Publications by authors named "Yaoyan Dun"

20 Publications

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The dynamic changes of Nrf2 mediated oxidative stress, DNA damage and base excision repair in testis of rats during aging.

Exp Gerontol 2021 09 24;152:111460. Epub 2021 Jun 24.

College of Medical Science, China Three Gorges University, Yichang, Hubei 443002, PR China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, Hubei 443002, PR China. Electronic address:

Accumulation of oxidative stress, DNA damage and impaired DNA repair appear to play critical roles in the decline of testicular function with aging. However, when those factors begin to lose control in testis during aging has not yet been well understood. This study was designed to assess the changes of oxidative stress and DNA damage status, and DNA repair capacity in testis during aging. Thus, male Sprague-Dawley rats at 3, 9, 15 and 24 months of age were used to delineate the dynamic changes in testicular weight and index, testosterone concentration, testicular histology, Nrf2-mediated oxidative stress, DNA damage, DNA repair and apoptosis. Results showed that testicular weight and index, testosterone concentration and spermatid number progressively declined from 9 to 24 months of age. Similarly, seminiferous tubule diameters and seminiferous epithelium heights gradually diminished with aging. Nrf2-mediated antioxidant defense ability was significantly impaired in testis with increasing age including decreased the activity of SOD and the expression levels of Nrf2, HO-1 and NQO-1, and increased the contents of MDA. In addition, DNA damage including DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) also progressively increased accompanied by increased levels of 8-hydroxydeoxyguanosine (8-OHdG) and γ-H2AX, and activated ATM/Chk2 and ATR/Chk1 pathway. Consistent with the results of Nrf2 pathway, the expression levels of APE1, OGG1 and XRCC1 involved in base excision DNA repair (BER) pathway increased from 3 to 9 months of age, and then gradually decreased after 9 months of age. Finally, TUNEL and Western blot results further confirmed germ cell apoptosis progressively increased from 3 to 24 months of age as evidenced by decreased ratio of Bcl-2/Bax and levels of Bcl-2 expression, and increased Bax expression levels. Taken together, our results suggest that downregulation of antioxidant ability mediated by Nrf2 pathway and impairment of BER capacity might correlate with increased DNA damage, and then induce declining testicular function during aging after adult.
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http://dx.doi.org/10.1016/j.exger.2021.111460DOI Listing
September 2021

Protective effects of saponins from Panax japonicus on neurons of the colon myenteric plexus in aging rats through reduction of α-synuclein through endoplasmic reticulum stress.

Geriatr Gerontol Int 2021 Jan 27;21(1):85-93. Epub 2020 Nov 27.

Medical College of China Three Gorges University, Yichang, China.

Aim: The enteric nervous system degenerates gradually with age, and α-synuclein (α-syn) is a suitable marker of enteric nervous system degeneration, which is intimately related with endoplasmic reticulum stress and unfolded protein response (UPR ). Saponins from Panax japonicus (SPJ) have obvious protective effects on neurons in several degenerative disease models. Here, the study was designed to investigate whether SPJ could reverse the neuron degeneration through regulating the UPR in the colon myenteric plexus of aging rats.

Methods: Aging rats had been treated with SPJ for 6 months since they were aged 18 months. Then, the colon samples were collected and neuron morphology in the myenteric plexus was observed. Immunohistochemistry staining was used to detect the expressions of NeuN, α-syn, GRP78 and three different UPR branches. Double immunofluorescence was used to determine the co-localization of α-syn and NeuN, GRP78 and NeuN.

Results: Neurons degenerated in the colon myenteric plexus of aging rats, but co-localization of α-syn and NeuN increased. In addition, both the expressions of GRP78 and three UPR branch signaling pathway proteins decreased in the colon myenteric plexus of aging rats. Treatment of SPJ almost alleviated the above effects in aging rats, except for ATF6.

