Gentaur Pub

#35752797   2022/06/25 To Up

Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway.

Globally, ischemic stroke is a major health threat to humans that causes lifelong disability and death. Mentha arvensis (MA) has been used in traditional medicine to alleviate oxidative stress and inflammation-related disorders. In the present study, the neuroprotective properties of fermented MA (FMA) extract were investigated in the gerbil and SH-SY5Y cells. model of transient global cerebral ischemia.
Md Sadikul Islam, Ha-Young Shin, Yeo-Jin Yoo, Eui-Yong Lee, Ryunhee Kim, Young-Jin Jang, Md Rashedunnabi Akanda, Hyun-Jin Tae, In-Shik Kim, Dongchoon Ahn, Byung-Yong Park

2607 related Products with: Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway.

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#35752418   2022/06/22 To Up

Corydecumine G Inhibits Microglia Activation via MAPK Pathway in a Rat Model of Neuropathic Pain.

Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability. The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms.
Liaoxi Tan, Yixin Hu, Xinyi Zhang, Chunlei Zhang, Chuchu Xi, Zhao Yang, Zhengyu Cao, Fang Zhao

2645 related Products with: Corydecumine G Inhibits Microglia Activation via MAPK Pathway in a Rat Model of Neuropathic Pain.

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#35752350   2022/06/22 To Up

Role of olmesartan in ameliorating diabetic nephropathy in rats by targeting the AGE/PKC, TLR4/P38-MAPK and SIRT-1 autophagic signaling pathways.

Diabetic nephropathy (DN) is one of the most serious consequences of diabetes and the most common reason for end-stage renal disease. The current study was set out to investigate the ability of olmesartan medoxomil (OM) to treat DN by evaluating the reno-protective effects of this drug on fat/fructose/streptozotocin (F/Fr/STZ)-induced diabetic rat model. This model was induced by feeding rats high F/Fr diet for 7 weeks followed by injection of a single sub-diabetogenic dose of STZ (35mg/kg; i.p). The F/Fr/STZ-induced diabetic rats were orally treated with either OM (10 mg/kg) or pioglitazone (10 mg/kg); as a standard drug daily for four consecutive weeks. F/Fr/STZ-induced diabetic rats propagated inflammatory, oxidative, and fibrotic events. OM was able to oppose the injurious effects of diabetes; it significantly reduced the elevated levels of advanced glycated end products (AGEs) and downregulated PKC gene expression, therefore, indicating its antioxidant capacity evidenced by mitigation in GSH, MDA renal content. Moreover, OM impaired the inflammatory cascade by suppressing the elevated level of renal TLR4 as well as diminished the inflammatory profibrotic cytokine TGF-β1. Additionally, OM was able to turn off the MAPK cascade mediated by an upsurge in renal angiotensin 1-7 content and decrease the level of renal tubular injury marker, KIM-1. Furthermore, OM enhanced the autophagic activity pathway by upregulating of gene expression of SIRT-1. The histopathological examination confirmed these results. Finally, OM protected against type 2 diabetes-related nephropathy complications by altering inflammatory pathways, oxidative, fibrotic, and autophagic processes triggered by renal glucose overload. This study shows that OM has a reno-protective effect against DN in rats by inhibiting the AGE/PKC, TLR4/P38-MAPK, and SIRT-1 autophagic signaling pathways.
Nesma M E Abo El-Nasr, Dalia O Saleh, Ingy M Hashad

1735 related Products with: Role of olmesartan in ameliorating diabetic nephropathy in rats by targeting the AGE/PKC, TLR4/P38-MAPK and SIRT-1 autophagic signaling pathways.

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#35752281   2022/06/22 To Up

Discovery of 7, 4'-dimethoxy-3-hydroxyflavone as a protease-activated receptor 4 antagonist with antithrombotic activity and less bleeding tendency in mice.

