Search Results (93)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron degeneration in the substantia nigra and striatum. Current treatments are largely palliative and frequently associated with adverse effects. This study aimed to evaluate the neuroprotective potential of an aqueous extract of Bacopa procumbens (B. procumbens) and the NAPEL formulation—composed of five neuroactive compounds (Naringenin, Apigenin, Paeoniflorin, (−)-Epicatechin, and Lupeol)—in a murine model of MPTP-induced parkinsonism. Behavioral, histological, and molecular parameters were examined to elucidate underlying mechanisms of neuroprotection. Male mice received MPTP to induce parkinsonism, followed by oral administration of B. procumbens extract or NAPEL. Motor function was assessed through open-field-related parameters. Substantia nigra neuronal morphology was analyzed histologically. Molecular analyses focused on the Keap1/Nrf2/ARE pathway, HSF1, HIF-1α, antioxidant enzymes, and lipid peroxidation. Additionally, in silico analyses (GeneMANIA, STRING) were performed to explore regulatory networks associated with Nrf2, HSF1, and HIF-1α. The aqueous extract significantly improved motor performance, increased rearing events, enhanced central exploration, and increased total distance traveled. It preserved neuronal number and soma diameter in the substantia nigra. Molecularly, the extract activated the Keap1/Nrf2/ARE axis and induced HSF1 and HIF-1α, accompanied by increased SOD-1, CAT, and GSR expression and reduced lipid peroxidation. NAPEL also produced behavioral and histological improvements but did not activate Nrf2, HSF1, or HIF-1α nor notably elevate antioxidant enzymes, except for CAT in the striatum. In silico analyses identified Nrf2, HSF1, and HIF-1α as central nodes integrating oxidative stress, proteostasis, hypoxia, inflammation, and apoptotic responses. These findings support the neuroprotective potential of both B. procumbens aqueous extract and the NAPEL formulation, highlighting their value as promising therapeutic candidates for Parkinson’s disease. Full article

Background: Chronic gastritis (CG) involves gastric mucosal imbalance, with H. pylori (>90% cases), acid-pepsin imbalance, and bile reflux as druggable mechanisms. FDA-approved drugs show limited efficacy against antibiotic-resistant strains and fail to target undruggable pathways (e.g., inflammation, autoimmune atrophy). Traditional Chinese Medicine (TCM), particularly Qing-Wei-Zhi-Tong micro-pills (QWZT), offers multi-target advantages, though its mechanisms remain poorly understood. Methods: The dual-algorithm integration framework predicts QWZT’s pharmacological effects to treat gastritis. For druggable processes (pathways targeted by existing drugs), the structure–target–pathway similarity algorithm quantifies QWZT similar activities to FDA drugs, validated by gastrointestinal smooth muscle experiments. For undruggable processes (novel biological mechanisms not addressed by current therapies), the multi-target perturbation algorithm predicts QWZT’s unique capacity to undruggable processes and is validated via LPS-induced inflammation in RAW264.7 and GES-1 cells. Results: Structure–target–pathway similarity algorithm identified QWZT compounds sharing prokinetic mechanisms with FDA drugs, validated by dopamine-induced relaxations and acetylcholine-induced contractions in gastrointestinal smooth muscle. Multi-target perturbation algorithm quantified QWZT’s superior disruption of undruggable immune/inflammation networks, confirmed by restored cell viability in LPS-injured GES-1 cells and significantly reduced the expression of NO, IL-6, and TNF-α in RAW264.7 cells via key compounds (paeoniflorin and berberine). Conclusions: QWZT may exert its regulatory effects on gastrointestinal smooth muscle by mediating muscarinic and dopamine receptor D2 (DRD2), and reduce the expression of NO, IL-6, and TNF-α to achieve anti-inflammatory effects, thereby effectively treating CG. The integration strategy that integrates algorithms and experiments to reveal the common and distinct mechanisms of QWZT compared to FDA-approved drugs, offering a novel approach for studying Traditional Chinese Medicine mechanisms. Full article

Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H₂O₂) or by subjecting retinal neuronal cells to 8 h of oxygen–glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties. Full article

