Antioxidant and Hepatoprotective Effects of Acidic-Hydrolysis Residue Polysaccharides from Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) in Mice.

The present work was designed to investigate the antioxidant and hepatoprotective effects of acidic-hydrolysis Lentinus edodes residue polysaccharides (Ac-LRP) on lipopolysaccharide-induced liver injury in mice. Hepatoprotective effects were observed in liver treated with Ac-LRP at doses of 200, 400, and 600 mg/kg body weight, respectively. Activities of superoxide dismutase, glutathione peroxide, catalase, total antioxidant capacity, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and levels of total cholesterol, triglyceride, malondialdehyde, and lipid peroxidation in liver or serum samples were analyzed. Ac-LRP reduced the incidence of liver necrosis detected via histological observations. In addition, Ac-LRP chemical bonds and ultrastructure were measured. These results provided valuable evidence supporting the utilization of Ac-LRP as a functional food and natural medicine for the treatment of liver injury.

Characteristic anti-inflammatory and antioxidative effects of enzymatic- and acidic- hydrolysed mycelium polysaccharides by Oudemansiella radicata on LPS-induced lung injury.

The present work investigated the antioxidative, anti-inflammatory and pulmonary protective effects of enzymatic- and acid- hydrolysed mycelia polysaccharides (En-MPS and Ac-MPS) from Oudemansiella radicata on LPS-induced acute lung injury (ALI) mice. The results demonstrated that both En-MPS and Ac-MPS showed potential pulmonary protective effects by decreasing serum levels of hs-CRP and C3, increasing pulmonary enzyme values of SOD, GSH-Px, CAT and the level of T-AOC; reducing the activity of MPO; and down-regulating the contents of MDA and LPO. In addition, the levels of TNF-ɑ, IL-1ß, and IL-6 in BALF of mice treated with En-MPS at a dosage of 400 mg/kg/d were significantly lower than those in the ALI mice. The in vitro antioxidant effects also showed that the En-MPS was more effective than Ac-MPS. Furthermore, the physical properties of polysaccharides were also investigated by GC, HPGPC, FT-IR and NMR. These results indicated that both En-MPS and Ac-MPS possessed potent antioxidant and anti-inflammatory activities, which could be used as an ingestible drug in preventing lung injury.

The characteristics and antioxidation of Oudemansiella radicata selenium polysaccharides on lipopolysaccharide-induced endo-toxemic mice.

The selenium polysaccharides (SPS) by Oudemansiella radicata were isolated, and two hydrolysates (enzymatic-SPS (ESPS) and acidic-SPS (ASPS)) were obtained by enzymolysis and acidolysis. The endo-toxemic-induced lung and kidney damages were successfully established by the lipopolysaccharides (LPS) injection (5 mg/kg/d). The in vivo mice experiments indicated that the ESPS showed superior antioxidant and protective effects against the LPS-toxicities by increasing the antioxidant activities, reducing lipid peroxidation, improving the inflammatory response and elevating the kidney and lung functions than SPS and ASPS. Furthermore, the selenium contents and structure of SPS, ESPS and ASPS were investigated through FAAS, GC, UV, HPGPC, FT-IR, NMR and the results indicated that SPS, ESPS and ASPS were homogeneous heteropolysaccharide with an average molecular weight of 3.12 × 104, 1.77 × 104, 1.41 × 104 Da, respectively. The conclusions demonstrated that the polysaccharides by O. radicata might be suitable for functional foods and natural drugs in preventing the endo-toxemia and its complications, and providing references for exploitation and utilization of natural substances.

The antioxidative and anti-aging effects of acidic- and alkalic-extractable mycelium polysaccharides by Agrocybe aegerita (Brig.) Sing.

Two extractable polysaccharides of Ac-MPS and Al-MPS were extracted from the mycelium of Agrocybe aegerita (Brig.) Sing and the in vitro antioxidant activities and in vivo anti-aging activities in a d-gal-induced aging mice were investigated in the present study. The in vitro antioxidant analysis showed that Ac-MPS showed superior scavenging effects on hydroxyl of 68.62±2.59% and DPPH of 85.19±3.26% at the concentration of 4500µg/mL. Biochemical indices and antioxidant analysis in vivo showed that Ac-MPS had better effects in raising hepatic activities of SOD, CAT, GPx and T-AOC, inhibiting hepatic contents of LPO and MDA, as well as improving serum lipid levels of LDL-C, HDL-C, LDL-C/HDL-C, TG and TC. Furthermore, HYP measurements suggested that skin collagen in aging mice could be maintained. This study suggested that both Ac-MPS and Al-MPS could be used as potential natural agents or dietary supplements in attenuating aging and its complications.

