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PHYTOMEDICINE · 2019 · IF 4.18

Discovery of quality-marker ingredients of Panax quinquefolius driven by high-throughput chinmedomics approach

Hui Xiong,Ai-hua Zhang,Qi-qi Zhao,Guang-li Yan,Hui Sun,Xi-jun Wang

Background Quality control of traditional Chinese medicine (TCM) has always been a hot issue to TCM. However, due to the complexity of TCM ingredients, the current quality standards of TCM have problems that are difficult to guarantee clinical efficacy. American ginseng , the dried roots of Pawajc quinquefolium L. (Araliaceae), is a valuable herbal medicine due to various pharmacological effects and huge health benefit, which are associated with numerous active ingredients such as ginsenosides . Although a large number of studies have investigated the active ingredients of American ginseng, Q-markers reflecting comprehensive review on its efficacies has yet been unrevealed. Purpose The study aims to discover the Q-markers of Panax quinquefolius (American ginseng), provides a powerful method to clarify the significant ingredents of TCM and help further discovering extensive quality evaluation model,contributing to a significant improvement of TCM quality standard. Methods Mice general status, biochemical indexes assay, urine metabolic profile, and serum metabolic profile were utilized for model replication and efficacy evaluation. The in vitro and in vivo constituents of American ginseng using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS) with Serum Pharmacochemistry of TCM were in-depth investigated. Q-markers that were associated with core markers of therapeutic effects were excavated by a plotting of correlation between marker metabolites and serum constituents (PCMS) approach. Results Correlation analysis of 41 blood and urine labeled metabolites with 14 serum components showed that 24-methyl-7-cholesten-3β-ol, zizybeoside II, betulin , ginsenoside Rd, cinnamyl alcohol , pseudoginsenoside F11 is highly correlated with the therapeutic effects of Compound Zaofan Pill (CZP), while pseudoginsenoside F11 and ginsenoside Rd are highly correlated with the therapeutic effects of American ginseng. The six absorbed blood compounds can be considered as potential Q-markers for compound, of which two compounds, such as pseudoginsenoside F11 and ginsenoside Rd, can be considered as potential Q-markers for American ginseng. Conclusion The study has demonstrated that the Chinmedomics is an effective, comprehensive and fire-new method for discovering the Q-markers of TCM, and it may be more reasonable choices to establish quality standards of TCM.

CAS / MDL: 64-18-6
研究领域: 中药学 · 分析化学 · 药理学
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ULTRASONICS SONOCHEMISTRY · 2024 · IF 8.7

Extraction of American ginseng polysaccharide by ultrasound-assisted deep eutectic solvents-based three-phase partitioning: Process optimization, structural characterization, and anti-ulcerative colitis study

Zhongnan Wu,Chong Li,Junhao Li,Tanggan Wang,Meifeng Li,Leyi Zhao,Huimei Ye,Jiaheng Chen,Jiajia Zan,Lijun Song,Qian Zhang,Shaojie Zhang

Three-phase partitioning (TPP) is promising for isolating bioactive polysaccharides, but t -butanol’s environmental impact limits its application. Deep eutectic solvents can serve as a green and recyclable alternative to t -butanol. This study introduces an ultrasonic-assisted DES three-phase partitioning (UA-TPP-DES) system to extract and purify American ginseng polysaccharides (AGPs). The optimized DES-4, composed of lauric acid and nonanoic acid (molar ratio = 1:1), achieved a 35.28 % extraction yield under specific conditions and can be recycled five times with minimal yield loss. AGP-DES-4 has a broad molecular weight distribution (2.48–174.64 kDa) and mainly consists of mannose, glucose, galactose, and arabinose. In vivo Drosophila models show that AGP-DES-4 improves UC fly survival and enhances intestinal barrier function by regulating the proliferation and differentiation of intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). Our results highlight the effectiveness of the AGP-DES-4 extraction method and its potential therapeutic value for treating UC.

