Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-24
·
IF 5.3
Cao Ting,Wang Xue-lian,Rao Jiang-yan,Zhu Hui-feng,Qi Hong-yi,Tian Zhen
Background Parkinson’s disease (PD) is a chronic neurodegenerative disorder that currently has no curable strategies. More and more evidence suggests that endoplasmic reticulum (ER) stress plays an essential role in PD pathogenesis. Periplaneta americana L. ( P. americana ) is a traditional Chinese medicine with diverse therapeutic properties. This study aims to investigate the neuroprotective effect and underlying mechanism of P. americana in in vitro and in vivo PD models. Methods The exposure of SH-SY5Y cells to 1-methyl-4-phenyl-pyridinium (MPP + ) was used as the in vitro PD model. MTT assay, Hoechst staining, Calcein AM-PI staining and flow cytometry were performed to measure the cell viability and apoptosis. DCFH-DA and JC-1 assay were used to measure the intracellular ROS and mitochondrial membrane potential (Δψm), respectively. Western-blot and immunostaining were conducted to detect the expression of key molecules related with ER stress. For the in vivo PD model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-pyridine (MPTP), the motor function of mice was assessed by behavioral tests, the level of TH was examined by western-blot and immunostaining, the expression of key molecules related with ER stress was measured by western-blot. Results Periplaneta americana ethanol extract (PAE) concentration-dependently inhibited MPP + -induced cell loss and increased cell viability. PAE also remarkably attenuated ROS accumulation, the decline of Δψm as well as the excessive ER stress. The neuroprotective effects of PAE could be blocked by ROS inducer trimethylamine N-Oxide or ER stress activator tunicaymycin, while the antioxidant N-Acetyl-L-cysteine or ER stress inhibitor sodium 4-phenylbutyrate mimicked the effects of PAE. Furthermore, we found that PAE could activate AKT/GSK3β/β-catenin pathway. The effect of PAE on ROS production, Δψm and ER stress was blocked by AKT inhibitor MK-2206. In in vivo model, PAE significantly improved motor function, prevented dopaminergic neuronal loss and attenuated ER stress in substantia nigra and striatum of MPTP-treated mice. Similarly, the effects of PAE on MPTP-treated mice were also abolished by MK-2206. Conclusions Our results suggest that P. americana exerts neuroprotective effects through inhibiting ER stress via AKT-dependent pathway. Periplaneta americana may represent a promising therapeutic agent for PD treatment and is worthy of further being exploited.
研究领域:
神经学
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药理学
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传统中药
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细胞生物学
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实验模型
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产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 9
·1-18
·
IF 2.6
Xu Wenyi,Guan Yinghua,Tian Liping,Fu Yu,Zhang Yinghui,Liu Yanhong,Hu Yanfei,Zhao Bowen,Wu Chongming
The global prevalence of type 2 diabetes mellitus (T2DM) is currently surging, posing significant health and socioeconomic burdens. Probiotics have emerged as promising interventions due to their safety and potential metabolic benefits. Gut microbiota plays a critical role in the pathophysiology of metabolic diseases in humans, offering valuable insights for therapeutic strategies such as probiotics. Here, aiming to identify novel probiotics from the human gut microbes to combat T2DM, a total of 203 human intestinal bacterial strains were screened in vitro to evaluate their enzymatic inhibition of α-glucosidase and α-amylase, in which Lacticaseibacillus paracasei Glu-07 (= QH-142 = CGMCC 23796) exhibited the highest inhibitory efficacy (81.05% and 72.56% for α-glucosidase and α-amylase, respectively). In HepG2 cells, L. paracasei Glu-07 elevated glucose uptake and consumption by 22.4% and 85.8%. Oral administration of strain Glu-07 in diabetic mice significantly improved hyperglycemia, hyperlipidemia, and restored the structure and composition of gut microbiota toward a healthier profile. Mechanistically, strain Glu-07 activated the AMPK-AKT1-GSK3β/FOXO1 signaling pathways by modulating the expression of key genes, enhanced glycolysis and fatty acid ꞵ-oxidation, and inhibited gluconeogenesis and lipogenesis. It also stimulated GLP-1 secretion, potentially via triggering the GPR41/43-GLP-1 axis, and increased the abundance of beneficial gut microbes, such as Akkermansia muciniphila (~ threefold). The dual regulations synergistically support strain Glu-07 as a promising probiotic candidate for T2DM management.
