Inhibitory effects of polysaccharides isolated from Phellinus gilvus on benzo(a)pyrene-induced forestomach carcinogenesis in mice

AIM: Although polysaccharides from Phellinus mushrooms are a well-known material with anti-tumor properties, there is no information about the effect of polysaccharides from Phellinus gilvus (PG) on tumor. The modulating effect of polysaccharides isolated from PG on the benzo(a)pyrene (BaP)-induced forestomach carcinogenesis in ICR female mice was investigated in this study.METHODS: A forestomach carcinogenesis model was established in 40 ICR female mice receiving oral administration of BaP for 4 wk. The mice were randomly assigned to 4 groups (10 each). The mice in each group were treated with sterile water or PG for 4 and 8 wk (SW4,PGW4, SW8, and PGW8 groups). Eight or 12 wk after the first dose of BaP, forestomachs were removed for histopathological and RT-PCR analysis.RESULTS: In histopathological changes and RT-PCR analysis, sterile water-treated mice showed significant hyperplasia of the gastric mucosa with a significantly increased expression of mutant p53 mRNA compared to mice treated with PG for 8 wk.CONCLUSION: Polysaccharides isolated from PG may inhibit BaP-induced forestomach carcinogenesis in mice bydown-regulating mutant p53 expression.

Evaluation of spermatogenesis and fertility in F1 male rats after in utero and neonatal exposure to extremely low frequency electromagnetic fields

Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control),5,83.3 or 500 μT from day 6 of gestation through to day 21 of lactation.The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study.Results:No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance,preputial separation,testis weight,testicular histology,sperm count,daily sperm production, sperm motility,sperm morphology and reproductive capacity of F1 offspring.Conclusion:Exposure of Sprague- Dawley rats to a 60 Hz EMF at field strengths of up to 500 μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.

Hepatic Protective Effects of <i>S</i>-Allyl-L-Cysteine (SAC) in Rats with Carbon Tetrachloride (CCl₄) Induced Liver Injury

S-allyl-L-cysteine (SAC) is an organosulfur compound derived from aged garlic extract (AGE). Studies have reported that AGE possesses bioprotective capacity, including antidiabetic, antimicrobial, antioxidant, and antitumor effects. The present study examined the protective effects of SAC against carbon tetrachloride (CCl4) induced hepatotoxicity in rats. Ten male Wistar rats aged 11 - 12 weeks were randomly divided into two groups (five rats/group) as control and SAC groups. All rats had ad libitum access to water, and the SAC group received water containing SAC intragastrically (200 mg/kg) once daily for five consecutive weeks. In the fifth experimental week, 50% CCl4 in olive oil (1 mL/kg) was administered intraperitoneally three times a week to induce liver injury in both groups. Rats were sacrificed at 24 hours after the last CCl4 injection, and liver tissues were excised for histopathological, immunohistochemical and antioxidant analyses. The rats in the SAC group did not show abnormal behavior, such as decreased water intake or food consumption, during the experimental period. Body weights in all groups did not change significantly over the experimental period. Histopathological analysis showed that the percentage of hepatic steatosis was lower in the SAC group at 12.75% ± 3.74% compared to 24.64% ± 5.29% in the control group (p < 0.05). The percentage of cytochrome P4502E1 (CYP2E1) distribution area in the SAC group was also lower at 19.61% ± 6.18% compared with 25.22% ± 6.21% in the control group (p < 0.05). These results suggest that SAC can alleviate CCl4-induced liver damage by decreasing hepatic steatosis and reducing CYP2E1 expression in rats.

Reduction of gastrointestinal motility by unilateral thyroparathyroidectomy plus subdiaphragmatic vagotomy in rats

AIM: To investigate whether the combined methods of unilateral thyroparathyroidectomy (TPX) and subdiaphragmatic vagotomy (VAX) can be adapted for rats and used as a reliable method to produce a rat model of long-term reduction of gastrointestinal (GI) motor function. METHODS: Male Sprague-Dawley rats were randomly divided into 3 groups, normal, sham-operated and unilateral TPX plus VAX. The TPX plus VAX rats received VAX 7 d after application of TPX, and dietary intake and fecal output were then measured daily for 1 wk.After completion of the experiments, gastric emptying and small bowel transit were measured in vivo, and the contractile responses of colonic strips to excitatory and inhibitory neurotransmitters were estimated using isometric force transducers in vitro. RESULTS: In comparison with normal and sham-operated rats, rats which received unilateral TPX plus VAX showed a significant decrease in body weight and in fecal pellet number and weight throughout the entire week. Application of TPX plus VAX to rats markedly delayed gastric emptying and small bowel transit. In TPX plus VAX rats, the longitudinal muscles of the proximal colon showed a significant reduction in contractile responses to acetylcholine (5 × 10-6 mol/L), and a dramatic attenuation of contractile responses was also observed in both the longitudinal and circular muscles of the distal colon. However, the spontaneous contractility of the colonic strips from TPX plus VAX rats was not significantly affected by treatment with N-nitro-Larginine-methyl ester (0.1 mol/L). CONCLUSION: The results indicate that unilateral TPX plus VAX reduced the motor function of the GI tract in rats, and the reduced gut motility is likely mediated, at least in part, by inhibition of the excitatory neurotransmitter system.

