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1.
Curr Med Chem ; 30(39): 4492-4503, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36642877

RESUMO

BACKGROUND: Lipopolysaccharide (LPS) is an endotoxin that causes inflammation, and the content of LPS increases gradually during the process of aging. Whether the response of the colon to LPS stimulation will increase with age is yet unknown. OBJECTIVE: The study investigated the effects of LPS stimulation on the colon of adult and aging rats. METHOD: 43 healthy male SD rats were divided into 4 different groups: adult group and LPS-stimulated adult group at the age of 4 months, and aging group and LPS-stimulated aging group at the age of 22 months. Rats were stimulated by intraperitoneal injection of LPS (1mg/kg) for 24 h. The morphological changes of the colon were observed, and intestinal inflammatory response, tight junction proteins, apoptosis, and proliferation in intestinal epithelial cells were detected. RESULTS: A series of morphology changes occurred in the colon of adult rats after LPS stimulation, the higher inflammatory response (TLR4, NF-κB, and IL-1ß), changes in the protein levels of tight junctions (ZO-1, Claudin1, and Claudin2), and increased apoptosis (Bax, Bcl2) and proliferation (PCNA) of intestinal epithelial cells. The above changes were also found in aging rats. LPS stimulation further promotes the above changes to some extent in the colon of aging rats. CONCLUSION: A series of colon changes in rats was significantly damaged during LPS stimulation and aging, and these changes were further aggravated to some extent in LPS-stimulated aging rats.


Assuntos
Células Epiteliais , Lipopolissacarídeos , Ratos , Masculino , Animais , Lipopolissacarídeos/farmacologia , Ratos Sprague-Dawley , Inflamação , NF-kappa B , Colo
2.
Front Pharmacol ; 13: 903762, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35754510

RESUMO

Inflammatory cytokines including TNF-α and IL-1ß impair intestinal barrier function in aging by disrupting intestinal tight junction integrity. Icariin (ICA) has a variety of pharmacological effects. Indeed, ICA produces anti-inflammatory, anti-oxidative stress, and inhibitory effects on microRNA (miRNA) expression. This study was to explore whether ICA could alleviate inflammation-associated intestinal barrier function impairment in aging and its underlying mechanism. Of particular interest, network pharmacology prediction indicated the potential therapeutic impacts of ICA for the treatment of colitis. Then, rats were used to study whether ICA has a protective effect on the reduction of tight junctions caused by inflammatory cytokines. Next, Caco-2 cell monolayers were used to explore the mechanism by which ICA alleviates the down-regulation of tight junctions. Network pharmacology prediction revealed that ICA alleviated colitis via suppressing oxidative stress. After ICA intervention, expressions of inflammatory cytokines were reduced, but tight junctions, antioxidant enzymes in aging rats were up-regulated. ICA reversed the TNF-α-induced decrease in abundance of Occludin protein in Caco-2 cell monolayers. Meanwhile, ICA alleviated the increase in permeability and expression of miR-122a. However, the protective effect of ICA was markedly attenuated after transfection with miR-122a mimics. In conclusion, ICA reduced the expressions of Occludin, Claudin1, and Claudin5 in colon, which were related to the reduction of TNF-α and IL-1ß and alleviation of colonic in vivore. And ICA attenuated TNF-α-induced Occludin disruption and epithelial barrier impairment by decreasing miR-122a expression in Caco-2 cell monolayers.

