NEUROCHEMICAL RESEARCH
·
2024
·Vol. 50
·期 1
·1-12
·
IF 3.7
Chen Hao,Zhao Haosen
Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.
研究领域:
神经科学
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干细胞研究
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yassmin Raafat Hassan,Riham A. El-Shiekh,Hala M. El Hefnawy,Osama G. Mohamed,Karema Abu-Elfotuh,Ahmed M. Hamdan,Alshaymaa Darwish,Ayah M.H. Gowifel,Ashootosh Tripathi,Camilia George Michael
Ethnopharmacological relevance Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill., also known as “African mango” or “bush mango”, belonging to family Irvingiaceae, has been mostly used as food and traditional medicine for weight loss and to enhance the health. Aim of the study The overconsumption of high-fat and high-carbohydrate (HFHC) food induces oxidative stress, leading to neurological and cognitive dysfunction . Consequently, there is an immediate need for effective treatment. Hence, this study explored the efficacy of orlistat , metformin , and I. gabonensis seeds' total aqueous extract (IG SAE) in addressing HFHC-induced cognitive impairment by mitigating oxidative stress and their underlying mechanistic pathways. Materials and methods Initially, the secondary metabolite profile of IG SAE is determined using high-performance liquid chromatography coupled with a mass detector (UHPLC/MS). The in vivo study involves two phases: an established model phase with control (10 rats on a standard diet) and HFHC diet group (50 rats) for 3 months. In the study phase, HFHC is divided into 5 groups. The first subgroup receives HFHC diet only, while the remaining groups each receive HFHC diet with either Orlistat, metformin, or IG SAE at doses of 100 mg/kg and 200 mg/kg, respectively, for 28 days. Results More than 150 phytoconstituents were characterized for the first holistic approach onto IG metabolome. Characterization of IG SAE revealed that tannins dominate metabolites in the plant. Total phenolics and flavonoids were estimated to standardize our extract (77.12 ± 7.09 μg Gallic acid equivalent/mg extract and 8.039 ± 0.53 μg Rutin equivalent/mg extract, respectively). Orlistat, metformin, and IG SAE successfully reduced the body weight, blood glucose level, lipid profile, oxidative stress and neurotransmitters levels leading to improved behavioral functions as well as histological alternation. Also, IG SAE halted inflammation, apoptosis, and endoplasmic reticulum stress, together with promoting autophagy, via modulation of PI3K/AKT/GSK-3β/CREB, PERK/CHOP/Bcl-2 and AMPK/SIRT-1/m-TOR pathways. Conclusion Metformin, orlistat, and IG SAE offer a promising multi-target therapy to mitigate HFHC diet-induced oxidative stress, addressing cognitive function. This involves diverse molecular mechanisms, particularly the modulation of inflammation, ER stress, and both PI3K/AKT/GSK-3β/CREB and AMPK/SIRT-1/m-TOR pathways. Furthermore, the higher dose of IG SAE demonstrated effects comparable to orlistat and metformin across most studied parameters.
研究领域:
民族药理学
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药理学
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神经科学
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代谢组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Wang Shuai,Bai Jie,Che Yilin,Qu Weikun,Li Jing
Background: Humans with hypertensive heart disease are more likely to experience heart failure, arrhythmia, myocardial infarction, and sudden death, and it is crucial to treat this condition. Fucoidan (FO) is a natural substance derived from marine algae that has antioxidant and immunomodulatory activities. FO has also been shown to regulate apoptosis. However, whether FO can protect against cardiac hypertrophy is unknown.Methods: We investigated the effect of FO in hypertrophic models in vivo and in vitro. C57BL/6 mice were given an oral gavage of FO (300 mg/kg/day) or PBS (internal control) the day before surgery, followed by a 14-day infusion of Ang II or saline. AC-16 cells were treated with si-USP22 for 4 h and then treated with Ang II (100 nM) for 24 h. Systolic blood pressure (SBP) was recorded, echocardiography was used to assess cardiac function, and pathological changes in heart tissues were assessed by histological staining. Apoptosis levels were detected by TUNEL assays. The mRNA level of genes was assessed by qPCR. Protein expression was detected by immunoblotting.Results: Our data showed that USP22 expression was lowered in Ang II-infused animals and cells, which could promote cardiac dysfunction and remodeling. However, treatment with FO significantly upregulated the expression of USP22 and reduced the incidence of cardiac hypertrophy, fibrosis, inflammation, and oxidative responses. Additionally, FO treatment lowered p53 expression and apoptosis while increasing Sirt 1 and Bcl-2 expression.Conclusion: By reducing the level of Ang II-induced apoptosis through the regulation of USP22/Sirt 1 expression, FO treatment might improve cardiac function. According to this study, FO might be potential targeted approach for treating heart failure.
