Scientific Reports
·
2025
·Vol. 15
·期 1
·1-19
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IF 3.9
Liu Yunxiao,Wang Shuanghu,Younas Ayesha,Lv Jiaojian,Al Mamun Abdullah,Shao Chuxiao
Nonalcoholic Fatty Liver Disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes and is closely associated with metabolic disturbances such as obesity, dyslipidemia, and insulin resistance. Despite its increasing prevalence and potential progression to severe liver conditions, there is currently no approved pharmaceutical intervention for NAFLD. Traditional Chinese Medicine (TCM) formulations, such as Xiaoyao San (XYS), have shown therapeutic efficacy in treating NAFLD, but the underlying mechanisms remain unclear. This study employed a multi-omics approach to elucidate the therapeutic mechanisms of XYS in NAFLD. A rat model of NAFLD was established using a high-fat diet (HFD). The chemical constituents of XYS were analyzed using UPLC-MS/MS. Transcriptomics and proteomics analyses were performed to identify potential biological targets and signaling pathways involved in the therapeutic effects of XYS. The results were validated using ELISA and Western blotting. UPLC-MS/MS identified 225 prototype chemical components of XYS in the blood. XYS significantly reduced body weight, liver index, and Lee’s index in NAFLD model rats. It ameliorated HFD-induced hepatic steatosis, down-regulated serum levels of ALT, AST, GGT, TG, TC, LDL-C, FBG, IL-1β, IL-6, TNF-α, and ROS, and up-regulated HDL-C levels. Transcriptomics and proteomics analyses revealed that XYS modulated key signaling pathways, including cAMP, TGF-β, NF-κB, and necroptosis. Specifically, XYS down-regulated the expressions of NF-κB, p-NF-κB, FOXO1, TGF-β1, RIP3, and p-MLKL, while up-regulating cAMP, PKA, p-PKA, and PPARα. XYS improves NAFLD by regulating the cAMP/PKA-mediated PPARα, FOXO1, and NF-κB signaling pathways. This study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of XYS in NAFLD and supports its potential as a novel therapeutic intervention for this condition.
研究领域:
药理学
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代谢疾病
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系统生物学
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PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Wen-Biao Zu,Zhao-Jie Wang,Dong-Mei Tang,Qin-Yu Lu,Yan-Yan Zhu,Zhong-Shun Zhou,Mei-Zhen Wei,Xiao-Dong Luo
Background Fungal diseases affect over one billion individuals worldwide and represent a significant public health concern. Oral candidiasis (OC) is a common fungal infection primarily caused by Candida albicans. Eriocapitella rivularis is a traditional medicinal herb for the treatment of oral fungal infections. Purpose This study aimed to identify potent antifungal compounds from E. rivularis and elucidate their underlying mechanisms of action. Methods Bio-guided isolation combined with network pharmacology was used to identify anti- C. albicans compounds from E. rivularis , followed by metabolomics analysis to explore potential regulatory pathways. Antifungal activity and synergistic efficacy were evaluated using broth microdilution, checkerboard, and time-kill assays. Biofilm inhibition was assessed through quantitative and biochemical analyses. Reverse transcription quantitative polymerase chain reaction was performed to elucidate molecular mechanisms. An in vivo murine OC model was employed to verify efficacy. Results Prosapogenin CP4 disrupted the fungal cell wall, targeted ergosterol to induce plasma membrane permeabilization, inactivated mitochondrial function, and inhibited hyphal growth, potentially through interference with ABC transporters, modulation of cAMP export, and induction of metabolic disorders. Prosapogenin CP4 and ursolic acid exhibited a synergistic inhibitory effect against fluconazole-resistant C. albicans (FICI = 0.375) with low resistance. This combination regulated genes in the Ras/cAMP/PKA signalling pathway, significantly inhibited biofilm formation and reduced fungal burden, inflammatory responses, and fungal colonisation in murine oral tissues, with efficacy comparable or superior to that of nystatin. Conclusion The finding presents a synergistic phytomedicine strategy using two triterpenoids from E. rivularis as a promising therapeutic approach for OC, particularly biofilm-associated infections.
