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GreenMedInfo

PMID:  Oncotarget. 2017 Nov 28 ;8(61):102989-103003. Epub 2017 Aug 3. PMID: 29262539Abstract Title:  mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α.Abstract:  We investigated the role of HIF-1α in the mitigation of cisplatin-induced nephrotoxicity by(PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular damage in cisplatin-treated rats and which were exacerbated by 2ME2. Renal tissues from PNS-treated rats showed increased HIF-1α mRNA and nuclear localized HIF-1α protein. Moreover, PNS treatment increased BNIP3 mRNA as well as LC3-II, BNIP3 and Beclin-1 proteins and the LC3-II/LC3-I ratio in rat renal tissues. This suggested that PNS treatment enhanced HIF-1α, which in turn increased autophagy. This was confirmed in transmission electron micrographs of renal tissues that showed autophagosomes in PNS-treated renal tissues. These findings demonstrate that PNS mitigates cisplatin-induced nephrotoxicity by enhancing mitophagy via a HIF-1α/BNIP3/Beclin-1 signaling pathway.

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Author: greenmedinfo
Posted: February 22, 2018, 7:58 pm
PMID:  Aging Dis. 2017 Dec ;8(6):721-739. Epub 2017 Dec 1. PMID: 29344413Abstract Title:  Therapeutic Potential and Cellular Mechanisms of Panax Notoginseng on Prevention of Aging and Cell Senescence-Associated Diseases.Abstract:  Owing to a dramatic increase in average life expectancy, most countries in the world are rapidly entering an aging society. Therefore, extending health span with pharmacological agents targeting aging-related pathological changes, are now in the spotlight of gerosciences.(Burk.) F. H. Chen, a species of the genus Panax, has been called the"Miracle Root for the Preservation of Life,"and has long been used as a Chinese herb with magical medicinal value.has been extensively employed in China to treat microcirculatory disturbances, inflammation, trauma, internal and external bleeding due to injury, and as a tonic. In recent years, with the deepening of the research pharmacologically, many new functions have been discovered. This review will introduce its pharmacological function on lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer properties, aiming to lay the ground for fully elucidating the potential mechanisms ofanti-aging effect to promote its clinical application.

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Author: greenmedinfo
Posted: February 22, 2018, 7:17 am
PMID:  BMC Complement Altern Med. 2018 Feb 5 ;18(1):51. Epub 2018 Feb 5. PMID: 29402262Abstract Title:  Effects of Panax notoginseng saponins on severe acute pancreatitis through the regulation of mTOR/Akt and caspase-3 signaling pathway by upregulating miR-181b expression in rats.Abstract:  BACKGROUND: In China, Panax notoginseng has been used to treat oxidative stress-related diseases for a long time. Panax notoginseng saponins is an extract from Panax notoginseng Ledeb. Its therapeutic potential is related to antioxidant activity, but related mechanisms are still unclear. The study aims to assess the protection effects of Panax notoginseng saponins in the taurocholate-induced rat model of acute pancreatitis (AP) and explore underlying mechanisms.METHODS: A rat model of severe acute pancreatitis (SAP) was established in rats induced with taurocholate. Panax notoginseng saponins was firstly administered in the treatment group via intravenous injection. After 2 h, taurocholate administration was performed. After 24 h, the expression levels of miR-181b, Beclin1, LC3-II, Akt and mTOR from pancreas tissues were measured by Western Blotting and RT-PCR. Then the expression levels of Caspase-3 and Blc-2 were determined by immunohistochemistry. Apoptosis was assessed by the TUNEL assay. Amylase and lipase in serum were determined by ELISA and pancreatic water contents in pancreatic tissue were measured. After eosin and hematoxylin staining, the histologic analysis was performed.RESULTS: After SAP induction by taurocholate and the treatment with Panax notoginseng saponins for 24 h, we detected the up-regulated miR-181b, the reduced Bcl-2 expression, the increased activity of mTOR/Akt, the blocked Beclin1 and LC3-II expressions, and the enhanced Caspase-3 expression. Serum lipase and amylase levels were significantly decreased in the treatment group of Panax notoginseng saponins compared to the control group. Histological analysis results verified the attenuation effects of Panax notoginseng saponins on taurocholate-induced pancreas injury, apoptosis, and autophagy.CONCLUSION: By up-regulating the miR-181b expression level, Panax notoginseng saponins significantly reduced taurocholate-induced pancreas injury and autophagy and increased apoptosis. The significant protection effects of Panax notoginseng saponins suggested its potential in treating taurocholate induced-acute pancreatitis.

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Author: greenmedinfo
Posted: February 22, 2018, 7:06 am
PMID:  Cell Prolif. 2018 Feb 19. Epub 2018 Feb 19. PMID: 29457293Abstract Title:  Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A.Abstract:  OBJECTIVES: Ginsenoside Rh2 (GRh2) has demonstrative therapeutic effects on a variety of diseases, including some tumours. However, the effects of GRh2 on prostate cancer (PC) cell growth remain unknown, and were, thus, addressed in the present study.MATERIALS AND METHODS: PC3 and DU145 PC cell lines were exposed to GRh2. Cell proliferation was assessed in an MTT assay and by BrdU incorporation. Apoptosis of the cells were assessed by TUNEL staining. Total RNA was assessed by RT-qPCR. Protein levels were assessed by Western blotting. Bioinformatics and dual luciferase reporter assay were applied to determine the functional binding of miRNA to mRNA of target gene.RESULTS: GRh2 dose-dependently decreased PC cell proliferation, but did not alter cell apoptosis. Mechanistically, GRh2 dose-dependently increased the protein, but not mRNA of a cell-cycle suppressor CDKN1A in PC cells, suggesting the presence of microRNA (miRNA)-mediated protein translation control of CDKN1A by GRh2. In all candidate miRNAs that bind to 3'-UTR of CDKN1A, miR-4295 was specifically found to be suppressed dose-dependently by GRh2 in PC cells. Moreover, miR-4295 bound CDKN1A to suppress its protein translation. Furthermore, cell proliferation in PC cells that overexpressed miR-4295 did not alter in response to GRh2.CONCLUSIONS: GRh2 may inhibit PC cell growth through suppression of microRNA-4295 that activates CDKN1A.