Conclusions: SPJ could reverse the neuron loss caused by accumulation of α-syn in the myenteric plexus of colon in aging rats, which is potentially associated with increased GRP78 and most URP changes. Geriatr Gerontol Int 2021; 21: 85-93.
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http://dx.doi.org/10.1111/ggi.13882DOI Listing
January 2021

Panax notoginseng Saponins Attenuate Neuroinflammation through TXNIP-Mediated NLRP3 Inflammasome Activation in Aging Rats.

Curr Pharm Biotechnol 2021 ;22(10):1369-1379

Pharmacy Department, Wuhan University of Science and Technology, Wuhan 430065, China.

Introduction: Microglia-mediated inflammatory responses play a crucial role in aging-related neurodegenerative diseases. The TXNIP/NLRP3 pathway is a key pathway leading to microglial activation. Panax notoginseng Saponins (PNS) have been widely used for the treatment of stroke in China.

Objective: This study evaluates the anti-neuroinflammatory effect of PNS and investigates the mechanism via TXNIP-mediated NLRP3 inflammasome activation in aging rats.

Material And Methods: Eighteen-month-old Sprague-Dawley rats were randomly divided into the aging control group and PNS treated groups (n=15 each group). For PNS-treated groups, rats were administrated food with PNS at the doses of 10 mg/kg and 30 mg/kg for consecutive 6 months until they were 24-month old. Rats from the aging control group were given the same food without PNS. Twomonth- old rats were purchased and given the same food until they were 6-months old as the adult control group (n = 15). Then, the cortex and hippocampus were rapidly harvested and deposited. H&E staining was used to assess histo-morphological changes. Western blotting was carried out to detect the protein expression. Immunofluorescence was employed to measure the co-localization of NLRP3, TXNIP and Iba-1. In vitro model was established by LPS+ATP co-incubation in the BV2 microglia cell line.

Results: Aging rats exhibited increased activation of microglia, accompanied by a high level of IL-1β expression. Meanwhile, aging rats showed enhanced protein expression of TXNIP and NLRP3 related molecules, which co-localized with microglia. PNS treatment effectively reduced the number of degenerated neurons and reversed the activation of the TXNIP/NLRP3 inflammatory pathway. In vitro results showed that PNS up to 100 μg/ml had no significant toxicity on BV2 microglia. PNS (25, 50 μg/ml) effectively reduced the inflammatory response induced by LPS and ATP co-stimulation, thus inhibiting the expression of TXNIP/NLRP3 pathway-related proteins.

Discussion And Conclusion: PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome activation, which provided a potential target for the treatment of inflammation-related neurodegenerative diseases.
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http://dx.doi.org/10.2174/1389201021999201110204735DOI Listing
August 2021

Icariin Improves Age-Related Testicular Dysfunction by Alleviating Sertoli Cell Injury Upregulation of the ER/Nrf2-Signaling Pathway.

Front Pharmacol 2020 12;11:677. Epub 2020 May 12.

College of Medical Science, China Three Gorges University, Yichang, China.

Sertoli cells play crucial roles in spermatogenesis and are impaired by aging. Icariin, a flavonoid from , has been reported to exhibit anti-aging effects and improve testicular dysfunction in the clinical setting. However, whether icariin improves age-related degeneration of testicular function protection from Sertoli cell injury remains unclear. In the present study, we evaluated the protective effect of icariin on Sertoli cell injury and explored the possible mechanism(s) and . Dietary administration of icariin for 4 months significantly ameliorated the age-related decline in testicular function by increasing testicular and epididymal weights and indices, sperm count and sperm viability, testicular testosterone and estradiol concentrations, and seminiferous tubule diameters and heights. In addition, icariin protected age-related Sertoli cells from injury as evidenced by an analysis of Sertoli cell number, ultrastructure, and function. Such changes were accompanied by upregulation of ER and Nrf2 signaling in Sertoli cells. Parallel studies also demonstrated that icariin inhibited untoward effects on the TM4 mouse Sertoli cell line with concomitant upregulation of ER and Nrf2 signaling. Conversely, ER siRNA reversed icariin-mediated protection of Sertoli cell injury. Our data suggest that icariin effectively ameliorates age-related degeneration of testicular function by alleviating Sertoli cell injury the ER/Nrf2 signal-transduction pathway. Thus, mitigating Sertoli cell damage the ER/Nrf2 signaling pathway likely represents a promising strategy for the prevention of age-related testicular dysfunction.
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http://dx.doi.org/10.3389/fphar.2020.00677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247842PMC
May 2020

Changes of Wnt/β-catenin signalling, BMP2, and BMP4 in the jejunum during ageing in rats.

