Frontiers in Pharmacology
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2025
·
IF 4.8
Junxi Liu,Youyun Liu,Feifei Wang,Yonglei Yuan,Hongyu Ma,Liping Qu
Introduction: The root of Paeonia suffruticosa Andrews (P. suffruticosa Andr.), is a traditional Chinese medicine. Numerous studies have shown that it possesses anti-inflammatory, antioxidant, and anti-aging effects due to its rich content of bioactive compounds such as polyphenols and paeonol. Thus, it finds extensively applied in the fields of medicine and cosmetics. However, there are few reports on the photoprotective effects of P. suffruticosa Andr. root bark, this study aims to investigate its research in this area.Methods: This study utilized P. suffruticosa Andr. root bark sourced from Kunming, Yunnan Province, China. The P. suffruticosa Andr. root extract (PSAE) was obtained using AB-8 resin. The photoprotective effect of PSAE was assessed using HaCaT cells, HFF cells, and a 3D Reconstructed Human full T-Skin™ model. Mechanistic investigations were performed using RT-qPCR, WB, IF, H&E staining, Masson’s trichrome staining and IHC staining. Finally, an assessment of the effects on humans was conducted.Results: The total phenolic content in the obtained PSAE was 48.9%. Antioxidant activity studies demonstrated that PSAE effectively inhibits DPPH radicals, superoxide anions, hydroxyl radicals, and ABTS radicals, while also enhancing the inhibition rates of collagenase and hyaluronidase. In vitro studies on photoaging resistance revealed that PSAE significantly reduced the UV-induced increases in reactive oxygen species (ROS) levels and senescence-associated β-galactosidase (SA-β-gal) activity. Mechanistic studies indicated that PSAE suppressed the overexpression of IRS1 and its downstream effectors, including PI3K, AKT, and mTOR induced by UV irradiation. A human efficacy assessment was conducted by evaluating parameters such as transepidermal water loss (TEWL), epidermal moisture content, roughness and elasticity, confirming the efficacy of PSAE in humans.Discussion: In summary, PSAE attenuates UV-induced oxidative damage, genetic damage, and collagen degradation associated with photoaging by modulating the IRS/PI3K/FOXO signaling pathway. This study elucidated the mechanism through which PSAE, thereby providing strong support for its application in cosmetic anti-aging formulations.
研究领域:
医学
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化妆品科学
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细胞生物学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Xingzhuo Song,Yu Du,Cen Liu,Wei Wang,Jing Han,Xinlou Chai,Yonggang Liu
Oxidative stress disrupts the homeostasis of the redox state in cells and induces apoptosis. Prolonged oxidative stress can impair the normal function of cells, tissues, and organs and lead to the development of several diseases. H-2 was synthesized by derivatising N- Alkylamides (NAAs) from Anacyclus pyrethrum (L.) DC, which is commonly used in the treatment of vitiligo in Uyghurs. The antioxidant activity and potential molecular mechanisms of H-2 were investigated using Caenorhabditis elegans ( C. elegans ) and mouse melanoma cell B16-F10 models. The in vivo anti-vitiligo activity of H-2 was studied using C57BL/6 mice. The results showed that H-2 could increase the survival time of nematodes under oxidative stress, promote the nuclear localization of DAF-16, and enhance the expression of Superoxide Dismutase 3 (SOD-3) in nematodes thereby activating the antioxidant enzyme system. H-2 could affect the survival rate of age-1 and akt-1 mutants under oxidative stress. H-2 could reverse the oxidative stress damage by reducing the reactive oxygen species (ROS) content in the Hydrogen peroxide (H 2 O 2 ) -induced oxidative stress damage model of mouse melanoma cells B16-F10. In addition, it was also able to increase the number of melanocytes in the hair follicles of vitiligo model mice and improve the phenomenon of skin damage in mice. In conclusion, our findings suggest that H-2 can alleviate oxidative stress damage in C. elegans and B16-F10, which may be associated with oxidative stress, suppression of antioxidant defences, and transcription factors DAF-16/FOXO, providing beneficial evidence for the application of H-2 in the vitiligo treatment.
