Pub Date : 2025-12-01Epub Date: 2024-06-03DOI: 10.1002/pca.3381
Yunyu Xie, Xuelian Shen, Funeng Xu, Xiaoxia Liang
Introduction: Traditional Chinese medicine (TCM) has been used for thousands of years in China, characterizing with novel pharmacological mechanisms, low toxicity, and limited side effects. However, the application of TCM active ingredients is often hindered by their physical and chemical properties, including poor solubility, low bioavailability, short half-life, toxic side effects within therapeutic doses, and instability in biological environments. Consequently, an increasing number of researchers are directing their attention towards the discovery of nano-delivery systems for TCM to overcome these clinical challenges.
Objectives: This review aims to provide the latest knowledge and results concerning the studies on the nano-delivery systems for the active ingredients from TCM.
Materials and methods: Recent literature relating to nano-delivery systems for the active ingredients from TCM is summarized to provide a fundamental understanding of how such systems can enhance the application of phytochemicals.
Results: The nano-delivery systems of six types of TCM monomers are summarized and categorized based on the skeletal structure of the natural compounds. These categories include terpenoids, flavonoids, alkaloids, quinones, polyphenols, and polysaccharides. The paper analyzes the characteristics, types, materials used, and the efficacy achieved by TCM-nano systems. Additionally, the advantages and disadvantages of nano-drug delivery systems for TCM are summarized in this paper.
Conclusion: Nano-delivery systems represent a promising approach to overcoming clinical obstacles stemming from the physical and chemical properties of TCM active ingredients, thereby enhancing their clinical efficacy.
{"title":"Research progress of nano-delivery systems for the active ingredients from traditional Chinese medicine.","authors":"Yunyu Xie, Xuelian Shen, Funeng Xu, Xiaoxia Liang","doi":"10.1002/pca.3381","DOIUrl":"10.1002/pca.3381","url":null,"abstract":"<p><strong>Introduction: </strong>Traditional Chinese medicine (TCM) has been used for thousands of years in China, characterizing with novel pharmacological mechanisms, low toxicity, and limited side effects. However, the application of TCM active ingredients is often hindered by their physical and chemical properties, including poor solubility, low bioavailability, short half-life, toxic side effects within therapeutic doses, and instability in biological environments. Consequently, an increasing number of researchers are directing their attention towards the discovery of nano-delivery systems for TCM to overcome these clinical challenges.</p><p><strong>Objectives: </strong>This review aims to provide the latest knowledge and results concerning the studies on the nano-delivery systems for the active ingredients from TCM.</p><p><strong>Materials and methods: </strong>Recent literature relating to nano-delivery systems for the active ingredients from TCM is summarized to provide a fundamental understanding of how such systems can enhance the application of phytochemicals.</p><p><strong>Results: </strong>The nano-delivery systems of six types of TCM monomers are summarized and categorized based on the skeletal structure of the natural compounds. These categories include terpenoids, flavonoids, alkaloids, quinones, polyphenols, and polysaccharides. The paper analyzes the characteristics, types, materials used, and the efficacy achieved by TCM-nano systems. Additionally, the advantages and disadvantages of nano-drug delivery systems for TCM are summarized in this paper.</p><p><strong>Conclusion: </strong>Nano-delivery systems represent a promising approach to overcoming clinical obstacles stemming from the physical and chemical properties of TCM active ingredients, thereby enhancing their clinical efficacy.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2266-2279"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-02-19DOI: 10.1002/pca.3516
Larisa N Frolova, Elena L Kovaleva, Valentina V Shelestova, Vladislav Yu Kuteynikov, Elena V Flisyuk, Olga N Pozharitskaya, Alexander N Shikov
Introduction: Harmonization of methodological approaches to the analysis of herbal substances containing triterpenoid saponins, considered the largest group of phytochemicals, is essential for the pharmaceutical industry worldwide.
Objectives: This review aimed to perform a comparative analysis of the requirements for the standardization of herbal substances, herbal medicinal products (HMPs), and other herbal materials containing triterpenoid saponins in the pharmacopeial texts of the Russian Federation and the world's leading pharmacopeias.
Materials and methods: The review covers the data on the quantitative and qualitative analysis of herbal substances containing triterpenoid saponins, as presented in the State Register of Medicinal Products of Russia and the monographs of the world's leading pharmacopeias: the European Pharmacopeia, United States Pharmacopeia, British Pharmacopeia, Japanese Pharmacopeia, and the national pharmacopeias of the Eurasian Economic Union (EEU) Member States.
Results: This review compares and discusses the analytical methods used for the standardization of Aesculus hippocastanum L. seeds, Aralia elata (Miq.) Seem roots, Glycyrrhiza spp. roots, Orthosiphon aristatus (Blume) Miq. leaves, and Polemonium caeruleum L. rhizomes with roots. The most common analytical methods used are (HP)TLC and (U)HPLC. The Russian Pharmacopeia also includes titrimetry and spectrophotometry.