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Author: greenmedinfo
Posted: February 22, 2018, 6:53 am
PMID:  Brain Res. 2018 Feb 17. Epub 2018 Feb 17. PMID: 29462607Abstract Title:  Ascorbic acid ameliorates lead-induced apoptosis in the cerebellar cortex of developing rats.Abstract:  We investigated the effects of the gestational administration of lead (Pb) and ascorbic acid on cerebellar development. Pregnant female rats were randomly assigned to the control, Pb, or Pb plus ascorbic acid (PA) groups; six offspring per cage were randomly selected for analysis. Compared to the control group, fewer Purkinje cells were observed in the Pb-exposed pups at postnatal day 21. However, co-administrating Pb and ascorbic acid inhibited the Pb-induced reduction in Purkinje cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, which detected DNA fragmentation in the dying cells, showed more TUNEL-positive cells in the Pb group, while co-treatment with Pb and ascorbic acid mitigated the Pb-induced cellular degeneration. Using immunohistochemistry and immunoblotting, we additionally found that Pb exposure induced a rise in the apoptotic factor Bax in the cerebellum, while Pb plus ascorbic acid treatment ameliorated this Bax induction. Since, Pb competes with the iron in the cell and the accumulation of free iron triggers oxidative stress, we performed iron staining, which revealed that ascorbic acid prevented the Pb-induced rises in iron-reactive cells and iron-reactivity. The anti-oxidant enzyme manganese-dependent superoxide dismutase showed change patterns that were similar to those of iron in the cerebellum. Finally, the pups' blood Pb levels were highest in the Pb group but were reduced in the PA group. Our findings suggest that ascorbic acid effectively ameliorates Pb-induced apoptosis and oxidative stress in the cerebellum. The present results imply that ascorbic acid treatment during pregnancy may protect against Pb-mediated developmental impairments in the cerebellum.

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Author: greenmedinfo
Posted: February 22, 2018, 6:39 am
PMID:  Endocrinology. 2018 Feb 7. Epub 2018 Feb 7. PMID: 29425287Abstract Title:  Perinatal bisphenol A exposure increases atherosclerosis in adult male PXR-humanized mice.Abstract:  Bisphenol A (BPA) is a base chemical used extensively in numerous consumer products, and human exposure to BPA is ubiquitous. Higher BPA exposure has been associated with increased risk of atherosclerosis and cardiovascular disease (CVD) in multiple human population-based studies, but the underlying mechanisms responsible for the associations remain elusive. We previously reported that BPA activates the xenobiotic receptor pregnane X receptor (PXR) which has pro-atherogenic effects in animal models. Since BPA is a potent agonist for human PXR but does not affect rodent PXR activity, a suitable PXR-humanized Apolipoprotein E-deficient (huPXR•ApoE-/-) mouse model was developed to study BPA's atherogenic effects, and chronic BPA exposure indeed increased atherosclerosis in huPXR•ApoE-/- mice. Here we report that BPA exposure can also activate human PXR signaling in the heart tubes of huPXR•ApoE-/- embryos, and perinatal BPA exposure exacerbated atherosclerosis in adult male huPXR•ApoE-/- offspring. However, atherosclerosis development in female offspring was not affected by perinatal BPA exposure. Perinatal BPA exposure did not affect plasma lipid levels but increased aortic and atherosclerotic lesional fatty acid transporter CD36 expression in male huPXR•ApoE-/- offspring. Mechanistically, PXR epigenetically regulated CD36 expression by increasing H3K4me3 levels and decreasing H3K27me3 levels in the CD36 promoter in response to perinatal BPA exposure. Findings from this study contribute to our understanding of theassociation between BPA exposure and increased atherosclerosis or CVD risk in humans, and activation of human PXR should be taken into consideration for future BPA risk assessment.

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Author: greenmedinfo
Posted: February 22, 2018, 6:24 am
PMID:  Biomed Pharmacother. 2018 Feb 8 ;100:213-220. Epub 2018 Feb 8. PMID: 29428670Abstract Title:  Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice.Abstract:  Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of an unknown etiology, glucocorticoid therapy is currently recognized as an effective treatment for AIH, but conventional application and patient compliance are both hindered by its side effects. The exploration of the AIH pathogenesis and the searching for the new candidate drugs that exert potential activity and low toxicity are urgently needed. Pomegranate peel extract (PoPx) is a natural extract of Punica granatum and has been reported to have anti-inflammatory and antioxidative properties. The present study aimed to clarify the effect of PoPx on the concanavalin A (ConA)-induced autoimmune hepatitis in a mouse model that is well established at 12h after tail vein injection with a dose of 20 mg/kg of ConA. C57BL/6 female mice were pretreated with PoPx (250 mg/kg, once daily for 3 days) followed by a ConA challenge. Pretreatment with PoPx significantly alleviated ConA-induced liver injury by down-regulating the levels of plasma alanine transaminase (ALT), aspartate transaminase (AST) and cytokine, including TNF-α, interferon (IFN) -γ and interleukin (IL)-6. Moreover, liver hematoxylin and eosin (H&E) staining displayed a lighter inflammatory infiltration around the portal area in the PoPx-pretreated mice. In addition, the flow cytometry (FCM) data showed that the immune response in the liver was died down in the PoPx-pretreated condition. Specially, pretreatment with PoPx reduced the infiltration of activated CD4and CD8T cells in the liver. Taken together, these findings contributed to a better understanding of the actions of PoPx against acute AIH and indicated that PoPx might be a potential compound in treating T cell-mediated autoimmune liver injury.