3.
Food Funct ; 13(6): 3674-3689, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35262540

RESUMO

Perfluorooctane sulfonate (PFOS) is widely recognized as causing Sertoli cell injury and testicular toxicity in males. Icariin is a flavonoid from Epimedium, which effectively improves spermatogenesis disturbance induced by several factors in clinic. However, it is unclear whether icariin improves PFOS-induced testicular toxicity. In vivo, fifty-two male mice were randomly separated into four groups: normal control group, model group, and low and high doses of icariin-treated groups, with 13 mice in each group. Except for the normal control group, the mice in the model group and icariin-treated groups were administered PFOS (10 mg kg-1) by gavage daily for 28 consecutive days, and concurrently treated with a diet containing different doses of icariin (0, 5 or 20 mg kg-1). In vitro, TM4 cells were treated with 150 µM PFOS to induce Sertoli cell injury, and were then utilized for icariin treatment. Our results demonstrated that icariin attenuated PFOS-induced testicular toxicity by increasing the testicular, epididymal and seminal vesicle weights, epididymal and seminal vesicle indices, sperm parameters, and seminiferous epithelium height. In addition, icariin improved the PFOS-induced blood-testis barrier (BTB) disruption by alleviating the Sertoli cell junctional injury, but without affecting Sertoli cell numbers in the testis of mice. Moreover, icariin increased the expression levels of tight junction proteins (ZO-1, Occludin and Claudin-11) and gap junction proteins (CX43 and p-CX43), and decreased the expression levels of p-p38MAPK and matrix metalloproteinase 9 (MMP9) both in vivo and in vitro. Furthermore, alleviation of the Sertoli cell injury by icariin exerted similar effects as SB203580 (an inhibitor of p38MAPK) in TM4 cells. This study revealed that icariin effectively reduces PFOS-induced testicular toxicity by alleviating the Sertoli cell injury and downregulating the p38MAPK/MMP9 pathway, indicating that icariin may be an attractive dietary supplement for the intervention of PFOS-induced testicular dysfunction.


Assuntos
Células de Sertoli , Testículo , Ácidos Alcanossulfônicos , Animais , Flavonoides/metabolismo , Flavonoides/farmacologia , Fluorocarbonos , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Células de Sertoli/metabolismo , Testículo/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Exp Gerontol ; 161: 111729, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35134475

RESUMO

Impaired tight junction (TJ) function and autophagy and the activated p38 mitogen-activated protein kinase (MAPK)/matrix metalloproteinase 9 (MMP9) pathway in Sertoli cells cause spermatogenic disorders. However, it is unclear whether reduced TJ barrier function and autophagy and the activated p38 MAPK/MMP9 pathway in Sertoli cells are closely associated with age-related testicular dysfunction. Thus, we evaluated these changes in Sertoli cells using 6-, 12-, 18-, and 24-month-old Sprague-Dawley rats. The results showed that testicular morphology gradually degenerated, as evidenced by increased exfoliated germ cells, decreased seminiferous tubule diameter and seminiferous epithelium height, and reduced the numbers of spermatogonia, primary spermatocytes and spermatids during the process of aging. In addition, the TJs formed by adjacent Sertoli cells were progressively destroyed accompanied by an abnormal ultrastructure and decreased expression of the TJ proteins zonula occludens-1 (ZO-1), occludin, and claudin-11 with aging. Furthermore, the expression of phosphorylated p38MAPK and MMP-9 in Sertoli cells and testis gradually increased, and the expression of occludin co-localizated with MMP-9 progressively decreased. Meanwhile, autophagy levels also gradually decreased, including decreased autophagic vacuole formation and weak expression of light chain 3 (LC3) and autophagy-related 5 (Atg5) in Sertoli cells. Taken together, our results indicate that aging causes impaired TJ barrier function and degeneration of seminiferous tubules. The mechanism might be related to the activated p38MAPK/MMP9 pathway and inactivated autophagy in Sertoli cells.


Assuntos
Células de Sertoli , Junções Íntimas , Envelhecimento , Animais , Autofagia , Masculino , Metaloproteinase 9 da Matriz , Ratos , Ratos Sprague-Dawley , Células de Sertoli/metabolismo , Células de Sertoli/ultraestrutura , Testículo , Junções Íntimas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Exp Gerontol ; 152: 111460, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34175407

RESUMO

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.


Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , Testículo , Envelhecimento , Animais , Apoptose , Dano ao DNA , Reparo do DNA , Masculino , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo
6.
Geriatr Gerontol Int ; 21(1): 85-93, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33244850

RESUMO

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 (UPRER ). 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 UPRER 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 UPRER 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 UPRER 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 URPER changes. Geriatr Gerontol Int 2021; 21: 85-93.