Conclusions: The appropriate selection of a group of biologically active compounds for HMP standardization is still challenging. We believe that a rational approach to the standardization of herbal substances and HMPs should be based on the use of herbal substances with maximum extractability and specific pharmacological activity. The harmonized procedures and reference substances for the identification and assay of active metabolites in HMPs must be implemented at all stages of production control from herbal substances to finished dosage forms.
{"title":"Comparison of Analytical Methods Used for Standardization of Triterpenoid Saponins in Herbal Monographs Included in the Russian and Other Pharmacopeias.","authors":"Larisa N Frolova, Elena L Kovaleva, Valentina V Shelestova, Vladislav Yu Kuteynikov, Elena V Flisyuk, Olga N Pozharitskaya, Alexander N Shikov","doi":"10.1002/pca.3516","DOIUrl":"10.1002/pca.3516","url":null,"abstract":"<p><strong>Introduction: </strong>Harmonization of methodological approaches to the analysis of herbal substances containing triterpenoid saponins, considered the largest group of phytochemicals, is essential for the pharmaceutical industry worldwide.</p><p><strong>Objectives: </strong>This review aimed to perform a comparative analysis of the requirements for the standardization of herbal substances, herbal medicinal products (HMPs), and other herbal materials containing triterpenoid saponins in the pharmacopeial texts of the Russian Federation and the world's leading pharmacopeias.</p><p><strong>Materials and methods: </strong>The review covers the data on the quantitative and qualitative analysis of herbal substances containing triterpenoid saponins, as presented in the State Register of Medicinal Products of Russia and the monographs of the world's leading pharmacopeias: the European Pharmacopeia, United States Pharmacopeia, British Pharmacopeia, Japanese Pharmacopeia, and the national pharmacopeias of the Eurasian Economic Union (EEU) Member States.</p><p><strong>Results: </strong>This review compares and discusses the analytical methods used for the standardization of Aesculus hippocastanum L. seeds, Aralia elata (Miq.) Seem roots, Glycyrrhiza spp. roots, Orthosiphon aristatus (Blume) Miq. leaves, and Polemonium caeruleum L. rhizomes with roots. The most common analytical methods used are (HP)TLC and (U)HPLC. The Russian Pharmacopeia also includes titrimetry and spectrophotometry.</p><p><strong>Conclusions: </strong>The appropriate selection of a group of biologically active compounds for HMP standardization is still challenging. We believe that a rational approach to the standardization of herbal substances and HMPs should be based on the use of herbal substances with maximum extractability and specific pharmacological activity. The harmonized procedures and reference substances for the identification and assay of active metabolites in HMPs must be implemented at all stages of production control from herbal substances to finished dosage forms.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2401-2416"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Langdu (SSC) is the dried root of Stellera chamaejasme L. Due to its toxicity, the milk-processed (NSC), Terminalia chebula decoction-processed (HSC), wine-processed (JSC), and vinegar-processed (CSC) products are predominantly employed in clinical practice.
Objective: To illuminate the difference in color, volatile, and non-volatile compounds among the processed products of SC.
Material and methods: SC was processed into five products. Color characteristics, volatile, and non-volatile compounds were systematically analyzed using electronic eye, electronic nose, and HPLC analyses. Multivariate statistical analyses comprising principal component analysis (PCA), hierarchical cluster analysis (HCA), discriminant factor analysis (DFA), partial least squares discriminant analysis (PLS-DA), and correlation analysis were performed.
Results: Following processing, significant differences in color, volatile, and non-volatile components were observed. The established chemometric models demonstrated rapid discriminative capability to the five products, with seven volatile components and 16 non-volatile components identified as potential chemical markers. Quantitative analysis revealed increased levels of daphnetin and scopoletin and decreased levels of bergenin and chamaechromone after processing. Pearson's correlation analysis revealed significant positive correlations between the lightness (L*) value in the CIELAB color space and scopoletin (p < 0.001) or 7-hydroxycoumarin (p < 0.001), while the b* (yellow-blue) axis showed significant positive correlations with daphnetin (p < 0.001) and isopimpinellin (p < 0.05) contents. Additionally, a* (red-green) axis showed significant negative correlations with daphnetin, 7-hydroxycoumarin, and daphnoretin levels (p < 0.01).
Conclusion: The established models efficiently, accurately, and reliably discriminated the different processed products of SC through multidimensional characterization. These potential chemical markers and correlation patterns provide the scientific foundation for toxicity reduction assessment and processing standardization.
