The gut microbiota-aromatic hydrocarbon receptor (AhR) axis mediates the anticolitic effect of polyphenol-rich extracts from Sanghuangporus.

Inflammatory bowel disease (IBD) is a significant global health concern. The gut microbiota plays an essential role in the onset and development of IBD. Sanghuangporus (SH), a traditional Chinese medicinal mushroom, has excellent anti-inflammatory effects and is effective at modulating the gut microbiota. Despite these attributes, the specific anticolitic effects of SH and the mechanisms through which the gut microbiota mediates its benefits remain unclear. Herein, we demonstrated that polyphenol-rich extract from SH effectively alleviated the pathological symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by modulating the gut microbiota. Treatment with SH distinctly enriched Alistipes, especially Alistipes onderdonkii, and its metabolite 5-hydroxyindole-3-acetic acid (5HIAA). Oral gavage of live A. onderdonkii or 5HIAA potently mitigated DSS-induced colitis in mice. Moreover, both 5HIAA and SH significantly activated the aromatic hydrocarbon receptor (AhR), and the administration of an AhR antagonist abrogated their protective effects against colitis. These results underscore the potent efficacy of SH in diminishing DSS-induced colitis through the promotion of A. onderdonkii and 5HIAA, ultimately activating AhR signaling. This study unveils potential avenues for developing therapeutic strategies for colitis based on the interplay between SH and the gut microbiota.

Mulberry leaf supplementation inhibits skatole deposition by regulating gut microbiota and upregulating liver cytochrome P450 1A1 expression in finishing pigs.

Skatole, a strong fecal odor substance, is generated through microbial degradation of tryptophan in the animal hindgut. It easily accumulates in adipose tissue and affects meat quality. In this study, the effect of mulberry leaf supplementation on skatole in finishing pigs was studied. In a 35-day trial, 20 finishing pigs (barrows and gilts) were fed with a basal diet or basal diet with 6% mulberry leaves. Growth performance of the pigs (n = 10) was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests. Skatole and short-chain fatty acids were detected using HPLC and gas chromatography, respectively. Fecal microbiota were analyzed using 16S rRNA gene sequencing. The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS. The major cytochrome P450 (CYP) enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot. Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line HepG2 in an in vitro test (n = 3). In finishing pigs, mulberry leaf supplementation had no significant effect on the average daily gain, average daily feed intake, and feed conversion ratio (P > 0.05), but reduced skatole levels in feces, serum, and backfat (P < 0.05), and increased acetic acid levels in feces (P = 0.027). Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella (P < 0.05). Indole-3-acetic acid, the intermediate that is essential for skatole production, was significantly reduced in feces by mulberry leaf supplementation (P < 0.05) and was positively correlated with skatole content in feces (P = 0.004). In pigs treated with mulberry leaves, liver CYP1A1 expression was increased (P < 0.05) and was negatively correlated with skatole content in backfat (P = 0.045). The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in hepatic cells. These findings suggest that mulberry leaf supplementation reduces skatole production and deposition in finishing pigs by regulating the gut microbiota and promoting skatole degradation in liver.

Alcohol extracts of Chinese bayberry branch induce S-phase arrest and apoptosis in HepG2 cells.

The alcohol extracts of Chinese bayberry (Myrica rubra) branches (MRBE) are rich in flavonoids which have a variety of medicinal benefits, but their effects on human HepG2 were unknown. In this study, the effects of MRBE on HepG2 cell growth and its potential for inhibiting cancer were explored. The results displayed that MRBE inhibited HepG2 proliferation both by arresting cells in S phase and promoting apoptosis. Quantitative reverse-transcription PCR (qRT-PCR), western blotting, and immunofluorescence showed that MRBE induced S-phase arrest by upregulating p21, which in turn downregulated cyclin and cyclin-dependent kinase messenger RNA (mRNA) and protein. Apoptosis was induced by blocking the expression of BCL-2 and suppression of the Raf/ERK1 signaling pathways. These results indicated that MRBE may have the potential for treatment of human liver cancer, highlighting novel approaches for developing new pharmacological tools for the treatment of this deadly type cancer. Meanwhile, it provides a new direction for the medicinal added values of Chinese bayberry, which helped to broaden the diversified development of its industry chain.

Preparation and Antioxidant Properties of Germinated Soybean Protein Hydrolysates.