Polysaccharides with Antioxidative and Antiaging Activities from Enzymatic-Extractable Mycelium by Agrocybe aegerita (Brig.) Sing.

This study aimed to investigate the antioxidant, antiaging, and organ protective effects of the water-extractable mycelium polysaccharides (MPS) and enzymic-extractable mycelium polysaccharides (En-MPS) by Agrocybe aegerita (Brig.) Sing in D-galactose-induced (D-gal-induced) aging mice. In in vitro assays, the En-MPS demonstrated stronger antioxidant activities in dose-dependent manners. The mice experiments revealed that both En-MPS and MPS had potential effects on antioxidation, antiaging, and organ protection mainly by improving the antioxidant enzyme activities, decreasing the lipid peroxidation, and remitting the lipid metabolism. Furthermore, chemical composition and monosaccharide composition of polysaccharides were also measured, and the results indicated that differences in biological activity of MPS and En-MPS samples showed a significant correlation to their purity. The findings demonstrated that the polysaccharides by A. aegerita (Brig.) Sing could be exploited as natural and functional foods for the prevention and alleviation of aging and its complications.

Characterization, antioxidation, anti-inflammation and renoprotection effects of selenized mycelia polysaccharides from Oudemansiella radicata.

The present work investigated the characteristics, antioxidative, anti-inflammative and renoprotective effects of mycelia selenized polysaccharides (MSPS) from Oudemansiella radicata on lipopolysaccharide (LPS)-induced kidney damaged mice. The results demonstrated that both MSPS and mycelia polysaccharides (MPS) showed potential renoprotective effects reflecting by decreasing the serum levels of CRE, BUN and UA, increasing the nephritic enzyme activities of SOD, GSH-Px, CAT and T-AOC, reducing the activities of MPO, as well as down-regulating the contents of MDA and LPO, respectively. And the MSPS showed superior effects. Furthermore, the selenium contents and physical properties of polysaccharides were investigated by FAAS, GC, HPGPC, FT-IR, NMR and AFM analysis, and the results indicated that MSPS was a homogeneous heteropolysaccharide with an average molecular weight of 3.12×104Da. These results may provide theoretical basis in applying natural and functional foods for the prevention and alleviation of kidney damages and its complications.

The Antioxidative, Antiaging, and Hepatoprotective Effects of Alkali-Extractable Polysaccharides by Agaricus bisporus.

The aim of this work was designed to investigate the antioxidant, antiaging, and hepatoprotective effects of alkali-extractable polysaccharides (AlAPS) and their three purified fractions (AlAPS-1, AlAPS-2, and AlAPS-3) from Agaricus bisporus in D-galactose induced aging mice. For in vitro antioxidant analysis, both AlAPS and its fractions exhibited moderate reducing power, Fe2+-chelating activities, and potent scavenging activities on hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The in vivo results demonstrated that the polysaccharides, especially AlAPS-2, showed potential antiaging and hepatoprotective effects by enhancing the antioxidant status, decreasing serum hepatic enzyme activities, and improving the lipid metabolism. This study suggested that the polysaccharides extracted and purified from A. bisporus could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases.

Antioxidative, anti-inflammation and lung-protective effects of mycelia selenium polysaccharides from Oudemansiella radicata.

The present work was designed to investigated the antioxidant, anti-inflammation, and pulmonary protective effects of SMPS and MPS from Oudemansiella radicata on LPS-induced lung injured mice. The results demonstrated that SMPS showed potential effects on relieving lung injury and preventing oxidative stress, reflecting by decreasing the serum levels of C3, CRP and GGT, increasing the pulmonary activities of SOD, GSH-Px, CAT and T-AOC, as well as down-regulating the MDA and LPO contents, respectively. Furthermore, the levels of TNF-α (224.211±3.12ng/mL), IL-1ß (254.557±2.18ng/L), and IL-6 (18.214±0.15ng/L) in BALF of mice treated with SMPS at the dosage of 400mg/kg/d significantly lower than that in the lung injured mice. These conclusions indicated that both SMPS and MPS possessed potent antioxidants and anti-inflammation activities, and could be used as functional foods and natural drugs in preventing lung injury.