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Author: greenmedinfo
Posted: February 22, 2018, 5:48 am
PMID:  Nutr Neurosci. 2018 Feb 13:1-6. Epub 2018 Feb 13. PMID: 29433376Abstract Title:  Pomegranate supplementation improves cognitive and functional recovery following ischemic stroke: A randomized trial.Abstract:  OBJECTIVES: We tested whether supplementing with pomegranate polyphenols can enhance cognitive/functional recovery after stroke.METHODS: In this parallel, block-randomized clinical trial, we administered commercially-available pomegranate polyphenol or placebo pills twice per day for one week to adult inpatients in a comprehensive rehabilitation setting starting approximately 2 weeks after stroke. Pills contained 1 g of polyphenols derived from whole pomegranate, equivalent to levels in approximately 8 oz of juice. Placebo pills were similar to the pomegranate pills except that they contained only lactose. Of the 163 patients that were screened, 22 were eligible and 16 were randomized (8 per group). We excluded one subject per group from the neuropsychological analyses since they were lost to follow-up, but we included all subjects in the analysis of functional data since outcome data were available. Clinicians and subjects were blinded to group assignment. Neuropsychological testing (primary outcome:Repeatable Battery for the Assessment of Neuropsychological Status) and functional independence scores were used to determine changes in cognitive and functional ability.RESULTS: Pomegranate-treated subjects demonstrated more neuropsychological and functional improvement and spent less time in the hospital than placebo controls.DISCUSSION: Pomegranate polyphenols enhanced cognitive and functional recovery after stroke, justifying pursuing larger clinical trials.

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Author: greenmedinfo
Posted: February 22, 2018, 5:29 am
PMID:  Curr Clin Pharmacol. 2018 Jan 3. Epub 2018 Jan 3. PMID: 29299989Abstract Title:  Curcuminoids plus piperine modulate adipokines in type 2 diabetes mellitus.Abstract:  OBJECTIVE: Curcumin is a naturally occurring polyphenol derived from tumeric that has been reported to have anti-inflammatory properties with effects on adipokine and ghrelin levels. Adiponectin, leptin and ghrelin modulate energy homeostasis but each have modulatory effects on inflammatory cytokines and the immune system. Therefore this analysis was performed to investigate the effect of curcumin on adiponectin, leptin and ghrelin.METHODS: A double blind randomised control trial comparing curcumin 1000mg with 10mg of piperine daily to placebo over a 12 week period. 118 patients with type 2 diabetes were recruited of whom 50 control and 50 active subjects completed the trial. Adiponectin, leptin, ghrelin and tumor necrosis factor-α (TNF-α) were measured at baseline and 12 weeks.RESULTS: Between group comparison of the magnitude of changes showed serum levels of leptin (p

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Author: greenmedinfo
Posted: February 22, 2018, 5:09 am
PMID:  Iran J Basic Med Sci. 2017 Nov ;20(11):1227-1231. PMID: 29299200Abstract Title:  Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.Abstract:  Objectives: In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue.Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies.Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats.Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

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Author: greenmedinfo
Posted: February 22, 2018, 4:56 am
PMID:  Oncogene. 2018 Jan 18. Epub 2018 Jan 18. PMID: 29348462Abstract Title:  Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC by targeting GSTP1.Abstract:  TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1(also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from Piper longum L., synergizes with APR-246 to selectively induce apoptosis and autophagic cell death in HNSCC cells, whereas primary and immortalized mouse embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin keratinocytes (HaCat) are spared from the damage by the co-treatment. Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation-independent. Instead, we demonstrated that glutathione S-transferase pi 1 (GSTP1), a GST family member that catalyzes the conjugation of GSH with electrophilic compounds to fulfill its detoxification function, is highly expressed in HNSCC tissues. Administration of PL and APR-246 significantly suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre-treatment with antioxidant N-acetyl-L-cysteine (NAC) abrogates the ROS elevation and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR-246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are selectively sensitive to the combination of PL and APR-246 due to a remarkably synergistic effect of the co-treatment in the induction of ROS by suppression of GSTP1.

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Author: greenmedinfo
Posted: February 22, 2018, 4:32 am
PMID:  Int J Oncol. 2018 Mar ;52(3):1011-1022. Epub 2018 Jan 31. PMID: 29393418Abstract Title:  Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis.Abstract:  Pancreatic cancer is one of the most lethal types of cancer with a mortality rate of almost 95%. Treatment with current chemotherapeutic drugs has limited success due to poor responses. Therefore, the development of novel drugs or effective combination therapies is urgently required. Piperlongumine (PL) is a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular reactive oxygen species (ROS) levels. In the present study, we demonstrated that PL induced cancer cell death through, at least in part, the induction of ferroptosis, as the cancer cell-killing activity was inhibited by the antioxidant, N‑acetylcysteine, ferroptosis inhibitors (ferrostatin‑1 and liproxstatin‑1) and the iron chelator, deferoxamine (DFO), but not by the apoptosis inhibitor, Z-VAD-FMK, or the necrosis inhibitor, necrostatin‑1. Cotylenin A (CN‑A; a plant growth regulator) exhibits potent antitumor activities in several cancer cell lines, including pancreatic cancer cell lines. We found that CN‑A and PL synergistically induced the death of pancreatic cancer MIAPaCa‑2 and PANC‑1 cells for 16 h. CN‑A enhanced the induction of ROS by PL for 4 h. The synergistic induction of cell death was also abrogated by the ferroptosis inhibitors and DFO. The present results revealed that clinically approved sulfasalazine (SSZ), a ferroptosis inducer, enhanced the death of pancreatic cancer cells induced by PL and the combined effects were abrogated by the ferroptosis inhibitors and DFO. SSZ further enhanced the cancer cell-killing activities induced by combined treatment with PL plus CN‑A. On the other hand, the synergistic induction of cell death by PL and CN‑A was not observed in mouse embryonic fibroblasts (MEFs), and SSZ did not enhance the death of MEFs induced by PL plus CN‑A. These results suggest that the triple combined treatment with PL, CN‑A and SSZ is highly effective against pancreatic cancer.

