aldehyde(14),(2R,3R)-5,7-dimethoxy-3',4'-methylenedioxyflavan-3-ol(15), cinnacassin L(16), E-cinnamic alcohol(17),(E)-3-(2-methoxyphenyl)-2-propen-1-ol(18), 2-hydroxyphenylpropanol(19), cinnamomulactone(20),(+)-syringaresinol(21) and cinnamomumolide(22), respectively. Among them, 1 is a new compound and 3-7, 9-11, 13, 15, 18 and 19 were isolated from the plant for the first time.

Hypoglycaemic effect and mechanism of an RG-II type polysaccharide purified from Aconitum coreanum in diet-induced obese mice.

The present study aimed to explore the effect of an anti-inflammatory RG-II type polysaccharide (KMPS) purified from Aconitum coreanum (Le'vl.) on glucose metabolism in high-fat diet-induced obese (DIO) mice. Treatment with KMPS for 4 weeks significantly reduced the fasting blood glucose, increased the sensitivity to insulin and improved glucose tolerance. Concurrently, KMPS supplementation also markedly inhibited inflammatory cytokine expression in serum and insulin target tissues and decreased the proportion of M1-type macrophages in adipose tissue, which was considered as the potential hypoglycaemic mechanism. In mechanism study, it was found that KMPS reduced the serine phosphorylation of IRS-1 by inhibiting the activation of the NF-κB pathway, thereby restoring the utilization of glucose by the PI3K/AKT pathway. These results suggested that KMPS may be a potential component for targeting inflammation in the treatment of type 2 diabetes.

Isolation and structural characterization of a non-competitive α-glucosidase inhibitory polysaccharide from the seeds of Litchi chinensis Sonn.

In this study, a novel homogeneous polysaccharide (LSP-W-4, MW = 6.70 kDa) was isolated and purified from the seeds of Litchi chinensis Sonn. Monosaccharide composition analysis indicated that LSP-W-4 is a heteropolysaccharide consisting of arabinose, mannose, glucose and galactose in a molar ratio of 6.33:3.88:10.35:1.00. A detailed structural analysis revealed that LSP-W-4 has a backbone consisting of 1,4-α-Glcp and 1,4-ß-Manp, as well as four branched chains including of T-α-Galp, T-α-Araf, α-Araf-(1 â†’ 5)-α-Araf-(1 â†’ and α-Araf-(1 â†’ 5)-α-Araf-(1 â†’ 5)-α-Araf-(1 â†’ attached to O6 of 1,4-ß-Manp and 1,4-α-Glcp. LSP-W-4 exhibited significant inhibitory activity both against yeast (Saccharomyces cerevisiae) and mammalian (rat-intestinal acetone powder) α-glucosidase, with IC50 values of 75.24 µM and 66.97 µM, respectively, with both such inhibitory activities being more powerful than those of acarbose. A kinetic analysis revealed that LSP-W-4 inhibited the activities of both yeast and mammalian α-glucosidase in a typical non-competitive manner, with KM values of 0.43 mmol/L and 0.53 mmol/L, respectively.

The components data of fuzheng huayu extracts, cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin.

Fuzheng Huayu (FZHY) capsule is a traditional Chinese medicine composed of six Chinese medicinal herbs Tian et al. [1] and approved by China food and drug administration for liver fibrosis treatment [2], [3] Liu et al., 2009 and Liu et al., 2005. CGA formula consisting of Cordyeps sinensis polysaccharide (CS-PS), gypenosides (G), and amygdalin (A), are derived from FZHY formula. It is necessary to identify the chemical profile of FZHY and CGA formula to describe the mechanisms and the corresponding components of anti-fibrosis. It is showed that FZHY contains adenosine (5.21 mg/g), amygdalin (5.31 mg/g), salvianolic acid b (18.22 mg/g) and deoxyschizandrin (2.62 mg/g), respectively. CS-PS contained 60.5 ± 2.2% total carbohydrate, including 14.17% arabinose, 25.35% glucose and 60.48% galactose. Gypenosides contain 10.34% gypenosides XLIX and 16.58% gypenosides A. These data provide the primary chemical profile of FZHY and CGA formula and an example for components analysis of traditional Chinese medicine.

Chinese medicine CGA formula ameliorates liver fibrosis induced by carbon tetrachloride involving inhibition of hepatic apoptosis in rats.

