Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Haijun Gao,Yan Zhang,Xiaojin Mo,Lele Huo,Yanping Luo,Ting Zhang,Xingming Ma,Wei Hu,Tao Jing
Background. Liver cancer, particularly hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related death worldwide. Sorafenib is a crucial drug for the treatment of advanced HCC, but it is difficult to meet the challenge of increasing clinical demands due to its severe side effects and drug resistance. Hence, development of novel antitumor drugs is urged. Previous studies showed that pseudolaric acid B (PAB) could reduce the expression of protein kinase B (PKB/Akt), a downstream effector of Notch signaling, facilitating cell apoptosis in HCC. The disruption of Notch signaling was verified to exacerbate malignant progression and drug resistance, however, the antitumor effect of PAB on Notch signaling in HCC remains unclear. Thus, this study aims to investigate the anti-HCC effect of PAB in association with the regulation of Notch1/Akt signaling. Methods. CCK-8 assay and transwell assay were used to examine the cell proliferation and invasion in Huh7 cells after treatment with PAB and a Notch inhibitor DAPT. Moreover, the cell cycle of Huh7 cells after treatment with PAB was analyzed using flow cytometry. Finally, the changes of Notch1, Jagged1, Hes1, and Akt expression at the protein and mRNA level in Notch1/Akt signaling in Huh7 cells after treatment with PAB and DAPT were analyzed using immunofluorescence assay and real-time qPCR. Results. The proliferation rate of Huh7 cells exposed to PAB of 0.5, 1, 2, 4, 8, 10, 20, 40, 80, 100, and 200 μmol/L revealed a time-and dose-dependent decrease in vitro, showing cell cycle arrest at G2/M phase . Furthermore, compared with the untreated group, at the concentration of 40 μmol/L, the proliferation rate and invasion rate of Huh7 cells in PAB, DAPT, and PAB-DAPT combination (PAB + DAPT) group were significantly decreased , but the PAB + DAPT showed no synergistic antiproliferation and anti-invasion effect in comparison with PAB treatment alone . In addition, compared with the untreated group, PAB and DAPT alone significantly downregulated the expression of Notch1, Jagged1, Hes1, Akt mRNA, or/and protein in Huh7 cells , but there was no significant difference in synergistic downregulated effect between the PAB + DAPT group and the PAB group . Conclusion. PAB can suppress proliferation and invasion of HCC cells through downregulating the expression of Notch1/Akt signaling protein and mRNA, and may be a potential novel antitumor drug candidate for the clinical treatment of HCC in the future.
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Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Yanxia Ma,Yu Liu,Linxin Teng,En Luo,Dekang Liu,Fuqiong Zhou,Kaiyuan Wang,Weiping Chen,Lei Bi
Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3β/β-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.
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Molecular Medicine Reports
·
2017
·Vol. 17
·期 2
·3062-3068
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IF 1.692
Kai‑Fei Li,Chun‑Min Kang,Xiao‑Feng Yin,Hai‑Xia Li,Zhuo‑Yu Chen,Yao Li,Qiong Zhang,Yu‑Rong Qiu
Ginsenoside Rh2 (G‑Rh2), the main bioactive component in American ginseng, is known to exert a wide variety of biological activities. Accumulating evidence suggests that G‑Rh2 inhibits cell proliferation and induces apoptosis of tumor cells. However, the possible mechanism through which G‑Rh2 exerts its action on malignant glioma cells have not been completely elucidated. The findings of the present study demonstrated that G‑Rh2 decreased the viability of glioma cells in a dose‑ and time‑dependent manner, and induced cell cycle arrest. G‑Rh2‑induced cell cycle arrest was accompanied by the downregulation of cyclin‑dependent kinase 4 and Cyclin E. In addition, G‑Rh2 markedly reduced the expression of total‑ RAC‑α serine/threonine‑protein kinase (Akt) and the levels of phosphorylated‑Akt. These findings provide mechanistic details of how G‑Rh2 acts on glioma cells and suggest that G‑Rh2 may function as a potential anti‑cancer drug for glioma treatment.