CAS / MDL: 89-25-8
研究领域: 生物化学 · 药理学 · 分子生物学
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JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES · 2019 · IF 0.987

A metabolomic study of Asian and American Ginseng based on RRLC-QTOF/MS methods

Yang-Fang He,Han-Qing Cai,Hong-Mei Zhang,Zhi-Hui Ren,Huan Tang,Yan Li,Xiao-Wei Zhou,Wen-Long Liu,Jin Pei,Shu-Ying Liu

In order to understand the significant differences in activities and effects between Asian ginseng (ASG) and American ginseng (AMG), it is important to study the correlation between chemical structures and biological activities in the two types of herbs. However, more attention has been paid to the analysis of ginsenosides in previous reports distinguishing between ASG and AMG. There are some other bioactive compounds besides ginsenosides, however, few studies have focused on a systematic comparison of these types of compounds. Two metabolomic methods were developed in this study by qualitative data acquisition using normal phase liquid chromatography mass spectrometry (NPLC-MS) and reverse phase liquid chromatography mass spectrometry (RPLC-MS) respectively, in combination with principal component analysis (PCA). Results show that both NPLC-MS and RPLC-MS-based metabolomic methods are feasible in composition profiling, biomarker screening as well as in discrimination of ASG and AMG. 17 ginsenosides were identified as analytical markers in RPLC-MS-based metabolomic method. In comparison, using NPLC-MS-based method, 5 ginsonosides, two amino acids as well as 1 oligosaccharide were identified as analytical markers. Therefore, RPLC-MS-based metabolomic method exhibits better profiling in ginsenosides, while NPLC-MS-based metabolomic method offers the advantage that multiple active ingredients can be determined simultaneously. The two methods are both helpful in identification of biomarker as well as in discrimination of American ginsengs from Asian ginsengs.

研究领域: 植物化学 · 分析化学 · 中药学
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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Multi-level fingerprinting and cardiomyocyte protection evaluation for comparing polysaccharides from six Panax herbal medicines

Jie Liu,Hong-da Wang,Fei-fei Yang,Bo-xue Chen,Xue Li,Qing-xia Huang,Jing Li,Xiang-yan Li,Zheng Li,He-shui Yu,De-an Guo,Wen-zhi Yang

The role of polysaccharides in quality control of ginseng is underestimated. Large-scale comparison on the polysaccharides of Panax ginseng (PG), P. quinquefolius (PQ), P. notoginseng (PN), Red ginseng (RG), P. japonicus (ZJS), and P. japonicus var. major (ZZS), was performed by both chemical and biological approaches. Holistic fingerprinting at polysaccharide and the hydrolyzed oligosaccharide and monosaccharide levels utilized various chromatography methods, while OGD and OGD/R models on H9c2 cells were introduced to evaluate the protective effects on cell viability and mitochondrial function. Polysaccharides from six ginseng species exhibited remarkable content difference (RG > PG/ZZS/ZJS/PQ > PN), but weak differentiations in molecular weight distribution and oligosaccharide profiles, while Glc and GalA were richer for monosaccharide compositions of PG and RG polysaccharides, respectively. RG polysaccharides (25/50/100 μg/mL) showed significant cardiomyocyte protection by regulating mitochondrial functions. These new evidences may provide support for the supplementary role of polysaccharides in quality control of ginseng.

CAS / MDL: 540-69-2
研究领域: 药用植物学 · 药物化学 · 细胞生物学 · 药理学
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MOLECULES · 2024 ·Vol. 29 ·期 15 ·3443 · IF 4.2

Nano-Characterization, Composition Analysis, and Anti-Inflammatory Activity of American-Ginseng-Derived Vesicle-like Nanoparticles

Taiping Li,Huan Wang,Wenjie Bi,Yonghui Su,Yongai Xiong,Songsong Wang,Liwen Han

Medicinal plant-derived vesicle-like nanoparticles can carry chemical components and exert intercellular activity due to the encapsulation of nanostructures. American ginseng is well known as a traditional herb and is commonly used in clinical decoctions. However, the nano-characteristics and chemical composition of American-ginseng-derived vesicle-like nanoparticles (AGVNs) in decoctions are unclear. In this study, the gradient centrifugation method was used to extract and isolate AGVNs. A metabolomic method based on high-resolution mass spectrometry was established to analyze small molecules loaded in AGVNs. Zebrafish and RAW264.7 cells were employed to investigate the anti-inflammatory effects of AGVNs. The results showed that the particle size of AGVNs was generally 243.6 nm, and the zeta potential was −14.5 mV. AGVNs were found to contain 26 ginsenosides (14 protopanaxadiols, 11 protopanaxatriols, and 1 oleanolic acid). Ginsenoside Rb1 and malonyl-ginsenoside Rb1 tended to be enriched in AGVNs. Moreover, AGVNs were found to exert anti-inflammatory effects by reducing macrophage migration in zebrafish and regulating inflammatory factor (NO, TNF-α, IL-6, IL-10) secretion in RAW 264.7 cells. The characterization and analysis of AGVNs provide references and data that support the development of nanoscale anti-inflammatory substances from medicinal plants.