Background: Despite advances in prostate cancer treatment, castration-resistant prostate cancer (CRPC) remains clinically challenging due to inherent therapy resistance and a lack of durable alternatives. Although traditional Chinese medicine offers untapped potential, the therapeutic role of paeoniflorin (Pae), a bioactive compound derived from Paeonia lactiflora, in prostate cancer has yet to be investigated. Methods: Using an integrative approach (network pharmacology, molecular docking, and experimental validation), we identified Pae key targets, constructed protein–protein interaction networks, and performed GO/KEGG pathway analyses. A Pae-target-based prognostic model was developed and validated. In vitro and in vivo assays assessed Pae effects on proliferation, migration, invasion, apoptosis, and tumor growth. Results: Pae exhibited potent anti-CRPC activity, inhibiting cell proliferation by 60% and impairing cell migration by 65% compared to controls. Mechanistically, Pae downregulated SRC proto-oncogene, non-receptor tyrosine kinase (SRC) mRNA expression by 68%. The Pae-target-based prognostic model stratified patients into high- and low-risk groups with distinct survival outcomes. Organoid and xenograft studies confirmed Pae-mediated tumor growth inhibition and SRC downregulation. Conclusions: Pae overcomes CRPC resistance by targeting SRC-mediated pathways, presenting a promising therapeutic strategy. Our findings underscore the utility of network pharmacology-guided drug discovery and advocate for further clinical exploration of Pae in precision oncology. Full article

Background: Liuwei Dihuang Pills, a classic traditional Chinese medicine formula, has been widely used in clinical practice for its multiple pharmacological effects. However, the systematic characterization and identification of its chemical constituents, especially the aqueous decoction, remain insufficient, which hinders in-depth research on its pharmacodynamic material basis. Thus, there is an urgent need for a comprehensive analysis of its chemical components using advanced analytical techniques. Methods: After screening chromatographic columns, the ACQUITY UPLC™ HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was selected. The column temperature was set to 40 °C, and the mobile phase consisted of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B). A gradient elution program was adopted, and the separation was completed within 20 min. Ultra-high performance liquid chromatography–Orbitrap mass spectrometry (UPLC-Orbitrap-MS) combined with a self-established information database was used for the analysis. Results: A total of 80 compounds were tentatively identified, including 13 monoterpenoids, 6 phenolic acids, 16 iridoids, 11 flavonoids, 25 triterpenoids, and 9 other types. Triterpenoids are mainly derived from Poria cocos and Alisma orientale; iridoids are mainly from Rehmannia glutinosa; monoterpenoids are mainly from Moutan Cortex; and flavonoids are mainly from Dioscorea opposita. Among them, monoterpenoids, iridoids, and triterpenoids are important pharmacodynamic components. The cleavage pathways of typical compounds (such as pachymic acid, catalpol, oxidized paeoniflorin, and puerarin) are clear, and their mass spectral fragment characteristics are consistent with the literature reports. Conclusions: Through UPLC-Orbitrap-MS technology and systematic optimization of conditions, this study significantly improved the coverage of chemical component identification in Liuwei Dihuang Pills, providing a comprehensive reference for the research on its pharmacodynamic substances. However, challenges remain in the identification of trace components and isomers. In the future, analytical methods will be further improved by combining technologies such as ion mobility mass spectrometry or multi-dimensional liquid chromatography. Full article

Paeoniflorin (PF), a monomeric compound extracted from the dry roots of Paeonia lactiflora, has been widely used in the treatment of nervous system diseases, marking it as a critical formula in Parkinson’s disease (PD). However, the action of PF against PD and its molecular mechanism are still unclear. In this study, tandem mass tags quantitative proteomics was performed to systematically clarify the underlying mechanism of action of PF against PD and to confirm it using in vivo and in vitro studies. The results showed that PF notably enhanced the viability of PC12 cells and mitigated MPP⁺-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Tandem mass tag-based quantitative proteome analysis revealed the identification of 6405 proteins, of which 92 were downregulated and 190 were upregulated. Among them, the levels of PI3K, AKT, CREB, and BDNF in the MPP⁺-induced PC12 cell and MPTP mice were considerably lower than in the control group, indicating the role of the BDNF/CREB pathway in the pathogenesis of neuroprotection. The related DEP (PI3K, AKT, CREB, and BDNF) expression levels were verified by Western blot. PF effectively restored the altered expression of the four DEPs induced by MPP⁺ and MPTP. Summarily, PF exerted remarkable neuroprotective effects in MPP⁺-induced PC12 cell and MPTP-induced mice. Further, our research may provide proteomics insights that contribute to the further exploration of PF as a potential treatment for PD. Full article