There is growing evidence of the importance of protease-activated receptor 4 (PAR4), one of thrombin receptors, as a therapeutic target in thrombotic cardiovascular diseases. In the present study, we utilized ligand-based virtual screening, bioassay, and structure-activity relationship study to discover PAR4 antagonists with new chemical scaffolds from natural origin, and examined their application as antiplatelet agents. By using these approaches, we have identified a flavonoid, 7, 4'-dimethoxy-3-hydroxyflavone, that exhibits anti-PAR4 activity. 7, 4'-Dimethoxy-3-hydroxyflavone inhibited PAR4-mediated human platelet aggregation, GPIIb/IIIa activation, and P-selectin secretion. Also, it inhibited PAR4 downstream signaling pathways, including Ca/protein kinase C, Akt, and MAP kinases ERK and p38, in human platelets, and suppressed PAR4-mediated β-arrestin recruitment in CHO-K1 cells exogenously expressed human PAR4. In a microfluidic system, 7, 4'-dimethoxy-3-hydroxyflavone reduced thrombus formation on collagen-coated chambers at an arterial shear rate in recalcified whole blood. Furthermore, mice treated with 7, 4'-dimethoxy-3-hydroxyflavone were significantly protected from FeCl-induced carotid arterial occlusions, without significantly affecting tail bleeding time. In conclusion, 7, 4'-dimethoxy-3-hydroxyflavone represents a new class of nature-based PAR4 antagonist, it shows effective in vivo antithrombotic properties with less bleeding tendency, and could be a potential candidate for developing new antiplatelet agents.
Ying-Ting Lin, Yu Li, Hui-Ching Hsu, Ju-Ying Tsai, Jia-Hau Lee, Chi-Jung Tai, Ming-Jung Wu, Chin-Chung Wu

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#35751164   // To Up

LGI3 promotes human keratinocyte migration in high-glucose environments by increasing the expression of β-catenin.

The leucine-rich repeat LGI family member 3 (LGI3) has been reported to regulate various functions in epidermal keratinocytes. In this study, we investigated the effects of LGI3 on keratinocyte migration in environments with different glucose concentrations. Our results showed that cell migration is markedly impaired in high-glucose environments compared to in low-glucose environments (control). Nevertheless, the use of LGI3 in high-glucose environments restores cell migration to the normal level. Therefore, we performed LGI3 knockdown to identify the role of LGI3 in cell migration. It was observed that transfecting LGI3 siRNA into HaCaT cells reduces the expression of LGI3 and inhibits wound closure. These results indicate that LGI3 is deeply involved in wound healing in high-glucose environments. Western blot analysis showed that in high-glucose environments, LGI3 increases the phosphorylation of Akt, forkhead box protein O1, and focal adhesion kinase. However, no change was observed in the levels of glycogen synthase kinase 3β, c-Jun N-terminal kinase, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. Further results showed that LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, reduced LGI3-induced cell migration. It is generally known that Akt activation leads to the accumulation of β-catenin, an important mediator of keratinocyte migration. LGI3 greatly increased the expression of β-catenin in high-glucose environments comparison to that in the low-glucose environments. Taken together, these data indicate that LGI3 induces keratinocyte migration in high-glucose environments as a result of β-catenin accumulation via Akt phosphorylation. Therefore, LGI3 can be considered a new treatment option for diabetic wound healing.
So Yeon Kim, Young-Yoon Kim, In Wook Kim, Hye-Young Yun, Dong-Seok Kim

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#35750096   2022/06/21 To Up