{"title":"Comparative Study Between Raw and Different Processed Stellera chamaejasme L. Based on Electronic Eye, Electronic Nose, HPLC, and Chemometrics.","authors":"Wenqi Hu, Xiaoran Zhao, Liying Liu, Gege Li, Rui Huang, Yanan Liu, Xiaoliang Ren","doi":"10.1002/pca.70005","DOIUrl":"10.1002/pca.70005","url":null,"abstract":"<p><strong>Introduction: </strong>Langdu (SSC) is the dried root of Stellera chamaejasme L. Due to its toxicity, the milk-processed (NSC), Terminalia chebula decoction-processed (HSC), wine-processed (JSC), and vinegar-processed (CSC) products are predominantly employed in clinical practice.</p><p><strong>Objective: </strong>To illuminate the difference in color, volatile, and non-volatile compounds among the processed products of SC.</p><p><strong>Material and methods: </strong>SC was processed into five products. Color characteristics, volatile, and non-volatile compounds were systematically analyzed using electronic eye, electronic nose, and HPLC analyses. Multivariate statistical analyses comprising principal component analysis (PCA), hierarchical cluster analysis (HCA), discriminant factor analysis (DFA), partial least squares discriminant analysis (PLS-DA), and correlation analysis were performed.</p><p><strong>Results: </strong>Following processing, significant differences in color, volatile, and non-volatile components were observed. The established chemometric models demonstrated rapid discriminative capability to the five products, with seven volatile components and 16 non-volatile components identified as potential chemical markers. Quantitative analysis revealed increased levels of daphnetin and scopoletin and decreased levels of bergenin and chamaechromone after processing. Pearson's correlation analysis revealed significant positive correlations between the lightness (L*) value in the CIELAB color space and scopoletin (p < 0.001) or 7-hydroxycoumarin (p < 0.001), while the b* (yellow-blue) axis showed significant positive correlations with daphnetin (p < 0.001) and isopimpinellin (p < 0.05) contents. Additionally, a* (red-green) axis showed significant negative correlations with daphnetin, 7-hydroxycoumarin, and daphnoretin levels (p < 0.01).</p><p><strong>Conclusion: </strong>The established models efficiently, accurately, and reliably discriminated the different processed products of SC through multidimensional characterization. These potential chemical markers and correlation patterns provide the scientific foundation for toxicity reduction assessment and processing standardization.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"1974-1989"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Introduction: </strong>Determining the hepatotoxic potential of Euodiae Fructus (EF) and exploring the methods and mechanisms of detoxification after processing and compatibility are critical for its rational use. The changes in components and endogenous metabolites after administration might provide a pathway to resolve the above issues.</p><p><strong>Objective: </strong>This study aims to investigate whether boiling water washing (BWW), drying after BWW, or compatibility in Wuzhuyu decoction (WZYD) can mitigate the hepatotoxicity of EF, and to explore the underlying mechanisms through chemical composition and metabolomics analysis.</p><p><strong>Methods: </strong>The hepatotoxicity of EF, processed EF, and WZYD were evaluated in normal mice, then the hepatotoxicity of WZYD was evaluated in migraine model mice. General physical signs (e.g., weight loss, reduced activity, and dull fur), biochemical markers (e.g., ALT, AST, TBIL, and ALP levels), and histopathological examination were observed. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to quantify the change of 14 specific ingredients in EF after processing and compatibility, including alkaloids (e.g., evodiamine, rutaecarpine), phenolic acids (e.g., chlorogenic acid), and flavonoids. Metabolomics based on ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS) was employed to identify key pathways, and protein expression in these pathways was assessed to confirm detoxification mechanisms.</p><p><strong>Results: </strong>The decocted extract of raw EF (SEF) induced liver injury in normal mice at a human equivalent dose, while the decocted extracts of boiling water-washed EF (TEF) and dried boiling water-washed EF (GEF) reduced this injury. WZYD did not induce liver injury in normal and migraine model mice, further supporting its safety profile. Significant differences in chemical composition were observed among SEF, TEF, GEF, and WZYD, including a reduction in phenolic acids (e.g., chlorogenic acid and caffeic acid) and an increase in alkaloids (e.g., evodiamine and rutaecarpine). Metabolomics analysis revealed that both boiling water washing (BWW) processing and WZYD compatibility influenced linoleic acid metabolism, oxidative stress, and inflammation. Specifically, CYP2E1 expression was significantly reduced in the TEF and WZYD groups, accompanied by decreased oxidative markers (MDA) and inflammatory cytokines (TNF-α and IL-6).</p><p><strong>Conclusion: </strong>In summary, BWW processing and WZYD compatibility reduce EF-induced hepatotoxicity by modulating linoleic acid metabolism, CYP2E1 activity, oxidative stress, and inflammation. These processes are interconnected and play a central role in the detoxification of EF. By altering the chemical composition of EF, these processes reduce the levels of potential hepatotoxic components such as phenolic acids, while increasing the concent