研究领域:
微生物学
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糖尿病研究
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分子生物学
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药理学
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营养科学
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代谢性疾病
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chunlan Tang,Zhiling Fang,Donghui Chu,Lulu Zhang,Yuqing Tang,Jinyue Zhou,Rui Fang,Jiaming Ying,Fang Wang,Yuping Zhou,Chunshuang Xu,Qinwen Wang
Alzheimer’s disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo . Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3β, ESR1, and AR targets based on the anti-β-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer’s disease pathway, APP and GSK3β, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3β protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.
研究领域:
神经学
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药理学
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中医药
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网络药理学
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药代动力学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-17
·
IF 6.4
Liu Jing,Li Wenqi,Jiao Ran,Liu Zhigang,Zhang Tiantian,Chai Dan,Meng Lingxin,Yang Zhongyi,Liu Yuming,Wu Hongliang,Gu Xiaoting,Li Xiaohe,Yang Cheng
Background Cardiac fibrosis is significant global health problem, which is associated with numerous cardiovascular diseases, and ultimately leads to the progression to heart failure. β-adrenergic receptor (β-AR) overactivation play a role in the development of cardiac fibrosis. Miglustat (Mig) has shown anti-fibrosis effects in multiple fibrotic diseases. However, it is unclear whether and how Mig can ameliorate cardiac fibrosis induced by β-AR overactivation. Methods In vivo, mice were injected with isoproterenol (ISO) to induce cardiac fibrosis and treated with Mig. In vitro, primary cardiac fibroblasts were stimulated by ISO and treated with Mig. Levels of cardiac fibrosis, cardiac dysfunction, activation of cardiac fibroblasts were evaluated by real-time polymerase chain reaction, western blots, sirius red staining, immunohistochemistry staining and echocardiography. Through GEO data and knockdown UDP-glucose ceramide glycosyltransferase (UGCG) in primary cardiac fibroblasts, whether Mig alleviates cardiac fibrosis by targeting UGCG was explored. Results The results indicated that Mig alleviated ISO-induced cardiac dysfunction. Consistently, Mig also suppressed ISO-induced cardiac fibrosis. Moreover, Mig attenuated ISO-induced cardiac fibroblasts (CFs) activation. To identify the protective mechanism of Mig on cardiac fibrosis, several classical β-AR downstream signaling pathways, including ERK, STAT3, Akt and GSK3β, were further analyzed. As expected, ISO activated the ERK, STAT3, Akt and GSK3β in both CFs and mouse hearts, but this effect was reversed pretreated with Mig. Besides, Mig ameliorates ISO-induced cardiac fibrosis by targeting UDP-glucose ceramide glycosyltransferase (UGCG) in CFs. Conclusions Mig ameliorates β-AR overactivation-induced cardiac fibrosis by inhibiting ERK, STAT3, Akt and GSK3β signaling and UGCG may be a potential target for the treatment of cardiac fibrosis.
研究领域:
心血管疾病
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药理学
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细胞生物学
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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 Pharmaceutical Analysis
·
2023
·
IF 8.8
Chen Hong,Yifan Zhang,Lili Yang,Haoyang Xu,Kang Cheng,Zhi Lv,Kaixian Chen,Yiming Li,Huali Wu
Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B [PKB])/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/MAP kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N -phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.