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Results in Chemistry
·
2025
·
IF 4.2
Dongqing He,Dongjun Liu,Zhuoyan Wu,Ruiguang Xiao,Wenjie Ruan,Zeqiang Lin,Qiuxia Chen,Chanling Yuan,Qiong Wu,Wenjie Mei
Acne is a chronic inflammatory skin disease that is highly prevalent in adolescents, and its recurrent flare-ups can affect facial aesthetics, severely impacting adolescents' mental health and quality of life. Screening for safer, more effective fruit acid molecules for daily acne treatment is crucial. This work examined potential mandelic acid derivatives. In a zebrafish model, mandelic acid showed a 78.17 % rate of inflammatory cell aggregation, outperforming supramolecular salicylic acid (86.96 % aggregation) at the same concentration. In a P. acnes -induced cell model, MMP9 protein expression was significantly upregulated in the model group. After treatment with mandelic acid, MMP9 expression decreased by 72.84 % compared to the model group, a better effect than that of supramolecular salicylic acid (36.78 %). Further mechanistic investigations indicate that mandelic acid may inhibit the PI3K/AKT signaling pathway activated by P. acnes , thereby blocking MAPK signaling and modulating MMP9 protein production, thereby averting the development of NLRP3 inflammatory vesicles. Mandelic acid has a favourable safety profile and notable anti-inflammatory properties, which can be further harnessed to mitigate acne in sensitive skin demographics, offering a novel approach to acne treatment.
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TISSUE & CELL
·
2025
·
IF 2.5
Yanfei Yang,Lili Yang,Yabin Li,Yanfen Wang
Background The gut microbiota is essential for the bidirectional communication between the gut and the brain. However, its specific role and underlying mechanisms in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis remain largely unclear. Methods An anti-NMDAR encephalitis model was induced by GluN1 peptide immunization, and brain histopathology was assessed by hematoxylin-eosin staining. Behavioral performance was assessed through the Y-maze and open field tests. Flow cytometry was employed to quantify T follicular helper (Tfh) and T follicular regulatory (Tfr) cell populations. Enzyme-linked immunosorbent assay and western blot were used to assess inflammatory cytokines and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway-related protein levels, respectively. 16S rRNA sequencing and Helicobacter rodentium gavage (1.5 mL, 1×10¹¹ CFU/mL) were used to assess microbiota composition and bacterial function. Results 16S rRNA sequencing revealed a trend toward reduced gut microbial diversity in anti-NMDAR encephalitis mice. Helicobacter rodentium colonization further exacerbated behavioral deficits and inflammatory cell infiltration in the cerebral cortex. This was accompanied by a marked increase in tumor necrosis factor alpha (TNF-α) and interleukin (IL)-21 levels and a reduction in IL-10 concentrations in both cerebrospinal fluid and serum. Moreover, the Tfh/Tfr cell ratio was further elevated following Helicobacter rodentium exposure. Targeted suppression of the PI3K/AKT pathway with LY294002 significantly restored Tfh/Tfr balance and alleviated neurobehavioral impairments and cortical inflammation. Conclusion Helicobacter rodentium exacerbates anti-NMDAR encephalitis by inducing PI3K/AKT-mediated Tfh/Tfr imbalance, highlighting a potential therapeutic target in autoimmune encephalitis.