研究领域:
心脏病学
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药理学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Dong-Shuai Shen,Ya-Jun Yang,Xiao-Jun Kong,Ning Ma,Xi-Wang Liu,Shi-Hong Li,Zeng-Hua Jiao,Zhe Qin,Mei-Zhou Huang,Jian-Yong Li
Aspirin eugenol ester (AEE) was a promising drug candidate for treating inflammation, pain and fever and preventing cardiovascular diseases with fewer side effects than its precursors. Previous researches indicated that AEE could markedly inhibit agonist-induced platelet aggregation in vitro and ex vivo , however, the anti-platelet aggregation mechanisms of AEE remain to be defined. Here, AEE in vitro effects on agonist-induced granule-secretion, intercellular Ca 2+ mobilization and thromboxane A 2 (TXA 2 ) generation were examined. Vasodilator-stimulated phosphoprotein (VASP), mitogen-activated protein kinase (MAPK), Akt, Sirt 1 and CD40L expressions were also studied. In agonist-activated platelets in vitro , AEE markedly attenuated granule secretion markers (P-selectin expression and ATP release), intercellular Ca 2+ mobilization and thromboxane B 2 (TXB 2 ) formation. AEE also attenuated CD40L activation, suppressed extracellular-signal-regulated protein kinase 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1) and Akt phosphorylation, and recovered Sirt1 expression, but the activation of p38, VASP Ser157 and VASP Ser239 , and the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were not affected by AEE. Overall, this study demonstrates that AEE inhibits agonist-induced platelet aggregation in vitro by regulating PI3K/Akt, MAPK and Sirt 1/CD40L pathways.
研究领域:
药理学
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心血管疾病
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分子生物学
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炎症研究
✓ 已验证
DOI
PubMed
高影响因子
Human Cell
·
2022
·Vol. 35
·期 5
·1424-1439
·
IF 4.374
Liu Wen,Li Guojuan,Li Jing,Chen Wei
The long-term treatment of glucocorticoids is a common cause of osteoporosis (OP). This study concentrated on inquiring into the regulatory role and potential mechanisms of TRG-AS1 on dexamethasone (Dex)-induced OP in rats. We adopted Dex to treat rat osteoblasts and rats to simulate in-vitro and in-vivo OP models, respectively. Gain-of-function assays of TRG-AS1, miR-802 and CAB39 were constructed in rat osteoblasts to make certain the influence of TRG-AS1, miR-802 and CAB39 on differentiation, proliferation and apoptosis of rat osteoblasts. TRG-AS1 and CAB39 were down-regulated in the Dex-induced OP model in rats, in contrast to miR-802. Overexpression of TRG-AS1 restrained Dex-induced inhibition of osteogenic differentiation, promoted CAB39/AMPK/SIRT-1 and inhibited NF-κB, while overexpression of miR-802 bridled the inhibitory effect of TRG-AS1 on OP. miR-802 was targeted by TRG-AS1, and inhibited CAB39. Inhibition of either AMPK or SIRT-1 abated the osteogenic differentiation-promoting effect of CAB39. Animal experiments displayed that overexpressing TRG-AS1 alleviated Dex-induced OP in rats. In conclusion, up-regulation of TRG-AS1 protected against glucocorticoid-induced OP in rats by modulating the miR-802-mediated CAB39/AMPK/SIRT-1/NF-κB axis.
研究领域:
分子生物学
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药理学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Shuo Deng,Qing Zhao,Daxu Liu,Zhiqiang Xiong,Siyu Zhang,Xuejiao Zhang,Fengchang Wu,Baoshan Xing
The widespread application of black phosphorus nanosheets (BPNSs) raises concerns about their potential impact on human health. Although that the autophagy-inducing properties of BPNSs in cancer cells are documented, their effects on macrophages—key components of the immune system and the mechanisms involved remain obscure, especially in terms of the influences of BPNS the size and surface modifications on the autophagic process. This study investigated the effects of bare BPNSs and PEGylated BPNSs (BP-PEG) on macrophage autophagy and its underlying mechanisms by comprehensive biochemical analyses. The results indicated that both BPNSs and BP-PEG are internalized by RAW264.7 cells through phagocytosis and caveolin-dependent endocytosis, leading to lysosomal accumulation. The internalized BPNSs induced mitochondrial dysfunction, which subsequently elevated the NAD + /NADH ratio and activated the SIRT-1 pathway, initiating autophagy. However, BPNSs disrupted the autophagic flux by impairing autolysosome formation, leading to apoptosis in a size-dependent manner. In contrast, BP-PEG preserved lysosomal integrity, maintaining autophagic activity and cell viability. These findings deepen our understanding of the influence of nanosheet size and surface modifications on macrophage autophagy, contributing to the formulation of regulatory guidelines to minimize the potential adverse effects and health risks associated with BPNS utilization in various applications.
研究领域:
纳米技术
·
细胞生物学
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免疫学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2021
·
IF 7.658
Xiaoang Li,Imran Khan,Wenrui Xia,Guoxin Huang,Liang Liu,Betty Yuen Kwan Law,Lin Yin,Weilin Liao,Waikit Leong,Ruixuan Han,Vincent Kam Wai Wong,Chenglai Xia,Xiaoling Guo,W.L. Wendy Hsiao
We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1 , 3 & 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3 , Calb1 , SNAP25 , and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.
研究领域:
药理学
·
衰老研究
·
微生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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