The Aqueous Soluble Polyphenolic Fraction of Psidium guajava Leaves Exhibits Potent Anti-Angiogenesis and Anti-Migration Actions on DU145 Cells

The aqueous extract of Psidium guajava budding leaves (PE) bears an extremely high content of polyphenolic and isoflavonoids. Whether it could be used as an anti-tumor chemopreventive in view of anti-angiogenesis and anti-migration, we performed the assay methods including the MTT assay to examine the cell viability; the ELISA assay to test the expressions of VEGF, IL-6 and IL-8; the western blot analysis to detect TIMP-2; the gelatinolytic zymography to follow the expression of MMPs; the wound scratch assay to examine the migration capability; and the chicken chorioallantoic membrane assay to detect the suppressive angiogenesis. Results indicated that the IC50 of PE for DU145 cells was ∼0.57 mg ml−1. In addition, PE effectively inhibited the expressions of VEGF, IL-6 and IL-8 cytokines, and MMP-2 and MMP-9, and simultaneously activated TIMP-2 and suppressed the cell migration and the angiogenesis. Conclusively, PE potentially possesses a strong anti-DU145 effect. Thus, clinically it owns the potential to be used as an effective adjuvant anti-cancer chemopreventive

Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

Glutamat je glavni ekscitacijski neurotransmiter u središnjem živčanom sustavu. Izmjena je glutamata i cistina (sustav xc-) glavni poveznik mehanizma obrane od oksidacijskog stresa s prijenosom živčanih podražaja i promjenom ponašanja. Prekomjerna aktivacija ionotropnih receptora glutamata dovodi do odumiranja neurona; taj se proces zove ekscitotoksičnost. Oksidacijski je stres uzrokovan glutamatom glavni uzročnik neurodegenerativnih bolesti, poput moždane ishemije, Alzheimerove i Huntingtonove bolesti. Kurkuma ima širok spektar bioloških aktivnosti, poput zaštite živčanog sustava i neurokognitivnih sposobnosti. Kurkumin smanjuje oksidacijski stres i time ublažava posljedice ishemijsko-reperfuzijske ozljede leđne moždine, epileptične napadaje i gubitak neurona u hipokampusu. Stanice PC12 feokromocitoma štakora imaju mnoge korisne osobine koje omogućuju proučavanje neurozaštitnih i neurokognitivnih aktivnosti. Ovo je istraživanje provedeno radi utvrđivanja mogućnosti praćenja aktivnost kurkumina u zaštiti živčanih stanica pomoću modela stanica PC12 oštećenih glutamatom. Rezultati pokazuju da glutamat (u koncentraciji od 20 mM) pojačava izražaj glutation peroksidaze 1, glutation disulfida, utoka iona kalcija, proizvodnju dušikovog oksida, oslobađanje citokroma c, omjer proteina Bax/Bxl-2, aktivnost kaspaze-3, oslobađanje laktat dehidrogenaze, reaktivnih kisikovih spojeva, vodikovog peroksida i malondialdehida, te smanjuje izražaj glutationa, glutation reduktaze, superoksid dismutaze i katalaze, čime se pojačava stanična apoptoza. Kurkumin ublažava sve te negativne učinke, pa se može zaključiti da učinkovito štiti stanice PC12 od oksidacijskog stresa uzrokovanog glutamatom. Njegova se aktivnost zasniva na uklanjanju reaktivnih kisikovih i dušikovih spojeva pomoću glutationa te u matriksu mitohondrija.Glutamate is a major excitatory neurotransmitter present in the central nervous system. The glutamate/cystine antiporter system xc– connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer’s and Huntington’s disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin attenuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12) cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective effects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM) upregulated glutathione peroxidase 1, glutathione disulphide, Ca2+ influx, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H2O2, and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse effects. Conclusively, curcumin can effectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway

Structural Characteristics and Antioxidative Capability of the Soluble Polysaccharides Present in Dictyophora indusiata

Dictyophora indusiata (Vent. ex Pers.) Fish Phallaceae (Chinese name Zhu-Sūn, the bamboo fungi) has been used as a medicinal mushroom to treat many inflammatory, gastric and neural diseases since 618 AD in China. We hypothesize that the soluble polysaccharides (SP) present in D. indusiata and their monosaccharide profiles can act as an important role affecting the antioxidative capability, which in turn would influence the biological activity involving anti-inflammatory, immune enhancing and anticancer. We obtained six SP fractions and designated them as D1, a galactoglucan; D2, a galactan; D3, the isoelectrically precipitated riboglucan from 2% NaOH; D4, a myoinositol; D5 and D6, the mannogalactans. The total SP accounted for 37.44% w/w, their molecular weight (MW) ranged within 801–4656 kDa. D3, having the smallest MW 801 kDa, exhibited the most potent scavenging effect against the α,α-diphenyl-β-picrylhydrazyl, •OH−, and •O2− radicals, yielding IC50 values 0.11, 1.02 and 0.64 mg mL−1, respectively. Thus we have confirmed our hypothesis that the bioactivity of D. indusiata is related in majority, if not entirely, to its soluble polysaccharide type regarding the MW and monosaccharide profiles

Swimming Exercise Prevents Fibrogenesis in Chronic Kidney Disease by Inhibiting the Myofibroblast Transdifferentiation