{"title":"Investigating the Material Basis and Mechanisms of Toxicity Reduction in Processing and Compatibility of Euodiae Fructus Based on UPLC-MS/MS Quantitative Analysis and UHPLC-Q-TOF-MS Metabolomics.","authors":"Keshu Wang, Meijing Li, Zhimin Song, Zekuan Zhang, Qi Wang, Jingjing Xu, Yuan Gao, Jiabo Wang, Jing Li, Muxin Gong","doi":"10.1002/pca.70006","DOIUrl":"10.1002/pca.70006","url":null,"abstract":"<p><strong>Introduction: </strong>Determining the hepatotoxic potential of Euodiae Fructus (EF) and exploring the methods and mechanisms of detoxification after processing and compatibility are critical for its rational use. The changes in components and endogenous metabolites after administration might provide a pathway to resolve the above issues.</p><p><strong>Objective: </strong>This study aims to investigate whether boiling water washing (BWW), drying after BWW, or compatibility in Wuzhuyu decoction (WZYD) can mitigate the hepatotoxicity of EF, and to explore the underlying mechanisms through chemical composition and metabolomics analysis.</p><p><strong>Methods: </strong>The hepatotoxicity of EF, processed EF, and WZYD were evaluated in normal mice, then the hepatotoxicity of WZYD was evaluated in migraine model mice. General physical signs (e.g., weight loss, reduced activity, and dull fur), biochemical markers (e.g., ALT, AST, TBIL, and ALP levels), and histopathological examination were observed. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to quantify the change of 14 specific ingredients in EF after processing and compatibility, including alkaloids (e.g., evodiamine, rutaecarpine), phenolic acids (e.g., chlorogenic acid), and flavonoids. Metabolomics based on ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS) was employed to identify key pathways, and protein expression in these pathways was assessed to confirm detoxification mechanisms.</p><p><strong>Results: </strong>The decocted extract of raw EF (SEF) induced liver injury in normal mice at a human equivalent dose, while the decocted extracts of boiling water-washed EF (TEF) and dried boiling water-washed EF (GEF) reduced this injury. WZYD did not induce liver injury in normal and migraine model mice, further supporting its safety profile. Significant differences in chemical composition were observed among SEF, TEF, GEF, and WZYD, including a reduction in phenolic acids (e.g., chlorogenic acid and caffeic acid) and an increase in alkaloids (e.g., evodiamine and rutaecarpine). Metabolomics analysis revealed that both boiling water washing (BWW) processing and WZYD compatibility influenced linoleic acid metabolism, oxidative stress, and inflammation. Specifically, CYP2E1 expression was significantly reduced in the TEF and WZYD groups, accompanied by decreased oxidative markers (MDA) and inflammatory cytokines (TNF-α and IL-6).</p><p><strong>Conclusion: </strong>In summary, BWW processing and WZYD compatibility reduce EF-induced hepatotoxicity by modulating linoleic acid metabolism, CYP2E1 activity, oxidative stress, and inflammation. These processes are interconnected and play a central role in the detoxification of EF. By altering the chemical composition of EF, these processes reduce the levels of potential hepatotoxic components such as phenolic acids, while increasing the concent","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"1990-2010"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-07-24DOI: 10.1002/pca.70012
Suvarna Yenduri, K G Venkatesh, K Naga Prashant
Polyphenols are the plant-derived chemicals that have antioxidant properties and provide a wide range of health applications. Traditional polyphenol extraction techniques are limited in scalability, efficiency, and environmental effect. To address these constraints, various advanced approaches came into existence, like ultrasound-assisted extraction, microwave-assisted extraction, and supercritical fluid extraction. These sophisticated approaches come with several benefits over traditional extraction approaches. These advanced extraction methods are more efficient, use very low amounts of solvents, and have minimal environmental effect. These techniques can retain the integrity of bioactive chemicals and are suitable for large-scale extraction, too. Polyphenol-rich extracts have a wide range of uses. They can be utilized as ingredients or additives in foods, cosmetics, and coatings and packing materials. The advancement of these new techniques will be critical for the future polyphenol extraction with an emphasis on sustainability-related factors. These approaches have the potential to address the growing demand for polyphenols while also helping to create more efficient and sustainable extraction procedures.
{"title":"Recent Advances in Extraction of Polyphenols by Advanced Extraction Methods.","authors":"Suvarna Yenduri, K G Venkatesh, K Naga Prashant","doi":"10.1002/pca.70012","DOIUrl":"10.1002/pca.70012","url":null,"abstract":"<p><p>Polyphenols are the plant-derived chemicals that have antioxidant properties and provide a wide range of health applications. Traditional polyphenol extraction techniques are limited in scalability, efficiency, and environmental effect. To address these constraints, various advanced approaches came into existence, like ultrasound-assisted extraction, microwave-assisted extraction, and supercritical fluid extraction. These sophisticated approaches come with several benefits over traditional extraction approaches. These advanced extraction methods are more efficient, use very low amounts of solvents, and have minimal environmental effect. These techniques can retain the integrity of bioactive chemicals and are suitable for large-scale extraction, too. Polyphenol-rich extracts have a wide range of uses. They can be utilized as ingredients or additives in foods, cosmetics, and coatings and packing materials. The advancement of these new techniques will be critical for the future polyphenol extraction with an emphasis on sustainability-related factors. These approaches have the potential to address the growing demand for polyphenols while also helping to create more efficient and sustainable extraction procedures.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"1875-1892"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Antibiotic-associated diarrhea (AAD) is a common side effect after the use of antibiotics, characterized by symptoms like diarrhea and abdominal pain. However, the active components and in vivo metabolism of the Coptidis Rhizoma-Aucklandiae Radix herb pair (CR-AR) in the treatment of AAD remain unclear.
Objective: This study aimed to (1) investigate the prototype components, metabolites, and potential metabolic pathways of CR-AR in AAD mice and (2) compare the concentration of six active components between healthy and AAD mice.