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ACS Applied Bio Materials
·
2020
·
IF 0
Benkai Bao,Dong Gao,Ning Li,Manman Wu,Chengfen Xing
Calmodulin (CaM), as a calcium binding protein involved in the signal pathways of many life activities such as cell proliferation and apoptosis, can be regulated with the near-infrared (NIR) light-based photothermal conversion. Here, we build a conjugated polymer nanoparticle (CPNs-C) by assembling polypyrrole dione and dipalmitoyl phosphatidylethanolamine-polyethylene glycol-maleimide with a calmodulin antibody modified on the surface, which is NIR light-responsive for photothermally inducing apoptosis of cancer cells. Under near-infrared light irradiation, protein kinase B (Akt) and phosphatidylinositol 3-kinase, which bind to CaM, reduce the degree of phosphorylation due to the photothermal effect of CPNs-C, thus inhibiting the recruitment of Akt on the cell membrane. Therefore, the phosphorylation of GSK-3β downstream of the signaling pathway is reduced, and the phosphorylation of FoxO3a is enhanced, which can promote apoptosis of cancer cells. Compared with the photothermal effect of traditional CPNs, CPNs-C exhibits higher efficiency to regulate signaling pathways to promote cancer cells toward apoptosis. This strategy of utilizing NIR light to regulate the tumor apoptotic signaling pathway provides an effective way to enhance cancer cell apoptosis with high efficiency.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2023
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IF 5.3
Li Liu,Rong Zhang,Chang Chen,Changbo Xia,Guangda Yao,Xiaogang He,Baomei Xia
It has been reported that Banxia-houpo decoction (BXHPD) serves as the anti-depressant treatment for a mild and severe depressive disease with limited side effects. The present study was performed to evaluate the protective effect of BXHPD on chronic unpredicted mild stress (CUMS)-induced depression and explore its effect on TrkA/Akt-mediated microglia polarization. The CUMS procedure was carried out, and the mice were intragastrically treated with BXHPD once daily. The selective TrkA inhibitor GW441756 was applied to further investigate the role of TrkA in BXHPD-mediated microglia polarization. The behaviour test including open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), tail suspension test (TST) and forced swim test (FST) was performed. The concentrations of pro-inflammatory cytokines IL-6, TNF-α, IL-1β, IL-12 and anti-inflammatory cytokines IL-4, IL-10 were determined using Enzyme-linked immunosorbent assay. The population of Iba1+ cells and the length of microglia processes were observed under the fluorescence microscope. The mRNA expressions of Arg1, Ym1 and Fizzl1 were measured by PCR. The protein expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3 were detected by western blot. Our results showed that BXHPD attenuated CUMS-induced depressive-like behaviour, promoted anti-inflammatory cytokines, inhibited pro-inflammatory cytokines, suppressed microglia activation, promoted M2 phenotype-specific indices and upregulated the expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3. The above beneficial effect of BXHPD can be blocked by TrkA inhibitor GW441756. This work demonstrated that BXHPD exerted an anti-depressant effect by promoting M2 phenotype microglia polarization via TrkA/Akt pathway.
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PHARMACEUTICAL BIOLOGY
·
2021
·
IF 3.503
Yue Cui,Yongqiang Wang,Gang Liu
Context Epigallocatechin gallate (EGCG) is the most abundant catechin from tea. Previous studies have indicated EGCG has a cardioprotective effect.Objective This manuscript mainly explores the role of EGCG in pressure-overload cardiac hypertrophy and its mechanism related to the Akt/mTOR pathway.Methods and methods Transverse aortic constriction (TAC) was utilized to establish the cardiac hypertrophy mice model. C57BL/6 mice were assigned into 6 groups. Starting from the first day after surgery, mice received different doses of EGCG (20, 40, 80 mg/kg) or vehicle orally for four weeks. Heart weight to body weight (HW/BW) ratio and heart weight to tibia length (HW/TL) ratio as well as hematoxylin-eosin staining were utilized to evaluate cardiac hypertrophy. Masson’s trichrome and Sirius red staining were used to depict cardiac fibrosis. The expressions of fibrosis and hypertrophy-related markers and Akt/mTOR pathway were quantified by western blot and qRT-PCR.Results EGCG significantly attenuated cardiac function shown by decreased HW/BW (TAC, 6.82 ± 0.44 vs. 20 mg/kg EGCG, 5.53 ± 0.45; 40 mg/kg EGCG, 4.79 ± 0.32; 80 mg/kg EGCG, 4.81 ± 0.38) and HW/TL (TAC, 11.94 ± 0.69 vs. 20 mg/kg EGCG, 11.44 ± 0.49; 40 mg/kg EGCG, 8.83 ± 0.58; 80 mg/kg EGCG, 8.98 ± 0.63) ratios as well as alleviated cardiac histology. After treatment, hemodynamics was improved, cardiac fibrosis was attenuated. The activated Akt/mTOR pathway was inhibited by EGCG.Discussion and conclusions EGCG plays a protective role in the TAC model by regulating the Akt/mTOR pathway, which provides a theoretical basis for its clinical treatment.