The objective of this study was to formulate a compound suspension comprising paeoniflorin and curcumin, assess its quality characteristics, and investigate its protective efficacy against acute liver injury in mice. The prescriptions were screened using a single-factor test, and nine groups of suspensions were prepared using the dispersion method. Fifty KM mice (four weeks old) were selected and randomly divided into five groups: the CON, LD, PF, CUR, and PC groups. The doses of both paeoniflorin and curcumin were 100 mg/kg BW, and different suspensions were given to different groups by gavage for 14 days. All the groups except the CON group were injected intraperitoneally with 20 μg/kg LPS and 700 mg/kg D-GalN on the last day. According to the results, the suspension prepared using the optimal prescriptions was orange-yellow in color, with homogeneous turbidity and good re-dispersibility. The combination treatment could reduce the severity of pathological injuries of liver, improve the ultrastructure of hepatocytes, increase the activities of T-SOD, GSH-Px, and CAT, decrease the levels of IFN-γ, TNF-α, and IL-1, and down-regulate the expression of genes such as TLR4, MyD88, IκBα, and NLRP3. The underlying mechanism might be associated with the enhancement of antioxidant enzyme activities, inhibition of the TLR4/NF-κB/NLRP3 signaling pathway, and suppression of inflammasome assembly and release in hepatic tissues. Full article

Aim of the study: Traditional Chinese herbs have a unique therapeutic effect on stroke and numerous successful clinical cases. However, these clinical cases are highly dispersed, creating challenges for translational research. This study employs a new paradigm to identify treatment patterns and the active compound interactions contained within these clinical cases, with experimental validation after target screening. Methods and Materials: Stroke-related targets were identified through GEO, DisGeNET, and Genecards. Active ingredients were extracted from BATMAN-TCM 2.0. All herbs and diseases were confirmed by the Pharmacopoeia of the People’s Republic of China (2020 edition) and Medical Subject Heading (MeSH). All networks in this study were constructed by Cytoscape, and data analysis was done by Python. All formulations and herbs were retrieved from the literature review. For the molecular docking process, Autodock was applied as the docking platform, and all the protein structures were downloaded from PDB. For experimental validation after target screening, HT22 cells were incubated with glucose-free DMEM and placed in an anaerobic chamber for 2 h. Subsequently, HT22 cells were reoxygenated for 24 h. Estrogen Receptor 1 (ESR1) protein levels were measured in vitro. Results: seven materials, including Angelicae Sinensis Radix, Pheretima, Chuanxiong Rhizoma, Persicae Semen, Astragali Radix, Carthami Flos, and Radix Paeoniae Rubra, were identified as the core herbs for the treatment of stroke. The targets of the stroke mechanism were screened, and the herbs-compound-target network was constructed. Among them, paeoniflorin (PF) was identified as the core active compound, and its interaction with ESR1 was verified by molecular docking as the key interaction for the treatment of stroke. In vitro experiments showed that PF inhibited cell apoptosis under hypoxia by increasing the expression of ESR1 compared with the oxygen-glucose deprivation-reperfusion (OGD/R) model group. Western showed that PF (100 μM, 200 μM) can significantly increase the decreased ESR1 protein level caused by the OGD/R model. Conclusions: seven key herbs were screened. Further bioinformatics and network pharmacology studies suggested that PF is expected to become a new active compound for the treatment of stroke. In vitro validation further demonstrated that PF enhanced neuronal survival and ESR1 expression under ischemic conditions, supporting its therapeutic candidacy. Full article

Depression is associated with bidirectional interactions between inflammatory responses and behavioral dysfunction. Paeoniflorin (PF), a monoterpene glycoside derived from Paeonia lactiflora, exhibits potent anti-inflammatory properties. This study investigates the therapeutic effects of PF on lipopolysaccharide (LPS)-induced depression-like behaviors in mice and neuroinflammation in BV2 microglial cells. Mice were co-administered PF (20, 40, or 80 mg/kg/day) and LPS (2 mg/kg) for 7 days. Behavioral tests; Nissl staining; and Golgi, Iba1, DLG4, and cytokine assays were conducted. Additionally, hippocampal NF-κB, Nrf2, and BDNF signaling pathways were analyzed using Western blots. In BV2 cells, oxidative stress and the Nrf2/HO-1 pathway were assessed using CCK-8, flow cytometry, and Western blotting after 24 h of LPS and PF treatment. PF significantly alleviated LPS-induced depression-like behaviors, increased hippocampal neuron and dendritic spine density, and upregulated synaptic proteins (PSD95, SNAP25, and BDNF). Mechanistically, PF suppressed NLRP3 inflammasome activation via the Akt/GSK3β pathway, reduced pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and enhanced the Nrf2/HO-1 antioxidant axis. In BV2 cells, PF restored mitochondrial membrane potential, inhibited apoptosis, and decreased cytokine levels (TNF-α, IL-1β, and IL-6) by inhibiting TLR4/NF-κB signaling. In conclusion, PF significantly improved LPS-induced depression-like behaviors and attenuated neuroinflammation in BV2 microglial cells, highlighting its potential as a therapeutic agent for inflammation-associated depression. Full article