In this study, soybeans during different germination stages were described and compared with regard to morphology, water content, protein, amino acids, and isoflavones. The optimal conditions for the hydrolysis of proteins obtained from germinated soybeans were determined using the response surface methodology. Gel filtration chromatography was used to separate germinated soybean protein hydrolysates after ultrafiltration, whereas 2,2-Diphenyl-1-picrylhydrazyl (DPPH), ABTS•+, and FRAP assays were used to assess the antioxidant activity of different fractions. Findings of this study revealed that protein and isoflavone contents were high in soybean at 24 h following germination (the bud was about 0.5-1 cm). The proteins from germinated soybeans were hydrolyzed and separated into five fractions (G1-G5) and evaluated in terms of their molecular weight and antioxidant activity. Interestingly, the antioxidant activity was found to be higher in germinated soybean protein hydrolysates than in other soybean protein hydrolysates derived from soybean meal protein. This suggests that germination can effectively improve the utilization rate of soybean proteins. The antioxidant activity of G3 was best among G1-G5. The results obtained in this study demonstrate that germination for 24 h when the bud length is about 0.5-1 cm can be applied as a special pretreatment of plant seeds in the development of germinated foods. These findings can be used to identify the structure of the potential antioxidative hydrolysates for their possible exploitation in functional foods.

Aqueous extracts of Sanghuangporus vaninii induce S-phase arrest and apoptosis in human melanoma A375 cells.

Sanghuangporus vaninii, also called 'Sanghuang' mushroom in Chinese, has various medicinal uses, but its effects on human melanoma cells have not been reported. The present study investigated the inhibitory ability and potential anticancer mechanism of the aqueous extracts of S. vaninii (SH). The results revealed that SH inhibited the proliferation of A375 human melanoma cells in a dose-dependent manner, and flow cytometry analysis suggested that SH induced A375 cell cycle arrest at S phase and apoptosis. Reverse transcription-quantitative PCR, western blotting and immunofluorescence analyses indicated that SH induced S-phase arrest by upregulating p21 expression, and p21 inhibited the expression of cyclin-cyclin-dependent kinases complexes at both the RNA and protein levels. In addition, SH induced apoptosis of A375 cells by inhibiting the expression levels of the anti-apoptosis gene Bcl-2. Therefore, the results suggested that SH may be a potential candidate for the treatment of human melanoma, thus providing new ideas for developing drugs that target melanoma.

Anti-Inflammatory Properties In Vitro and Hypoglycaemic Effects of Phenolics from Cultivated Fruit Body of Phellinus baumii in Type 2 Diabetic Mice.

Dietary intervention in type 2 diabetes mellitus (T2DM) is a hotspot in international research because of potential threats to human health. Phellinus baumii, a wild fungus traditionally used as a food and medicine source, is now cultivated in certain East Asian countries, and is rich in polyphenols, which are effective anti-inflammatory ingredients useful in treatment of T2DM, with fewer side effects than drugs. To examine the hypoglycaemic effects of Phellinus baumii phenolics (PPE), the metabolite profiles of T2DM mice induced by streptozotocin after PPE intervention were systematically analyzed. Here, 10 normal mice were given normal saline as control group, and 50 model mice were randomly assigned to five groups and daily intragastric administrated with saline, metformin (100 mg/kg), and PPE (50, 100, 150 mg/kg of body weight), for 60 days. The pro-inflammatory factor contents of lipopolysaccharide stimulation of RAW 264.7 cells were decreased in a dose-dependent manner after PPE treatment, we propose that PPE could exert anti-inflammatory properties. PPE could also effectively reduce blood glucose levels, increased insulin sensitivity, and improved other glucolipid metabolism. Q-PCR results suggested that the hypoglycemic effects of PPE might be through activating IRS1/PI3K/AKT pathway in diabetic mice. These results suggest that PPE has strong potential as dietary components in the prevention or management of T2DM.

Safety evaluation of aqueous extracts of Sanghuangporus vaninii fruiting body in Sprague-Dawley rats.

Sanghuangporus vaninii, called "Sanghuang," is orally used for health care, tumor, and inflammation treatment in Asia. However, the safety of S. vaninii has not been evaluated. The major compounds analysis showed that aqueous extracts of S. vaninii fruiting body were rich in polysaccharides, nucleotides, and polyphenols. Then, the aqueous was given orally to Sprague-Dawley rats for toxical test. In acute toxicity study, the maximum tolerated dose was 21 g/kg. In 17-week repeated dose toxicity experiment, all rats had no abnormal reaction among control group, low dose group (0.15 g/kg) and middle dose group (1.00 g/kg). At high dose group (6.00 g/kg), the feces began to darken on 16th day (D16), and turned to drug stained stool on D21, all rats recovered on the 3rd day (D92) of recovery period. During the whole experiment, there were no animal death and no treatment-related changes in any of the parameters under the all doses. These results indicated the No-Observed Adverse Effect Level of aqueous extract of S. vaninii fruiting body was 1.0 g/kg.