Arab J Gastroenterol 2020 Mar 30;21(1):43-48. Epub 2020 Mar 30.

Medical College of China Three Gorges University, Yichang 443002, China. Electronic address:

Background And Study Aims: The renewal of intestinal epithelium is maintained by intestinal stem cells (ISCs). Studies have found an age-dependent increase of Esg/Dl progenitor cells in the midgut of Drosophila. However, changes of ISCs and the molecular regulation in mammalian animals with age are yet unknown. The aim of this study was to find out the changes of ISCs and molecular regulation in mammalian animals during the process of ageing.

Material And Methods: Thirty Sprague-Dawley rats were divided into three groups: young (3 months old), adult (6 months old), and ageing (24 months old). Levels of PCNA, Bmi1, β-catenin and BMP4 were examined by Immunohistochemistry staining. Levels of Bmi1, GSK-3β, Dkk1 and BMP2 were determined by Western Blot.

Results: Our results showed that the proliferation of ISCs was decreased and the number of intestinal stem cells declined in ageing rats. The niches of ISCs, including Wnt signalling pathway and some proteins of Bone morphogenetic protein (BMP) signalling pathway, were downregulated in the jejunum of ageing rats.

Conclusion: Our study indicated that age-related decreased proliferation of intestinal stem cells in the jejunum could be associated with the alleviation of niches, including Wnt signalling pathway and some proteins of BMP signalling pathway.
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http://dx.doi.org/10.1016/j.ajg.2019.12.004DOI Listing
March 2020

Distinct expression patterns of aging effects on the UPR signaling pathway in rat colon and regulatory role of saponins from .

Int J Clin Exp Pathol 2019 1;12(9):3279-3289. Epub 2019 Sep 1.

Medical College of China Three Gorges University Yichang 443002, Hubei, China.

Background: Studies have reported that the unfolded protein response of ER (UPR) declines in the several organs of aging mice. However, changes of UPR during the aging process in the intestine are rarely reported. Our previous studies have demonstrated that Saponins from (SPJ) have anti-aging effects in different murine models and can modulate ER stress. In the present study, we focused on age-dependent expressions of UPR in the intestine of 6- to 24-month-old rats by an immunohistochemical (IHC) method and determined whether SPJ could regulate the three different UPR branches of the colon in aging rats.

Methods: Aging rats had been treated with different doses (10 and 30 mg/kg) of SPJ for 6 months, which were mixed with feed, since they were 18 months old. Then the expressions of GRP78 and three different UPR branches were determined by immunohistochemistry (IHC). : Total expressions of GRP78 and p-JNK increased, and other UPR proteins decreased in the colon of aging rats, while SPJ treatment relieved the corresponding changes in aging rats. Here we also found different patterns of GRP78 and the three UPR branches in the different layers of colon in rats.

Conclusion: The study demonstrated that UPR declined and GRP78 increased in the colon of aging rats. SPJ could reverse most URP changes in the colon of aging rats. This study also showed different expression patterns of the three branches of UPR in different layers of the colon in rats.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949813PMC
September 2019

Protective effect of Wuzi Yanzong recipe on testicular dysfunction through inhibition of germ cell apoptosis in ageing rats via endoplasmic reticulum stress.

Andrologia 2019 Mar 4;51(2):e13181. Epub 2018 Nov 4.

College of Medicine, China Three Gorges University, Yichang, China.