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Frontiers in Pharmacology
·
2026
·
IF 5.4
Kanglu Yang,Lanyibo Liu,Caifeng Li,Shiwen Deng,Junxian Cao,Junqi Chen,Shaoping Wang,Qiangpu Chen,Peng Chen
Introduction Cellular senescence drives aging and age-related diseases, posing a critical barrier to stem cell-based regeneration. While selective elimination of senescent cells (senolysis) remains a theoretically promising strategy, safe natural senotherapeutic agents are limited. Human exfoliated deciduous tooth stem cells (SHED) possess high regenerative potential yet are vulnerable to senescence, compromising their therapeutic utility. Methods We performed a phenotypic screen of 800 natural compounds in replicatively senescent SHED. The hit compound, the phytochemical melissic acid, was then validated in two independent senescence models—replicative exhaustion and doxorubicin-induced stress. Melissic acid (5–20 μM) was assessed for cytotoxicity and anti-senescence efficacy via SA-β-Gal staining and senescence marker expression. Transcriptomic profiling and mechanistic assays were performed to dissect the underlying molecular pathways. Results Melissic acid exhibited minimal cytotoxicity but significantly reduced SA-β-Gal positivity and senescence markers in both models. Transcriptomic profiling revealed marked upregulation of ADCY5 and coordinated changes in cAMP signaling, autophagy, and lipid metabolism genes. Mechanistically, melissic acid increased CREB Ser133 phosphorylation, enhanced Beclin-1 expression, and reduced p62/SQSTM1, indicating activation of cAMP/CREB-dependent autophagy. It also decreased lipid peroxidation, restored mitochondrial membrane potential, and relieved G0/G1 arrest via upregulation of Cyclin D1 and Rb Ser780 phosphorylation. Discussion Collectively, melissic acid alleviates SHED senescence through the ADCY5/cAMP/CREB-autophagy axis, promoting autophagic clearance, mitochondrial recovery, and cell-cycle re-entry—thereby ameliorating senescence-associated phenotypes in senescent stem cells. This study identifies melissic acid as a natural senomorphic candidate for stem cell function restoration and provides a mechanistic link between cAMP-dependent autophagy and amelioration of stem cell aging, offering a potential strategy to overcome stem cell exhaustion and regenerative limits imposed by cellular senescence.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Dongxu Yuan,Bingbing Liu,Xinsong Yuan,Leilei Feng,Xudong Xu,Jialin Zhu,Zhengjie Chen,Renhao Xu,Jiao Chen,Gang Xu,Jianping Lin,Lirong Yang,Mian Li,Jiazhang Lian,Mianbin Wu
The bioproduction of xylitol from hemicellulose hydrolysate has good potential for industrial development. However, xylitol productivity has always been limited due to corncob hydrolysate toxicity and glucose catabolic repression. To address these challenges, this work selected the S83 and S128 amino acid residues of the cyclic AMP receptor protein (CRP) as the modification target. By introducing multisite mutation in CRP, this approach successfully enhanced xylose catabolism and improved the strain’s tolerance to corncob hydrolysate. The resulting mutant strain, designated as CPH (CRP S83H-S128P), underwent fermentation in a 20 L bioreactor with semicontinuous feeding of corncob hydrolysate. Remarkably, xylitol yield and xylitol productivity for 41 h fermentation were 175 and 4.32 g/L/h, respectively. Therefore, multisite CRP mutation was demonstrated as an efficient global regulatory strategy to effectively improve xylitol productivity from lime-pretreated corncob hydrolysates.