研究领域:
药理学
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化妆品学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOFACTORS
·
2021
·Vol. 47
·期 4
·587-599
·
IF 6.113
Ninghua Wu,Wu Liu,Jiawen Wang,Yanqi Han,Yu Ye,Xiufen Liu,Yuandong Yu,Qingjie Chen,Yongfen Bao,Chao Liu
IR (insulin resistance) in diabetic brain gave rise to the generation of toxic factor Aβ42 and axon collapse which were the marker of AD (Alzheimer's disease)-like lesions in the circumstance of diabetes mellitus. But the underling molecular mechanism was not clear. Chronic HGHI (high glucose and high insulin) exposure accelerates IR has been reported in type II diabetes models. Berberine has been shown to promising effect for IR in vitro and in vivo. This study demonstrates the protective effect and the underlying mechanism of berberine on HGHI-induced IR. HGHI-induced cells were used to mimic the hyperinsulinemia resulting in IR. Berberine was used to uncover the mechanisms for the treatment of hyperinsulinemia in IR model. Morris water maze (MWM), PET imaging, CCK8 assay, ELISA assay, glucose kits, microscopy, and western blot analysis were performed to evaluate the protective effects of berberine. Berberine-improved HGHI-induced IR was correlated with the increase of glucose application in neurons. Meanwhile, the expressions of Pi3K, as well as GLUT3, PKCε, and APP were downregulated in the model, while p-IRS Ser307 was upregulated compared with Normal group. Fortunately, these scenes were reversed by berberine administration. Furthermore, berberine decreased GSK3β Y216 expressions, inhibited the production of oligomer Aβ42 and extended neuronal axon. The monomeric berberine treatment improves IR that may be involved in glucose effective application, rectifying the related proteins of the aberrant insulin pathway. Additionally, it suppressed the generation of Aβ42 and ameliorated neuron axon damage. Finally, berberine improves DM (diabetes mellitus)-induced cognitive impairment.
研究领域:
药理学
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神经科学
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糖尿病学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
研究领域:
药理学
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代谢学
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胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Licong Yang,Yabin Wang,Zhiwei Li,Xiaohua Wu,Jingtao Mei,Guodong Zheng
The pathology of Alzheimer's disease (AD) is highly correlated with obesity-induced insulin resistance. Resveratrol (Res) is a natural phenol that demonstrates a neuroprotective effect, but the bioactivity of Res is low in vivo . Here, chitosan (CS) was cross-linked with sodium tripolyphosphate (TPP) to encapsulate low water solubility Res. Next, a brain-targeted peptide (TG: TGNYKALHPHNG) was modified on the surface of Res-loaded CS/TPP nanoparticles (TG-Res-CS/TPP-NPs) to specifically deliver Res to the brain. Morris water maze results indicated that cognitive impairments were ameliorated by TG-Res-CS/TPP-NPs in obesity-related AD mice. Obesity-related insulin resistance promotes Tau phosphorylation and Aβ aggregation in the brain. Administration of TG-Res-CS/TPP-NPs alleviated lipid deposition-induced insulin resistance and decreased the level of phosphorylated Tau and Aβ aggregation via the JNK/AKT/GSK3β pathway. Additionally, TG-Res-CS/TPP-NPs transported across blood-brain barrier which in turn increased glucose transporter expression levels, antioxidant enzyme activity and inhibited microglial cell activation . Thus, TG-Res-CS/TPP-NPs were more effective than Res-CS/TPP-NPs at regulating glucose homeostasis , oxidative stress and neuroinflammation in the brain. Moreover, inflammatory , lipid metabolism and oxidative stress-related gut microbiota including Helicobacter , Colidextribacter , Anaerotruncus , Parasutterella , Allobaculum , Alloprevotella , Alistipes , Bifidobacterium and Candidatus_Saccharimonas were also regulated by TG-Res-CS/TPP-NPs. This work indicates the potential use of TG-Res-CS/TPP-NPs for the delivery of Res.
研究领域:
药理学
·
神经科学
·
分子生物学
·
生物技术
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微生物学
✓ 已验证
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）