研究领域:
分子生物学
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药理学
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皮肤病学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2025
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IF 4
Xudong Zhao,Yuting Ding,Zirou Duan,Di Deng,Zhiyue Mao,Yan Zhu,Xiaoxi Fan,Guohui Yu,Linquan Ge
The brown planthopper (BPH), Nilaparvata lugens is a typical pesticide-induced resurgent rice pest. A previous study showed that a fungicide, jinggangmycin (JGM)-treated rice led to markedly increased sugar content and (Insulin-like Peptide 2) ILP2 in response to sugar-mediated TOR signaling and stimulated fecundity in BPH. However, the role of the other ILPs in response to types of carbohydrate compounds remained poorly understood. The present studies showed that JGM treatment led to strongly increased glucose content and slightly increased sucrose and trehalose contents in rice plants. The 5th instar nymphs feeding with JGM-treated rice or exogenous glucose-supplied artificial diets markedly upregulated transcription of ILP2 and ILP3 , triggered ILP/Foxo signaling transduction, and further induced ILP3 secretion in the female brain. Moreover, silencing of ILP3 in the nymphal stage through RNAi led to a significant decrease of ILP3 secretion in the brain compared with dsGFP-treated females and inhibited ILP/Foxo signaling transduction. Suppression of ILP3 decreased soluble protein content in the ovary and fat body, inhibited Vg expression and protein synthesis, and further blocked ovarian development in female adults. Finally, depletion of ILP3 significantly influenced reproductive parameters, including the number of laid eggs, oviposition period, number of offspring, hatching rate, and population growth indexes of BPH. The current study revealed the mechanism of diet glucose regulating BPH reproduction by inducing ILP3 expression, which complements the theory of pesticide-induced resurgence of rice pests and also provides an important gene target for green control of BPH.
研究领域:
昆虫学
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农药毒理学
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分子生物学
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信号转导
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植物保护
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农业科学
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DOI
PubMed
高影响因子
BIOGERONTOLOGY
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2025
·Vol. 27
·期 1
·6
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IF 4.1
Wang Jiahui,Li Shuqi,Lei Zichen,Xing Yantao,Li Jieshu,Guo Jie,Duan Boshi,Liu Yonggang
Aging not only significantly reduces the quality of life for the elderly but also poses multifaceted challenges to society. Its progression involves the synergistic interaction of multidimensional, multipathway molecular mechanisms, including mitochondrial dysfunction, oxidative stress accumulation, chronic inflammation, and genomic damage. Quercetagetin (QG), as a natural flavanol monomer, exhibits significant potential in anti-aging due to its simultaneous targeting of key aging pathways such as oxidative stress and chronic inflammation. We first evaluated QG’s safety profile, finding that 0.02 mg/ml QG did not adversely affect motility, feeding, growth, and reproductive capacity in Caenorhabditis elegans ( C. elegans ). At this concentration, in vivo experiments using wild-type C. elegans confirmed QG’s ability to extend lifespan and enhance oxidative stress resistance. The antioxidant and anti-aging effects of QG were further validated using the daf -16 mutant C. elegans DR26. Subsequently, observation of QG’s impact on C. elegans mitochondrial morphology revealed significant reductions in area/perimeter and mitochondria coverage ratio following treatment. This indicates that QG treatment shifts the mitochondrial network from fusion toward fission and reduces overall mitochondrial content. QG can also improve age-related dopaminergic, 5-hydroxytryptaminergic and cholinergic neuron degeneration. Mass spectrometry metabolome analysis revealed that QG significantly affected citrate cycle and glycerophospholipid metabolism. Collectively, QG extends C. elegans lifespan by regulating redox homeostasis, DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming. This multi-target regulatory capacity positions QG as an ideal candidate molecule for anti-aging drug development.