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PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
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2018
·
IF 4.185
Qiuping Zhong,Hui Yu,Chang Huang,Jiahong Zhong,Haitao Wang,Jiangping Xu,Yufang Cheng
The canonical phosphodiesterase 4 (PDE4) inhibitors produce antidepressant-like effects in a variety of animal models. However, severe side effects, particularly vomiting and nausea, limit their clinical application. FCPR16 is a novel PDE4 inhibitor with less vomiting potential. However, whether it will exert an antidepressant-like effect remains unclear. Here, we aimed to evaluate the effect of FCPR16 in mice subjected to chronic unpredictable mild stress (CUMS). Our results showed that FCPR16 produced antidepressant-like effects in multiple behavioral tests, including a forced swimming test, tail suspension test , sucrose preference test and novelty suppression feeding test. Simultaneously, data indicated that FCPR16 enhanced the levels of several proteins, including cAMP, brain derived neurotrophic factor , exchange protein directly activated by cAMP 2 (EPAC-2), synapsin1, postsynaptic density protein 95 , phosphorylated cAMP response element binding protein and extracellular regulated protein kinases 1/2, which were downregulated by CUMS in both the cerebral cortex and hippocampus . The number of DCX + cells in the hippocampus of CUMS mice was increased after FCPR16 treatment. Moreover, treatment with FCPR16 resulted in decreased expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and increased expression of anti-inflammatory cytokines (IL-10) in mice challenged with CUMS. Consistently, the mRNA levels of microglial M1 markers (iNOS and TNF-α) were downregulated, while M2 markers (Arginase 1 and CD206) were upregulated in CUMS-exposed mice after FCPR16 treatment. Immunofluorescence analysis showed that FCPR16 inhibited the activation of microglial cells and increased the number of CD206 + in CUMS-exposed mice. Collectively, these results suggested that FCPR16 is a potential compound with effects against depressive-like behaviors , and the antidepressant-like effect of FCPR16 is possibly mediated through activation of the cAMP-mediated signaling pathways and inhibition of neuroinflammation in both the cerebral cortex and hippocampus.
研究领域:
药理学
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神经科学
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行为科学
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分子生物学
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2025
·
IF 1.3
Ying Liu,Miao Wang,Guang-Xiong Zhou
The threat posed by microorganisms to food safety in development necessitates the discovery of new antimicrobial agents. Here, we unravel the antifungal activity of 6-methoxydihydrosanguinarine (6-ME) derived from Hylomecon japonica. 6-ME disrupted the biofilm formation of Candida albicans (C. albicans). 6-ME could cause the blockage of filamentation and classical cyclic adenosine monophosphate (cAMP) signaling pathway is involved in this process. 6-ME downregulated the expression of EFG1, CDC35, RAS1, and TPK2, all of which are critical components of the cAMP pathway. Furthermore, 6-ME changed the membrane permeability of C. albicans and caused reactive oxygen species accumulation, leading to cell death.
研究领域:
微生物学
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药理学
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真菌学
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生物化学
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食品安全
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Frontiers in Pharmacology
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2021
·
IF 5.811
Zhang Bo,Gao Lihua,Shao Chunsheng,Deng Mingsi,Chen Liangjian
Chewing areca nut (betel quid) is strongly associated with oral submucous fibrosis (OSF), a pre-cancerous lesion. Among the areca alkaloids, arecoline is the main agent responsible for fibroblast proliferation; however, the specific molecular mechanism of arecoline affecting the OSF remains unclear. The present study revealed that arecoline treatment significantly enhanced Transforming growth factor-β (TGF-β)-induced buccal mucosal fibroblast (BMF) activation and fibrotic changes. Arecoline interacts with phosphodiesterase 4A (PDE4A) to exert its effects through modulating PDE4A activity but not PDE4A expression. PDE4A silence reversed the effects of arecoline on TGF-β-induced BMFs activation and fibrotic changes. Moreover, the exchange protein directly activated by cAMP 1 (Epac1)-selective Cyclic adenosine 3′,5′-monophosphate (cAMP) analog (8-Me-cAMP) but not the protein kinase A (PKA)-selective cAMP analog (N6-cAMP) remarkably suppressed α-smooth muscle actin(α-SMA) and Collagen Type I Alpha 1 Chain (Col1A1) protein levels in response to TGF-β1 and arecoline co-treatment, indicating that cAMP-Epac1 but not cAMP-PKA signaling is involved in arecoline functions on TGF-β1-induced BMFs activation. In conclusion, arecoline promotes TGF-β1-induced BMFs activation through enhancing PDE4A activity and the cAMP-Epac1 signaling pathway during OSF. This novel mechanism might provide more powerful strategies for OSF treatment, requiring further in vivo and clinical investigation.