BACKGROUND: The renal function of chronic kidney disease (CKD) patients may be improved by a number of rehabilitative mechanisms. Swimming exercise training was supposed to be beneficial to its recovery. METHODOLOGY/PRINCIPAL FINDINGS: Doxorubicin-induced CKD (DRCKD) rat model was performed. Swimming training was programmed three days per week, 30 or 60 min per day for a total period of 11 weeks. Serum biochemical and pathological parameters were examined. In DRCKD, hyperlipidemia was observed. Active mesangial cell activation was evidenced by overexpression of PDGFR, P-PDGFR, MMP-2, MMP-9, α-SMA, and CD34 with a huge amount collagen deposition. Apparent myofibroblast transdifferentiation implicating fibrogenesis in the glomerular mesangium, glomerulonephritis and glomeruloscelorosis was observed with highly elevated proteinuria and urinary BUN excretion. The 60-min swimming exercise but not the 30 min equivalent rescued most of the symptoms. To quantify the effectiveness of exercise training, a physical parameter, i.e. "the strenuosity coefficient" or "the myokine releasing coefficient", was estimated to be 7.154 × 10(-3) pg/mL-J. CONCLUSIONS: The 60-min swimming exercise may ameliorate DRCKD by inhibiting the transdifferentiation of myofibroblasts in the glomerular mesangium. Moreover, rehabilitative exercise training to rescue CKD is a personalized remedy. Benefits depend on the duration and strength of exercise, and more importantly, on the individual physiological condition

Anisotropic Diffusion Deviates Chicken Embryo Chorioallantoic Membrane Assay (CAM) to Reflect Inherent Therapeutic Behaviors

[[abstract]]Chorioallantoic membrane assay (CAM) has become a widely used tool for determination of anti-angiogenesis capability of many drugs including herbal extracts. Because varying results in same set of chicken embryos are often encountered, we developed the complex diffusion model that combined the Fick's second diffusion law, chemical–protein interaction (or binding) to explain the diffusion- or kinetic-limiting phenomena in egg white when performing CAM. In addition, we performed diffusion studies in egg white with Color Blue No. 1, Evans Blue, Color Red No. 40, and the aqueous extract of Psidium guajava budding leaves (PE) to support our model. Under same conditions, the diffusion coefficients of Blue No. 1, Evans Blue, Red No. 40, and PE were (2.0–2.8) × 10−9, (0.89–31) × 10−9, (2.8–12) × 10−9, and (7.0–21) × 10−9 m2 s−1, respectively, depending upon the distance diffused. Whilst at the interface of egg white and embryo (egg yolk), a site about 1 cm apart from the aeration sac, the percent concentration reached only 10.5, 3.0, 3.6, and 2.2% of the original applied medicine, respectively. We conclude that CAM could only serve as a preliminary screening tool for angiogenesis, because the anisotropic diffusion in egg white affects greatly the effective dosages of medicines tested

Mathematical Differentiation to Reveal the Fermentative Characteristics of Lactobacillus helveticus ATCC 15009

[[abstract]]Fermentative characteristics of Lactobacillus helveticus ATCC15009 were investigated by varying size of initial inocula, the pH values of fermentation, respectively by a pH-controlled and a pH-uncontrolled processes at 38�C. The first and the second differentiation of lactic acid production (P vs. t) and growth (X vs. t) data were taken. Their maximum peaks and reflection points were solved, whence the relationship of the model was derived. Alternatively, Henderson-Hasselbalch equation was utilized to criticize the dependencies of the feed back inhibition on the total lactate cncentration and pH. Results revealed that in lactose medium lactic acid production rate (dP/dt) of L. helveticus B1075 obeys the growth ( dX/dt) associated model, dP/dt = dX/dt. Furthermore, the non-competitive end product inhibition is entirely dependent on the total lactate concentration

Exercise Ameliorates Renal Cell Apoptosis in Chronic Kidney Disease by Intervening in the Intrinsic and the Extrinsic Apoptotic Pathways in a Rat Model

We hypothesized that doxorubicin (DR) induced chronic kidney disease (CKD) could trigger the intrinsic and the extrinsic renal cell apoptotic pathways, while treadmill exercise could help prevent adverse effects. Male Sprague-Dawley rats were subjected to treadmill running exercise at a speed of 30 m/min, 30 or 60 min/day, 3 times per week, for a total period of 11 weeks. The physiological and biochemical parameters were seen substantially improved (DR-CKD control, 30 min, 60 min exercise): the ratio of kidney weight/body weight (0.89, 0.74, and 0.72); the WBC (1.35, 1.08, and 1.42 × 104 cells/μL); RBC (5.30, 6.38, and 6.26 × 106 cells/μL); the platelet count (15.1, 12.8, and 11.3 × 105/μL); serum cholesterol (659, 360, and 75 mg/dL); serum triglyceride (542, 263, and 211 mg/dL); BUN (37, 25, and 22 mg/dL). Bcl-2 and intramitochondrial cytochrome c were upregulated, while the levels of Bax, SOD, MDA, cleaved caspases 9, 3, 8, 12, and calpain were all downregulated in DRCKD groups with exercise. CHOP (GADD153) and GRP78 were totally unaffected. FAS (CD95) was only slightly suppressed in the 60 min exercise DRCKD group. Conclusively, exercise can ameliorate CKD through the regulation of the intrinsic and extrinsic apoptosis pathways. The 60 min exercise yields more beneficial effect than the 30 min counterpart