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PubMed
高影响因子
Microbiome
·
2025
·Vol. 13
·期 1
·1-26
·
IF 12.7
Li Daojie,Meng Kun,Liu Guohua,Wen Zhiguo,Han Yunsheng,Liu Weiwei,Xu Xin,Song Liye,Cai Hongying,Yang Peilong
Background Fatty liver hemorrhage syndrome (FLHS) has become one of the major factors leading to the death of laying hen in caged egg production. FLHS is commonly associated with lipid peroxidation, hepatocyte injury, decreased antioxidant capacity, and inflammation. However, there are limited evidences regarding the preventive effect of Lactiplantibacillus plantarum on FLHS in laying hens and its mechanisms. Our previous results showed that Lp. plantarum FRT4 alleviated FLHS by regulating lipid metabolism, but did not focus on its antioxidant and anti-inflammatory functions and mechanisms. Therefore, this study aimed to investigate the preventive mechanisms of Lp. plantarum FRT4 in alleviating FLHS, with a focus on its role in antioxidant activity and inflammation regulation. Results Supplementation with Lp. plantarum FRT4 enhanced the levels of T-AOC, T-SOD, and GSH-Px, while reducing the levels of TNF-α, IL-1β, IL-8, and NLRP3 in the liver and ovary of laying hens. Additionally, Lp. plantarum FRT4 upregulated the mRNA expressions of SOD1 , SOD2 , CAT , and GPX1 , downregulated the mRNA expressions of pro-inflammatory factors IL-1β , IL-6 , and NLRP3 , and upregulated the mRNA expressions of anti-inflammatory factors IL-4 and IL-10 . Lp. plantarum FRT4 improved the structure and metabolic functions of gut microbiota, and regulated the relative abundances of dominant phyla (Bacteroidetes, Firmicute, and Proteobacteria) and genera ( Prevotella and Alistipes ). Additionally, it influenced key KEGG pathways, including tryptophan metabolism, amino sugar and nucleotide sugar metabolism, insulin signaling pathway, FoxO signaling pathway. Spearman analysis revealed that the abundance of microbiota at different taxonomic levels was closely related to antioxidant enzymes and inflammatory factors. Furthermore, Lp. plantarum FRT4 modulated the mRNA expressions of related factors in the FoxO / TLR - 4 / NF-κB signaling pathway by regulating gut microbiota. Moreover, the levels of E 2 , FSH, and VTG were significantly increased in the ovary after Lp. plantarum FRT4 intervention. Conclusions Lp. plantarum FRT4 effectively ameliorates FLHS in laying hens. This efficacy is attributed to its antioxidant and anti-inflammatory properties, which are mediated by modulating the structure and function of gut microbiota, and further intervening in the FoxO / TLR - 4 / NF-κB signaling pathway. These actions enhance hepatic and ovarian function and increase estrogen levels.
