Scientific Reports
·
2025
·Vol. 15
·期 1
·1-11
·
IF 3.9
Hu Lili,Wu Na,Wang Jue,Cai Donghui
The anti-inflammatory effect of phellodendrine (PHE), derived from Phellodendri Chinensis Cortex, has been verified in previous studies. Major depressive disorder (MDD) is associated with immune dysregulation and inflammatory processes. This study aimed to explore the therapeutic effects of PHE on MDD through network pharmacology and experimental validation. Multiple databases were used to predict the targets of PHE and MDD. The intersection targets between PHE and MDD were obtained to identify as targets for PHE against MDD, followed by protein–protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Molecular docking was applied to further confirm the anti-MDD effects of PHE. The mitochondrial DNA (mtDNA) copy number, inflammatory cytokines and pathway-related mRNA expressions in PC12 cell were determined via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay to verify our finding. Thirty-eight intersection targets were obtained between PHE and MDD. PHE exerted an anti-MDD effect by regulating SLC6A4, SLC6A3, SLC6A2, MAOA and other targets through serotonergic synapse, salivary secretion, dopaminergic synapse, and cAMP signalling pathway. In vitro, PHE induced an increment in mtDNA copy number compared with the CORT group. PHE affected the levels of IL6 and IL1β with different concentrations. The mRNA levels of CHRM1, HTR1A and key targets of the PI3K/Akt signalling pathway were also influenced. Our research reveals novel mechanisms underlying the anti-MDD effects of PHE through network pharmacology and experiments, which provides a new direction for the development of antidepressants.
研究领域:
药理学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Minhua Li,Zehui Qin,Qiuxia Yu,Ziwei Huang,Juanjuan Cheng,Linjiang Zhong,Yuhong Liu,Jianhui Xie,Yucui Li,Jiannan Chen,Ruoting Zhan,Ziren Su
Background Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC. Methods The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed. Results Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage. Conclusion BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.
研究领域:
药理学
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中药学
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生物化学
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DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2021
·Vol. 35
·期 18
·e9157
·
IF 2.419
Feng-Xiang Zhang,Yu-Lin-Lan Yuan,Shuang-Shuang Cui,Min Li,Rui-Man Li
Rationale Characterizing the functional mechanism of quality control marker (Q-marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug-related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q-marker of Cortex Phellodendri, the role of phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine-related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti-DM mechanism of Cortex Phellodendri. Methods An ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was developed to profile metabolites of phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. Results A total of 19 phellodendrine-related metabolites were screened out in rats for the first time. Among them, M4 , M5 , M9 , and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of phellodendrine and three main metabolites ( M4 , M5 , and M12 ) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of phellodendrine to treat DM. Conclusion The metabolic feature of phellodendrine in vivo was revealed for the first time, and its anti-DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM.
研究领域:
药理学
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代谢组学
✓ 已验证
DOI
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2023
·
IF 1.6
Su Jiangtao,Zhang Yuxuan,Ye Lu,Chen Xue,Hu Yuchen
Psoriasis is a chronic papulosquamous skin disease whose current treatments have severe side effects, which limits their long-term application. Developing effective treatments for psoriasis is an important and challenging task. Coptis chinensis Franch., Ranunculaceae, and Phellodendron amurense Rupr., Rutaceae, are widely used in traditional Chinese medicine to treat psoriasis. Therefore, this article aims to construct a thermo-sensitive local administration system based on multiple alkaloids from C. chinensis and P. amurense . The methods of extracting the effective components of C. chinensis and P. amurense were screened by single-factor experiment and orthogonal experiment. Furthermore, the optimal gel formulation was determined, and the obtained CPG-S hydrogel ( C. chinensis and P. amurense gel with S -nitrosated acetylpenicillamine as a penetration promoter) exhibited thermo-sensitivity and excellent transdermal ability. Then, the therapeutic effect of the CPG-S hydrogel was examined in a psoriasis mouse model. The effectiveness of the CPG-S hydrogel in reducing the symptoms of redness, swelling, and squamous epidermis, as well as downregulating the related inflammatory factors IL-17A and IL-23, was confirmed. The CPG-S hydrogel was found to be more effective than the commercially available psoriasis treatment drug mometasone furoate cream, indicating its potential application as an effective psoriasis treatment drug. Graphical abstract
研究领域:
药剂学
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中医药学
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皮肤病学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jia-Lin Yu,Zhen-Yang Zhang,Sheng-Ping Liu,Hong-Ping Long,Ting-Ting Wang,Feng-Qing Huang,Jia Guo,Wei-Long Xu,Fei Li
Ethnopharmacological relevance Type 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear. Aim of the study This study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both in vitro and in vivo experiments. Materials and methods In this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients. Results Serum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1. Conclusion PCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM.