Materials and methods: AAD model mice received oral administration of the CR-AR extract. UPLC-Q-Exactive-Orbitrap-HRMS was used to analyze the prototype components and metabolites in serum, feces, and intestines of AAD mice. A prototype components-targets-pathways-AAD network was developed using network pharmacology to identify active components and effective targets of CR-AR in treating AAD, based on prototypes detected in serum, fecal, and intestinal samples. Additionally, a comparative analysis of the concentration of six active components was conducted between healthy and AAD mice using UPLC-QqQ-MS.
Results: A total of 45 components were identified in the extract of CR-AR. Among them, 16 prototype compounds and 47 metabolites were identified, and potential metabolic pathways (including hydroxylation, demethylation, reduction, hydrolysis, hydrogenation, and glucuronidation) were proposed. Based on the 16 prototype components, six potentially active components (berberine, jatrorrhizine, palmatine, columbamine, epiberberine, and dehydrocostus lactone) were screened from the prototype components-targets-pathways-AAD disease network. Targeted quantitative analysis showed that alkaloid-based active components were significantly more concentrated in the intestines of AAD mice than in healthy mice after 6 h (p < 0.05).
{"title":"Integrated LC-MS and Network Pharmacology Reveal Metabolic Profile and Quantitative Analysis of Active Components in Coptidis Rhizoma-Aucklandiae Radix Herb Pair Between Healthy and Diarrheal Mice.","authors":"Lujia Yang, Muyao Li, Xianglan Deng, Fang Deng, Chuanyang Zhang","doi":"10.1002/pca.70019","DOIUrl":"10.1002/pca.70019","url":null,"abstract":"<p><strong>Introduction: </strong>Antibiotic-associated diarrhea (AAD) is a common side effect after the use of antibiotics, characterized by symptoms like diarrhea and abdominal pain. However, the active components and in vivo metabolism of the Coptidis Rhizoma-Aucklandiae Radix herb pair (CR-AR) in the treatment of AAD remain unclear.</p><p><strong>Objective: </strong>This study aimed to (1) investigate the prototype components, metabolites, and potential metabolic pathways of CR-AR in AAD mice and (2) compare the concentration of six active components between healthy and AAD mice.</p><p><strong>Materials and methods: </strong>AAD model mice received oral administration of the CR-AR extract. UPLC-Q-Exactive-Orbitrap-HRMS was used to analyze the prototype components and metabolites in serum, feces, and intestines of AAD mice. A prototype components-targets-pathways-AAD network was developed using network pharmacology to identify active components and effective targets of CR-AR in treating AAD, based on prototypes detected in serum, fecal, and intestinal samples. Additionally, a comparative analysis of the concentration of six active components was conducted between healthy and AAD mice using UPLC-QqQ-MS.</p><p><strong>Results: </strong>A total of 45 components were identified in the extract of CR-AR. Among them, 16 prototype compounds and 47 metabolites were identified, and potential metabolic pathways (including hydroxylation, demethylation, reduction, hydrolysis, hydrogenation, and glucuronidation) were proposed. Based on the 16 prototype components, six potentially active components (berberine, jatrorrhizine, palmatine, columbamine, epiberberine, and dehydrocostus lactone) were screened from the prototype components-targets-pathways-AAD disease network. Targeted quantitative analysis showed that alkaloid-based active components were significantly more concentrated in the intestines of AAD mice than in healthy mice after 6 h (p < 0.05).</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2129-2147"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144744151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: The role of macromolecular components in traditional Chinese medicines (TCMs) decoction remains poorly understood, primarily because of their structural complexity and limited systemic bioavailability. In the modernization of TCMs' decoctions, macromolecular components are often removed as "poor bioavailable impurities" by ethanol precipitation that might attenuate the efficacy thereof.
Purpose: A novel strategy integrating LC-MS-based serum pharmacochemistry, network pharmacology, and pharmacodynamics was developed to reveal the role of macromolecular components in TCMs' decoction, using Qi-Huo-Yi-Fei decoction (QH) treating chronic obstructive pulmonary disease (COPD) as a case study.
Materials and methods: QH was separated into macromolecular components (QH-M) and small molecular components (QH-S) by ethanol precipitation. The absorbed components of QH and QH-S in serum were qualitatively and semiquantitatively analyzed by UPLC-QTOF-MS/MS. The differences in targets and pathways of the absorbed components were predicted by network pharmacology analysis. The therapeutic effects on pulmonary function, histopathology, and inflammation of QH, QH-S, and QH-M were comparatively investigated on a COPD rat model.
Result: A total of 103 components were identified in QH and QH-S, whereas 86 and 72 were detectable in QH- or QH-S-treated serum, respectively. The highest levels of absorbed components appeared from 15 to 60 min for QH-S and at 15 min for QH. The concentrations of most absorbed components of QH were twofold higher than those of QH-S. Their protein-protein interaction (PPI), herb-component-target networks, and GO/KEGG enrichment pathways were quite different, mainly in inflammatory, immunity, and cell apoptosis processes. QH-M improved pulmonary function, histopathology, and inflammatory infiltration, mainly on FVC (p < 0.05), thickness/external diameter (p < 0.01), Wac/Pbm (p < 0.01), TNF-α (p < 0.01), and IL-17 (p < 0.05). Meanwhile, QH was more effective than QH-S, mainly on FEV0.3/FVC, MAN, GC/CC, TNF-α, and IL-17.