Impact of Phellinus gilvus mycelia on growth, immunity and fecal microbiota in weaned piglets.

BACKGROUND: Antibiotics are the most commonly used growth-promoting additives in pig feed especially for weaned piglets. But in recent years their use has been restricted because of bacterial resistance. Phellinus, a genus of medicinal fungi, is widely used in Asia to treat gastroenteric dysfunction, hemrrhage, and tumors. Phellinus is reported to improve body weight on mice with colitis. Therefore, we hypothesize that it could benefit the health and growth of piglets, and could be used as an alternative to antibiotic. Here, the effect of Phellinus gilvus mycelia (SH) and antibiotic growth promoter (ATB) were investigated on weaned piglets. METHODS: A total of 72 crossbred piglets were randomly assigned to three dietary treatment groups (n = 4 pens per treatment group with six piglets per pen). The control group was fed basal diet; the SH treatment group was fed basal diet containing 5 g/kg SH; the ATB treatment group was feed basal diet containing 75 mg/kg aureomycin and 20 mg/kg kitasamycin. The experiment period was 28 days. Average daily gain (ADG), average daily feed intake (ADFI), and feed intake to gain ratio were calculated. The concentrations of immunoglobulin G (IgG), interleukin-1ß (IL-1ß), tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) in serum were assessed. Viable plate counts of Escherichia coli in feces were measured. Fecal microbiota was analyzed via the 16S rRNA gene sequencing method. RESULTS: The ADG (1-28 day) of piglets was significantly higher in SH and ATB treatment groups (P < 0.05) compared to the control, and the ADG did not show significant difference between SH and ATB treatment groups (P > 0.05). Both SH and ATB treatments increased the MPO, IL-1ß, and TNF-α levels in serum compared to the control (P < 0.05), but the levels in SH group were all significantly higher than in the ATB group (P < 0.05). Fecal microbiological analysis showed that viable E. coli counts were dramatically decreased by SH and ATB. The 16S rRNA gene sequencing analysis showed that ATB shifted the microbiota structure drastically, and significantly increased the relative abundance of Prevotella, Megasphaera, and Faecalibacterium genera. But SH slightly influenced the microbiota structure, and only increased the relative abundance of Alloprevotella genus. CONCLUSION: Our work demonstrated that though SH slightly influenced the microbiota structure, it markedly reduced the fecal E. coli population, and improved growth and innate immunity in piglets. Our finding suggested that SH could be an alternative to ATB in piglet feed.

Whole-genome sequence of Phellinus gilvus (mulberry Sanghuang) reveals its unique medicinal values.

Phellinus gilvus (Schwein.) Pat, a species of 'Sanghuang', has been well-documented for various medicinal uses, but the genome information and active constituents are largely unknown. Here, we sequenced the whole-genome of P. gilvus, identified phenylpropanoids as its key anti-cancer components, and deduced their biosynthesis pathways. A 41.11-Mb genome sequence was assembled and the heatmap created with high-throughput chromosome conformation capture techniques data suggested all bins could be clearly divided into 11 pseudochromosomes. Cellular experiments showed that P. gilvus fruiting body was more effective to inhibit hepatocellular carcinoma cells than mycelia. High resolution electrospray ionization mass spectroscopy (HR-ESI-MS) analysis revealed P. gilvus fruiting body was rich in phenylpropanoids, and several unique phenylpropanoids in Phellinus spp. exhibited potent anti-carcinogenesis activity. Based on genomic, HR-ESI-MS information and differentially expressed genes in transcriptome analysis, we deduced the biosynthesis pathway of four major phenylpropanoids in P. gilvus. Transcriptome analysis revealed the deduced genes expressions were synergistically changed with the production of phenylpropanoids. The optimal candidate genes of phenylpropanoids' synthesis pathway were screened by molecular docking analysis. Overall, our results provided a high-quality genomic data of P. gilvus and inferred biosynthesis pathways of four phenylpropanoids with potent anti-carcinogenesis activities. These will be a valuable resource for further genetic improvement and effective use of the P. gilvus.