It has been demonstrated that excessively activated endoplasmic reticulum stress (ERS) is closely associated with ageing-related diseases and male reproductive dysfunction. Wuzi Yanzong recipe (WZ) is a classical Traditional Chinese Medicine prescription for treatment of male reproductive system diseases. However, it remains unknown whether WZ improves testicular dysfunction with ageing via ERS. In this study, we investigated the protective effects and its mechanism of WZ on testicular dysfunction in ageing rats. The results showed that treatment with WZ for 4 months significantly increased the testicular weight and index, sperm count and viability, and the levels of testosterone and decreased the levels of estradiol. In addition, WZ significantly activated the onset of ERS and prevented germ cell apoptosis by upregulating the expression levels of ERS-responsive proteins GRP78, phospho-PERK, phospho-eIF2α, ATF4, phospho-IRE-1α, XBP1 and ATF6α, and downregulating the expression levels of pro-apoptotic proteins p-JNK, Caspase12 and CHOP in testicular germ cell of ageing rats. Besides, WZ significantly decreased the numbers of TUNEL-positive cells. Taken together, WZ effectively improves ageing-related testicular dysfunction through inhibition of germ cell apoptosis via ERS.
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http://dx.doi.org/10.1111/and.13181DOI Listing
March 2019

Preventive effects of total saponins of on fatty liver fibrosis in mice.

Arch Med Sci 2018 Mar 26;14(2):396-406. Epub 2016 Oct 26.

Medical College of China Three Gorges University, Yichang, China.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Fatty liver fibrosis, a severe form of NAFLD, is a key step which can be reversed by effective medical intervention. This paper aims to describe the protective role and mechanisms of action of total saponins of (SPJ) against fatty liver fibrosis in mice. In this study, fatty liver fibrosis was induced by a high-fat (HF) diet combined with intraperitoneal injection of porcine serum.

Material And Methods: The fatty liver fibrosis model was induced by HF diet combined with intraperitoneal injection of porcine serum. The endoplasmic reticulum stress (ERS) response and C/EBP homologous protein (CHOP) and p-Jun N-terminal kinase (JNK)-mediated apoptosis and inflammation were assessed by serum biochemistry, hematoxylin-eosin (H + E), Masson and electronic microscopy staining, Hyp content detection, Western blotting and real time polymerase chain reaction (RT-PCR).

Results: Saponins of could significantly improve liver function and decrease the lipid level in the serum. The liver steatosis, collagen fibers and inflammatory cell infiltration were significantly improved in the SPJ group according to microscope observation. The RT-PCR analysis revealed that the collagen I (Coll), α smooth muscle actin (α-SMA), tissue inhibitors of MMPs (TIMP), CHOP and GRP78 mRNA expression levels were distinctly weakened by SPJ treatment; and western blotting analysis indicated that the phosphorylated JNK (p-JNK), Coll and 78 kD glucose-regulated protein (GRP78) protein expression levels were significantly alleviated, which might be associated with the inhibition of the ERS response and the CHOP and JNK-mediated apoptosis and inflammation pathway.

Conclusions: Based on this research, SPJ as a preventive medicine has great potential in prevention of liver fibrosis.
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http://dx.doi.org/10.5114/aoms.2016.63260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868672PMC
March 2018

Regulatory effects of saponins from on colonic epithelial tight junctions in aging rats.

J Ginseng Res 2018 Jan 31;42(1):50-56. Epub 2016 Dec 31.

Renhe Hospital of China Three Gorges University, Yichang, China.

Background: Saponins from (SPJ) are the most abundant and main active components of , which replaces ginseng roots in treatment for many kinds of diseases in the minority ethnic group in China. Our previous studies have demonstrated that SPJ has the effects of anti-inflammation through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The present study was designed to investigate whether SPJ can modulate intestinal tight junction barrier in aging rats and further to explore the potential mechanism.

Methods: Aging rats had been treated with different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they were 18 mo old. After the rats were euthanized, the colonic samples were harvested. Levels of tight junctions (claudin-1 and occludin) were determined by immunohistochemical staining. Levels of proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) were examined by Western blot. NF-κB and phosphorylation of MAPK signaling pathways were also determined by Western blot.