Conclusion: QH-M was not only effective independently on COPD but also showed integrative effects with the coexisting QH-S in improving their absorption, thus strengthening the component-target interactions, and consequently contributing to the COPD therapeutic effects of QH. Therefore, it was confirmed that QH-M was essential for QH's COPD therapy and should not be removed during the modern preparation development.
{"title":"LC-MS-Based Serum Pharmacochemistry Combined With Network Pharmacology and Pharmacodynamics to Evaluate the Role of Macromolecular Components in TCMs' Decoction: A Case Study on Qi-Huo-Yi-Fei Decoction for COPD Therapy.","authors":"Peng Yang, Hu-Dong Lv, Jie Wu, Fang Long, Jing Zhou, Cheng-Ying Wu, Jin-Di Xu, Shan-Shan Zhou, Qing-Ling Xiao, Song-Lin Li, Hong Shen","doi":"10.1002/pca.70021","DOIUrl":"10.1002/pca.70021","url":null,"abstract":"<p><strong>Introduction: </strong>The role of macromolecular components in traditional Chinese medicines (TCMs) decoction remains poorly understood, primarily because of their structural complexity and limited systemic bioavailability. In the modernization of TCMs' decoctions, macromolecular components are often removed as \"poor bioavailable impurities\" by ethanol precipitation that might attenuate the efficacy thereof.</p><p><strong>Purpose: </strong>A novel strategy integrating LC-MS-based serum pharmacochemistry, network pharmacology, and pharmacodynamics was developed to reveal the role of macromolecular components in TCMs' decoction, using Qi-Huo-Yi-Fei decoction (QH) treating chronic obstructive pulmonary disease (COPD) as a case study.</p><p><strong>Materials and methods: </strong>QH was separated into macromolecular components (QH-M) and small molecular components (QH-S) by ethanol precipitation. The absorbed components of QH and QH-S in serum were qualitatively and semiquantitatively analyzed by UPLC-QTOF-MS/MS. The differences in targets and pathways of the absorbed components were predicted by network pharmacology analysis. The therapeutic effects on pulmonary function, histopathology, and inflammation of QH, QH-S, and QH-M were comparatively investigated on a COPD rat model.</p><p><strong>Result: </strong>A total of 103 components were identified in QH and QH-S, whereas 86 and 72 were detectable in QH- or QH-S-treated serum, respectively. The highest levels of absorbed components appeared from 15 to 60 min for QH-S and at 15 min for QH. The concentrations of most absorbed components of QH were twofold higher than those of QH-S. Their protein-protein interaction (PPI), herb-component-target networks, and GO/KEGG enrichment pathways were quite different, mainly in inflammatory, immunity, and cell apoptosis processes. QH-M improved pulmonary function, histopathology, and inflammatory infiltration, mainly on FVC (p < 0.05), thickness/external diameter (p < 0.01), Wac/Pbm (p < 0.01), TNF-α (p < 0.01), and IL-17 (p < 0.05). Meanwhile, QH was more effective than QH-S, mainly on FEV0.3/FVC, MAN, GC/CC, TNF-α, and IL-17.</p><p><strong>Conclusion: </strong>QH-M was not only effective independently on COPD but also showed integrative effects with the coexisting QH-S in improving their absorption, thus strengthening the component-target interactions, and consequently contributing to the COPD therapeutic effects of QH. Therefore, it was confirmed that QH-M was essential for QH's COPD therapy and should not be removed during the modern preparation development.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2148-2181"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-08-14DOI: 10.1002/pca.70015
Hui Zhi, Sen Shi, Yun Guo, Zhonghua Tang
Background: Saposhnikovia divaricata (Turcz.) Schischk. (S. divaricata), a traditional Chinese medicine, is renowned for its dried roots rich in phenolic compounds, which exhibit significant medicinal values in anti-inflammatory, analgesic, and other therapeutic fields. Cultivating medicinal plants has been validated as an effective strategy to enhance the supply of phenolic-rich raw materials. However, the efficient fertilization strategy of nitrogen-a key nutrient-and its regulatory mechanisms on plant growth and phenolic metabolism in S. divaricata remain unclear.
Purpose and study design: This study aimed to explore nitrogen's effects on S. divaricata growth and phenolic accumulation. Field experiments used four nitrogen treatments: no nitrogen fertilization (CK), low nitrogen fertilization (9 g/m²), medium nitrogen fertilization (18 g/m²), and high nitrogen fertilization (27 g/m²). Growth indices and phenolic metabolites were analyzed via UPLC-MS and multivariate statistics.