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Author: greenmedinfo
Posted: February 22, 2018, 4:20 am
PMID:  Oncol Lett. 2018 Feb ;15(2):1789-1798. Epub 2017 Nov 24. PMID: 29399195Abstract Title:  Piperlongumine inhibits cancer stem cell properties and regulates multiple malignant phenotypes in oral cancer.Abstract:  Piperlongumine (PL), a natural product of, inhibits multiple malignant phenotypes. Therefore, the present study examined whether PL suppresses cancer stemness in oral cancer. The cellular effects of PL were determined by examining alterations in tumor sphere formation, cell migration, invasion, proliferation ability, chemosensitivity and radiosensitivity. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were performed in order to determine molecular expression levels. The present study revealed that PL inhibited cancer stem cell-forming ability and suppressed the expression of the stemness-related transcription factors SRY-Box 2, POU class 5 homeobox 1, and Nanog homeobox. However, it increased the expression of the differentiation marker cytokeratin 18. PL also suppressed cell migration and invasion, resulting in the elimination of the epithelial-mesenchymal transition. Furthermore, PL increased chemo- and radiosensitivity and suppressed tumor growthand. The results of the present study suggested that PL inhibits malignant phenotypes via the suppression of cancer stemness in oral cancer. Thus, PL may serve as an effective therapeutic agent for oral cancer.

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Author: greenmedinfo
Posted: February 22, 2018, 4:10 am
PMID:  Autophagy. 2018 Feb 13:1-17. Epub 2018 Feb 13. PMID: 29433359Abstract Title:  Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models.Abstract:  : Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is caused by genetics, environmental factors and aging, with few treatments currently available. Apoptosis and macroautophagy/autophagy play critical roles in PD pathogenesis; as such, modulating their balance is a potential treatment strategy. BCL2 (B cell leukemia/lymphoma 2) is a key molecule regulating this balance. Piperlongumine (PLG) is an alkaloid extracted from Piper longum L. that has antiinflammatory and anticancer effects. The present study investigated the protective effects of PLG in rotenone-induced PD cell and mouse models. We found that PLG administration (2 and 4 mg/kg) for 4 wk attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra induced by oral administration of rotenone (10 mg/kg) for 6 wk. PLG improved cell viability and enhanced mitochondrial function in primary neurons and SK-N-SH cells. These protective effects were exerted via inhibition of apoptosis and induction of autophagy through enhancement of BCL2 phosphorylation at Ser70. These results demonstrate that PLG exerts therapeutic effects in a rotenone-induced PD models by restoring the balance between apoptosis and autophagy.ABBREVIATIONS: 6-OHDA, 6-hydroxydopamine; ACTB, actin, beta; BafA1, bafilomycin A; BAK1, BCL2-antagonist/killer 1; BAX, BCL2-associated X protein; BCL2, B cell leukemia/lymphoma2; BECN1, Beclin 1, autophagy related; CoQ10, coenzyme Q; COX4I1/COX IV, cytochrome c oxidase subunit 4I1; CsA, cyclosporine A; ED50, 50% effective dose; FITC, fluorescein isothiocyanate; GFP, green fluorescent protein; HPLC, high-performance liquid chromatography; JC-1, tetraethylbenz-imidazolylcarbocyanine iodide; LC3, microtubule-associated protein 1 light chain3; LC-MS/MS, liquid chromatography-tandem mass spectrometry; LDH, lactate dehydrogenase; l-dopa, 3, 4-dihydroxyphenyl-l-alanine; MAPK8/JNK1, mitogen-activated protein kinase 8; MMP, mitochondrial membrane potential; mPTP, mitochondrial permeability transition pore; mRFP, monomeric red fluorescent protein; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NFE2L2/NRF2, nuclear factor, erythroid derived 2, like 2; PD, Parkinson disease; PLG, piperlongumine; pNA, p-nitroanilide; PI, propidium iodide; PtdIns3K, phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol-3-phosphate; PTX, paclitaxel; Rap, rapamycin; SQSTM1/p62, sequestosome 1; TH, tyrosine hydroxylase; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; WIPI2, WD repeat domain, phosphoinositide interacting 2; ZFYVE1/DFCP1, zinc finger, FYVE domain containing 1.

