The plant extract PNS mitigates atherosclerosis via promoting Nrf2‐mediated inhibition of ferroptosis through reducing USP2‐mediated Keap1 deubiquitination

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 3, 2024

Background and purpose Atherosclerosis is the basis of cardiovascular disease. Ferroptosis a form programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS ( Panax notoginseng saponins ), containing main active ingredients , exhibits anti‐atherogenic properties. Herein, we determined whether its major components could attenuate atherosclerosis suppressing ferroptosis revealed underlying mechanism(s). Experimental approach effects their association with inhibition was in apoE −/− mice. In vitro, anti‐ferroptotic effect mechanism(s) were demonstrated presence inducers. Expression markers ubiquitination Keap1 evaluated USP2 macrophages. Finally, knockout using mice treated high‐fat diet (HFD) AAV‐PCSK9. Key results inhibited vivo. suppressed ferroptosis‐aggravated foam formation inflammation vitro. Mechanistically, activated Nrf2 antagonizing Keap1, attributed expression. antagonized inflammation, thus mitigating atherosclerosis. abolished inhibitory on Conclusion implications reduced USP2‐mediated de‐ubiquitination promoted degradation, thereby activating Nrf2, improving iron metabolism reducing contributing an anti‐atherosclerotic outcome. Our study PNS.

Язык: Английский

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Unveiling the Neurodegenerative Alterations through Oral Stem Cells

Journal of Dental Research, Год журнала: 2024, Номер unknown

Опубликована: Сен. 14, 2024

Parkinson’s disease (PD) is a neurodegenerative condition characterized by the progressive and selective loss of dopaminergic (DAergic) neurons in midbrain. The replacement neuromelanin (NM)–containing DAergic substantia nigra enhancement NM concentration could offer promising safe approach to treating PD symptoms. objective this study was investigate compare potential human periapical-cysts mesenchymal stem cells (hPCy-MSCs) dental pulp (DPSCs) differentiate into NM-producing generate functional 3-dimensional (3D) midbrain-like organoids vitro. We assessed changes morphology behavior neuron-like (NLCs) as well expression molecular markers characterizing neurons. Furthermore, we observed electrically active functionally mature means electrophysiological assays, dosage quantification dopamine release high-performance liquid chromatography. Our results demonstrate for first time that both hPCy-MSCs DPSCs are capable differentiating NLCs, further confirmed increase lactate levels medium exposed neurogenic conditions. Importantly, have induced such NLCs Finally, 3D been produced from oral cells: they appear neurosphere-like structures diffusely expressing neural marker β-III tubulin containing NM-like granules. findings open up novel fascinating opportunity rethink cells, derived models, strategic reliable tool unveiling alterations.

Язык: Английский

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Antioxidant peptides from silver carp steak by alkaline protease and flavor enzyme hydrolysis: Characterization of their structure and cytoprotective effects against H₂O₂‐induced oxidative stress

Journal of Food Science, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Abstract Silver carp steak is a rarely utilized silver processing byproduct. This study aimed to optimize dual enzymatic method extract antioxidant peptide components from and characterize their structure in vitro activity through ultrafiltration purification, response surface methodology, molecular docking, radical scavenging analysis. The optimal extraction conditions for peptides (SCSAP) were determined as 1:6 solid–liquid ratio, 1500 U/g alkaline protease addition, 4 h hydrolysis time, 1946 flavor enzyme 2.5 time. <3 kDa SCSAP component (SCSAP‐3kDa) showed the strongest activity, with its 1,1‐diphenyl‐2‐trinitrophenyl hydrazine (DPPH) rate, ABTS hydroxyl metal ion chelating reducing capacity reaching 88.75%, 91.21%, 67.02%, 69.07%, 0.985, respectively. Moreover, three (PF‐7, GP‐8, YF‐10) of 100 µg/mL could protect HepG2 cells oxidative stress damage by level activating Keap1‐Nrf2‐ARE pathways, enabling an increase superoxide dismutases (SOD) decrease malondialdehyde (MDA) content reactive oxygen species (ROS) level. integrated results indicate enormous potential SCSAP‐3kDa functional food ingredient industry. Practical Application selected index developed facile obtain biological providing theoretical basis bioavailability contributing application new foods.

Язык: Английский

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Ellagic Acid Supplementation Ameliorates Cisplatin-Induced Liver Injury in Mice via the Activation of Nrf2/HO-1 Pathway and the Inhibition of NF-kB Pathway

Опубликована: Окт. 2, 2023

Cisplatin (CDDP), an important chemotherapeutic agent, could result in potential hepatotoxicity, but the precious molecular mechanisms remain unclear. In this study, protective effect of ellagic acid (EA) on CDDP exposure-induced hepatotoxicity and underlying were investigated using a mouse model. Mice randomly divided into control, model, EA100 (i.e., EA 100 mg/kg/day), plus 25, 50, mg/kg/day. all CDDP-treated groups intraperitoneally injected with 20 mg/kg/day for 2 days. co-treatments, mice orally administrated 7 Our results found that, compared to control group, treatment resulted liver dysfunction, oxidative stress, hepatocyte necrosis, which are effectively revised by supplementation dose-dependent manner. Meanwhile, inhibited CDDP-induced elevation caspases-9 -3 activities tissues mice. Furthermore, significantly downregulated increases NF-&kappa;B, IL-1&beta;, TNF-&alpha;, IL-6 proteins mRNAs, while further upregulated expression Nrf2, HO-1 mRNAs. Taken together, our reveal that ameliorate CCDP-induced injury via opposite regulation Nrf2/HO-1 NF-kB pathways.

Язык: Английский

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International Journal of Pharmaceutical Sciences and Research, Год журнала: 2023, Номер 14(9)

Опубликована: Сен. 1, 2023

Parkinson's disease (PD) is the second most prevalent type of neurodegenerative disorder and a chronic, progressive condition.In current investigation, we used rotenone (ROT)-developing rat model PD to assess neuroprotective efficacy ethanolic Withania somnifera root extract (EWSR) in comparison known neuroprotectants i.e., Doxycycline (Doxy), ellagic acid (EA) individually combination (EWSR-Doxy-EA).Male Wistar rats were given ROT at dose 2.5 mg/kg body weight daily for 4 weeks develop invivo model.Once confirmed, treated with individual next 5 kept under observation 7 days reversal PD.ROT administration has altered behavioural parameters (Cognitive, motor dysfunction, sniffing, grooming, raring, crossing, etc.) neurotransmitter profile (Acetylcholine, epinephrine, nor-epinephrine, dopamine, glutamate aspartate) rats.The ameliorated deleterious effects restored cognitive control by rectifying levels neurotransmitters which are responsible functions.EWSR protective was significantly better that (Doxy EA) EWSR increased when combined other neuroprotectants.Based on study observations, it can be inferred good agent act as potential alternative therapeutic approach or drugs treating diseases.INTRODUCTION: progressive, late-onset condition marked development fibrillar cytoplasmic inclusions containing α-synuclein ubiquitin relatively selective nigrostriatal dopaminergic loss.

Язык: Английский

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