Hepatoprotection of enzymatic-extractable mycelia zinc polysaccharides by Pleurotus eryngii var. tuoliensis.

The purpose of this work was designed to investigate the hepatoprotective and antioxidant effects of enzymatic-extractable mycelia zinc polysaccharides (En-MZPS) from Pleurotus eryngii var. tuoliensis on the hyperlipidemic mice induced by high-fat-high-cholesterol emulsion (HFHCM). The results showed that the supplementation of En-MZPS had potential anti-hyperlipidemia effects on reducing hepatic lipid levels by monitoring the serum enzyme activities (ALP, ALT and AST) and serum lipid levels (TC, TG, HDL-C, LDL-C and VLDL-C), enhancing the antioxidant enzymes (SOD, GSH-Px, CAT and T-AOC), and decreasing the lipid peroxidation (MDA and LPO). Furthermore, the in vitro scavenging results indicated that the inhibition effects of En-MZPS on hydroxyl radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals reached 59.98±6.29% and 37.01±2.15%, respectively. These conclusions demonstrated that the En-MZPS might be suitable for functional foods and natural drugs in preventing the HFHCM-induced hyperlipidemia and non-alcoholic fatty liver.

Optimization of Mycelia Selenium Polysaccharide Extraction from Agrocybe cylindracea SL-02 and Assessment of their Antioxidant and Anti-Ageing Activities.

The aim of the present study was to optimize the purification of mycelia selenium polysaccharides (MSPS) from Agrocybe cylindracea SL-02 and characterize their in vitro antioxidant and in vivo anti-ageing activities. The Box-Behnken experimental design (BBD) was evaluated, which showed that the optimum conditions included an extraction temperature of 94.99°C, a pH of 9 and a precipitation temperature of 12°C, and the predicted yield was 11.036 ± 0.31%. The in vitro antioxidant assay demonstrated that MSPS had potential effects on scavenging and enhanced the reducing power of reactive oxygen species. The in vivo anti-ageing evaluation showed that MSPS significantly reduced the malonaldehyde (MDA) contents and total cholesterol (CHOL) levels, and remarkably improved the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in mice in response to D-galactose-induced ageing. Furthermore, the characteristic analysis of MSPS indicated a selenium content of 1.76 ± 0.10 mg/g at a concentration of 6 µg/mL in liquid media and a monosaccharide composition of rhamnose, arabinose, mannose, glucose and galactose at a molar ratio of 29:3:1:18.8:2.7. These results suggest that MSPS might be suitable for functional foods and natural drugs on preventing the ageing progress induced by toxic chemicals.

Purification, Characterization, Antioxidation, and Antiaging Properties of Exopolysaccharides and Endopolysaccharides of the Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Agaricomycetes).

Exopolysaccharides (ExPSs) and endopolysaccharides (EnPSs) were isolated from mycelia and culture medium of Agaricus brasiliensis. Four polysaccharide fractions (ExPS-1-2, ExPS-2, EnPS-1, and EnPS-2) were puri¬fied from ExPSs and EnPSs using diethylaminoethyl anion exchange and a Sephadex G-100 gel filtration column, respectively, and their physicochemical properties were analyzed and evaluated to determine antioxidant activity. The results showed that rhamnose and mannose were the main monosaccharides of the polysaccharide fractions. ExPS-2 and EnPS-2 were acidic polysaccharide fractions and showed higher scavenging effects on 1,1-diphenyl-2-picryl- hydrazyl and hydroxyl radicals, and had higher reducing power in the in vitro antioxidant assays. In addition, the malondialdehyde contents, the total antioxidant capacity, and the alanine transaminase activity were also assessed to determine the antiaging effects; ExPSs showed more antiaging effects compared with EnPSs. The results suggest that polysaccharides extracted from A. brasiliensis have significant potential as natural antioxidants and antiaging agents.

[Anti-inflammatory mechanism research of flavonoid compounds in Dalbergiae Odoriferae Lignum by module-based network analysis].