研究领域:
分子生物学
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细胞生物学
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口腔医学
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药理学
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DOI
PubMed
高影响因子
THERIOGENOLOGY
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2026
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IF 2.9
Jiahao Zhao,Xiangyu Zhou,Baoyi You,Bowen Cheng,Jiashuo Hu,Yuxuan Lu,Dianrui Xu,Xiwei Zhang,Chunlong Yan,Qingshan Gao,Haixing Liu,Qingguo Jin
Florfenicol (FLO) is widely used to treat bacterial respiratory diseases and hoof rot in cattle at various physiological stages. However, residues of FLO that accumulate in cattle may have adverse effects on animal health. Although FLO has been reported to exhibit embryotoxic and cytotoxic properties, the mechanism underlying its effects on bovine granulosa cells (GCs) remains poorly understood. In this study, we treated GCs with FLO at concentrations of 0, 10, and 100 μg/mL for 48 h to evaluate the effects of FLO on cell viability, mitochondrial function, and steroid hormone synthesis. The results showed that FLO treatment was associated with increased apoptosis, reduced GC proliferation, and impaired mitochondrial function. In addition, FLO treatment was accompanied by decreased ATP levels and increased intracellular reactive oxygen species (ROS). Furthermore, FLO exposure was associated with changes in PROG and E2 production, decreased protein expression of StAR and CYP11A1, and reduced levels of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). The antioxidant N-acetyl-L-cysteine (NAC) partially attenuated these changes. In conclusion, our findings suggest that FLO exposure is associated with GC dysfunction and impaired steroidogenesis. These effects may be related to oxidative stress, mitochondrial dysfunction, and alterations in the cAMP/PKA/StAR signaling pathway, although direct causal relationships remain to be further elucidated.
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MICROBIAL PATHOGENESIS
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2026
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IF 3.9
Zhen-ye Luo,Zhe Chen,Feng-lin Zhang,Chang-shun Liu,Fei-long Chen,Ze-zhong Zheng,Xiao-mei Tan
Bacterial diarrhea involves colonic water absorption dysfunction and gut microbiota disruption. Gegen Qinlian decoction (GQD) is clinically used to treat infectious diarrhea, yet its mechanisms remain incompletely understood. This study aimed to investigate how GQD modulates gut microbiota and enhances colonic water absorption in E. coli -induced diarrhea. Using an E. coli -induced piglet diarrhea model together with a rat colonic perfusion model, results show that GQD alleviates diarrhea-associated intestinal injury and inflammation and improves colonic water absorption. Mechanistically, GQD was associated with increased colonic aquaporin-3 (AQP3) expression and attenuation of the cAMP-protein kinase A-cystic fibrosis transmembrane conductance regulator (cAMP-PKA-CFTR) secretory signaling axis. 16S rRNA sequencing indicated enrichment of Lactobacillus amylovorus after GQD treatment, and administration of L. amylovorus partially reproduced the anti-diarrheal phenotype and transport-related signaling changes. In vitro assays further suggested that GQD suppresses E. coli growth while promoting L. amylovorus metabolic activity, and molecular docking provided hypothesis-generating predictions of candidate phytochemicals and bacterial targets. Overall, GQD may improve bacterial dysbiosis by enriching L. amylovorus and inhibiting E. coli , thereby restoring colonic water transport via the cAMP/CFTR/AQP3 pathway and ultimately improving bacterial diarrhea.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 15
Ma Tianyu,Li Qiang,Chen Xingwu,Dong Jixiang,Jiang Yuqing,Li Shanshan