ETHNOPHARMACOLOGICAL REVELVANCE: CGA consisting of Cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin, was demonstrated to be the effective components formula in Fuzheng Huayu (FZHY) capsule, a traditional Chinese medicine approved by China food and drug administration for treatment of liver fibrosis and to inhibit transforming growth factor-ß1 (TGF-ß1) signaling, previously. AIM OF THE STUDY: To evaluate the effects of CGA on hepatic apoptosis in liver fibrosis induced by carbon tetrachloride (CCl4). MATERIALS AND METHODS: The hepatic injury and histology was detected by serum biomarker assay and hematoxylin-eosin staining. The hepatic collagen was illustrated by Sirius red staining and hydroxyproline (Hyp) concentration. The hepatic stellate cells (HSCs) activation and hepatic apoptosis was visualized by immunohistochemical analysis of α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase-mediated dUPT nick-end labeling (TUNEL) assay respectively. The protein expression of collagen type I (Col-I), α-SMA, TGF-ß1, Fas, tumor necrosis factor receptor 1 (TNF-R1), cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, cleaved-caspase-3, mitochondrial Bcl-2, Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), cytochrome C and cytoplasmic cytochrome C was detected by western-blot. RESULTS: CGA or FZHY ameliorated liver histological changes, decreasing serum alanine aminotransferase, aspartate aminotransferase, hepatic Hyp, TUNEL positive-stained area, and down-regulated the protein expression of α-SMA, TGF-ß1, Col-I, Fas, TNF-R1, cleaved-caspase-8, cleaved-caspase-10, cleaved-caspase-9, and cleaved-caspase-3, mitochondrial Bax, Bak, and cytoplasmic cytochrome C, while restored the expression of mitochondrial Bcl-2 and cytochrome C. CONCLUSION: CGA formula ameliorates liver fibrosis induced by CCl4, which is correlated to its inhibition on hepatic apoptosis.

A polysaccharide from Eclipta prostrata alleviates experimental autoimmune encephalomyelitis through inhibiting Th17 cells.

Eclipta prostrata has long been used as a medicinal herb in China. EAP20-1, a homogeneous polysaccharide with anti-complementary activity had been obtained from E. prostrate by using anion-exchange and size-exclusion chromatography. In this study, we found that EAP20-1 could inhibit in vitro lymphocyte proliferation stimulated by concanavalin-A or anti-CD3/anti-CD28 antibodies. Furthermore, in experimental autoimmune encephalomyelitis (EAE) mice, EAP20-1 treatment relieved the clinical symptoms, accompanied by reduced neuroinflammation and demyelination in spinal cords. Mechanistically, EAP20-1 reduced the mRNA expression of interleukin (IL)-17, IL-22, and RAR-related orphan receptor gamma t (RORγt) in the spleen; inhibited auto-reactive T cell proliferation and decreased the percentage of Th17 cells in response to myelin oligodendrocyte glycoprotein (MOG35-55) ex vivo. Moreover, EAP20-1 directly inhibited naïve CD4 + T cells differentiate into Th17 cells in vitro. These results indicating EAP20-1 could benefit EAE through inhibiting Th17 cell differentiation and suggesting a therapeutic potential of EAP20-1 in MS.

Homoisoflavonoids Are Potent Glucose Transporter 2 (GLUT2) Inhibitors: A Potential Mechanism for the Glucose-Lowering Properties of Polygonatum odoratum.

Foods of high carbohydrate content such as sucrose or starch increase postprandial blood glucose concentrations. The glucose absorption system in the intestine comprises two components: sodium-dependent glucose transporter-1 (SGLT1) and glucose transporter 2 (GLUT2). Here five sappanin-type (SAP) homoisoflavonoids were identified as novel potent GLUT2 inhibitors, with three of them isolated from the fibrous roots of Polygonatum odoratum (Mill.) Druce. SAP homoisolflavonoids had a stronger inhibitory effect on 25 mM glucose transport (41.6 ± 2.5, 50.5 ± 7.6, 47.5 ± 1.9, 42.6 ± 2.4, and 45.7 ± 4.1% for EA-1, EA-2, EA-3, MOA, and MOB) than flavonoids (19.3 ± 2.2, 11.5 ± 3.7, 16.4 ± 2.4, 5.3 ± 1.0, 3.7 ± 2.2, and 18.1 ± 2.4% for apigenin, luteolin, quercetin, naringenin, hesperetin, and genistein) and phloretin (28.1 ± 1.6%) at 15 µM. SAP homoisoflavonoids and SGLT1 inhibitors were found to synergistically inhibit the uptake of glucose using an in vitro model comprising Caco-2 cells. This observed new mechanism of the glucose-lowering action of P. odoratum suggests that SAP homoisoflavonoids and their combination with flavonoid monoglucosides show promise as naturally functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.