Multi-faceted small molecule for Alzheimer’s disease

The main pathologies of Alzheimer’s disease(AD)are the accumulation of amyloid-B(AB)and tau ta ngles,and these two fundamental pathologies accompany the va rious neuropathological features,such as neuroinfla mmation,loss of syna pse and neurogenesis,disruption of the blood-brain barrier(BBB),autophagy dysfunction。

Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling

The prevalence of cardiovascular diseases(CVDs)is increasing at a rapid pace in developed countries,and CVDs are the leading cause of morbidity and mortality.Natural products and ethnomedicine have been shown to reduce the risk of CVDs.Schizonepeta(S.)tenuifolia is a medicinal plant widely used in China,Korea,and Japan and is known to exhibit anti-inflammatory,antioxidant,and immunomodulatory activities.We hypothesized that given herbal plant exhibit pharmacological activities against CVDs,we specifically explored its effects on platelet function.Platelet aggregation was evaluated using standard light transmission aggregometry.Intracellular calcium mobilization was assessed using Fura-2/AM,and granule secretion(ATP release)was measured in a luminometer.Fibrinogen binding to integrin a_(Ⅱb)β_3,was assessed using flow cytometry.Phosphorylation of mitogen-activated protein kinase(MAPK)signaling molecules and activation of the protein kinase B(Akt)was assessed using Western blot assays.S.tenuifolia,extract potently and significantly inhibited platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin a_(Ⅱb)β_3.Moreover,all extracts significantly inhibited MAPK and Akt phosphorylation.S.tenuifolia extract inhibited platelet aggregation and granule secretion,and attenuated collagen mediated GPVI downstream signaling,indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function.We suggest that S.tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.

Fermented rice bran prevents atopic dermatitis in DNCB-treated NC/Nga mice

The fermentation of natural plants has a favorable effect on the functional and biological activities of living systems. These include anti-oxidative, anti-inflammatory, and anti-platelet aggregation activities. This is attributed to the chemical conversion of the parent plants to functional constituents, which show more potent biological activity. In our study, rice bran along with oriental medicinal plants （Angelicae gigantis, Cnidium officinale, Artemisia princeps, and Camellia sinensis） was fermented by Lactobacillus rhamnosus and Pichia deserticola （FRBE）. We evaluated the effects of oral administration of FRBE on atopic dermatitis in 1-chloro-2,4-dinitrobenzene （DNCB）-treated NC/Nga mice. FRBE significantly ameliorated the macroscopic and microscopic appearance of skin lesions in DNCB-induced atopic dermatitis and reduced levels of serum immunoglobulin E and the differential white blood cell count. In addition, it reduced skin thickness compared to that of atopic dermatitis-affected skin. FRBE treatment also reduced mast cell incorporation in skin lesions of atopic dermatitis. The total cell number in dorsal skin tissue and the axillary lymph node increased following DNCB application, and this was normalized by FRBE treatment. Moreover, it decreased the levels ofCD8＋ helper T cells and Gr-1 ＋/CD1 lb＋ B cells in peripheral blood mononuclear cells and skin lesions in DNCB-induced atopic dermatitis. Using real-time polymerase chain reaction analysis, we demonstrated that FRBE significantly inhibited mRNA expression of cytokines （e.g., interleukin-5 and interleukin-13） and cyclooxygenase-2 in AD skin lesions. These results suggest that FRBE could be a valuable herbal remedy for the treatment of atopic dermatitis.

Ascorbic Acid Attenuates Acute Ethanol-Induced Liver Injury in SMP30 Knockout Mice

Ascorbic acid (AA) is recognized as a free radical scavenger that protects cells from oxidative stress-induced damage. However, no studies have investigated the role of AA in acute alcoholic liver disease using senescence marker protein-30 (SMP30) knockout (KO) mice. SMP30 is a novel 34-kDa protein involved in AA biosynthesis. The present study aimed to elucidate the physiological functions of AA in acute ethanol-induced liver injury using SMP30 KO mice, which cannot synthesize AA in vivo. After a 4-week experimental period, mice were divided into six groups. The following three groups comprised the ethanol treatment groups: WT-E group (wild-type), KV-E group (AA-supplemented), and KT-E group (AA-deficient). Mice were exposed to an acute dose of ethanol (6 g ethanol/kg) administered by gavage once a day for three days. The other three control groups, namely, WT-C, KV-C, and KT-C control groups, received an equal volume of water via oral administration. Analysis of changes in body weight showed that mice in the KT-E group had significant loss of body weight compared to the control, KV-E, and WT-E groups. Behavioral analysis revealed that alcohol exposure significantly increased alcohol sensitivity in the KT-E group, whereas the WT-E, KV-E, and control groups developed ethanol tolerance. Aspartate transaminase (AST) levels in the KT-E group were significantly higher than those in the control, KV-E, and WT-E groups. The number of large and binucleated hepatocytes was significantly higher in the KT-E group than in the KV-E and WT-E groups. In addition, cytochrome P450 2E1 (CYP2E1) was over expressed in the central vein in the KT-E group when compared to the KV-E and WT-E groups. Our current findings indicate that AA supplementation in SMP30 KO mice can alleviate alcohol-induced liver damage by down regulating CYP2E1 expression. These results suggest that reduced CYP2E1 expression is a novel mechanism responsible for AA-induced reduction of ethanol-mediated oxidative stress.

Rumex acetosella Inhibits Platelet Function via Impaired MAPK and Phosphoinositide 3-Kinase Signaling

Objective:To examine the antiplatelet and antithrombotic activity of Rumex acetosella extract.Methods:Standard light aggregometry was used for platelet aggregation,intracellular calcium mobilization assessed using Fura-2/AM,granule secretion(ATP release)by luminometer,and fibrinogen binding to integrin α_(Ⅱb)β_(3) detected using flow cytometry.Western blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase(MAPK)and phosphoinositide 3-kinase(PI3K)/Akt signaling.Results:Rumex acetosella displayed the ability to inhibit platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin α_(Ⅱb)β_(3).Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation(all P<0.01).Conclusion:Rumex acetosella extract exhibits antiplatelet activity via modulating GPVI signaling,and it may protect against the development of platelet-related cardiovascular diseases.