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Bioengineered
·
2021
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IF 3.269
Jiazhen Yin,Jiazhen Lin,Jin Yu,Xia Wei,Bin Zhu,Caifeng Zhu
Membranous glomerulopathy (MGN) is an autoimmune kidney disease that is the primary cause of nephrotic syndrome (NS) in adults. Tetrandrine, a bisbenzylisoquinoline alkaloid, is known to have numerous pharmacological effects. In this study, network pharmacology analysis and experimental validation were conducted to analyze the mechanisms by which tetrandrine functions as a therapeutic intervention for MGN. A systematic network pharmacology method was applied to identify potential targets and determine the therapeutic mechanism of tetrandrine in MGN treatment. A Heymann nephritis (HN) rat model was developed to assess the therapeutic effects of tetrandrine on NS and validate the predicted molecular mechanisms. We obtained 86 potential targets of tetrandrine for the treatment of NS. In vivo experiments showed that tetrandrine could reduce the 24-h urine protein content, decrease glomerular basement membrane proliferation, and significantly decrease thylakoid stroma and cell proliferation in the HN rat kidney tissue. Moreover, tetrandrine suppressed kidney cell apoptosis and upregulated the expression of nephrin and podocin in HN model rats. qRT-PCR results revealed that tetrandrine inhibited IL-1β, TNFα, and MCP-1 levels in HN model rats. Western blot results indicated that tetrandrine can protect against MGN via the PI3K/Akt signaling pathway. Thus, by using a combination of network and experimental pharmacology methods, we demonstrate that tetrandrine can treat MGN via the PI3K/Akt signaling pathway and provide novel insights into the mechanisms underlying tetrandrine-mediated management of MGN.
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CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Fanyu Wang,Weiming Kong,Juntian Gan,Sen Yang,Xiaojuan Feng,Caixuan Zhang,Mingzhu Guo
A homogeneous arabinogalactan, UA-SRP1, was isolated from Stevia rebaudiana . • UA-SRP1 alleviated DSS-induced colitis and restored gut barrier integrity in mice. • UA-SRP1 supported epithelial regeneration, reduced inflammation and oxidative stress. • UA-SRP1 alleviates colitis via microbiota-dependent and independent mechanisms. Stevia rebaudiana polysaccharides have great potential to intervene in ulcerative colitis (UC) as functional food ingredients for gut health. This study isolated and structurally characterized a homogeneous arabinogalactan (UA-SRP1, 1.44 × 10 6 Da), mainly composed of galactose and arabinose. It possesses a (1 → 6)-β-D-Gal p backbone with heterogeneous side-chain substitutions occurring at the O-3 positions of the galactopyranosyl residues. In a DSS-induced UC mice model, UA-SRP1 treatment effectively alleviated clinical symptoms and histopathological damage, strengthened the intestinal barrier by upregulating ZO-1 and MUC-2, and attenuated inflammation and oxidative stress. It was also associated with remodeling of the gut microbiota (e.g., enrichment of Lactobacillus and Akkermansia ) and restoration of beneficial metabolites, such as short-chain fatty acids. Transcriptomic and Western blot analyses showed treatment-associated changes in PI3K-Akt and NF-κB signaling. Antibiotic depletion further indicated that microbiota status influenced part of the UA-SRP1-associated response. Collectively, these findings demonstrate the protective effects of UA-SRP1 against DSS-induced colitis and reveal coordinated changes in gut microbiota, microbial metabolites, and host signaling, supporting its further investigation as a potential functional food ingredient for gut health. Download: Download high-res image (287KB) Download: Download full-size image
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CELLULAR SIGNALLING
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2026
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IF 4.7
Chunju Yang,Hanfeng Hu,Yang Yang,Pengrui Jing,Shaofeng Yang,Jiangbo Guo,Li Chu,Hao Ni,Bin Meng,Shuli Yang,Fanqi Kong,Jinhui Shi
Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, affecting 619 million people worldwide in 2020, yet no effective disease-modifying therapy is clinically available to reverse its progression. Ferroptosis has been proven to be a core driver of IVDD by inducing injury to nucleus pulposus cells (NPCs). The regulatory role of cystathionine β-synthase (CBS) in IVDD and its underlying molecular mechanisms remain unclear. This study aimed to investigate the biological function of CBS in IVDD and elucidate the mechanism by which it regulates NPC ferroptosis. We found that CBS expression was significantly downregulated in degenerated human NP tissues and rat IVDD models and was negatively correlated with degeneration severity and ferroptosis activation. Functional assays showed that CBS knockdown markedly exacerbated TBHP-induced matrix metabolic imbalance, senescence, and ferroptosis in NPCs, while CBS overexpression effectively alleviated these pathological phenotypes. Transcriptomic analysis, biochemical validation, and pharmacological inhibition experiments implicated PI3K-AKT signaling in the ferroptosis-related effects associated with CBS modulation in NPCs. In vivo, S-Adenosyl-L-methionine (SAM) administration attenuated needle puncture-induced IVDD in rats, restored disc height and NP water content, and suppressed intradiscal ferroptosis. Because SAM has pleiotropic biological actions, these in vivo effects cannot be attributed exclusively to CBS. Collectively, our findings support a protective role for CBS against IVDD through suppression of NPC ferroptosis and implicate PI3K-AKT signaling as a contributing pathway.
