MOLECULAR BIOLOGY REPORTS
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2026
·Vol. 53
·期 1
·1271
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IF 3.2
Luan Haiyan,Li Jingyuan,Gao Lili,Li Mengyu,Liu Ying,Liu Xingyuan
Background Cardiac remodeling induced by continuous pressure overload exacerbates heart failure (HF), yet effective treatments remain limited. This study investigates the therapeutic efficacy and underlying mechanisms of paeoniflorin (Pae) in the treatment of HF. Methods A transverse aortic constriction (TAC)-induced HF model in male Sprague-Dawley (SD) rats was used to evaluate four groups: Sham, TAC, TAC + Pae (10 mg/kg/day, i.p.), and TAC + fosinopril (5 mg/kg/day, p.o.). Cardiac function, morphology, and biomarker expression were assessed via echocardiography, hemodynamics, histology, ELISA, Western blot, and qPCR. Therapeutic targets were identified using network pharmacology, molecular docking, pull-down, and cellular thermal shift assays. Additionally, in vitro rescue assays were performed using Ang II-treated H9c2 cells and the AKT1 agonist SC79. Results Pae improved cardiac function, characterized by enhanced myocardial contractility and decreased serum NT-proBNP levels. Pae treatment decreased cardiomyocyte cross-sectional area (CSA), collagen deposition, and the expression of ANP , BNP , and β-MHC . Mechanistic studies identified AKT1 as a key binding partner of Pae. Pae binding to AKT1 inhibited its phosphorylation, thereby suppressing the downstream NF-κB inflammatory pathway and reducing the expression of pro-inflammatory cytokines ( IL-1β , IL-6 , and TNF-α ). Pae reversed Ang II-induced hypertrophy, fibrosis, and NF-κB nuclear translocation in H9c2 cells. Furthermore, the protective effects of Pae against hypertrophy, fibrosis, and inflammation were abolished by SC79. Pae demonstrated an excellent safety profile. Conclusion Pae alleviates HF by targeting the AKT1/NF-κB signaling axis to mitigate pathological remodeling and inflammation, presenting a safe and promising therapeutic candidate for heart failure management.
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XENOBIOTICA
·
2026
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IF 1.5
Jia-ou Chen,Ling-li Zhou,Jian-heng Lin,Hao-tian Zhou,Lai-fang Sun,Cheng-ke Huang
1. This study aims to investigate the effects of orally administered paeoniflorin (PF), a major bioactive compound from Paeonia lactiflora, on cytochrome P450 (CYP450) enzyme activity in rats to assess potential drug-drug interactions (DDIs). Following PF treatment, rats received a mixed probe drug solution containing phenacetin (PHE), tolbutamide (TOL), omeprazole, and metoprolol, and plasma concentrations of the substrates and metabolites were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. The metabolic ratio, calculated as the ratio of metabolite to parent drug area under the curve (AUC), was used to evaluate CYP activity.2. Results showed that AUCAcetaminophen/AUCPHE values were significantly elevated in PF-treated groups, indicating induction of CYP1A2, whereas AUCOHTOL/AUCTOL values were significantly reduced, suggesting inhibition of CYP2C11. No significant effects were observed on CYP2C or CYP2D2 activities.3. These findings indicate that PF can modulate CYP1A2 and CYP2C11 activities under the experimental conditions tested, as assessed using PHE and TOL as functional markers. However, the magnitude of these effects was modest and observed only at relatively high PF doses (50 and 100 mg/kg). Given the inherent species differences between rat and human CYP enzymes, direct extrapolation of these findings to human CYP1A2 and CYP2C11 requires further validation in human-relevant models.