研究领域:
中药学
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代谢组学
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糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
·
IF 4.36
Xiao-Ling Fu,Jie Zhou,Wei-Wei Tang,Yang Liu,Zi-Lu Li,Ping Li,Jun Chen
Ethnopharmacological relevance Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named “Tong Feng”, which is described as “ache in bones and joints” with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. Aim of the study Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). Materials and methods Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine , phellodendrine, magnoflorine , jatrorrhizine , berberrubine , palmatine , and tetrahydropalmatine , in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. Results PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. Conclusions The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.
研究领域:
民族药理学
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中医药
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2021
·Vol. 60
·期 5
·433-439
·
IF 1.618
Tan Jingling,Zhang Xueqiong,Fang Jiangji,Shen Huadan,Ding Xiaoping,Zheng Guohua
We developed a new on-line method of ultra-performance liquid chromatography coupled with biochemical detection (UHPLC-BCD) to screen acetylcholinesterase (AChE) inhibitors in complex matrixes. Chromatography separation was performed using an Xtimate UHPLC C18 column (100 mm × 2.1 mm, 1.8 μm) and a gradient elution with methanol–0.1% formic acid at a flow rate of 0.08 mL/min. The BCD was based on a colorimetric method using Ellman’s reagent, and the detection wavelength was at 405 nm. Galanthamine was used as a positive reference to validate the methodology. The detection and quantitation limits of the UHPLC-BCD method were 0.018 and 0.060 μg, respectively. A functional equation was generated in terms of the negative peak area (X) and galanthamine concentration (Y, μg/mL). The regression equation was Y = 0.0028X2 + 0.4574X + 50.7776, R2 = 0.9993. UHPLC-fourier-transform mass spectrometry detection results revealed that five alkaloids showed obvious AChE inhibitory activities including coptisin, epiberberine, jatrorrhizine, berberine and palmatine. The relative AChE inhibitory activities of jatrorrhizine, berberine and palmatine in the Coptidis Rhizoma sample were equal to that of 257.0, 2355 and 283.9 μg/mL of galanthamine, respectively. This work demonstrated that the UHPLC-BCD method was convenient and feasible, and could be widely used for the screening and activity evaluation of the bioactive components in the complex extracts.
研究领域:
药理学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2025
·
IF 2.3
Yu-yao Qin,Zi-yi Qin,Tao Liang,Dong-er Qin,Sheng-yi Hua,Ming-hui Tan,Shun Guo,Fan Yang,Le Shi,Yun Yu,Guang-ji Zhang
Background Phellodendrine, a primary bioactive constituent of Phellodendron chinense Schneid (PCS), is crucial in its pharmacological profile. Phellodendrine exhibits potent anti-nephritic properties and demonstrates a marked inhibitory effect on the cellular immune response. However, the effects of phellodendrine on proteoglycan depletion and cartilage degeneration in gouty arthritis remain insufficiently understood. Therefore, the objective of this study is to elucidate the therapeutic potential and underlying mechanisms of phellodendrine chloride (PC) in the treatment of gouty arthritis. Methods A monosodium urate (MSU)-induced arthritis model in rats, along with a peritonitis model in mice, was developed, in combination with a chondrocyte model. Neutrophil proportions were quantified using flow cytometry. The expression levels of MMP-3, STAT3, and phosphorylated STAT3 (p-STAT3) in chondrocytes were determined by Western blot analysis. Proteoglycan levels in chondrocytes were assessed using toluidine blue staining and quantitative reverse transcription PCR (qRT-PCR). Joint swelling rates were monitored at 0–24 h in rats, and histopathological changes in joint tissues were subsequently analyzed. Results Phellodendrine chloride mitigated the rise in neutrophil proportions within MSU-induced peritoneal lavage fluid in mice and decreased inflammatory cell infiltration in rat ankle tissues. Treatment with phellodendrine chloride led to a downregulation of MMP-3 protein levels and inhibited IL-1β-induced proteoglycan degradation in chondrocytes. Additionally, results from experiments combining IL-1β with AG490 or IL-6 demonstrated that phellodendrine chloride attenuated IL-1β-induced MMP-3 expression and proteoglycan degradation. Conclusion Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.