Results: We found that SPJ increased the expression of the tight junction proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ decreased the levels of interleukin-1β and tumor necrosis factor-α, reduced the phosphorylation of three MAPK isoforms, and inhibited the expression of NF-κB in the colon of aging rats.

Conclusion: The studies demonstrated that SPJ modulates the damage of intestinal epithelial tight junction in aging rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK and NF-κB signaling pathways.
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http://dx.doi.org/10.1016/j.jgr.2016.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766693PMC
January 2018

Panax notoginseng saponins attenuate cardiomyocyte apoptosis through mitochondrial pathway in natural aging rats.

Phytother Res 2018 Feb 12;32(2):243-250. Epub 2017 Nov 12.

Medical College of China Three Gorges University, Yichang, 443002, P. R. China.

Panax notoginseng saponins (PNS) have been widely used in the cardiovascular system for the treatment of cardiovascular diseases and stroke in China. In this study, we investigated the anti-apoptotic effect of PNS on cardiomyocytes in the natural aging rat and explored the potential mechanisms regarding oxidative stress and mitochondrial function signaling pathways. Male Sprague-Dawley rats were randomly divided into five groups: adult control (3-month old), aging control (24-month old), and different doses of PNS-treated aging rat groups (10, 30, 60 mg/kg/day, orally). After treatment of PNS or saline for 6 months, the effects of PNS on the cardiomyocytes were evaluated. Results showed that PNS significantly improved the morphological changes in myocardium, prevented the increase of cardiomyocyte apoptosis in the aging rats, and improved mitochondrial dysfunction associated aging in a dose-dependent manner. PNS also significantly reversed the down-regulation of FoxO3a and Mn-SOD and up-regulated PGC-1α, LC3β, and Beclin-1 levels. Our data demonstrated that during aging, mitochondrial dysfunction caused an increase of oxidative damage, which played a key role in cardiomyocyte apoptosis. PNS exerted an anti-apoptotic effect via attenuating oxidative damage through oxidative stress- and mitochondrial function-related signaling pathways.
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http://dx.doi.org/10.1002/ptr.5961DOI Listing
February 2018

Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose tissue of mice through inhibition of NLRP3 inflammasome activation and NF-κB signaling.

Oncotarget 2017 May;8(19):31023-31040

Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China.

Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice. Moreover, CS treatment also inhibited the activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs). Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed HFD-induced NF-κB signaling in vivo and LPS-induced NF-κB activation as reflected by the fact that their phosphorylated forms and the ratios of pNF-κB/NF-κB, pIKK/IKK, and pIκB/IκB were all decreased in EAT from HFD-fed mice treated with CS as compared with those of HFD mice. Taking together, this study has revealed that CS effectively inhibits HFD-induced inflammation in adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and NF-κB signaling. Thus, CS can serve as a potential therapeutic drug in the prevention and treatment of inflammation-associated diseases.
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http://dx.doi.org/10.18632/oncotarget.16052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458186PMC
May 2017

Oleanolic acid rejuvenates testicular function through attenuating germ cell DNA damage and apoptosis via deactivation of NF-κB, p53 and p38 signalling pathways.

J Pharm Pharmacol 2017 Mar 9;69(3):295-304. Epub 2016 Dec 9.

Medical College of China Three Gorges University, Yichang, China.

Objectives: Inflammation can cause degenerative changes of reproductive function. Oleanolic acid (OA), the effective component from Ligustrum lucidum Ait., exhibits significantly anti-inflammation and antiageing activity. However, whether OA restores testicular dysfunction via inhibition of inflammation with ageing is unclear. Here, in a natural ageing rat model, we investigated the protection effects of OA and its mechanism of action.

Methods: Eighteen-month-old Sprague Dawley (SD) rats were randomly divided into ageing control group and two OA-treated groups (5 and 25 mg/kg). Nine-month-old SD rats were used as adult controls. All rats were received either vehicle or OA for 6 months. Then, histomorphology, weight and index of testis, protein expression and immunohistochemistry were examined.