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ACS Applied Materials & Interfaces
·
2026
·
IF 8.2
Mingjing Wang,Kang Liu,Peng She,Tianci Gao,Zhansen Shi,Yunlai Wang,Xiaoya Ding,Ye Yang,Dengke Yin,Wei Shen,Hanmeng Liu
Rheumatoid arthritis (RA) tissues exhibit high levels of reactive oxygen species (ROS) and free Ca2+, which contribute to a vicious cycle of sustained inflammatory responses. This study developed an in situ Ca2+-reinforced injectable full-active HPAP hydrogel. The full-active hydrogel is formed by cross-linking phenylboronic acid-functionalized hyaluronic acid (HA-PBA) with sodium alginate (ALG) and paeoniflorin (PF) through boronate ester bonds, all of which play significant roles in RA treatment. HPAP hydrogel exhibits relatively low strength in vitro, allowing for easy injection into the joint cavity. Then, ALG can trigger secondary cross-linking in the RA joint cavity using Ca2+, forming the HPAP/Ca2+ hydrogel in situ and enhancing drug retention (with significant signals detectable in vivo even 17 days postinjection). Furthermore, a decrease in the free Ca2+ concentration can inhibit the activation of the NLRP3 inflammasome pathway. HA-PBA participates in the formation of ROS-responsive boronate ester bonds in hydrogel, thereby reducing ROS levels in RA tissues. Additionally, the released PF inhibits the activation of the NF-κB pathway, mitigating the inflammatory response. In vitro and in vivo experiments demonstrate that the HPAP hydrogel can effectively scavenge ROS, inhibit the NF-κB and NLRP3 pathways, reprogram macrophages, and reduce osteoclast differentiation and cartilage matrix degradation. In the RA animal models, HPAP hydrogel significantly improved arthritis scores, bone erosion, and inflammation levels, showing better treatment efficacy compared to commercial dexamethasone. Given the simplicity of the components of this full-active hydrogel, all of which are natural and safe compounds, it exhibits promising clinical translation potential in RA treatment.
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Frontiers in Microbiology
·
2026
·
IF 5.8
Xiao-Long Wang,Chang Zhang,De-Shuang Lu,Zhuo-Yue Dong,Bai-Ming Jin,Si-Yuan Wan,Zi-Wen Zhang,Chun-Jing Zhang,Lin Li
Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, inflammation and gut dysbiosis. Paeoniflorin (PAF) exhibits potential against NAFLD, yet its antioxidant mechanism via the gut-liver axis remains unclear. In a high-fat/sucrose (HFS) diet-induced NAFLD mouse model, C57BL/6 mice received PAF (50 or 100 mg/kg/day) for 10 weeks. Oxidative stress markers, histopathology, gut microbiota, and serum metabolomics were conducted, with fecal microbiota transplantation (FMT) applied for causal validation. PAF ameliorated metabolic disorders by suppressing hepatic lipogenesis and promoting cholesterol excretion. PAF significantly ameliorated oxidative stress by enhancing hepatic and colonic anti-oxidant capacity, evidenced by increased SOD activity and decreased MDA levels. It concurrently reduced systemic inflammation and enhanced intestinal barrier integrity via upregulation of tight junction proteins. Furthermore, PAF reshaped the gut microbiota, elevating beneficial Akkermansia and microbial-derived SCFAs, while suppressing pro-oxidant and pro-inflammatory pathogens like Desulfovibrio and Helicobacter. FMT confirmed that these antioxidant and metabolic benefits were mediated by the gut microbiota. In conclusion, PAF alleviates NAFLD primarily through potent antioxidant actions and anti-inflammatory, achieved via remodeling gut microbial ecology and reinforcing intestinal barrier.