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研究领域:
动物营养学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Danping Liu,Yi Wang,Hongyi Zhao,Xiuwen Xia,Jie Zhou,Li Xie,Pei Guo,Weihong Li
Ethnopharmacological relevance Wenyang-Tianjing-Jieyu Decoction (WTJD) is a traditional Chinese herbal formula with a history of ethnopharmacological use for depression, specifically targeting the Kidney-Yang deficiency (KYD) subtype. Its therapeutic rationale is well-documented in classical Chinese materia medica. However, the molecular mechanisms underpinning its clinical efficacy remain largely unelucidated. Aim of the study This study aimed to investigate the therapeutic effects and elucidate the underlying molecular mechanisms of WTJD, a traditional herbal formula, in ameliorating KYD-type depression in a rat model. Materials and methods The chemical profile of WTJD was characterized using UPLC-Q-Exactive/MS. Using a rat model of KYD-type depression established by combining Phellodendri chinensis Cortex decoction gavage, cold exposure, and chronic unpredictable mild stress (CUMS), we evaluated the therapeutic effects of WTJD. This randomized controlled study included five groups (n = 7/group): Control, Model, Fluoxetine, WTJD-Medium, and WTJD-High, with a 3-week intervention period. Furthermore, we integrated network pharmacology with hippocampal transcriptomics to identify key therapeutic targets, which converged on the FOXO signaling pathway. Finally, the predicted mechanism was validated by assessing key protein phosphorylation, nuclear translocation, hippocampal neurogenesis, and synaptic plasticity. Moreover, the regulatory mechanism was further corroborated in vitro using LPS-induced PC12 cells treated with WTJD-containing serum and the AKT inhibitor MK-2206. Results WTJD administration significantly ameliorated both the KYD phenotype and depressive-like behaviors in the rat model. Strikingly, both network pharmacology and hippocampal transcriptomic analyses converged on the FOXO signaling pathway as the central therapeutic target. Mechanistically, it was confirmed that WTJD activated the FOXO pathway by inhibiting AKT phosphorylation, which in turn promoted the nuclear translocation of FOXO4. Consistently, in vitro assays demonstrated that WTJD-containing serum protected PC12 cells and rescued downstream gene expression by modulating the FOXO signaling pathway, effects that were mimicked by AKT inhibition. This cascade of molecular events ultimately restored impaired adult hippocampal neurogenesis and synaptic plasticity. Conclusion WTJD ameliorates KYD-type depression by modulating the hippocampal FOXO signaling pathway to restore neurogenesis and synaptic plasticity. These results validate the FOXO pathway as a high-value target for subtype-specific antidepressant drug design.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Chen Wang,Yeyong Li,Lingjun Zeng,Chongli Shi,Yi Peng,Hui Li,Haibo Chen,Jun Yu,Jin Zhang,Biao Cheng,Ruolin Pan,Xiaoli Wang,Minghui Xiang,Yuan Huang,Yongdi Liu
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has received concerns due to its frequent detection in environmental media and biological samples. Our previous study has indicated TDCPP reduced the lifespan of Caenorhabditis elegans ( C. elegans ) by triggering an unconventional insulin/insulin-like growth factor signaling (IIS) pathway. This study continued to investigate the possible deleterious effects of TDCPP relating to longevity regulation signal pathways and biological processes. Specifically, this study uniquely performed small RNA transcriptome sequencing (RNA-seq), focusing on the underlying mechanisms of TDCPP-reduced the longevity of C. elegans in-depth in microRNAs (miRNAs) . Based on Small RNA-seq results and transcript levels of mRNA involved in the unconventional IIS pathway, a small interaction network of miRNAs-mRNAs following TDCPP exposure in C. elegans was preliminarily established. Among them, up-regulated miR-48 and miR-84 ( let-7 family members) silence the mRNA of daf-16 (the crucial member of the FoxO family and pivotal regulator in longevity) via post-transcription and translation dampening abilities, further inhibit its downstream target metallothionein-1 ( mtl-1 ), and ultimately contributed to the reduction of nematode longevity and locomotion behaviors. Meanwhile, the high binding affinities of TDCPP with miRNAs cel-miR-48–5p and cel-miR-84–5p strongly support their participation in the regulation of nematode mobility and longevity. These findings provide a comprehensive analysis of TDCPP-reduced longevity from the perspective of miRNAs.
