PURPOSE: To explore the underlying mechanism of AP in exerting anti-fatigue effects.
METHODS: In this study, we developed a chronic sleep deprivation-induced fatigue model and used physiological, hematological, and biochemical indicators to evaluate the anti- fatigue efficacy of AP. Additionally, a multi-omics approach was employed to reveal the anti-fatigue mechanisms of AP from the perspective of microbiome, metabolome, and proteome.
RESULTS: The detection of physiology, hematology and biochemistry index indicated that AP markedly alleviate mice fatigue state induced by sleep deprivation. The 16S rRNA sequencing showed the AP promoted the abundance of probiotics (Odoribacter, Dubosiella, Marvinbryantia, and Eubacterium) and suppressed harmful bacteria (Ruminococcus). On the other hand, AP was found to regulate the expression of colonic proteins, such as increases of adenosine triphosphate (ATP) synthesis and mitochondrial function related proteins, including ATP5A1, ATP5O, ATP5L, ATP5H, NDUFA, NDUFB, NDUFS, and NDUFV. Serum metabolomic analysis revealed AP upregulated the levels of anti-fatigue amino acids, such as taurine, leucine, arginine, glutamine, lysine, and l-proline. Hepatic proteins express levels, especially tricarboxylic acid (TCA) cycle (CS, SDHB, MDH2, and DLST) and redox-related proteins (SOD1, SOD2, GPX4, and PRDX3), were significantly recovered by AP administration. Spearman correlation analysis uncovered the strong correlation between microbiome, metabolome and proteome, suggesting the anti-fatigue effects of AP is attribute to the energy homeostasis and redox balance through gut-liver axis.
CONCLUSION: AP increased colonic ATP production and improve mitochondrial function by regulating gut microbiota, and further upregulated anti-fatigue amino acid levels in the blood. Based on the gut-liver axis, AP upregulated the hepatic tricarboxylic acid cycle and oxidoreductase-related protein expression, regulating energy homeostasis and redox balance, and ultimately exerting anti-fatigue effects. This study provides insights into the anti-fatigue mechanisms of AP, highlighting its potential as a therapeutic agent.
MATERIAL AND METHODS: Thirty Sprague Dawley rats (3-monthold, 200 to 300 gm) were randomly divided into six groups, namely control (C), 4 weeks diabetes mellitus (DM1), 8 weeks DM (DM2) and three DM1 groups (VD1, VD2, and VD3) who received Vitamin D doses of 0.125, 0.25 and 0.50 μg/kg BW, respectively. After 4 weeks, daily VD was administered intraperitoneally for 30 days. Lung tissues were taken for IL- 6, MCP-1, NFKB and CD68 mRNA expression analysis and paraffin embedding. Immunohistochemical staining against CD68 and MCP-1 was conducted. Data were analysed using one-way ANOVA. p < 0.05 was considered statistically significant.
RESULTS: DM2 group represented significantly higher IL6, MCP1, NFKB and CD68 mRNA expression than Control group (p < 0.05). Meanwhile, VD2 and VD3 groups revealed significantly lower mRNA expression of IL-6, MCP1, NFKB and CD68 than DM2 (p < 0.05). Immunostaining revealed the spreading of MCP1 protein expression in lung tissue along with macrophage infiltration in the DM2 group, which was reduced in the VD2 and the VD3 groups.
CONCLUSION: VD shows a protective effect on diabetesinduced lung damage by regulating inflammation factors.
MATERIALS AND METHODS: This was a randomised post-testonly study. A total of 28 rats were assigned into four groups: Group 1 is control group (C), samples had bile duct ligation and UDCA monotherapy 20 mg; Group 2, bile duct ligation + UDCA 10 mg + glutathione 10 mg (P1); Group 3, bile duct ligation + UDCA 20 mg + glutathione 15 mg (P2); Group 4, bile duct ligation + UDCA 30 mg + glutathione 20 mg (P3). Serum AST, ALT, ALP activity, total, direct and indirect bilirubin were collected. Shapiro-Wilk test was used for the normality test. All groups' data were compared using Kruskall-Wallis and Mann-Whitney tests.
RESULTS: There was a significant difference in the ALP level in all rats and between the C and P2 groups. ALP level of all groups decreased significantly compared to the control group. Combination therapy group showed lower bilirubin levels. ALT levels significantly differed between the C-P1, P1-P2, and P1-P3 groups.
CONCLUSION: UDCA-GSH therapy improves liver function in BDL rats' models compared to UDCA monotherapy.