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MOLECULAR PHARMACEUTICS
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2026
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IF 4.9
Jiachang Lin,Pei Huang,Yongqi Wang,Jiaxiang Wu,Yushi Jian,Lina Zhu,Huaying Wen,Wenhui Gao,Yingling Miao,He Wang,Xiyong Yu,Chunfang Liu,Yi Zhou
The intrinsic resistance of tumor cells to apoptosis frequently results in chemoresistance and therapeutic failure in clinical settings. The main active ingredients of traditional Chinese medicine, in combination with chemotherapy drugs, have become one of the effective treatment methods to overcome this kind of drug resistance by targeting double subcellular organelles to promote apoptosis. In this study, we developed a Cu2+-coordinated paeoniflorin (PF)/doxorubicin (DOX) biocomplex, referred to as PCD, with the aim of overcoming cellular apoptosis resistance for combinational lung cancer therapy. PCD demonstrates remarkable water solubility and superior in vivo biocompatibility. Owing to the coordination effect, the self-assembled PCD exhibits a nanoscale particle size, a narrow and homogeneous grain distribution, as well as exceptional dispersion stability. Furthermore, PCD has the potential to disassemble under conditions of high glutathione levels and low pH, thereby facilitating effective drug release. PF-mediated endoplasmic reticulum stress (ERS) can downregulate the expression of FDX1 and DLAT proteins. Ca2+ overload induced by ERS disrupts mitochondrial matrix ion balance, accelerates water efflux, and ultimately leads to mitochondrial volume reduction and a decrease in mitochondrial membrane potential. Ultimately, this process synergizes with DOX-induced reactive oxygen species production to enhance apoptosis in lung cancer cells. PCD exhibits significant superiority over monotherapy in inhibiting tumor growth while minimizing systemic toxicity via enhanced induction of lung cancer apoptosis. This study may provide a promising avenue for advancing self-delivery nanomedicine to overcome apoptosis resistance in lung cancer therapy.
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JOURNAL OF MEMBRANE SCIENCE
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2026
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IF 8.8
Longping Jin,Kunmei Su,Maliang Zhang,Xi Du,Zhenhuan Li
Ineffective impurities in traditional Chinese medicine extracts can cause numerous issues, making the development of efficient and environmentally friendly purification technologies imperative. An ideal separation membrane must combine high selectivity, high permeability, and reliability under harsh environments. This study proposes a "homologous reinforcement" strategy, specifically, polyphenylene sulfide (PPS) fibers treated with sulfonation were employed as multifunctional reinforcement to fabricate the fibers reinforced PPS membrane via thermally induced phase separation (TIPS). The sulfonated PPS (SPPS) fibers exhibit the perfect interfacial compatibility with PPS matrix, significantly enhancing the mechanical strength as reinforcing skeletons while serving as effective nucleation sites during phase separation, which optimizes the composite membrane crystalline morphology and pore structure. Additionally, the tensile strength of the optimal composite membrane is enhanced by over three times compared to pure PPS membrane. In terms of separation performance, this prepared membrane achieves an effective balance between retaining five typical active components of traditional Chinese medicine and removing impurities. Furthermore, the introduction of SPPS fiber endowed the membrane with persistent hydrophilicity and negative charge, conferring the excellent anti-fouling properties and high flux recovery. More importantly, this SPPS modified composite membrane maintained outstanding structural integrity and separation stability under harsh environments such as harsh pH and organic solvents, ensuring reliable long-term operation.
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Microbiology Spectrum
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2025
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IF 3.8
Ru Qu,Ming Li,Ping Li,Ying Song,Biao Dong,Juan Liu,Xuan Mo,Zhenjiang Zech Xu,Xiaochang Huang
Porphyromonas gingivalis is a well-known periodontal pathogen that has also been linked to systemic diseases. In this study, our results revealed that P. gingivalis exacerbated inflammation, as indicated by weight loss, decreased colon length, and increased colonic tissue inflammation. Furthermore, P. gingivalis increased the population of Th17 cells in the spleen and upregulated the expression of pro-inflammatory cytokines in mice. Additionally, P. gingivalis aggravated the gut microbiota dysbiosis by reducing the beneficial bacteria like S24-7. In addition, we discovered that paeoniflorin, a widely recognized biologically active phytochemical, had the potential to mitigate the exacerbated inflammation caused by P. gingivalis. Specifically, paeoniflorin treatment rebalanced immune cell populations, reduced the levels of inflammatory cytokines, and reshaped the composition of the gut microbiota. In summary, our findings suggest that paeoniflorin holds promise as a potential therapeutic agent for alleviating the inflammatory effects induced by P. gingivalis.