研究领域:
毒理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
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IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Luyao Zhang,Liting Guo,Bufan Xu,Di Wu,Yongning Wu,Guoliang Li
Taurine, an important nutritional fortifier in infant formula, is closely associated with neurodevelopment and immune homeostasis. However, existing studies have mainly focused on its immediate promoting effects on neurodevelopment, while whether early-life taurine supplementation confers long-term neuroprotective effects during later developmental stages remains unclear. In this study, a three-stage zebrafish model was established, including early-life taurine supplementation, cessation of supplementation, and subsequent exposure to acrylamide during later development, to evaluate the long-term neuroprotective potential of taurine. The results showed that early-life taurine supplementation significantly alleviated neurobehavioral deficits, oxidative damage in brain tissue, and inflammatory responses induced by acrylamide exposure during later developmental stages. Mechanistically, taurine may exert these effects through coordinated regulation of neuroimmune and metabolic pathways. At the immune level, taurine inhibited NF-κB-related inflammatory activation, suppressed M1-associated microglial markers, and promoted M2-associated responses, thereby improving the neuroimmune microenvironment. At the metabolic level, taurine regulated FOXO pathway-related gene expression and improved glycolysis-related metabolic disturbance, which was associated with reduced oxidative damage and improved energy homeostasis. Overall, these findings suggest that transient taurine supplementation during early life may reduce later susceptibility to foodborne neurotoxicant exposure, which is associated with nutritional programming-like changes in neuroimmune and metabolic pathways. This study provides a new perspective for early-life nutritional intervention and dietary risk assessment.
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DOI
高影响因子
Cell Reports
·
2024
·
IF 7.5
Xiaohan Sun,Dafa Zhou,Yuanfei Sun,Yunhe Zhao,Yanran Deng,Xiaolin Pang,Qingxin Liu,Zizhang Zhou
The transcriptional coactivator Yorkie (Yki) regulates organ size by promoting cell proliferation. It is unclear how cells control Yki activity when exposed to harmful stimuli such as oxidative stress. In this study, we show that oxidative stress inhibits the binding of Yki to Scalloped (Sd) but promotes the interaction of Yki with another transcription factor, forkhead box O (Foxo), ultimately leading to a halt in cell proliferation. Mechanistically, Foxo normally exhibits a low binding affinity for Yki, allowing Yki to form a complex with Sd and activate proliferative genes. Under oxidative stress, Usp7 deubiquitinates Foxo to promote its interaction with Yki, thereby activating the expression of proliferation suppressors. Finally, we show that Yki is essential for Drosophila survival under oxidative stress. In summary, these findings suggest that oxidative stress reprograms Yki from a proliferation-promoting factor to a proliferation suppressor, forming a self-protective mechanism.
研究领域:
细胞生物学
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分子生物学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2025
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IF 2.5
Yanru Liu,Ya Hu,Xiaoxia Xie,Gongjun Yang,Fang Feng
Wen-Pi-Tang (WPT), a Traditional Chinese Medicine (TCM) prescription, is commonly used to treat chronic renal failure. However, the material basis and potential mechanisms of WPT against chronic renal failure have not been clarified. UHPLC-Q-Exactive Orbitrap-MS was utilized in this work to investigate the chemical components of WPT and their prototypes or metabolites in vivo. 227 chemical compounds were identified in the WPT. Meanwhile, 56 exogenous components (24 prototype components and 32 metabolic components) were examined in rat plasma. Meanwhile, network pharmacology revealed that liquiritigenin-O-sulfate, 3-keto-18β-glycyrrhetinic acid, 22-hydroxy-18-β-glycyrrhetinic acid, and hydroxyliquiritigenin (B ring)-O-sulfate with related targets AKT1, EGFR, STAT3, ESR1, SRC, MAPK3, MTOR, and PIK3CA were considered as the effective components and core targets. Furthermore, the findings suggested that the therapeutic effects of WPT on chronic renal failure may be substantially influenced by the PI3K-Akt, HIF-1, and FoxO signaling pathways. The outcomes of molecular docking and molecular dynamics simulations indicate that the key targets have strong binding capacities with effective components. Our study offers a comprehensive method for examining the molecular foundation and underlying mechanisms of WPT against chronic renal failure, opening up new therapeutic opportunities.
研究领域:
中药学
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药理学
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代谢组学
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产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
·
IF 4.872
Yuhao Wu,Junke Wang,Tianxin Zhao,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro . The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.
研究领域:
生殖生物学
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毒理学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）