Background: This study aims to develop a fingerprint analysis method using ultra-high performance liquid chromatography (UPLC) for Moutan Cortex sourced from different regions. The objective is to establish quality control standards validated through the integration of chemometric methods and component structure theory. Methods: The mobile phase for UPLC consisted of acetonitrile (A) and a 0.1% aqueous formic acid solution (B), with gradient elution set as follows: 0–1 min, 8% A → 15% A; 1–8 min, 15% A → 18% A; 8–10 min, 18% A → 30% A; 10–15 min, 30% A → 35% A; 15–20 min, 35% A → 85% A; 20–21 min, 85% A → 8% A; and 21–26 min, 8% A → 8% A. Chemical markers significantly affecting Moutan Cortex from various regions were screened, and their identification was based on comparison with reference materials and content determination. Results: A total of 15 chemical markers were identified, including gallic acid, oxypaeoniflorin, catechin, methyl gallate, paeonolide, apiopaeonoside, albiflorin, paeoniflorin, benzoic acid, 1,2,3,6-tetra-O-galloyl-D-glucose, 1,2,3,4,6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, and paeonol. These markers align with component structure theory, allowing for an analysis of the structural characteristics of Moutan Cortex from different regions. Conclusions: The findings provide a valuable reference for the future quality evaluation of traditional Chinese medicine preparations, enhancing the understanding of the material basis components in Moutan Cortex from diverse sources. Full article

The chronic autoimmune disease multiple sclerosis (MS) now remains incurable. Paeoniflorin (PF), which is a monoterpene glucoside obtained from Paeonia lactiflora Pall, is recognized for neuroprotective and anti-inflammatory properties. However, the precise mechanism by which PF regulates MS is unclear. This work aims to elucidate the underlying mechanisms of PF in EAE, a well established animal model of MS, and to discover the target proteins that PF directly acts on. Our results revealed that PF administration can significantly attenuate the clinical symptoms of EAE and alleviate the central nervous system (CNS) inflammatory environment by inhibiting M1-type microglia/macrophages. Mechanistically, PF was found to directly interact with the glycolytic enzyme α-enolase (ENO1), inhibiting its enzymatic activity and expression to impair glucose metabolism, thereby suppressing microglia/macrophage M1 polarization and ameliorating CNS inflammation. Significantly, Eno1 knockdown in microglia/macrophages diminished their pro-inflammatory phenotype, while treatment with ENOBlock or the specific knockout of Eno1 in microglia led to EAE remission, underscoring the critical role of ENO1 in EAE progression. This study uncovers the molecular mechanism of PF in treating EAE, linking the anti-inflammatory property of PF to the glucose metabolism process, which will broaden the prospective applications of PF. Full article

Background: Peripheral artery disease (PAD) is a high-risk vascular condition, and vascular remodeling has become a promising therapeutic approach. Paeoniflorin (PF) is the main bioactive compound in the roots of Paeonia lactiflora Pall, which is commonly used to treat a range of cardiovascular disorders. However, the mechanisms underlying the ameliorating effects of PF on PAD remain unclear. Therefore, the purpose of this study was to explore the therapeutic efficiency of PF on PAD and determine its mechanisms. Methods: The blood flow of mice was detected with a laser Doppler dot scanning imaging system. HE staining was used to observe the morphological changes of ischemic muscle. The changes in the serologic indexes were detected with an automatic biochemical assay, and the capillary density of ischemic gastrocnemius was detected with a Lectin immunofluorescence assay. The expression of angiogenesis-related proteins in ischemic gastrocnemius was detected with Western blotting, and the proportion of macrophages and neutrophils in total cells was detected with flow cytometry. Results: PF significantly increased blood flow, capillary density and protein expressions of vascular endothelial growth factor A (VEGFA), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 2 (MMP9), and estrogen receptor α (ERα) in mouse ischemic tissue in a PAD model. PF enhances the migration of endothelial cells and promotes the formation of tubular structures, involving the ERα/ROCK2 signaling pathway. Furthermore, PF was found to promote the phenotypic transformation of macrophages and alleviated grave inflammatory responses during vascular remodeling. Conclusions: We determined that PF as a potent compound in promoting angiogenesis and mitigating inflammatory responses during revascularization. Full article