Characterization of a pectin from Lonicera japonica Thunb. and its inhibition effect on Aß42 aggregation and promotion of neuritogenesis.

Pectin is a class of complex polysaccharides and recognized for its potential bioactivities. In this study, we showed that a pectic polysaccharide, LFA03-a, was extracted from Lonicera japonica Thunb. flowers and purified with DEAE-cellulose and Sephacryl S-100HR. LFA03-a was composed of rhamnose, arabinose, galactose and galacturonic acid in the molar ratio of 18.1:25.3:36.8:19.5. Its structure was determined to possess a rhamnogalacturonan I (RG-I) backbone consisting of α-l-1,2-Rhap and α-d-1,4-GalAp disaccharide repeating unit, substituted at O-4 of l-rhamnose. The side chain was involved with ß-d-1,4-Galp, ß-d-1,3-Galp, ß-d-1,3,6-Galp and branched α-l-1,5-Araf. Fluorescence spectroscopic analysis with thioflavine T (ThT) and atomic force microscopy (AFM) results showed that LFA03-a inhibited Aß42 aggregation in a dose dependent manner and impeded Aß42 oligomerization and fibril formation. In addition, LFA03-a mildly induced the differentiation of PC12 cells and promoted neuritogenesis.The results suggested that pectin LFA03-a might be a potential targeted therapeutic drug for Alzheimer's disease.

Can highly cited herbs in ancient Traditional Chinese medicine formulas and modern publications predict therapeutic targets for diabetes mellitus?

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of diabetes among all age groups worldwide was estimated to be more than 382 million in 2013. Traditional Chinese medicine (TCM) has been practiced for thousands of years, and substantial valuable experience and prescriptions have been accumulated in the TCM system for the treatment of diabetes. In recent decades, a large amount of experimental and clinical data has been published on the use of herbal medicines related to these ancient TCM prescriptions. AIM OF THE STUDY: This study aimed to discover a method for the investigation of potential antidiabetic herbs from the large amount of data in ancient TCM formulas and modern publications and to verify this method through an in vitro bioactivity study. MATERIALS AND METHODS: In our review, the most frequently cited TCM herbs were selected as potential antidiabetic herb candidates on the basis of TCM philosophical theory (ancient TCM formulas) and Western medicine philosophical theory (modern publications). The ethanol and aqueous extracts of the selected herbs were screened for their α-glucosidase inhibitory, glucose-stimulated insulin secretion (GSIS), and intestinal glucose transport inhibitory effects. RESULTS: Twelve herbs [Terminalia chebula Retz., fructus immaturus, dried; Poria cocos (Schw) Wolf., sclerotium, dried; Zea mays L., stigma, dried; Pueraria lobata (Willd.) Ohwi, radix, dried; Cucurbita moschata (Duch. ex Lam.) Duch. ex Poiret, fructus, dried; Lycium barbarum L., fructus, dried; Glycine max (L.) Merr., semen, fermented; Glycyrrhiza uralensis Fisch., radix and rhizoma, dried; Dioscorea opposita Thunb., rhizoma, dried; Morus alba L., folium, dried, Morus alba L., fructus, dried; and Polygonatum odoratum (Mill.) Druce, rhizoma, dried] were finally selected as candidates with potential glucose-lowering effects after a review was performed of herbs that are frequently cited in ancient TCM formulas and modern publications. The bioactive study results demonstrated that both the ethanol extracts and crude polysaccharides of M. alba L., fructus, dried, and M. alba L., folium, dried, and the crude polysaccharides of T. chebula Retz., fructus immaturus, dried, exhibited α-glucosidase inhibitory effects. Moreover, the crude polysaccharides of P. cocos (Schw) Wolf., sclerotium, dried; Z. mays L., stigma, dried; and T. chebula Retz., fructus immaturus, dried, exhibited favorable GSIS effects, and the ethanol extracts of P. odoratum (Mill.) Druce, rhizoma, dried; T. chebula Retz., fructus immaturus, dried; and G. uralensis Fisch., radix and rhizoma, dried, significantly decreased glucose transport across the cell monolayer. CONCLUSIONS: Our review and the preliminary bioactive study revealed that 10 of the 12 recommended edible TCM herbs had favorable antidiabetic effects, demonstrating that TCM herbs with a high prescription and publication frequency may provide insights into the potential therapeutic targets of diabetes mellitus and may aid in the discovery of effective compounds complementary to currently used medicines. Such a literature and medicine review is a useful method of exploring potential antidiabetic herbs by using the wealth of information in ancient TCM formulas and modern publications.