Phellinus gilvus­derived protocatechualdehyde induces G0/G1 phase arrest and apoptosis in murine B16­F10 cells.

Protocatechualdehyde (PCA) is considered to be the main phenolic component of Phellinus gilvus responsible for its anticancer properties. Previous studies have demonstrated that PCA can have an anticancer effect on multiple cancer types, but little is known about the effect of PCA on melanoma cells. The present study investigated the inhibitory abilities and potential anticancer mechanisms of PCA on B16­F10 cells using MTT assay. Cell apoptosis and cell cycle were assessed by flow cytometry using Annexin V­FITC and propidium iodide staining. Whole­transcriptome analysis was used to investigate the effects of PCA on gene expression. PCA significantly decreased cell viability, induced cell cycle arrest at G0/G1 phase and promoted apoptosis of B16­F10 cells, suggesting that PCA could have anticancer effects against melanoma cells. Whole­transcriptome analysis indicated that PCA treatment upregulated genes involved in histone modification and decreased the transcription of genes involved in DNA repair and replication. Kyoto Encyclopedia of Genes and Genomes analysis showed that PCA treatment enhanced the complement and coagulation cascades, and the p53 signaling pathway. The present results indicated that PCA could act as an antitumor agent in melanoma cells, which may provide experimental support for the development of novel therapies to treat melanoma.

Enantioselective Conjugate Addition of Aryl Halides and Triflates to Electron-Deficient Olefins via Nickel- and Rhodium-Catalyzed Sequential Relay Reactions.

Asymmetric conjugate addition of aryl halides or aryl triflates to electron-deficient olefins was realized by sequential Miyaura borylation and Hayashi-Miyaura conjugate addition in one pot. A nickel-catalyzed borylation of aryl halides or triflates and a rhodium-chiral diene complex catalyzed enantioselective conjugate addition was executed as a pair of relay reactions as a more efficient and greener protocol.

Butylene fipronil induces apoptosis in PC12 murine nervous cells via activation of p16-CDK4/6-cyclin D1 and mitochondrial apoptotic pathway.

Butylene fipronil (BFPN) is a phenylpyrazole insecticide, acting at the γ-aminobutyric acid (GABA) receptor. Here, we show that BFPN inducedcytotoxicity in PC12 murinenervous cells, which lacks GABA receptor. Treatment with BFPN for 48 hours significantly enhanced G0/G1 arrest and induced apoptosis. BFPN decreased the expression of cyclin-dependent kinase (CDK4 and CDK6) and increased P16 and cyclin D1. Simultaneously, Bcl-2 protein was declined while Bax and cytochrome c were significantly enhanced in BFPN-treated groups. The apoptotic enzymes caspase-8, -9, and -3 were also activated by BFPN. Furthermore, treatment with BFPN significantly stimulated reactive oxygen species (ROS) generation, and pretreatment with antioxidant diphenyleneiodonium, substantially reduced cell death. Overall, these results suggest that BFPN is effective to induce G0/G1-phase arrest and apoptosis in PC12 murine nervous cell. Stimulating ROS generation and activation of P16-CDK4/6-cyclin D1 and mitochondrial apoptotic pathway may participate in the cytotoxicity of BFPN.

The aqueous extract of Phellinus igniarius (SH) ameliorates dextran sodium sulfate-induced colitis in C57BL/6 mice.

Phellinus igniarius, which is called Sanghuang in Chinese, is a fungal herb widely used in Traditional Chinese Medicine to treat stomachache, inflammation and tumors. Recent studies have demonstrated the antitumor, anti-diabetic, anti-inflammatory and immunity-modulating activities of P. igniarius. In the present study, we investigated that ameliorating effect of the aqueous extract of P. igniarius fruiting body (SH) on dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice. Treatment with SH (250 and 400 mg/kg) for 8 weeks effectively alleviated the pathological indicators of colitis such as bodyweight reduction, disease activity index score, shortening of colon length and abnormal colon histology. The plasma levels of lipopolysaccharide (LPS) and inflammatory factors such as interleukin-6 (IL-6), IL-1ß and tumor necrosis factor (TNF)-α were all significantly reduced. Supplementation of SH (10 mg/L) also inhibited LPS-elicited IL-1ß production by RAW264.7 macrophages. Real-time PCR and western blot showed that treatment with SH significantly inhibited the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and decreased the expression of IL-6/IL-1ß-maturation genes such as apoptosis-associated speck-like protein (ASC3) and caspase-1 in the colon of DSS-induced colitis mice. These results suggest that SH is adequate for the treatment of colitis. Inhibiting the expression and release of inflammatory factors may participate in the colitis-ameliorating effect of SH.

Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27(KIP1)-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells.

Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA treatment on cell proliferation, cell cycle distribution, apoptosis, and expression of several cell cycle-related genes in HT-29 cells. The treatment enhanced S-phase cell cycle and apoptosis in HT-29 cells in a dose-dependent manner. Western blot results showed that PCA treatment decreased the expression levels of cyclin A, cyclin D1, and p27(KIP1) but increased those of cyclin-dependent kinase 2 (CDK2) in HT-29 cells. Furthermore, the expression levels of B-cell lymphoma/leukemia-2 (Bcl-2) and B-cell lymphoma/leukemia-xL (Bcl-xL) were down-regulated, whereas the levels of BH3-interacting domain death agonist (Bid), Bcl-2 homologous antagonist/killer (Bak), and cytosolic cytochrome c were significantly upregulated. Thus, the enzymes caspases-9, -3, -8, and -6 were found to be activated in HT-29 cells with PCA treatment. These results indicate that PCA-induced S-phase cell cycle arrest and apoptosis involve p27(KIP1)-mediated activation of the cyclin-A/D1-Cdk2 signaling pathway and the mitochondrial apoptotic pathway.

Activation of P27kip1-cyclin D1/E-CDK2 pathway by polysaccharide from Phellinus linteus leads to S-phase arrest in HT-29 cells.

Our previous study showed that polysaccharide (P1) from Phellinus linteus exhibits a significant inhibitive activity on human colorectal carcinoma cells (HT-29). However its novel molecular mechanism remains unknown. To obtain insights into P1's mechanism of action, we examined its effects on cell proliferation in vitro and in vivo, cell cycle distribution, apoptosis, autophagy, and expression of several cell cycle interrelated proteins in HT-29 cells. Interestingly, we found that volume and weight of the solid tumor significantly decreased in P1 (200mg/kg)-treated mice compared with the control. However, slightly increased the body weight of the P1 treated tumor-bearing mice, with no significant increased ALT, AST levels in serum and LPO concentration in liver and kidney indicated that P1 has no toxicity to mammals at a dose of 200mg/kg. Furthermore, P1 caused a significantly dose-dependent increase in the S-phase cell cycle, but no apoptosis and autophagy in HT-29 cells. RT-PCR and Western blot results showed significantly down-regulated expressions of cyclin D1, cyclin E, and CDK2, as well as increased expressions of P27kip1 in P1 (100 µg/mL)-treated HT-29 cells. These results suggested that the activation of P27kip1-cyclin D1/E-CDK2 pathway is involved in P1-induced S-phase cell cycle arrest in HT-29 cells.

Polysaccharide from Phellinus linteus induces S-phase arrest in HepG2 cells by decreasing calreticulin expression and activating the P27kip1-cyclin A/D1/E-CDK2 pathway.

ETHNOPHARMACOLOGY RELEVANCE: Our previous study showed that the proteoglycan P1 from Phellinus linteus (Mesima) exhibits significant anti-tumor activity against human hepatocellular carcinoma cells (HepG2); however, its molecular mechanism remains unknown. This study aims to provide insights into the mechanism of the anti-tumor activity of P1 against HepG2 cells. METHODS: We examined the effects of P1 on HepG2 cell proliferation in vitro and in vivo. Flow cytometry was used to analyze the cell cycle distribution and apoptosis. Proteomic analysis, real-time (RT)-PCR, and Western blot were carried out to observe the expression of several cell cycle control proteins in HepG2 cells. RESULTS: Both the volume and the weight of solid tumors were significantly decreased in P1-treated mice (200mg/kg) compared with the control. The HepG2 cells in the P1-treated tumors were significantly decreased, irregularly shaped, and smaller. P1 slightly increased the body weight of the tumor-bearing mice, which indicates that P1 is nontoxic to mammals at 200mg/kg. P1 also caused a significant dose-dependent increase in S phase arrest, but no apoptosis was observed in HepG2 cells. The results of the proteomic analysis, RT-PCR, and Western blot analysis showed that significantly downregulated expression of calreticulin, cyclin D1, cyclin E, and CDK2 and upregulated expression of P27 kip1 and cyclin A in the P1-treated HepG2 cells (200 µg/ml). CONCLUSION: These results suggest that calreticulin expression and the P27 kip1-cyclin A/D1/E-CDK2 pathway were involved in P1-induced S-phase cell cycle arrest in HepG2 cells.