研究领域: 药理学 · 纳米技术 · 分析化学 · 炎症研究 · 传统中药
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PHYTOTHERAPY RESEARCH · 2024 · IF 6.1

Identification and mechanistic exploration of key anti-inflammatory molecules in American ginseng: Impacts on signal transducer and activator of transcription 3 STAT3 phosphorylation and macrophage polarization

Taiping Li,Yougang Zhang,Rong Dong,Wenjie Bi,Songsong Wang,Kewu Zeng,Liwen Han

American ginseng (AG) has been reported to have anti-inflammatory effects in many diseases, but the key molecules and mechanisms are unclear. This study aims to evaluate the anti-inflammatory mechanism of AG and identify the key molecules by in vivo and in vitro models. Zebrafish was employed to assess the anti-inflammatory properties of AG and the compounds. Metabolomics was utilized to identify potential anti-inflammatory molecules in AG, while molecular dynamics simulations were conducted to forecast the interaction capabilities of these compounds with inflammatory targets. Additionally, macrophage cell was employed to investigate the anti-inflammatory mechanisms of the key molecules in AG by enzyme-linked immunosorbent assay and western blotting. Seven potential anti-inflammatory molecules were discovered in AG, with ginsenoside Rg1, ginsenoside Rs3 (G-Rs3), and oleanolic acid exhibiting the strongest affinity for signal transducer and activator of transcription 3. These compounds demonstrated inhibitory effects on macrophage migration in zebrafish models and the ability to regulate ROS levels in both zebrafish and macrophages. The cell experiments found that ginsenoside Rg1, ginsenoside Rs3, and oleanolic acid could promote macrophage M2/M1 polarization ratio and inhibit phosphorylation overexpression of signal transducer and activator of transcription 3. This study revealed the key anti-inflammatory molecules and mechanisms of AG, and provided new evidence of anti-inflammatory for the scientific use of AG.

研究领域: 药理学 · 免疫学 · 分子生物学 · 生物化学
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Frontiers in Pharmacology · 2022 · IF 5.988

Identification of key pharmacodynamic markers of American ginseng against heart failure based on metabolomics and zebrafish model

Dong Rong,Zhang Yougang,Chen Shanjun,Wang Huan,Hu Kaiqing,Zhao Huanxin,Tian Qingping,Zeng Kewu,Wang Songsong,Han Liwen

Background: American ginseng (Panax quinquefolium L., AG) is a traditional Chinese medicine with multiple cardiovascular protective properties. Many bioactive components have been discovered in AG over these years. However, the understanding of these key pharmacodynamic components of activity against heart failure is insufficient.Methods: A heart failure model was established using AB line wild-type zebrafish (Danio rerio) to evaluate the anti-heart failure activity of AG. Untargeted metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap-mass spectrometry technology (UHPLC-QE-Orbitrap-MS) was performed to screen differential components from AG samples. The potential active components were verified using the zebrafish model. Simultaneously, network pharmacology and molecular docking techniques were used to predict the possible mechanism. Finally, the key targets of six key pharmacodynamic components were verified in zebrafish using quantitative real-time-polymerase chain reaction (Q-PCR) techniques.Results: The heart failure model was successfully established in 48 h of post-fertilization (hpf) zebrafish larvae by treating with verapamil hydrochloride. The zebrafish assay showed that the anti-heart failure effects of AG varied with producing regions. The result of the herbal metabolomic analysis based on UHPLC-QE-Orbitrap-MS indicated that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, L-argininosuccinic acid, 3-methyl-3-butenyl-apinosyl (1→6) glucoside, pseudoginsenoside F11, and annonaine were differential components, which might be responsible for variation in efficacy. Further analysis using zebrafish models, network pharmacology, and Q-PCR techniques showed that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, and pseudoginsenoside F11 were the pharmacodynamic markers (P-markers) responsible for anti-heart failure.Conclusion: We have rapidly identified the P-markers against heart failure in AG using the zebrafish model and metabolomics technology. These P-markers may provide new reference standards for quality control and new drug development of AG.