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Author: greenmedinfo
Posted: February 22, 2018, 3:56 am
PMID:  Oncol Lett. 2018 Feb ;15(2):1423-1428. Epub 2017 Nov 29. PMID: 29434833Abstract Title:  Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways.Abstract:  Piperlongumine is an alkaloid compound extracted fromL. It is a chemical substance with various pharmacological effects and medicinal value, including anti-tumor, lipid metabolism regulatory, antiplatelet aggregation and analgesic properties. The present study aimed to understand whether piperlongumine induces the apoptosis and autophagy of leukemic cells, and to identify the mechanism involved. Cell viability and autophagy were detected using MTT, phenazine methyl sulfate and trypan blue exclusion assays. The apoptosis rate was calculated using flow cytometry. The protein expression levels of microtubule-associated protein 1A/1B-light chain 3, Akt and mechanistic target of rapamycin (mTOR) were measured using western blotting. The cell growth of leukemic cells was completely inhibited following treatment with piperlongumine, and marked apoptosis was also induced. Dead cells as a result of autophagy were stained using immunofluorescence and observed under a light microscope. Phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling was suppressed by treatment with piperlongumine, while p38 signaling and caspase-3 activity were induced by treatment with piperlongumine. It was concluded that piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways.

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Author: greenmedinfo
Posted: February 22, 2018, 3:03 am
PMID:  Chin J Nat Med. 2018 Feb ;16(2):143-149. PMID: 29455730Abstract Title:  Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine.Abstract:  Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg) administered alone or in combination with piperine (10 and 20 mg·kg) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.

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Author: greenmedinfo
Posted: February 22, 2018, 2:38 am
PMID:  Life Sci. 2018 Feb 9. Epub 2018 Feb 9. PMID: 29432759Abstract Title:  Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit.Abstract:  Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised themolecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.

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Author: greenmedinfo
Posted: February 22, 2018, 2:18 am
PMID:  Hum Exp Toxicol. 2018 Jan 1:960327118758150. Epub 2018 Jan 1. PMID: 29441827Abstract Title:  Urinary bisphenol A concentrations in relation to asthma in a sample of Egyptian children.Abstract:  BACKGROUND: Bronchial asthma is one of the top disabling diseases in pediatrics. Limited research has been studied the association of the widely used plastic monomer bisphenol A (BPA) with childhood asthma.OBJECTIVE: To compare the levels of urinary BPA in asthmatic and control children and to investigate the implication of BPA among other risk factors for the development of asthma.SUBJECTS AND METHODS: This case-control study included 97 children (45 asthmatic and 52 healthy controls) aged 3-8 years. Asthmatic children were diagnosed according to Global initiative for asthma (GINA) guidelines. Sociodemographic factors were assessed and urinary levels of BPA were determined in spot urine samples using high-performance liquid chromatography. The contribution of BPA among predictors for developing asthma was studied in asthmatic children.RESULTS: Median total urinary BPA levels were significantly higher in asthmatic children than in control group (1.56 ng/mL in asthmatic children compared to 0.790 ng/mL in control group, p = 0.001). Children who had total urinary BPA levels>1.3 ng/mL were more likely to be asthmatic (odds ratio: 2.84, 95% confidence interval 1.22-6.59, p = 0.015). Multiple logistic regression analysis for predictors of asthma showed the importance of higher levels of BPA (>1.3 ng/mL) as a more significant predictor than passive smoking ( p = 0.006 for BPA categories vs. p = 0.049 for passive smoking).CONCLUSION: Association of higher levels of urinary BPA with the diagnosis of asthma in children may indicate the potential risk of BPA exposure in the precipitation of bronchial asthma. Further clinical and biochemical research are needed to clarify the proper mechanism explaining this association.

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Author: greenmedinfo
Posted: February 22, 2018, 2:09 am
PMID:  Curr Alzheimer Res. 2017 ;14(11):1229-1237. PMID: 28413985Abstract Title:  Decrease in the Generation of Amyloid-β Due to Salvianolic Acid B by Modulating BACE1 Activity.Abstract:  OBJECTIVE: Generation and accumulation of the amyloid-β (Aβ) peptide after proteolytic processing of the full length amyloid precursor protein (FL-APP) by β-secretase (β-site APP cleaving enzyme or BACE1) and γ-secretase are the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a rate-limiting enzyme in the production ofAβ, is an attractive therapeutic approach for the treatment of AD. Recent studies suggest that salvianolic acid B (Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal medicine commonly used for the treatment of cardiovascular, cerebrovascular and liver diseases in China.METHOD: In this study, we discovered that Sal B acted as a BACE1 modulator and reduced the level of secreted Aβ in two different Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B significantly and dose-dependently decreased the generation of extracellular Aβ, soluble APPβ (by-product of APP cleaved by BACE1), and intracellular C-terminal fragment β from APP without influencing α-secretase and γ-secretase activity and the levels of FL-APP. In addition, using protein-docking, we determined the potential conformation of Sal B on BACE1 docking and revealed the interactions of Sal B with the BACE1 catalyticcenter.RESULTS: The docking provides a feasible explanation for the experimental results, especially in terms of the molecular basis of Sal B's action. Our results indicate that Sal B is a BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD.

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Author: greenmedinfo
Posted: February 22, 2018, 1:57 am
PMID:  Circ Res. 2008 Mar 14 ;102(5):597-606. Epub 2008 Jan 17. PMID: 18202313Abstract Title:  Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan.Abstract:  Heart failure is the leading cause of death in the elderly, but whether this is the result of a primary aging myopathy dictated by depletion of the cardiac progenitor cell (CPC) pool is unknown. Similarly, whether current lifespan reflects the ineluctable genetic clock or heart failure interferes with the genetically determined fate of the organ and organism is an important question. We have identified that chronological age leads to telomeric shortening in CPCs, which by necessity generate a differentiated progeny that rapidly acquires the senescent phenotype conditioning organ aging. CPC aging is mediated by attenuation of the insulin-like growth factor-1/insulin-like growth factor-1 receptor and hepatocyte growth factor/c-Met systems, which do not counteract any longer the CPC renin-angiotensin system, resulting in cellular senescence, growth arrest, and apoptosis. However, pulse-chase 5-bromodeoxyuridine-labeling assay revealed that the senescent heart contains functionally competent CPCs that have the properties of stem cells. This subset of telomerase-competent CPCs have long telomeres and, following activation, migrate to the regions of damage, where they generate a population of young cardiomyocytes, reversing partly the aging myopathy. The senescent heart phenotype and heart failure are corrected to some extent, leading to prolongation of maximum lifespan.