(1) Liver injury caused by an overdose of acetaminophen (APAP) represents a major public health concern. Paeoniflorin (PF) has been reported to have anti-inflammatory and liver-protective effects, but the underlying mechanisms remain unclear. This study aimed to investigate the effect of PF on the crosstalk between pyroptosis and NETs in AILI. (2) APAP-treated C57BL/6J mice were used to demonstrate the protective effect of PF on liver injury. HepG2 and dHL-60 cells were cultured to study the effects of PF on hepatocyte pyroptosis and neutrophil extracellular traps (NETs) in vitro. Moreover, cell co-culture experiments were performed, and mice were treated with a NETs-depleting agent and hepatocyte pyroptosis inhibitor to investigate the improvement of AILI induced by PF through regulating the crosstalk between hepatocyte pyroptosis and NETs. (3) PF significantly alleviated AILI. Additionally, PF inhibited the expression of pyroptosis-related proteins, high-mobility group box 1 (HMGB1), and NETs-associated proteins in vitro and in vivo. The co-culture experiments demonstrated that PF not only inhibited the NETs triggered by hepatocyte pyroptosis, but also suppressed the hepatocyte pyroptosis induced by NETs. In mice with depleted neutrophils, the level of hepatocyte pyroptosis notably decreased, indicating a diminished impact of PF. Similarly, NETs formation was reduced in mice receiving a pyroptosis inhibitor compared to the APAP group. Compared with DNase I alone, the reduction effect of PF combined with DNase I on serum ALT and AST levels decreased from 46.857% and 39.927% to 44.347% and 33.419%, respectively. Compared with DSF alone, PF combined with DSF reduced the ALT and AST levels from 46.857% and 39.927% to 45.347% and 36.419%, respectively. (4) PF demonstrated therapeutic effects on AILI. Its mechanism involves the regulation of the crosstalk between hepatocyte pyroptosis and NETs. This research substantiates the pharmacological promise of PF as a therapeutic intervention for acute AILI. Full article

Porcine circovirus type 2 (PCV2) is an important pathogen that leads to great economic losses to the swine industry. Paeoniflorin (PF), a novel plant extract, has been reported to have antiviral properties. However, the role of paeoniflorin in regulating PCV2 replication remains unclear. Here, we used the CCK8 assay to demonstrate that PF within safe concentrations (0–275 mM) significantly inhibits PCV2 replication in a dose-dependent manner in porcine kidney cells. Subsequently, comparative transcriptome and functional verification revealed that PF probably inherits PCV2 replication via targeting AKT/mTOR signaling. Further experimental data show that the AKT/mTOR signaling pathway is highly relevant to autophagy. Thus, experimental data from Western blot, qPCR, and the indirect immunofluorescence test indicate that PF inhibits PCV2 replication by inhibiting autophagy by targeting the AKT/mTOR signaling pathway. Together, our results provide insight into the mechanism of paeoniflorin in regulating PCV2 replication and offer new ideas for the treatment of PCV2 infection in pigs. Full article

Irritable bowel syndrome (IBS) is a chronic disorder of the gastrointestinal tract. Its pathogenesis involves multiple factors, including visceral hypersensitivity and immune activation. NLRP3 inflammasome is part of the nucleotide-binding oligomerization domain-like receptor (NLR) family, a crucial component of the innate immune system. Preclinical studies have demonstrated that inhibiting NLRP3 reduces visceral sensitivity and IBS symptoms, like abdominal pain, and diarrhea, suggesting that targeting the NLRP3 might represent a novel therapeutic approach for IBS. This review aims to assess the NLRP3 inhibitors (tranilast, β-hydroxybutyrate, Chang-Kang-fang, paeoniflorin, coptisine, BAY 11-7082, and Bifidobacterium longum), highlighting the signaling pathways, and their potential role in IBS symptoms management was assessed. Although premature, knowledge of the action of synthetic small molecules, phytochemicals, organic compounds, and probiotics might make NLRP3 a new therapeutic target in the quiver of physicians’ therapeutic choices for IBS symptoms management. Full article