Results: The results showed that the medium nitrogen treatment (18 g/m²) significantly promoted the growth of S. divaricata, with plant height and single-plant biomass reaching 26 ± 0.3 cm and 19.04 ± 0.96 g, respectively, and optimal root development (root length 14.7 ± 0.2 cm). Additionally, nitrogen application significantly promoted the synthesis of phenolic compounds and enhanced the tolerance of S. divaricata to nitrogen stress, which is conducive to safeguarding and elevating its medicinal value. For specific bioactive substances, the contents of prim-o-glucosyl-cimifugin, 4'-o-β-glucosyl-5-o-methylvisamminol, cimifugin, and sec-o-glucosylhamaudol in S. divaricata under medium nitrogen concentration were notably higher than those in the no-nitrogen fertilization group.
Conclusion: This study confirms that medium nitrogen levels can synergistically enhance the growth and accumulation of medicinal active components in S. divaricata, providing a theoretical basis for the precise application of nitrogen fertilizers and quality regulation in medicinal plant cultivation.
{"title":"Metabolomics-Based Comprehensive Exploration of the Bioactive Compound in Saposhnikovia divaricata (Turcz.) Schischk. in Response to Exogenous Nitrogen.","authors":"Hui Zhi, Sen Shi, Yun Guo, Zhonghua Tang","doi":"10.1002/pca.70015","DOIUrl":"10.1002/pca.70015","url":null,"abstract":"<p><strong>Background: </strong>Saposhnikovia divaricata (Turcz.) Schischk. (S. divaricata), a traditional Chinese medicine, is renowned for its dried roots rich in phenolic compounds, which exhibit significant medicinal values in anti-inflammatory, analgesic, and other therapeutic fields. Cultivating medicinal plants has been validated as an effective strategy to enhance the supply of phenolic-rich raw materials. However, the efficient fertilization strategy of nitrogen-a key nutrient-and its regulatory mechanisms on plant growth and phenolic metabolism in S. divaricata remain unclear.</p><p><strong>Purpose and study design: </strong>This study aimed to explore nitrogen's effects on S. divaricata growth and phenolic accumulation. Field experiments used four nitrogen treatments: no nitrogen fertilization (CK), low nitrogen fertilization (9 g/m<sup>²</sup>), medium nitrogen fertilization (18 g/m<sup>²</sup>), and high nitrogen fertilization (27 g/m<sup>²</sup>). Growth indices and phenolic metabolites were analyzed via UPLC-MS and multivariate statistics.</p><p><strong>Results: </strong>The results showed that the medium nitrogen treatment (18 g/m<sup>²</sup>) significantly promoted the growth of S. divaricata, with plant height and single-plant biomass reaching 26 ± 0.3 cm and 19.04 ± 0.96 g, respectively, and optimal root development (root length 14.7 ± 0.2 cm). Additionally, nitrogen application significantly promoted the synthesis of phenolic compounds and enhanced the tolerance of S. divaricata to nitrogen stress, which is conducive to safeguarding and elevating its medicinal value. For specific bioactive substances, the contents of prim-o-glucosyl-cimifugin, 4'-o-β-glucosyl-5-o-methylvisamminol, cimifugin, and sec-o-glucosylhamaudol in S. divaricata under medium nitrogen concentration were notably higher than those in the no-nitrogen fertilization group.</p><p><strong>Conclusion: </strong>This study confirms that medium nitrogen levels can synergistically enhance the growth and accumulation of medicinal active components in S. divaricata, providing a theoretical basis for the precise application of nitrogen fertilizers and quality regulation in medicinal plant cultivation.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2080-2090"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Goat bezoar (Houzao in Chinese, also called "monkey" bezoar or Caprae Calculus) is a valued traditional Chinese medicine (TCM) used in the treatment of pediatric cough for centuries. However, its undefined chemical composition hinders quality control and mechanistic understanding, limiting its modernization and further development.
Objective: This study aims to comprehensively characterize the chemical composition of goat bezoar and develop a robust quality control method.
Method: UPLC-qTOF-MS was first utilized to analyze the methanol extract of goat bezoar reference material. Markers specific to the medicinal portion were identified by comparing the chemical profiles with the non-medicinal portion and 50 co-formulated TCMs. Amino acid composition and ash content were also determined. Validated quantitative methods for these markers were subsequently developed using both UPLC-qTOF-MS and UPLC-DAD and applied to assess the quality of 13 batches of raw goat bezoar material and 38 batches of commercial products.
Results: Eight characteristic markers, including ellagic acid and seven of its gut microbial metabolites (urolithins), were identified exclusively within the medicinal portion. Ellagic acid (72.72%-89.41%) and total urolithins (2.14%-5.13%) were major components. These, along with amino acids (1.19%-5.91%) and total ash (2.09%), account for over 90% of the medicinal portion's composition. The analysis of commercial materials and products using this method revealed that goat bezoar may be absent in 20 commercial products while all the goat bezoar powder samples were authentic.
Conclusion: This study provides the first comprehensive chemical characterization of goat bezoar, revealing its unique composition and establishing it as the only known TCM with urolithins. Validated quantitative methods for ellagic acid and urolithins provide a crucial quality control tool, paving the way for further research, development, and modernization of this valuable TCM.