Tectoridin exhibits anti-rheumatoid arthritis activity through the inhibition of the inflammatory response and the MAPK pathway in vivo and in vitro.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation infiltration of the synovial tissues and the fibroblast-like synoviocytes. Tectoridin is a botanical active ingredient with anti-inflammatory properties. In this study, the anti-arthritic effects of tectoridin and its mechanism of action are examined in TNF-α-induced human fibroblast-like synovial cells (HFLSs cells) and complete Freund's adjuvant (CFA)-stimulated arthritic mice. Arthritis progression was evaluated via bodyweight, hind paw swelling, organ index, and synovial pathology. IL-1β, IL-6 and other pro-inflammatory factors concentrations, and the expression of MAPK pathway proteins in HFLSs cells and arthritic mice were measured using ELISA and western blotting. Results showed that tectoridin significantly decreased the swelling of the paws and joints as well as the increased immune organ index within CFA-induced arthritic mice. Histopathological analysis showed that tectoridin alleviated the lesions of ankle joints and synovial tissues induced by CFA. Secretion of pro-inflammatory cytokines in TNF-α-induced HFLSs cells and CFA-stimulated arthritic mice were also abated by tectoridin. Similarly, the presence of tectoridin significantly inhibited the abnormal phosphorylation levels of ERK, JNK, and p38 in vivo and in vitro. All those results highlighted that tectoridin exhibits anti-arthritis effects by inhibiting MAPK-mediated inflammatory responses.
Qiuxia Huang, Xin Xiao, Jinjin Yu, Yajie Yang, Jiabao Yu, Yang Liu, Huixin Song, Tengfei Han, Dezhu Zhang, Xiaofeng Niu, Weifeng Li

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#35749999   2022/06/21 To Up

miR-146b suppresses LPS-induced M1 macrophage polarization via inhibiting the FGL2-activated NF-κB/MAPK signaling pathway in inflammatory bowel disease.

M1 macrophage polarization and phenotype in Inflammatory Bowel Disease (IBD) are common biological responses.
Yang Pan, Dan Wang, Fan Liu

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#35749612   2022/06/24 To Up

DPP-4 inhibitor linagliptin ameliorates imiquimod-induced psoriasis-like skin alterations in type 2 diabetic mice by inhibiting the MAPK/NF-κB inflammatory pathway.

Studies have shown that the DPP-4 inhibitor was effective in improving skin damage in patients with psoriasis, but the exact mechanism was not known. To investigate the therapeutic effects of linagliptin in mice with type 2 diabetes mellitus (T2DM) with psoriasis and its possible therapeutic mechanisms. A total of 32 db/db mice and 16 db/m mice were randomly divided into six groups: normal group, psoriasis group, diabetes group, diabetes combined with psoriasis group, linagliptin-treated diabetes group, and linagliptin-treated diabetes combined with psoriasis group. The levels of serum fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured; the levels of serum FINS were determined by enzyme-linked immunoassay and the insulin resistance index was calculated. Basic parameters of diabetes, Psoriasis Area and Severity Index, histopathology of skin, the expression of interleukin (IL)-17A, IL-23, IL-22, and tumor necrosis factor (TNF)-α, and expression levels of measuring p-ERK, p-MAPK and p-nuclear factor kappa B (NF-κB) in skin tissues were measured. After treatment with linagliptin, insulin resistance, and TC and TG levels were reduced in mice with T2DM and psoriasis (p < .05). Moreover, the degree of epidermal tissue thickening, number of keratinized layers, and inflammatory cell infiltration were also reduced (p < .05), as well as the expression levels of inflammatory factors: TNF-α, IL-1β, IL-17A, IL-23, and p-P38/P38, p-ERK/ERK, p-P65/P65 proteins (p < .05). Linagliptin significantly reduced the extent of skin lesions and skin inflammation. The underlying mechanism of this compound may be related to the inhibition of MAPK/NF-κB inflammatory pathways and the consequential improvement of insulin resistance.Significance Statement: In this study, we evaluated the therapeutic effect of the DPP-4 inhibitor linagliptin using a murine model of type 2 diabetes combined with psoriasis, and its potential mechanisms of action were further explored. The results of this study will help to uncover the pathogenesis of type 2 diabetes and psoriasis and, more importantly, provide a theoretical basis for the search for safe and effective drugs in the treatment of this specific patient population.
Zhulin Shao, Xiaohong Li, Xiangjin Xu, Pin Chen

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#35748981   2022/06/24 To Up

Lactose on the basolateral side of mammary epithelial cells inhibits milk production concomitantly with signal transducer and activator of transcription 5 inactivation.