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Author: greenmedinfo
Posted: February 22, 2018, 1:48 am
PMID:  Toxicol Lett. 2017 Jul 5 ;276:21-30. Epub 2017 May 8. PMID: 28495616Abstract Title:  Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3 and TRPC6 mediated Caoverload in rat cardiomyocytes.Abstract:  Doxorubicin (DOX)-induced cardiotoxicity is a clinically complex syndrome that leads to significant pain to cancer survivors. Endoplasmic reticulum (ER) stress has been suggested to be an important contributor to myocardium dysfunction during this phenomenon. Our previous study proved that Salvianolic acid B (Sal B) protected against doxorubicin induced cardiac dysfunction by inhibiting ER stress and cardiomyocyte apoptosis. However, the underlying molecular mechanism is not yet clearly. In this study, we investigated the protective effect and mechanisms of Sal B againest DOX-induced cardiac injury and ER stress in vivo and in vitro. After pretreatment with Sal B (0.25, 0.5, 1mg/kg i.v.) for 7 days, male SD rats were intraperitoneally injected with a single dose of DOX (3mg/kg) every 2 days for three injections. The cardioprotective effect of Sal B was observed 2 weeks after the first administration. Adult rat ventricular myocytes were isolated and treated with Sal B (20μg/ml) for 6h and then exposed in DOX (1μm) for 4h. The cardiomyocyte contractility and the level of intracellular Cawere determined. Sal B ameliorated DOX-induced apoptosis damage in heart tissues. In vitro studies showed that DOX induced adult rat ventricular myocytes contractile dysfunction and intracellular Cahandling derangement, disrupted mitochondrial membrane potential, raised the level of ER stress related proteins. However, Sal B pretreatment suppressed all of these adverse effects of DOX. The effects of Sal B were closely related to the inhibition of transient receptor potential canonical (TRPC) channels, as characterized by inhibiting the expression of TRPC 3 and TRPC6. These results indicate that Sal B protects against DOX-induced cardiac apoptosis and ER stress via TRPC3 and TRPC6 inhibition.

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Author: greenmedinfo
Posted: February 22, 2018, 1:28 am
PMID:  Braz J Med Biol Res. 2017 May 15 ;50(6):e5954. Epub 2017 May 15. PMID: 28513773Abstract Title:  Attenuation of renal ischemic reperfusion injury by salvianolic acid B via suppressing oxidative stress and inflammation through PI3K/Akt signaling pathway.Abstract:  Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

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Author: greenmedinfo
Posted: February 22, 2018, 12:55 am
PMID:  J Cell Biochem. 2018 Jan ;119(1):701-711. Epub 2017 Aug 2. PMID: 28636082Abstract Title:  Salvianolic acid B protects against acute lung injury by decreasing TRPM6 and TRPM7 expressions in a rat model of sepsis.Abstract:  This study aimed to investigate the protective effects of salvianolic acid B (SA-B) on acute lung injury (ALI) through decreasing the expressions of channel kinase's TRPM6 and TRPM7. Wistar Septic rat models were established by lipopolysaccharide (LPS), which were separated into the control, lipopolysaccharide (LPS), SA-B, SA-B + si-TRPM6, SA-B + si-TRPM7, si-TRPM6, and si-TRPM7 groups. Arterial blood gas, protein content, total white blood cell (WBC) count and the percentage of polymorphonuclear neutrophils (PMN%) were measured. Levels of TNF-α and IL-6 levels in bronchoalveolar lavage fluid (BALF) were monitored. Lung coefficient, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were conducted by MPO and SOD kit. The mRNA expressions of TRPM6 and TRPM7 were detected by qRT-PCR. Compared with the control group, the PaOand PaO/FiOvalues exhibited decreases in other group, while the PaCOvalueprotein content, total WBC, PMN%, TNF-α, IL-6 levels and lung coefficient values all increased. MPO activity in lung tissue increased, while SOD activity decreased. TRPM6 and TRPM7 expressions increased significantly. Compared with the LPS group, the SA-B, SA-B + si-TRPM6, SA-B + si-TRPM7, si-TRPM6, and si-TRPM7 groups had increased PaOand the PaO/FiO, while decreased PaCOprotein content, total WBC, PMN%, TNF-α, IL-6 levels, and lung coefficient. MPO activity in lung tissue decreased while SOD activity increased. Decreased mRNA expressions of TRPM6 and TRPM7 in the SA-B, SA-B + si-TRPM6, and SA-B + si-TRPM6 groups were observed. Through decreasing the expressions of the channel kinase TRPM6 andTRPM7, SA-B protects against ALI in septic rats.