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CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Binbin Hu,Huaqiang Fang,Zhixin Huang,Wenjing Huang,Li Huang,Huijie Liu,Fanzhen Lv,Wei Huang,Xiaolei Wang
Parkinson’s disease (PD) is a complex neurodegenerative disease affected by many factors. Although there are treatments to combat the symptoms of PD, such as levodopa and deep electrical stimulation, there is currently no ideal therapy to delay or prevent the progression of PD. Oxidative stress and neuroinflammation have been considered as the key mechanisms in the occurrence and development of PD. In theory, anti-oxidative stress and anti-neuroinflammation are effective strategies for the treatment of PD. In this work, we have attempted for the first time to construct a nitric oxide (NO) gas and drug combination therapeutic nanoplatform (Lf-UZSP) that can penetrate the blood–brain barrier (BBB) and target PD microenvironment through upconversion nanoparticles (UCNPs). The nanoplatform can target the PD microenvironment in the brain and subsequently convert near-infrared (NIR) light into ultraviolet (UV) light, which in turn releases NO, and the disintegration of NO gas further promotes the release of paeoniflorin (Pae). The controllable release of NO and Pae is used to achieve short-acting and long-acting synergistic therapy. In vitro experiments demonstrate that Lf-UZSP exhibits promising neuroprotective effects in PD cell models by scavenging excessive reactive oxygen species (ROS) and inhibiting neuroinflammation. Further in vivo experiments confirm that Lf-UZSP can significantly improve the motor impairment and alleviate the loss of dopaminergic (DA) neurons in the substantia nigra and striatum in PD mice.
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ANALYTICAL BIOCHEMISTRY
·
2023
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IF 2.9
Yuting Xue,Haotian Zhong,Bin Liu,Shuo Qin,Zhengbo Chen,Kai Li,Lirong Zheng,Xia Zuo
Nanozymes have been relatively well explored, and bimetal-doped nanozymes have attracted much exploration due to their superior catalytic activity . We developed bimetallic FeCu/NPCs and Cu/NPCs nanozymes, which have good catalytic properties due to the coordination of Fe and Cu with N and P. The nanozymes acted as sensing elements in a cascade reaction system to effectively recognize seven terpenoids , including menthol (Men), paeoniflorin (Pae), camphor (Cam), paclitaxel (Pac), andrographolide (Andro), ginkgolide A (Gin A), and piperone (Pip). Terpenoids act as inhibitors of acetylcholinesterase (AChE) and reduce the hydrolysis of acetylcholine (ATCh), providing insight into establishing a simple and distinct assay for terpenoids . Notably, the sensor array distinguished seven terpenoids with concentrations as low as 10 ng/mL and achieved high-precision detection of mixed samples with different molar ratios and 21 unknown samples. Finally, the sensor array successfully distinguished and identified multiple terpenoids in herbal samples.