研究领域:
药理学
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免疫学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Nani Wang,Pingcui Xu,Can Wu,Renjie Wu,Dan Shou
Cell membrane chromatography is a promising technique for screening active components from complex matrices. Unfortunately, the large consumption of cells and low resolutions of analytes limit the applications of this method. Herein, we report polyether ether ketone tube as a novel cellular membrane carrier for cell membrane chromatography. Its inner surface is firstly coated by polyvinyl alcohol and then cell membranes are physically adsorbed onto the polyvinyl alcohol layer. To verify this approach, osteoclast and osteoblast micro-column were prepared and characterized by calcitonin and verapamil , respectively. Comparing with common cell membrane chromatographic column, the micro-cell membrane chromatographic columns showed about 1000-fold decrease of cell consumption and satisfactory retention behavior. The developed column was applied to screen potential active components from Cortex Phellodendri Chinensis . A total of 18 components in Cortex Phellodendri Chinensis extract were observed as having retention property of osteoclast micro-cell membrane chromatographic column, while 10 components retained on osteoblast micro-cell membrane chromatographic column. The results of in vitro assay showed that berberine , obacunoic acid and phellodendrine had an obvious inhibitory effect on osteoclast differentiation and function. Berberine and tetrahydropalmatine increased the osteoblast proliferations and mineralized nodules density. This cell membrane/polyvinyl alcohol column can be applied to various biological chromatography models.
研究领域:
药理学
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色谱分析
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材料科学
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生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2017
·Vol. 40
·期 14
·2933-2940
·
IF 2.557
Ling-Feng Jiang,Bo-Cheng Chen,Ben Chen,Xue-Jian Li,Hai-Lin Liao,Wen-Yan Zhang,Lin Wu
The extraction adsorbent was fabricated by immobilizing the highly specific recognition and binding of aptamer onto the surface of Fe 3 O 4 magnetic nanoparticles, which not only acted as recognition elements to recognize and capture the target molecule berberine from the extract of Cortex phellodendri , but also could favor the rapid separation and purification of the bound berberine by using an external magnet. The developed solid-phase extraction method in this work was useful for the selective extraction and determination of berberine in Cortex phellodendri extracts. Various conditions such as the amount of aptamer-functionalized Fe 3 O 4 magnetic nanoparticles, extraction time, temperature, pH value, Mg 2+ concentration, elution time and solvent were optimized for the solid-phase extraction of berberine. Under optimal conditions, the purity of berberine extracted from Cortex phellodendri was as high as 98.7% compared with that of 4.85% in the extract, indicating that aptamer-functionalized Fe 3 O 4 magnetic nanoparticles-based solid-phase extraction method was very effective for berberine enrichment and separation from a complex herb extract. The applicability and reliability of the developed solid-phase extraction method were demonstrated by separating berberine from nine different concentrations of one Cortex phellodendri extract. The relative recoveries of the spiked solutions of all the samples were between 95.4 and 111.3%, with relative standard deviations ranging between 0.57 and 1.85%.
研究领域:
分析化学
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纳米技术
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药学
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天然产物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Xueyu Pu,Yuanyuan Wang,Xi Wang,Xiaoqing Sang,Miaomiao Jiang,DaWei Qi,Xin Zhao,Rong Chen,Jianwei Li,Xiang Liu,Zhidong Liu,Jian Yang
Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen’s cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen’s cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatis─an alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.
研究领域:
药学
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纳米技术
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微生物学
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药物递送系统
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抗菌治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Plant Pathology Journal
·
2021
·
IF 1.795
Yanling Zeng,Han Liu,Tianhui Zhu,Shan Han,Shujiang Li
Brown leaf spot disease caused by Nigrospora guilinensis on Phellodendron chinense occurs in a large area in Dayi County, Chengdu City, Sichuan Province, China each year. This outbreak has severely reduced the production of Chinese medicinal plants P. chinense and caused substantial economic losses. The bacterial isolate JKB05 was isolated from the healthy leaves of P. chinense , exhibited antagonistic effects against N. guilinensis and was identified as Bacillus megaterium . The following fermentation medium and conditions improved the inhibitory effect of B. megaterium JKB05 on N. guilinensis : 2% glucose, 0.1% soybean powder, 0.1% KCl, and 0.05% MgSO 4 ; initial concentration 6 × 10 6 cfu/ml, and a 42-h optimal fermentation time. A composite of 0.1% nano-SiO 2 JKB05 improved the thermal stability, acid-base stability and ultraviolet resistance by 16%, 12%, and 38.9%, respectively, and nano-SiO 2 was added to the fermentation process. The best formula for the wettable powder was 35% kaolin, 4% polyethylene glycol, 8% Tween, and 2% humic acid. The following quality test results for the wettable powder were obtained: wetting time 87.0 s, suspension rate 80.33%, frequency of microbial contamination 0.08%, pH 7.2, fineness 95.8%, drying loss 1.47%, and storage stability ≥83.5%. A pot experiment revealed that the ability of JKB05 to prevent fungal infections on P. chinense increased considerably and achieved levels of control as high as 94%. The use of nanomaterials significantly improved the ability of biocontrol bacteria to control this disease.
研究领域:
植物病理学
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微生物学
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纳米技术
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药学
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农业科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）