Key Findings: Oleanolic acid significantly restored testicular morphology and improved testicular weight and index. Moreover, OA significantly inhibited phospho-NF-κB p65 and its downstream proinflammatory cytokines' expressions, including IL-1β, COX-2 and TNF-α in testis tissues. Similarly, OA remarkably inhibited IL-1β and TNF-α production. OA significantly attenuated germ cells' DNA damage and apoptosis. Such changes were accompanied by downregulation of γH2AX, p-P53 and Bax expressions, and upregulation of Bcl-2 and Bcl-2/Bax ratio. In addition, OA remarkably inhibited p38 signalling.

Conclusions: Oleanolic acid effectively rejuvenates testicular function via attenuating germ cell DNA damage and apoptosis through deactivation of NF-κB, p53 and p38 signalling pathways.
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http://dx.doi.org/10.1111/jphp.12668DOI Listing
March 2017

Chikusetsu saponin V attenuates H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells through Sirt1/PGC-1α/Mn-SOD signaling pathways.

Can J Physiol Pharmacol 2016 Sep 19;94(9):919-28. Epub 2016 Apr 19.

a College of Medical Science, Three Gorges University, Yichang, Hubei 443002, China.

Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Chikusetsu saponin V (CsV), the most abundant member of saponins from Panax japonicus (SPJ), has attracted increasing attention for its potential to treat neurodegenerative diseases. However, the mechanisms are unclear. Our study intended to investigate the antioxidative effects of CsV in human neuroblastoma SH-SY5Y cells. Our data showed that CsV attenuated H2O2-induced cytotoxicity, inhibited ROS accumulation, increased the activities of superoxide dismutase (SOD) and GSH, and increased mitochondrial membrane potential dose-dependently. Further exploration of the mechanisms showed that CsV exhibited these effects through increasing the activation of oxidative-stress-associated factors including Sirt1, PGC-1α, and Mn-SOD. Moreover, CsV inhibited H2O2-induced down-regulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. In conclusion, our study demonstrated that CsV exhibited neuroprotective effects possibly through Sirt1/PGC-1α/Mn-SOD signaling pathways.
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http://dx.doi.org/10.1139/cjpp-2015-0262DOI Listing
September 2016

Vaccine adjuvant ginsenoside Rg1 enhances immune responses against hepatitis B surface antigen in mice.

Can J Physiol Pharmacol 2016 Jun 4;94(6):676-81. Epub 2016 Mar 4.

a College of Medical Science, Three Gorges University, Yichang, Hubei 443002, China.

The adjuvant effect of ginsenoside Rg1 on immune responses against hepatitis B surface antigen (HBsAg) in mice was investigated. Female BALB/c mice were subcutaneously injected with saline or HBsAg antigen with or without Rg1 on days 7 and 21. Samples were collected 2 weeks after the boosting for the detection of anti-HBsAg immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced in splenocytes. The innate and adaptive immune responses were measured in mice immunized as described above. The results showed that ginsenoside Rg1 had adjuvant properties in stimulating IgG, splenocyte proliferation, and mRNA expression of cytokines IFN-γ and IL-4, as well as the expression of cell surface marker TLR4 in the HBsAg-immunized mice. These results indicate that Rg1 enhances both Th1 (IgG2b and IFN-γ) and Th2 (IgG1 and IL-4) responses. In addition, the TLR4 signaling pathway is involved in the adjuvant activities of ginsenoside Rg1.
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http://dx.doi.org/10.1139/cjpp-2015-0528DOI Listing
June 2016

Saponins from Panax japonicus attenuate D-galactose-induced cognitive impairment through its anti-oxidative and anti-apoptotic effects in rats.

J Pharm Pharmacol 2015 Sep 18;67(9):1284-96. Epub 2015 Apr 18.

College of Medical Science, Three Gorges University.

Objective: To investigate the neuroprotective effects of saponins from Panax japonicus (SPJ) on D-galactose (D-gal)-induced brain ageing, and further explore the underlying mechanisms.