Mammary epithelial cells (MECs) are the only cells capable of synthesizing lactose. During lactation, alveolar MECs secrete lactose through the apical membrane into the alveolar lumen, whereas alveolar tight junctions (TJs) block the leakage of lactose into the basolateral sides of the MECs. However, lactose leaks from the alveolar lumen into the blood plasma in the mastitis and after weaning. This exposes the basolateral membrane of MECs to lactose. The relationship between lactose in blood plasma and milk production has been suggested. The present study determined whether lactose exposure on the basolateral membrane of mouse MECs adversely affects milk production in vitro. Restricted exposure to lactose on the basolateral side of the MECs was performed using a culture model, in which MECs on the cell culture insert exhibit milk production and less-permeable TJs. The results indicated that lactose exposure on the basolateral side inhibited casein and lipid production in the MECs. Interestingly, lactose exposure on the apical side did not show detectable effects on milk production in the MECs. Basolateral lactose exposure also caused the inactivation of STAT5, a primary transcriptional factor for milk production. Furthermore, p38 and JNK were activated by basolateral lactose exposure. The activation of p38 and JNK following anisomycin treatment reduced phosphorylated STAT5, and inhibitors of p38 blocked the reduction of phosphorylated STAT5 by basolateral lactose exposure. These findings suggest that lactose functions as a partial inhibitor for milk production but only when it directly makes contact with the basolateral membrane of MECs.
Ken Kobayashi, Haruka Wakasa, Liang Han, Taku Koyama, Yusaku Tsugami, Takanori Nishimura

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#35747752   2022/06/07 To Up

Antifibrotic Mechanism of Piceatannol in Bleomycin-Induced Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by myofibroblast accumulation and extracellular matrix deposition, which lead to irreversible damage of the lung's architecture and the formation of fibrotic lesions. IPF is also a sequela in serious patients with the coronavirus disease 2019 (COVID-19). The molecular mechanisms under pulmonary fibrosis remain unclear, and there is no satisfactory treatment currently available. Piceatannol (PIC) is a naturally occurring resveratrol analog found in a variety of dietary sources such as grapes, passion fruit, and white tea. It has been reported to inhibit liver fibroblast growth and exhibited various antitumor activities, although its role in pulmonary fibrosis has not been established yet. In the present study, we evaluated the anti-fibrotic role of PIC in bleomycin (BLM)-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with PIC, and fibrotic changes were measured by hematoxylin-eosin (H&E) staining and hydroxyproline assay. Luciferase assay, Western blot assay, histological analysis, and immunofluorescence staining were used to evaluate the effect of PIC on fibroblast activation and autophagy in mouse embryonic fibroblast cells (NIH-3T3) and human lung fibroblast cells (HFL1). The anti-fibrotic mechanisms of PIC were either confirmed . Our results showed that PIC significantly alleviated the bleomycin-induced collagen deposition and myofibroblast accumulation. and studies indicated that PIC plays a role in activating autophagy in the process of anti-fibroblast activation. Further mechanism studies demonstrated that PIC can promote autophagy inhibiting the TGF-β1-Smad3/ERK/P38 signaling pathway, which leads to a decreased number of activated myofibroblasts. Our study demonstrated for the first time that PIC possesses the protective effects against bleomycin-induced pulmonary fibrosis due to the direct pulmonary protective effects which enhance the effect of autophagy and and finally leads to the decreased number of activated myofibroblasts. PIC may serve as a candidate compound for pulmonary fibrosis therapy and attenuates the sequelae of SARS-COV-2 pulmonary fibrosis.
Hanjing Sheng, Gang Lin, Shengxian Zhao, Weibin Li, Zhaolin Zhang, Weidong Zhang, Li Yun, Xiaoyang Yan, Hongyu Hu

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