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Chinese Journal of Integrative Medicine
·
2026
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IF 3.1
Zhang Di,Zhuang Zi-feng,Lin Shao-zi,Chen Zen-ni,Chen Hong-ling,Gu Jun-yan,Hao Yu-ting,Li Yi-xuan,Chen Jia-xu,Zhao Guo-ping
Objective To elucidate whether Danggui Sini Decoction (DGSD) relieves sciatica by downregulating transient receptor potential (TRP) channels involved in peripheral sensitization. Methods After conducting chronic constriction injury of sciatic nerve (CCI) operation, 32 SD rats, randomly assigned to the sham, CCI 7d, CCI 14d, and CCI 21d groups ( n =8 per group), were used to observe the course of sciatica. mRNA sequencing of dorsal root ganglia (DRG) was conducted on rats in the sham and CCI 21d groups. Another 32 rats were divided into the sham, CCI, mecobalamin, and DGSD groups, 8 in each group. mRNA sequencing analysis and single-cell RNA-sequencing (scRNA-seq) data analysis were conducted. Behavioural tests were conducted to evaluate the therapeutic effects of DGSD. The levels of TRP vanilloid (TRPV)1–4, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8), Ras homolog family member A (RhoA), and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) were measured via Western blot, and the serum levels of C-C motif chemokine ligand 2 and 5 (CCL2, CCL5), substance P (SP), and prostaglandin E2 (PGE2) were conducted via ELISA. Results scRNA-seq and mRNA sequencing analysis revealed that inflammatory mediator regulation of TRP channels played a role in the development of sciatica. CCI rats exhibited cold hyperalgesia from day 4 to 21, increased the DRG protein expression levels of TRP channels, including TRPV1–4, TRPA1, TRPM8, RhoA, p-p38MAPK, CCL2, CCL5, SP, and PGE2. Treatment with DGSD decreased the serum levels of CCL2, CCL5, SP, and PGE2, and reduced the levels of RhoA, p-p38MAPK, TRPV1–4, TRPA1, and TRPM8 in DRG ( P <0.05). Conclusion CCI increased the levels of TRP channels and inflammatory factors, inducing cold hyperalgesia, whereas DGSD relieved pain via inhibiting peripheral sensitization to relieve cold hyperalgesia by reducing the inflammatory factors and TRP.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Xingyao Pei,Shusheng Tang,Haiyang Jiang,Wenjuan Zhang,Gang Xu,Zonghui Zuo,Zhenhui Ren,Chun Chen,Yao Shen,Cun Li,Daowen Li
The risks of Zinc oxide nanoparticles (ZnO NPs) applications in biological medicine, food processing industry, agricultural production and the biotoxicity brought by environmental invasion of ZnO NPs both gradually troubled the public due to the lack of research on detoxification strategies. TFEB-regulated autophagy-pyroptosis pathways were found as the crux of the hepatotoxicity induced by ZnO NPs in our latest study. Here, our study served as a connecting link between preceding toxic target and the following protection mechanism of Paeoniflorin (PF). According to a combined analysis of network pharmacology/molecular docking-intestinal microbiota-metabolomics first developed in our study, PF alleviated the hepatotoxicity of ZnO NPs from multiple aspects. The hepatic inflammatory injury and hepatocyte pyroptosis in mice liver exposed to ZnO NPs was significantly inhibited by PF. And the intestinal microbiota disorder and liver metabolic disturbance were rescued. The targets predicted by bioinformatics and the signal trend in subacute toxicological model exhibited the protectiveness of PF related to the SIRT1-mTOR-TFEB pathway. These evidences clarified multiple protective mechanisms of PF which provided a novel detoxification approach against ZnO NPs, and further provided a strategy for the medicinal value development of PF.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
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IF 4.932
Jingjing Li,Suiyuan Ren,Meng Li,Jingai Bi,Guang Yang,Erguang Li
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes inflammation and ulcers in the digestive tract. The treatment commonly includes anti-inflammatory agents like 5-aminosalicylic acid or corticosteroids or biologics for people with UC who are no longer responding to corticosteroids. The radices of Paeonia lactiflora Pall. or similar plants of the Paeonia genus have been used in Chinese medicine to treat certain diseases that resemble the symptoms of UC. Paeoniflorin, a terpenoid glycoside, is a major active component for the anti-inflammatory and antitumor activity. In this study, we evaluated the therapeutic effect of paeoniflorin (PF) against dextran sulfate sodium (DSS)-induced colitis in mice and found that PF exhibited protective activity against colitis. PF treatment suppressed NF-κB pathway activation, resulting down regulation of pro-inflammatory factor expression. In addition, we detected reduction in eosinophil-related chemokine gene expression and eosinophil infiltration. The treatment also reversed Treg cell population suppression. Although PF treatment did not block COX2 induction, the compound weakly inhibited COX2 activity in an enzymatic assay. Taken together, PF exerts its therapeutic activity against UC through inhibition of inflammation and eosinophil infiltration.
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