Methods: SPJ were analysed using high-pressure liquid chromatography. Male Wistar rats weighing 200 ± 20 g were randomly divided into four groups: control group (saline), D-gal-treated group (400 mg/kg, subcutaneously), D-gal + SPJ groups (50, 100 and 200 mg/kg, orally) and vitamin E group (100 mg/kg). Rats were injected corresponding drugs once daily for 8 weeks. Neuroprotective effects of SPJ were evaluated by Morris water maze, histopathological observations, biochemical assays, western blot analysis and quantitative real-time polymerase chain reaction (PCR) analysis in vivo as well as reactive oxygen species (ROS) measurement and apoptosis assay in vitro.

Key Findings: Our present study showed that D-gal had a neurotoxic effect in rats and in SH-SY5Y cells due to oxidative stress induction, including decreased total anti-oxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase activity, ultimately leading to spatial learning and memory impairment in rats and ROS accumulation in SH-SY5Y cells. SPJ improved spatial learning and memory deficits, attenuated hippocampus histopathological injury and restored impaired anti-oxidative as well as anti-apoptotic capacities in D-gal-induced ageing rats. In addition, SPJ remarkably decreased lipofuscin levels, increased hippocampus nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homologue (SIRT1) protein levels and anti-oxidant genes expression such as manganese superoxide dismutase (Mn-SOD), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1) and cysteine ligase catalytic (GCLC) in D-gal-induced brain ageing.

Conclusions: Our data suggested that D-gal induced multiple molecular and functional changes in brain similar to natural ageing process. SPJ protected brain from D-gal-induced neuronal injury through decreasing oxidative stress and apoptosis, and ultimately improving cognitive performance in D-gal-induced brain ageing. It is possibly related to Nrf2 and SIRT1-mediated anti-oxidant signalling pathways.
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http://dx.doi.org/10.1111/jphp.12413DOI Listing
September 2015

A case of rheumatoid arthritis associated with Hashimoto's thyroiditis and thymoma.

Int J Rheum Dis 2017 Nov 10;20(11):1792-1793. Epub 2014 Oct 10.

Jingmen No. 2 People's Hospital, Jingmen, China.

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http://dx.doi.org/10.1111/1756-185X.12453DOI Listing
November 2017

Chikusetsusaponin V inhibits inflammatory responses via NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophages.

Immunopharmacol Immunotoxicol 2014 Dec 17;36(6):404-11. Epub 2014 Sep 17.

Department of Pharmacology .

Excessive activation of macrophages is implicated in various inflammation resulted injuries. Saponins from Panax japonicus (SPJ) have been shown to possess anti-inflammatory activities. However, whether Chikusetsusaponin V (CsV), the most abundant component of SPJ, can exert anti-inflammatory activities is unknown. The present study was aimed to investigate the anti-inflammatory effects of CsV in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells and the underlying mechanisms. Our data showed that CsV dose-dependently inhibited NO, iNOS, TNF-α and IL-1β expressions in LPS-stimulated RAW264.7 cells. Increased protein levels of nuclear NF-κB and elevated phosphorylation levels of ERK and JNK in LPS-stimulated RAW 264.7 cells were also found downregulated by CsV treatment. Furthermore, the increase of CD14 and TLR4 mRNA expression due to LPS stimulation were significantly reversed by CsV treatment. These results suggested that CsV attenuated LPS-induced inflammatory responses partly via TLR4/CD14-mediated NF-κB and MAPK pathways.
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http://dx.doi.org/10.3109/08923973.2014.960088DOI Listing
December 2014

Sphingosine kinase-1 protects differentiated N2a cells against beta-amyloid25-35-induced neurotoxicity via the mitochondrial pathway.

Neurochem Res 2014 May 30;39(5):932-40. Epub 2014 Mar 30.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Dadao, Wuhan, 430022, Hubei Province, China.