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Author: greenmedinfo
Posted: February 22, 2018, 12:42 am
PMID:  Exp Ther Med. 2017 Jul ;14(1):759-764. Epub 2017 Jun 1. PMID: 28672996Abstract Title:  Salvianolic acid B attenuates lipopolysaccharide-induced acute lung injury in rats through inhibition of apoptosis, oxidative stress and inflammation.Abstract:  The present study was performed to assess the protective effect of salvianolic acid B on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Sprague Dawley rats were injected with 100µg/kg LPS through a 24-gauge catheter. One group of rats was pre-treated with salvianolic acid B (1 mg/ml; 20 ml/kg body weight) 1 h prior to LPS challenge, then 20 ml/kg salvianolic acid B every 2 days for 4 weeks thereafter. Salvianolic acid B attenuated LPS-induced increases in the lung wet/dryweight rate and lung tissue injury in ALI model rats. LPS-induced changes in the content of caspase-3, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, tumor necrosis factor-α and interleukin-6 in ALI model rats were attenuated by treatment with salvianolic acid B. Furthermore, treatment with salvianolic acid B inhibited the protein expression of type I collagen I, endogenous transforming growth factor-β1 production and α-smooth muscle actin in ALI model rats. These findings indicated that salvianolic acid B attenuates LPS-induced ALI through inhibition of apoptosis,oxidative stress and inflammation in rats and therefore exertsa protective effect against ALI.

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Author: greenmedinfo
Posted: February 22, 2018, 12:26 am
PMID:  J Food Sci. 2017 Aug ;82(8):1953-1960. Epub 2017 Jul 28. PMID: 28753232Abstract Title:  Salvianolic Acid B Inhibits High-Fat Diet-Induced Inflammation by Activating the Nrf2 Pathway.Abstract:  Salvianolic acid B (Sal B) is a major water-soluble bioactive component of Salvia miltiorrhiza, which is a traditional Chinese medicine. We investigated the ways in which Sal B affects high-fat diet (HFD)-induced immunological function disorder remission using a C57BL/6 mouse model. We gave groups of C57BL/6 mice a normal diet (Control), a normal diet supplemented with Sal B (Control + Sal B), a high-fat diet (HF), and a high-fat diet supplemented with Sal B (HF + Sal B) for 10 wk. Sal B supplementation decreased the body weight and plasma lipids, increased the fecal excretion of lipids, prevented the accumulation of chronic oxidative stress, and reversed the disproportionality of CD3CD4and CD3CD8T lymphocytes compared to HFD. We found an increase in IL-6 and TNF-α, while IL-10 decreased in plasma after the HFD and Sal B reversed the deregulation of the Thl/Th2 ratio. In addition, HFD-induced inflammation was stopped by Sal B through the downregulation of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible NO synthesis (iNOS), and the upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2)-regulated genes. These findings demonstrated that Sal B could effectively attenuate inflammation by activating the Nrf2-mediated antioxidant defense system.

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Author: greenmedinfo
Posted: February 21, 2018, 11:52 pm
PMID:  Afr J Tradit Complement Altern Med. 2016 ;13(4):157-161. Epub 2016 Jul 3. PMID: 28852731Abstract Title:  SALVIANOLIC ACID B ALLEVIATING MYOCARDIUM INJURY IN ISCHEMIA REPERFUSION RATS.Abstract:  BACKGROUND: Salvia miltiorrhiza (SM) Bunge is one of the widely-used Chinese medicinal herbs. Salvianolic acid B (Sal B), a bioactive compound isolated from the Chinese herb Radix Salviae Miltiorrhizae, has been reported to exhibit anti-inflammatory and anti-oxidantive effects.MATERIAL AND METHOD: To study the cardioprotective effects of salvianolic acid B (Sal B) on acute myocardial ischemia reperfusion (MIR) injury rats, on the basis of this investigation, the possible mechanism of salvianolic acid B was elucidated. Male Sprague- Dawley rats (200-220 g) were randomly divided into five groups: sham-operated, MIR, MIR + Sal B (10 mg/kg/day, orally), MIR + Sal B (20 mg/kg/ day, orally) and MIR + Sal B (30 mg/kg/ day, orally). Before operation, the foregoing groups were pretreated with homologous drug once a day for 7 days, respectively. After twelve hours in MIR, the cardioprotective effects of SPJ were evaluated by infarct size, biochemical values, and the antioxidative and antiapoptotic relative gene expressions.RESULTS: Sal B significantly improved heart function and decreased infarct size; remarkably decreased levels of serum TNF-α and IL-Ιβ levels, increased contents of myocardium antioxidant enzymes activities; western blot results showed that Sal B ameliorate the increased Bax and caspase-3 protins expressions and decreased Bcl-2 proteins expression and ratios of Bcl-2 to Bax.CONCLUSION: In ischemic myocardium, oxidative stress caused the overgeneration and accumulation of reactive oxygen species (ROS), which was central of cardiac ischemic injury. Sal B exerted beneficially cardioprotective effects on myocardial ischemia injury rats, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial ischemia injury and cardiac cell death. List of abbreviations: salvianolic acid B (Sal B); myocardial ischemia reperfusion (MIR); reactive oxygen species (ROS); Left ventricular end-diastolic pressure (LVEDP); left ventricular end-diastolic volume (LVEDV); Malondialdehyde (MDA); superoxide dismutase (SOD); catalase (CAT); Glutathione peroxidase (GSH-Px); glutathione reductase (GR).