Bioactive peptides are promising candidates for hair regeneration, but their topical application is often limited by poor skin delivery and the need for frequent dosing. To overcome these challenges, we designed a palmitoylated peptide, Pal-MPAPO, and incorporated it into a hyaluronic acid-based hydrogel microneedle (MN) system for localized transdermal delivery. The fabricated MNs showed adequate mechanical strength for skin insertion and provided a time-dependent, prolonged release of Pal-MPAPO. In human dermal papilla cells (DPCs), Pal-MPAPO activated the Wnt/β-catenin pathway and increased intracellular cyclic adenosine monophosphate (cAMP) levels in a predominantly VPAC1-dependent manner. Additional VPAC2 validation did not reveal a significant contribution to cAMP signaling under the tested conditions. Functional interactions between Pal-MPAPO and VPAC1 were supported by molecular docking, molecular dynamics simulations, receptor knockdown, and fluorescence imaging. In a C57BL/6 mouse model, Pal-MPAPO-loaded MNs significantly promoted hair regrowth, achieving efficacy comparable to minoxidil but at a reduced application frequency. These findings identify Pal-MPAPO as a potential peptide candidate for hair regeneration and suggest that hydrogel MN-assisted delivery provides a localized peptide administration strategy. Graphical The alternative text for this image may have been generated using AI.
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PHYTOTHERAPY RESEARCH
·
2025
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IF 6.3
Xian Zheng,Yuanyue Jiang,Wenbo Wang,Kekang Sun,Libin Zhou,Yanru Zhang,Jie Cui,Haiyan Yu,Wenbin Dong,Baofei Yan
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica , has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.
研究领域:
药理学
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胃肠病学
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微生物组研究
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炎症性疾病
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代谢组学
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PubMed
高影响因子
Nutrients
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2025
·Vol. 17
·期 21
·3335
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IF 5
Cuiping Xu,Hao Cui,Qionglian Fang,Pengfei Tu,Xiuming Cui
Background: Steamed Panax notoginseng saponins (SPNSs) can alleviate cyclophosphamide-induced anemia. However, the hepatointestinal effects of SPNSs and their role in ameliorating cyclophosphamide-induced anemia remain unexplored. Objective: To elucidate the hepatointestinal effects of SPNSs and their role in ameliorating cyclophosphamide-induced anemia. Methods: Blood samples were collected and analyzed on days 7 and 14. Liver tissues and small intestinal villi structures were observed via HE staining. Liver and colon content metabolites were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Liver proteins were analyzed by using an Orbitrap Astral mass spectrometer. Colon content microbiota composition was assessed via metagenomics. Signaling pathway protein expression was analyzed via Western blotting (WB). Results : SPNSs significantly increased the red blood cell (RBC) count and hemoglobin (HGB) level by day 14 and alleviated hepatointestinal damage. Hepatic metabolomics revealed: the most abundant metabolites were fatty acids and stachyose on day 7 and amino acid and arachidonic acid derivatives on day 14. KEGG analysis implicated cAMP signaling. Proteomics revealed upregulated immune-related proteins and enhanced PI3K pathway activity (WB-validated). Colon content metabolomics showed increased daidzein, 3-(2,5-dimethoxyphenyl) propanoic acid, γ-CEHC, and adenosine in SPNS groups on day 14. Metagenomics indicated differential abundances of Heminiphilus faecis , Phocaeicola sartorii , and s-bacterium_J10.2018 on day 14. Multiomics integration demonstrated significant correlations between hepatic metabolites, hematopoietic proteins, colon content metabolites, and probiotic bacteria. Conclusions: SPNS alleviates cyclophosphamide-induced hepato-intestinal injury in anemic mice by modulating the gut microbiota and enhancing hepato-intestinal immune defense. Additionally, SPNSs ameliorate anemia in cyclophosphamide-treated mice by activating the cAMP/PI3K/AKT pathway, promoting hepatocyte proliferation, and increasing hematopoietic protein expression.
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