1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice.

We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled (13)C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na(+)/K(+)-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes.

Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma.

Proteoglycan (P1) purified from Phellinus linteus has been reported to have anti-disease activities. The objectives of our research were to determine the anti-tumor effect and possible mechanisms of P1 on human cancer cells. Cell inhibition assay showed that P1 has an antiproliferative effect on HepG2, HT-29, NCI-H 460 and MCF-7 human colon cancer cells, especially it was very effective in inhibiting HT-29 cells. When HT-29-bearing mice were treated with P1(100mg/kg), there was relative increase in spleen and thymus weights, the plasmatic pIgR and IgA levels were significantly increased, also there was a notable decrease in plasmatic PGE2, Reg IV, EGFR and Akt concentrations measured by ELISA. RT-PCR analysis suggested that P1-induced HT-29 apoptosis appeared to be associated with a decrease in the levels of expression of Reg IV and EGFR. These results suggest that P1 might have two potential roles in treating cancer; it acts as an immunopotentiator partly through protecting T cells from escaping PGE2 attack and enhancing the mucosal IgA response, and as a direct inhibitor by disrupting the Reg IV/EGFR/Akt signaling pathway.

Protective effect of sericin peptide against alcohol-induced gastric injury in mice.

BACKGROUND: Sericin peptide (SP) has shown a powerful anti-oxidant property in a host of studies. The present study was designed to investigate the possible protective effects of SP against alcohol-induced gastric lesions in mice and to explore the potential mechanisms. METHODS: Animals were randomly divided into 5 groups: control, alcohol (56%, 14.2 ml/kg), SP-treated mice (0.2, 0.4, 0.8 g/kg). Mice were pretreated with SP before administering alcohol, the concentration of ethanol in serum and urine, the contents of malondialdehyde (MDA), glutathione (GSH) and the glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD) activities in the gastric mucosa were measured, subsequently, the pathological evaluation of stomach was also observed. RESULTS: Of the animals pre-treated with SP (0.4, 0.8 g/kg), the concentration of ethanol in serum was significantly decreased, while increased in urine as compared to the alcohol-administered alone animals. Alcohol administration caused severe gastric damage as indicated by markedly increased MDA levels and decreased antioxidants, such as reduced GSH, GSH-PX and SOD in the gastric tissue while the CAT activity was not altered. On SP administration there was a reversal in these values towards normal. Histopathological studies confirmed the beneficial role of SP, which was in accordance with the biochemical parameters. CONCLUSIONS: SP could protect gastric mucosa from alcohol-induced mucosal injury. These gastroprotective effects might be due to increasing 'first-pass metabolism' in the stomach and hastening ethanol elimination directly through the urine. SP might also play an important role in the protection of the structure and function of gastric mitochondria, at least partly based on their anti-oxidant effect.

[Protective effect of panax japonics on ethanol-induced mice gastric lesion].

OBJECTIVE: To study the protective effects of Panax japonics (PJ) on alcohol-induced gastric lesion in mice and the possible mechanisms. METHOD: Male ICR mice were randomized into six groups: normal, control, PJ (1.5, 3.0, 6.0 g x kg(-1)) and Yinduoan (1.5 g x kg(-1)). The mice were pretreated with PJ before administering ethanol to observe the effect on the concentration of ethanol in serum and urine. The contents of MDA, GSH and GSH-PX, CAT and SOD activities were measured in serum and gastric mucosa, and subsequently, the pathological evaluation of stomach was also observed. RESULT: The concentration of ethanol in serum was evidently decreased after PJ (1.5, 3.0 g x kg(-1)) was administrated because the ethanol was eliminated fleetly through urine. Synchronously the PJ reduced the content of MDA and increased the GSH increased in serum and gastric, besides, it increased the enzymatic activities of GSHPX, CAT and SOD, and the ethanol-induced gastric mitochondria structure injury were ameliorated so as to make the function to normal. CONCLUSION: Based on these observations, one could conclude that the PJ is a potent protective agent against ethanol-induced gastric damages. One mechanism may be related with inhibiting the absorbability of ethanol at gastrointestinal tract, decreasing the concentration of ethanol in serum, and accelerating the ethanol elimination through urine so as to alleviate the ethanol-induced damage to gastrointestinal mucosal, enhancing the first-pass metabolism in stomach, and particularly increasing the antioxidant levels in serum and gastric. These gastroprotective effects might be, at least partly, through ameliorating the gastric mitochondria structure.