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Author: greenmedinfo
Posted: February 21, 2018, 11:09 pm
PMID:  Cell Physiol Biochem. 2017 ;43(4):1381-1391. Epub 2017 Oct 9. PMID: 28992623Abstract Title:  Salvianolic Acid B Ameliorates Cognitive Deficits Through IGF-1/Akt Pathway in Rats with Vascular Dementia.Abstract:  : BackgroundAims: Salvianolic acid B (SalB) is a natural polyphenolic compound enriched in Salvia miltiorrhiza Bunge. Our study was designed to explore the role of Sal B on cognitive impairment in vascular dementia (VD) model rats, as well as its possible molecular mechanisms.METHODS: Rats were randomly divided into four groups (n = 15 for each group): Control group, Sal B group (normal Sprague Dawley rats treated with Sal B), VD group and VD + Sal B group. The VD group rats were established by permanent bilateral common carotid artery occlusion (BCCAO). Animals in the Control and Sal B group received the same operation without bilateral common carotid arteries occlusion. The animals in Sal B group and VD + Sal B group received Sal B (20 mg/kg) orally once a day for consecutive 6 weeks. We investigated the effects of SalB on BCCAO-induced cognitive deficits rats models via the Morris water maze experiment. To explore the mechanisms of Sal B on cognitive function, we detected the expression of IGF-1, Akt and p-Akt, and the rate of cell apoptosis in CA1 region.RESULTS: Our results observed that hippocampal IGF-1 was decreased in VD model rats, while SalB reversed the alteration of IGF-1 levels. The expression of hippocampal Akt showed no significant difference between control and VD group, however, p-Akt level was significantly decreased in VD group. After 6 weeks of SalB treatment, p-Akt level was significantly increased. A large number of apoptotic neurons were found in VD model rats, while SalB prevented apoptosis of hippocampal neurons in CA1 region in VD model rats.CONCLUSION: SalB significantly ameliorated cognitive deficits in BCCAO-induced VD model rats. The potential mechanism underlying the protective effects may be mediated through IGF-1/Akt pathway.

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Author: greenmedinfo
Posted: February 21, 2018, 10:40 pm
PMID:  Brain Res. 2018 01 15 ;1679:125-133. Epub 2017 Nov 24. PMID: 29180227Abstract Title:  Mechanism of salvianolic acid B neuroprotection against ischemia/reperfusion induced cerebral injury.Abstract:  The purpose of this study was to evaluate the cerebral protection of salvianolic acid B (Sal B) against cerebral I/R injury and investigate the underlying mechanism. As shown by 2,3,5-Triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI) analyses, Sal B significantly reduced cerebral infarct size, and accompanied with improved neurobehavioral functions as indicated by the modified Bederson score and Longa five-point scale. Sal B decreased the production of reactive oxygen species (p 

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Author: greenmedinfo
Posted: February 21, 2018, 10:24 pm
PMID:  J Neuroinflammation. 2017 Dec 6 ;14(1):239. Epub 2017 Dec 6. PMID: 29212498Abstract Title:  Salvianolic acid B protects against lipopolysaccharide-induced behavioral deficits and neuroinflammatory response: involvement of autophagy and NLRP3 inflammasome.Abstract:  BACKGROUND: The NLRP3 inflammasome activation and neuroinflammation are known to be involved in the pathology of depression, whereas autophagy has multiple effects on immunity, which is partly mediated by the regulation of inflammasome and clearance of proinflammatory cytokines. Given the emerging evidence that autophagy dysfunction plays an essential role in depression, it is very likely that autophagy may interact with the inflammatory process in the development and treatment of depression. Salvianolic acid B (SalB), a naturally occurring compound extracted from Salvia miltiorrhiza, contains anti-inflammatory and antidepression properties and has recently been proven to modulate autophagy. In this study, we sought to investigate whether autophagy is involved in the inflammation-induced depression and the antidepressant effects of SalB.METHODS: The effects of prolonged lipopolysaccharide (LPS) treatment and SalB administration on behavioral changes, neuroinflammation, autophagic markers and NLRP3 activation in rat hippocampus were determined by using behavioral tests, real-time PCR analysis, western blot, and immunostaining.RESULTS: Our data showed that periphery immune challenge by LPS for 2 weeks successfully induced the rats to a depression-like state, accompanied with enhanced expression of pro-inflammatory cytokines and NLRP3 inflammasome activation. Interestingly, autophagic markers, including Beclin-1, and the ratio of LC3II to LC3I were suppressed following prolonged LPS exposure. Meanwhile, co-treatment with SalB showed robust antidepressant effects and ameliorated the LPS-induced neuroinflammation. Additionally, SalB restored the compromised autophagy and overactivated NLRP3 inflammasome in LPS-treated rats.CONCLUSIONS: Collectively, these data suggest that autophagy may interact with NLRP3 activation to contribute to the development of depression, whereas SalB can promote autophagy and induce the clearance of NLRP3, thereby resulting in neuroprotective and antidepressant actions.

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Author: greenmedinfo
Posted: February 21, 2018, 10:02 pm
PMID:  Arch Med Res. 2017 Dec 7. Epub 2017 Dec 7. PMID: 29224910Abstract Title:  Regulation of SIRT3/FOXO1 Signaling Pathway in Rats with Non-alcoholic Steatohepatitis by Salvianolic Acid B.Abstract:  AIMS: To explore the effect of salvianolic acid B (Sal B) on regulation of SIRT3/FOXO1 signaling pathway in rats with non-alcoholic steatohepatitis (NASH).METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into control, model and treatment groups. After 12 weeks of successful model establishment with high fat diet, treatment group was given Sal B by intragastric administration. After 12 weeks of treatment, rats were sacrificed and livers were taken to test indicators such as liver index, TG, TC, ALT, AST, reactive oxygen species (ROS) by DCFH-DA probe, SOD2 activity by WST-8 test. mRNA and protein expression of SIRT3, SOD2, catalase were detected by real time PCR and western blot, respectively. The acetylation level of FOXO1 and SOD2 was detected by immuno-precipitation (IP).RESULT: Liver index, ALT, AST, TG, TC, and ROS of model group were higher than those of control and treatment groups, which the difference was statistically significant (p 

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Author: greenmedinfo
Posted: February 21, 2018, 9:13 pm
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