Assuntos
Panax , Saponinas , Envelhecimento , Animais , Colo , Estresse do Retículo Endoplasmático , Plexo Mientérico , Neurônios , Ratos , Sinucleínas
7.
Curr Pharm Biotechnol ; 22(10): 1369-1379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33176641

RESUMO

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-1ß 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.


Assuntos
Panax notoginseng , Saponinas , Animais , Proteínas de Ciclo Celular , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ratos Sprague-Dawley
8.
Front Pharmacol ; 11: 677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528279

RESUMO

Sertoli cells play crucial roles in spermatogenesis and are impaired by aging. Icariin, a flavonoid from Epimedium, 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 via 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) in vivo and in vitro. 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 ERα and Nrf2 signaling in Sertoli cells. Parallel in vitro studies also demonstrated that icariin inhibited untoward effects on the TM4 mouse Sertoli cell line with concomitant upregulation of ERα and Nrf2 signaling. Conversely, ERα 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 via the ERα/Nrf2 signal-transduction pathway. Thus, mitigating Sertoli cell damage via the ERα/Nrf2 signaling pathway likely represents a promising strategy for the prevention of age-related testicular dysfunction.

9.
Arab J Gastroenterol ; 21(1): 43-48, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32241700

RESUMO

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, ß-catenin and BMP4 were examined by Immunohistochemistry staining. Levels of Bmi1, GSK-3ß, 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.


Assuntos
Envelhecimento/fisiologia , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/metabolismo , Jejuno/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Animais , Proliferação de Células , Glicogênio Sintase Quinase 3 beta/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Jejuno/patologia , Masculino , Complexo Repressor Polycomb 1/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/fisiologia
10.
Curr Pharm Biotechnol ; 21(8): 667-680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31840608

RESUMO

BACKGROUND: Oxidative stress and mitochondrial dysfunction play a vital role in the pathogenesis of brain aging. Saponins from Panax japonicus (SPJ) have attracted much attention for their potential to attenuate age-related oxidative stress as the main ingredient in rhizomes of Panax japonicus. OBJECTIVE: This study aimed to investigate the neuroprotective effects of SPJ on natural aging rats as well as the underlying mechanisms regarding oxidative stress and mitochondrial pathway. METHODS: Sprague-Dawley rats were divided into control groups (3-, 9-, 15- and 24-month old groups) and SPJ-treated groups. For SPJ-treated groups, SPJ were orally administrated to 18-month old rats at doses of 10 mg/kg, 30 mg/kg and 60 mg/kg once daily. Control groups were given the same volume of saline. After the treatment with SPJ or saline for six months, the cortex and hippocampus were rapidly harvested and deposited at -80°C after the rats were decapitated under anesthesia. The neuroprotective effects of SPJ were estimated by histopathological observation, TUNEL detection, biochemical determination and western blotting. RESULTS: SPJ improved pathomorphological changes in neuronal cells and decreased apoptosis in the cortex and hippocampus of aging rats, increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na+/K+-ATPase, Ca2+-ATPase and Ca2+/Mg2+-ATPase whereas, decreased malondialdehyde (MDA) contents in the cortex of aging rats. Furthermore, the SPJ increased silent mating type information regulation 2 homolog-1 (SIRT1) protein expression, decreased acetylated level of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the cortex and hippocampus of aging rats, and reversed the aging-induced decline of Forkhead box O3 (Foxo3a), Superoxide Dismutase 2 (SOD2), microtubule-associated protein light chain 3 (LC3II) and Beclin1 levels in the cortex and hippocampus. CONCLUSION: Our data showed that SPJ conferred neuroprotection partly through the regulation of oxidative stress and mitochondria-related pathways in aging rats.