Dalbergiae Odoriferae Lignum as a traditional Chinese medicine (TCM) has been widely used for promoting blood circulation and removing blood stasis. Flavonoid compounds are main chemical constituents of Dalbergiae Odoriferae Lignum, which exert anti-inflammatory property. However, the underlying anti-inflammatory mechanisms of flavonoid compounds are incompletely understood. It has been reported that isoliquiritigenin, liquiritigenin, naringenin and butein possess anti-inflammatory property. The purpose of this study is to illuminate the anti-inflammatory mechanism of flavonoid compounds based on the protein interaction network (PIN) analysis on molecular network level. 130 targets of the main medicinal ingredients of flavonoid compounds were gained though database retrieval. A protein interaction network of flavonoid compounds was constructed with 589 nodes and 216 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 26 modules were identified and analyzed by Gene ontology (GO) enrichment. Two modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of flavonoid compounds may be partly attributable to inhibite FOS, PTGS2 expression, inhibite of IL-1beta release, and block the MAPK pathway and toll-like receptor pathway.

[Study on relations between transient receptor potential vanilloid 1 and pungent property of traditional Chinese medicines].

The five-flavor theory of traditional Chinese medicines (TCM) and the flavor efficacy generation mechanism has long been focuses and difficulties in studies on traditional Chinese medicinal properties. In this paper, by using the pharmacophore-based virtual screening technique, the authors discussed the relations between the pungent property and transient receptor potential vanilloid 1 (TRPV1) by studying the TCM components' role in regulating TRPV1 ion channel. The results showed that the matching relationship between TRPV1 agonist pharmacophore model and TCM chemical components could identify the active ingredients from pungent herbs. Therefore, the authors proposed that TRPV1 is one of the potential targets for efficient pungent herbs. The pungent property of TCMs is decided by its chemical components, and consistent with the inherited and additive characteristics.

[Protein interaction network analysis of Panax notoginseng saponins].

Panax notoginseng (PN) is one of the commonly used clinical medicines for cardiovascular diseases and possesses a variety of pharmacological effects. P. notoginseng saponins (PNS) are the most important bioactive components in PN. The purpose of this study was to explain the mechanism of PNS on molecular network level. 18 targets of the main medicinal ingredients of PNS were gained by virtual screening based on pharmacophores and data mining. A protein interaction network of PNS was constructed with 189 nodes and 721 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 14 modules were detected. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of PNS played in cardiovascular disease related to multiple biological processes, which could represent the characteristics of traditional Chinese medicine (TCM) as a whole to regulate the disease. The results showed that the blood circulation and hemostasis efficacy of PN related with the biological processes such as positive regulation of cAMP metabolic and biosynthetic process, platelet activation and regulation of blood vessel size, regulation of T cell proliferation and differentiation and so on. Therefore, the module-based network analysis will be an effective method for better understanding TCM.

Cycloastragenol, a triterpene aglycone derived from Radix astragali, suppresses the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.

Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 value of 13.0 µM. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 µM. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50 value was determined as 21.9 µM. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.

A combination of pharmacophore modeling, molecular docking and virtual screening for iNOS inhibitors from Chinese herbs.

Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover new iNOS inhibitors. This study was performed to identify natural iNOS inhibitors from traditional Chinese herbs through a combination of pharmacophore modeling, molecular docking and virtual screening. First, the pharmacophore models were generated though six known iNOS inhibitors and validated by a test database. The pharmacophore model_017 showed good performance in external validation and was employed to screen Traditional Chinese Medicine Database (Version 2009), which resulting in a hit list of 498 compounds with matching score (QFIT) above 40. Then, the hits were subjected to molecular docking for further refinement. An empirical scoring function was used to evaluate the affinity of the compounds and the target protein. Parts of compounds with high docking scores have been reported to have the related pharmacological activity from the literatures. The results provide a set of useful guidelines for the rational discovery of natural iNOS inhibitors from Chinese herbs.

Mechanism of action of salvianolic acid B by module-based network analysis.

Salvianolic Acid B (Sal B) is one of the main medicinal ingredients of Radix Salvia miltiorrhiza (Danshen) and possesses a variety of pharmacological effects. The purpose of this study was to discover the new mechanism of action of Sal B based on the protein interaction network (PIN) analysis. A PIN of Sal B was constructed with 852 nodes and 8,626 interactions. By fast agglomerate algorithm based on the edge clustering coefficients (FAG-EC), 11 modules were detected from the network. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of Sal B played in cardiovascular disease were related to multiple biological processes, which could represent the characteristics of Chinese Material Medica (CMM) as a whole to regulate the disease. The most interesting finding of this work was that the anti-inflammatory effect of Sal B was due to the immune response of T lymphocytes by regulating IL-2 family, CD3E, CD79A, MAP3K7 and PRKCQ. Therefore, the module-based network analysis will be an effective method for better understanding CMM.