Although the etiology of Alzheimer's disease (AD) is not fully understood, multiple lines of evidence suggests the importance of amyloid-β (Aβ) in the initiation/progression of the disease. Aβ has been shown to induce neuronal apoptosis via the sphingomyelin/ceramide pathway. This study was designed to elucidate whether the sphingosine kinase-1 (SPK1), a critical regulator of the ceramide/sphingosine 1-phosphate rheostat, plays a pivotal role in the regulation of death and survival of differentiated neuro-2a cells in response to beta-amyloid peptide fragment 25-35 (Aβ25-35). These results show that the expression of SPK1 was markedly decreased in Aβ25-35-induced neurotoxicity, as evidenced by the decreased cell viability and the increased apoptotic rate. Overexpression of SPK1 significantly attenuated Aβ25-35-induced neurotoxicity, whereas silencing the expression of SPK1 exacerbated it. Moreover, overexpression of SPK1 can significantly attenuate Aβ25-35-induced upregulation of Bax and rehabilitate the level of Bcl-2; concomitantly, it can ameliorate mitochondrial ultrastructure. These studies demonstrate that overexpression of SPK1 may moderate Aβ25-35-induced neurotoxicity by regulating the Bcl-2/Bax ratio and improving mitochondrial ultrastructure. Based on these findings, SPK1 is a potential therapeutic target for AD.
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http://dx.doi.org/10.1007/s11064-014-1290-6DOI Listing
May 2014

Induction of Dickkopf-1 contributes to the neurotoxicity of MPP+ in PC12 cells via inhibition of the canonical Wnt signaling pathway.

Neuropharmacology 2013 Apr 16;67:168-75. Epub 2012 Nov 16.

Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, Hubei Province, China.

The secreted glycoprotein Dickkopf-1 (Dkk1), an antagonist of the Wnt/β-catenin pathway, has been implicated in many neurodegenerative diseases. However, it is unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease (PD). In this study, we discovered that Dkk1 was induced in MPP(+)-treated PC12 cells and the increase of Dkk1 preceded PC12 cell loss. RhDkk1 aggravated the neurotoxicity of MPP(+) in PC12 cells. Furthermore, the level of Dkk1 was correlated with the number of apoptotic PC12 cells. The apoptosis could be decreased by Dkk1-siRNA in MPP(+)-induced PC12 cells and Dkk1-siRNA regulated the expression of β-catenin and p-Ser9-GSK-3β in MPP(+)-induced PC12 cells. LiCl (an inhibitor of GSK-3β) also rescued the loss of PC12 cell viability and the apoptosis induced by MPP(+). These data suggest that the induction of Dkk1 contributes to the MPP(+)-induced neurotoxicity in PC12 cells via inhibition of the canonical Wnt pathway and Dkk1 antagonists which could rescue the Wnt pathway might be neuroprotective in PD.
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http://dx.doi.org/10.1016/j.neuropharm.2012.10.031DOI Listing
April 2013

Inhibition of the canonical Wnt pathway by Dickkopf-1 contributes to the neurodegeneration in 6-OHDA-lesioned rats.

Neurosci Lett 2012 Sep 9;525(2):83-8. Epub 2012 Aug 9.

Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.

Dickkopf-1 (Dkk1), an antagonist of the Wnt/β-catenin pathway, has been implicated in many neurodegenerative diseases. However, it's unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease. In this study, we discovered that Dkk1 was increased in 6-hydroxydopamin(6-OHDA)-lesioned rats. In the meanwhile, inhibition of the canonical Wnt signaling pathway, including the activation of glycogen synthase kinase-3β (GSK-3β) and decrease of β-catenin, was also found in 6-OHDA-lesioned rats. Treatment with rhDkk1 aggravated the dopaminergic neuron damage of the substantia nigra and the inhibition of the canonical Wnt signaling pathway in 6-OHDA-lesioned rats, while the above effects in these rats were abolished by pretreatment with LiCl, an inhibitor of GSK-3β, for consecutive 7 d. These data suggest that Dkk1 plays an important role in the etiology of PD models and it contributes to the neurodegeneration in 6-OHDA-lesioned rats via inhibition of the canonical Wnt pathway.
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http://dx.doi.org/10.1016/j.neulet.2012.07.030DOI Listing
September 2012
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