MATERIALS AND METHODS: TGBII was performed in male Wistar rats (3 to 5 months, 150 to 300 g) which underwent bilateral common carotid artery occlusion (BCCAO) for 20 minutes, then reperfused for 10 days (BCCAO group, n = 6). Two groups of BCCAO were treated with intraperitoneal injection of calcitriol 0.125 μg/kgBW (VD1 group) and 0.5 μg/kgBW (VD2 group). The spatial memory function was tested using a probe test with Morris water maze (MWM). mRNA expression of BAX and SOD2 were assessed by the RT-PCR method. Meanwhile, immunohistochemical staining was used for identification of SOD2 protein. Statistical analysis is tested using one-way ANOVA followed by post-hoc LSD.
RESULTS: MWM showed a shorter duration in target quadrant of BCCAO group than the SO group, which is associated with BAX upregulation and SOD2 downregulation. The VDtreated groups had longer duration probe test compared to BCCAO. Furthermore, VD-treated groups had a longer duration in probe test with lower mRNA expression of BAX and higher expression of SOD2. However, there was no significant difference in VD1 and VD2. Immunostaining showed a reduced SOD2 signal in pyramidal cell of CA1 area in BCCAO group and ameliorated in VD1 and VD2 groups.
CONCLUSION: Vitamin D ameliorates memory function and attenuates oxidative stress and apoptosis in the TGBII model.
Methods: Using a pilocarpine-induced epileptic mouse model, sensory-motor and visual cortical slices were prepared, and the whole-cell patch clamp technique was used to record spontaneous inhibitory post-synaptic currents (sIPSCs).
Results: The primary finding was that the mean amplitude of sIPSC from the sensory-motor cortex increased significantly in epileptic mice when the recording pipette contained MK-801 compared to control mice, whereas the mean sIPSC frequency was not significantly different, indicating that post-synaptic mechanisms are involved. However, there was no significant pre-synaptic inhibition through preNMDARs in the acute brain slices from pilocarpine-induced epileptic mice.
Conclusion: In the acute case of epilepsy, a compensatory mechanism of post-synaptic inhibition, possibly from ambient GABA, was observed through changes in the amplitude without significant changes in the frequency of sIPSC compared to control mice. The role of preNMDAR-mediated inhibition in epileptogenesis during the chronic condition or in the juvenile stage warrants further investigation.
Methods: Mice (n = 48) were fed high-fat diet (HFD) for 25 weeks to induce obesity, after which half were maintained on HFD and half switched to low-fat diet (LFD)while they were given normal water (H2O) or 0.1% (w/v) SCE in water at week 0-4 which was increased to 1% (w/v) at week 5-9. Effects of treatment with SCE were compared between HFDH2O, HFDSCE, LFDH2O and LFDSCE groups. Respiratory exchange ratios (RER) were measured at weeks 0, 5 and 10. Food, water intake and body weight were measured weekly. Plasma lipid profile and organ weights were determined at week 10.
Results: SCE had significantly reduced RER at week 9 (P = 0.011). Food intake, body weight, and abdominal adipose tissue weight were not altered by SCE at weeks 5 and 10. However, significant increase in plasma and liver cholesterol (P < 0.050) was observed.
Conclusion: Our findings suggest that SCE induced lipolysis and body fat oxidation and increased energy expenditure. Further studies in other animal models should be done to confirm the consistency of these results.
METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33(-/-) mice than in WT mice. After 8-weeks, IL-33(-/-) mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33(-/-) mice than those in WT mice.
CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.
Methods: Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.
Results: Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.
Conclusion: Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.
Materials and methods: Hepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied.
Results: Histopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents.
Conclusion: Cabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects.
METHODS: Gerbils, 5-7 weeks old were infected by PbA via intraperitoneal injection of 1 × 106 (0.2 mL) infected red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red blood cell count and body temperature changes in both control and infected groups were monitored over a duration of 13 days. RNA was extracted from the brain, spleen and whole blood to assess the immune response to PbA infection. Organs including the brain, spleen, heart, liver, kidneys and lungs were removed aseptically for histopathology.
RESULTS: Gerbils were susceptible to PbA infection, showing significant decreases in the hemoglobin concentration, RBC counts, body weights and body temperature, over the course of the infection. There were no neurological signs observed. Both pro-inflammatory (IFNγ and TNF) and anti-inflammatory (IL-10) cytokines were significantly elevated. Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were observed in the organs, using routine light microscopy and in situ hybridization.
CONCLUSION: Gerbils may serve as a good model for severe malaria to further understand its pathogenesis.