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International Journal of Genomics
·
2025
·Vol. 2025
·期 1
·9710652
·
IF 1.9
Jin Cai,Shuang Shi,Yuhang Wang,Xiangdong Zhang,Xinghua Wei,Yanjing Wu,Yunlong Shi,Bin Li,Daorong Hou
Purpose This research sought to investigate the impact and underlying mechanisms of growth hormone (GH) on atherosclerosis (AS) based on the analysis of single-cell RNA sequencing (scRNA-seq) data. Methods We analyzed the impact of GH on arterial vascular smooth muscle cells (VSMCs) by utilizing scRNA-seq data obtained from both atherosclerotic and healthy vascular tissues in mice. AS was induced in C57BL/6 and ApoE −/− mice through hypophysectomy performed via the parapharyngeal approach, followed by a high-fat diet (HFD), resulting in the C57-Hx and ApoE −/− -Hx models. AS was evaluated by measuring arterial lipid deposition, plaque progression, collagen loss, vascular inflammation, and oxidative stress. Serum metabolite alterations were assessed using liquid chromatography-mass spectrometry (LC-MS). RNA sequencing was employed to examine the underlying mechanisms of GH in the context of AS treatment, with findings further confirmed through western blot analysis. In vitro experiments involved treating VSMCs with oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerotic injury. The formation of foam cells was evaluated by measuring lipid accumulation, inflammatory responses, apoptosis, and the expression levels of foam cell-related markers. Finally, the PI3K/AKT inhibitor LY294002 confirmed that GH alleviates AS via the PI3K/AKT signaling pathway. Results scRNA-seq data analysis showed that growth hormone signaling was reduced in VSMCs of atherosclerotic arteries. HFD led to elevated levels of serum total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), accompanied by increased lipid deposition, inflammatory responses, and oxidative stress. In contrast, high-density lipoprotein cholesterol (HDL-C) and insulin-like growth factor 1 (IGF-1) levels were lower in C57-Hx mice. GH treatment improved HFD-induced AS in ApoE −/− -Hx mice. LC-MS analysis revealed that GH altered lipid metabolism in serum samples from C57-sham, C57-Hx, ApoE −/− -Hx, and ApoE −/− -Hx-GH(3) mice. GH maintained lipid balance by increasing 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), PE-NMe2(18:1(9z)/18:1(9z)) (DMPE), and 4-chloro-2-nitrobenzylalcohol levels and decreasing 1-heptadecanoyl-sn-glycerol-3-phosphocholine. RNA sequencing showed significant gene expression differences in the aortas of C57-sham and C57-Hx mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that GH inhibited the progression of AS by modulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, a finding that was validated through western blotting. Further in vitro studies demonstrated that GH exerted protective effects on VSMCs against ox-LDL-induced damage through activation of the PI3K/AKT pathway, as evidenced by experiments using the specific PI3K inhibitor LY294002. Conclusion GH alleviates the development of AS through the activation of the PI3K/AKT pathway. The findings of this research emphasize the therapeutic potential of GH in inhibiting AS and highlight the importance of the PI3K/AKT pathway as a promising target for clinical intervention.
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