Assuntos
Envelhecimento/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Saponinas/farmacologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Masculino , Malondialdeído/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Fármacos Neuroprotetores/isolamento & purificação , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo
11.
Int J Clin Exp Pathol ; 12(9): 3279-3289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934171

RESUMO

BACKGROUND: Studies have reported that the unfolded protein response of ER (UPRER) declines in the several organs of aging mice. However, changes of UPRER during the aging process in the intestine are rarely reported. Our previous studies have demonstrated that Saponins from Panax japonicus (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 UPRER in the intestine of 6- to 24-month-old rats by an immunohistochemical (IHC) method and determined whether SPJ could regulate the three different UPRER 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 UPRER branches were determined by immunohistochemistry (IHC). Results: Total expressions of GRP78 and p-JNK increased, and other UPRER 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 UPRER branches in the different layers of colon in rats. CONCLUSION: The study demonstrated that UPRER declined and GRP78 increased in the colon of aging rats. SPJ could reverse most URPER changes in the colon of aging rats. This study also showed different expression patterns of the three branches of UPRER in different layers of the colon in rats.

12.
Andrologia ; 51(2): e13181, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30393883

RESUMO

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.


Assuntos
Envelhecimento/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Espermatozoides/metabolismo , Testículo/metabolismo
13.
Arch Med Sci ; 14(2): 396-406, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29593815

RESUMO

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 Panax japonicus (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 Panax japonicus 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.

14.
J Ginseng Res ; 42(1): 50-56, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29348722

RESUMO

BACKGROUND: Saponins from Panax japonicus (SPJ) are the most abundant and main active components of P. japonicus, 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-1ß 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-1ß 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.

15.
Phytother Res ; 32(2): 243-250, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29130614

RESUMO

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, LC3ß, 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.


Assuntos
Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Panax notoginseng/química , Saponinas/uso terapêutico , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia
16.
Neural Regen Res ; 12(11): 1877-1884, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29239335

RESUMO

Neuroinflammation is recognized as an important pathogenic factor for aging and related cognitive disorders. Mitogen-activated protein kinase and nuclear factor kappa B signaling pathways may mediate neuroinflammation. Saponins from Panax japonicus are the most abundant and bioactive members in rhizomes of Panax japonicus, and show anti-inflammatory activity. However, it is not known whether saponin from Panax japonicus has an anti-inflammatory effect in the aging brain, and likewise its underlying mechanisms. Sprague-Dawley rats were divided into control groups (3-, 9-, 15-, and 24-month-old groups) and saponins from Panax japonicus-treated groups. Saponins from Panax japonicus-treated groups were orally administrated saponins from Panax japonicus at three doses of 10, 30, and 60 mg/kg once daily for 6 months until the rats were 24 months old. Immunohistochemical staining and western blot assay results demonstrated that many microglia were activated in 24-month-old rats compared with 3- and 9-month-old rats. Expression of interleukin-1ß, tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase increased. Each dose of saponins from Panax japonicus visibly suppressed microglial activation in the aging rat brain, and inhibited expression levels of the above factors. Each dose of saponins from Panax japonicus markedly diminished levels of nuclear factor kappa B, IκBα, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. These results confirm that saponins from Panax japonicus can mitigate neuroinflammation in the aging rat brain by inhibition of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways.

17.
Oncotarget ; 8(19): 31023-31040, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28415686

RESUMO

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-1ß 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.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Oleanólico/análogos & derivados , Paniculite/etiologia , Paniculite/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Ácido Oleanólico/farmacologia , Paniculite/tratamento farmacológico , Paniculite/patologia
19.
J Pharm Pharmacol ; 69(3): 295-304, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27935635

RESUMO

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-1ß, COX-2 and TNF-α in testis tissues. Similarly, OA remarkably inhibited IL-1ß 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.


Assuntos
Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Células Germinativas/efeitos dos fármacos , Ácido Oleanólico/farmacologia , Testículo/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Células Germinativas/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Can J Physiol Pharmacol ; 94(9): 919-28, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27332950

RESUMO

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.


Assuntos
Peróxido de Hidrogênio/farmacologia , Neuroblastoma/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Naftóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Saponinas/antagonistas & inibidores
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