研究领域: 药理学 · 心脏病学 · 代谢组学 · 斑马鱼模型
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Characterization and comparison of cardiomyocyte protection activities of non-starch polysaccharides from six ginseng root herbal medicines

Jie Liu,Xue Li,Jing-wen Guo,Bo-xue Chen,He Sun,Jia-qi Huang,Ying Hu,Xiao-yan Xu,Mei-ting Jiang,Xiu-mei Gao,Wen-zhi Yang,Qi-long Wang,De-an Guo

Ginseng is rich of polysaccharides, however, the evidence supporting polysaccharides to distinguish various ginseng species is rarely reported. Focusing on six root ginseng ( e.g. , Panax ginseng - PG , P. quinquefolius - PQ , P. notoginseng - PN , red ginseng- RG , P. japonicus - PJ , and P. japonicus var. major - PJM ), the contained non-starch polysaccharides (NPs) were structurally characterized and compared by both the chemical and biological evaluation. Holistic fingerprinting at three levels (the NPs and the acid hydrolysates involving oligosaccharides and monosaccharides) utilized various chromatography methods, and the treatment of H9c2 cells with the NPs by OGD and H 2 O 2 -induced injury models was used to assess the protective effect. NPs from six Panax herbal medicines occupied about 20 % of the total polysaccharides, which were of the highest content in RG and the lowest in PN. NPs from six ginseng exhibited weak differentiations in the molecular weight distribution, while marker oligosaccharides were found to distinguish PN and RG from the others. Glc and GalA were more abundant in the NPs for PG and RG, respectively. NPs from PQ (100/200 μg/mL) showed significant cardiomyocyte protection effect by regulating the mitochondrial functions. This work further testifies the role of polysaccharides in quality control of herbal medicine, with new markers discovered beneficial to distinguish the ginseng.

CAS / MDL: 540-69-2
研究领域: 药理学 · 生物化学 · 药物化学 · 中药学
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BIOMEDICINE & PHARMACOTHERAPY · 2022 · IF 7.419

Protective effect of total Saponins from American ginseng against cigarette smoke-induced COPD in mice based on integrated metabolomics and network pharmacology

Hongqiang Lin,Caixia Wang,Hui Yu,Yunhe Liu,Luying Tan,Shanmei He,Zhuoqiao Li,Cuizhu Wang,Fang Wang,Pingya Li,Jinping Liu

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease. Aiming at assessing the effect of total saponins from American ginseng on COPD, both the chemical composition and anti-COPD activity of total saponins from wild-simulated American ginseng (TSW) and field-grown American ginseng (TSF) were investigated in this study. Firstly, a HPLC-ELSD chromatographic method was established to simultaneously determine the contents of 22 saponins in TSW and TSF. Secondly, CS-induced COPD mouse model was established to evaluate the activity of TSW and TSF. The results indicated that both TSW and TSF had the protective effect against COPD by alleviating oxidative stress and inflammatory response. TSW showed a stronger effect than TSF. Thirdly, an integrated approach involving metabolomics and network pharmacology was used to construct the "biomarker-reaction-enzyme-target" correlation network aiming at further exploring the observed effects. As the results, 15 biomarkers, 9 targets and 5 pathways were identified to play vital roles in the treatment of TSW and TSF on COPD. Fourthly, based on network pharmacology and the CS-stimulated A549 cell model, ginsenoside Rgl, Rc, oleanolic acid, notoginsenoside R1, Fe, silphioside B were certified to be the material basis for the stronger effect of TSW than TSF. Finally, the molecular docking were performed to visualize the binding modes. Our findings suggested that both TSW and TSF could effectively ameliorate the progression of COPD and might be used for the treatment of COPD.

研究领域: 药理学 · 呼吸病学 · 代谢组学 · 网络药理学 · 动物模型
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