METHODS: MEMC and its fractions were subjected to HPLC analysis to identify and quantify the presence of its phyto-constituents. The mechanism of gastroptotection of EAF was further investigated using pylorus ligation-induced gastric lesion rat model (100, 250, and 500 mg/kg). Macroscopic analysis of the stomach, evaluation of gastric content parameters such as volume, pH, free and total acidity, protein estimation, and quantification of mucus were carried out. The participation of nitric oxide (NO) and sulfhydryl (SH) compounds was evaluated and the superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the ethanol induced stomach tissue homogenate was determined.
RESULTS: HPLC analysis confirmed the presence of quercetin and gallic acid in EAF. In pylorus-ligation model, EAF significantly (p <0.001) prevent gastric lesion formation. Volume of gastric content and total protein content reduced significantly (p
MATERIALS AND METHODS: The MEZZ was prepared by macerating oven-dried (50 degrees C) powdered rhizomes (1.2 kg) of Z. zerumbet in 80% methanol in a ratio of 1:20 (w/v) for 48 h. The supernatant was collected, filtered and evaporated to dryness under reduced pressure (50 degrees C) yielding approximately 21.0 g of the crude dried extract. The crude dried extract was stored at -20 degrees C prior to use and was dissolved in normal saline (0.9% NaCl) immediately before administration at concentrations required to produce doses of 25, 50 and 100 mg/kg.
RESULTS: All dosages of MEZZ showed significant (p < 0.05) antiedema activity when assessed using the carrageenan-induced paw edema test and the cotton-pellet-induced granuloma test. The MEZZ exhibited significant (p < 0.05) antinociceptive activity when assessed by the writhing, hot plate and formalin tests. Pretreatment with naloxone (5 mg/kg) significantly decreased the latency of discomfort produced by the 100 mg/kg dose of MEZZ in the hot plate test.
CONCLUSION: MEZZ produced antiinflammatory and antinociceptive activities which may involve the inhibition of bradykinin-, prostaglandin-, histamine- and opioid-mediated processes.
MATERIAL AND METHODS: The composition of Danshen water extract was determined using (High Performance Liquid Chromatography (HPLC). Then Thioflavin T assay was used to determined if Danshen water extract could prevent the aggregation of amyloid-β peptide (Aβ). Alzheimer's disease C.elegans model was used to determine the effect of Danshen water extract. Finally, the reactive oxygen species (ROS) was determined using the 2,7-dichlorofuorescein diacetate method.
RESULTS: In this study, we found that standardized Danshen water extract that contains danshensu (1.26%), salvianolic acid A (0.35%) and salvianolic acid B (2.21%) are able to bind directly to Aβ and prevents it from aggregating. The IC50 for the inhibition of Aβ aggregation by Danshen water extract was 0.5 mg/ml. In the AD model of C.elegans, Danshen water extract managed to alleviates the paralysis phenotype. Furthermore, the administration of Danshen water extract displayed antioxidant properties toward the Aβ-induced oxidative stress.
CONCLUSIONS: AD is a widespread neurodegenerative disease attributed to the accumulation of extracellular plaques comprising Aβ. Danshen water extract could significantly reduce the progress of paralysis in the AD model of C. elegans, showing promising results with its antioxidant properties. It can be concluded that Danshen water extract could potentially serve as a therapeutic for AD.
APPROACH AND RESULTS: Human atherosclerotic plaques showed marked mitochondrial dysfunction, manifested as reduced mtDNA copy number and oxygen consumption rate in fibrous cap and core regions. Vascular smooth muscle cells derived from plaques showed impaired mitochondrial respiration, reduced complex I expression, and increased mitophagy, which was induced by oxidized low-density lipoprotein. Apolipoprotein E-deficient (ApoE-/-) mice showed decreased mtDNA integrity and mitochondrial respiration, associated with increased mitochondrial reactive oxygen species. To determine whether alleviating mtDNA damage and increasing mitochondrial respiration affects atherogenesis, we studied ApoE-/- mice overexpressing the mitochondrial helicase Twinkle (Tw+/ApoE-/-). Tw+/ApoE-/- mice showed increased mtDNA integrity, copy number, respiratory complex abundance, and respiration. Tw+/ApoE-/- mice had decreased necrotic core and increased fibrous cap areas, and Tw+/ApoE-/- bone marrow transplantation also reduced core areas. Twinkle increased vascular smooth muscle cell mtDNA integrity and respiration. Twinkle also promoted vascular smooth muscle cell proliferation and protected both vascular smooth muscle cells and macrophages from oxidative stress-induced apoptosis.
CONCLUSIONS: Endogenous mtDNA damage in mouse and human atherosclerosis is associated with significantly reduced mitochondrial respiration. Reducing mtDNA damage and increasing mitochondrial respiration decrease necrotic core and increase fibrous cap areas independently of changes in reactive oxygen species and may be a promising therapeutic strategy in atherosclerosis.