{"title":"Quality Analysis of Raw Material and Products of Goat Bezoar (Houzao), a Mysterious Traditional Medicine.","authors":"Sing-Wan Pun, Hau-Yee Fung, Peili Zhu, Zhu Zhang, Hanting Hu, Yinan Feng, Zhongzhen Zhao, Lifeng Li, Quanbin Han","doi":"10.1002/pca.70022","DOIUrl":"10.1002/pca.70022","url":null,"abstract":"<p><strong>Background: </strong>Goat bezoar (Houzao in Chinese, also called \"monkey\" bezoar or Caprae Calculus) is a valued traditional Chinese medicine (TCM) used in the treatment of pediatric cough for centuries. However, its undefined chemical composition hinders quality control and mechanistic understanding, limiting its modernization and further development.</p><p><strong>Objective: </strong>This study aims to comprehensively characterize the chemical composition of goat bezoar and develop a robust quality control method.</p><p><strong>Method: </strong>UPLC-qTOF-MS was first utilized to analyze the methanol extract of goat bezoar reference material. Markers specific to the medicinal portion were identified by comparing the chemical profiles with the non-medicinal portion and 50 co-formulated TCMs. Amino acid composition and ash content were also determined. Validated quantitative methods for these markers were subsequently developed using both UPLC-qTOF-MS and UPLC-DAD and applied to assess the quality of 13 batches of raw goat bezoar material and 38 batches of commercial products.</p><p><strong>Results: </strong>Eight characteristic markers, including ellagic acid and seven of its gut microbial metabolites (urolithins), were identified exclusively within the medicinal portion. Ellagic acid (72.72%-89.41%) and total urolithins (2.14%-5.13%) were major components. These, along with amino acids (1.19%-5.91%) and total ash (2.09%), account for over 90% of the medicinal portion's composition. The analysis of commercial materials and products using this method revealed that goat bezoar may be absent in 20 commercial products while all the goat bezoar powder samples were authentic.</p><p><strong>Conclusion: </strong>This study provides the first comprehensive chemical characterization of goat bezoar, revealing its unique composition and establishing it as the only known TCM with urolithins. Validated quantitative methods for ellagic acid and urolithins provide a crucial quality control tool, paving the way for further research, development, and modernization of this valuable TCM.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2182-2196"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Tangerine peel tea, a bioactive-rich plant beverage containing hydrophobic flavonoids (hesperidin, naringin, and neohesperidin), faces analytical challenges in quality control due to poor aqueous solubility.
Objectives: In order to determine the hydrophobic flavonoids components in tangerine peel tea and evaluate its quality, this experiment was carried out.
Method: An eco-friendly offline-online capillary electrophoresis stacking strategy integrating polyethylene glycol (PEG)-based aqueous biphasic extraction with borate complexation-assisted micelle-to-cyclodextrin stacking was developed. Critical parameters influencing separation, enrichment, and extraction efficiency were systematically optimized. The method was subsequently validated for accuracy, precision and green evaluation.
Results: Following single-factor optimization, the online stacking parameters were defined as 90 mmol/L sodium tetraborate and 35% (v/v) methanol in the background solution, with injection times fixed at 40 s (SDS), 20 s (cyclodextrin), and 200 s (sample). Offline pretreatment employed a salt PEG sample aqueous biphasic system (ABS) for extraction. Under optimized conditions, the method demonstrated excellent linearity (r ≥ 0.998) and low detection limits (40-50 ng/mL), achieving a 723-fold sensitivity enhancement over conventional detection. Greenness assessment confirmed superior sustainability, and the method successfully quantified three hydrophobic targets (hesperidin, naringenin, and neohesperidin) in tangerine peel tea and spiked rat urine with high accuracy.
Conclusion: The proposed strategy establishes a robust analytical platform for nutraceutical quality control, resolving critical challenges in quantifying poorly soluble bioactive compounds through optimized online stacking and aqueous biphasic extraction.
陈皮茶是一种富含生物活性的植物饮料,含有疏水性黄酮类化合物(橙皮苷、柚皮苷和新橙皮苷),由于水溶性差,在质量控制方面面临分析挑战。目的:测定陈皮茶中疏水类黄酮成分,并对其品质进行评价。方法:建立了聚乙二醇(PEG)双水相萃取与硼酸盐络合辅助胶束-环糊精叠加的生态友好型离线-在线毛细管电泳叠加策略。系统优化了影响分离、富集和萃取效率的关键参数。随后对该方法进行了准确性、精密度和绿色评价验证。结果:通过单因素优化,确定在线堆积参数为90 mmol/L四硼酸钠和35% (v/v)甲醇,注射时间固定为40 s (SDS)、20 s(环糊精)和200 s(样品)。离线预处理采用盐聚乙二醇样品双水相体系(ABS)进行萃取。在优化条件下,该方法线性良好(r≥0.998),检出限低(40 ~ 50 ng/mL),灵敏度比常规检测提高723倍。绿色评价证实了该方法具有较好的可持续性,并且该方法成功地定量了陈皮茶和大鼠尿液中的三个疏水靶点(橙皮苷、柚皮苷和新橙皮苷),准确度较高。结论:该方法为保健品质量控制建立了一个强大的分析平台,通过优化的在线叠加和双水相萃取,解决了难溶性生物活性化合物定量的关键挑战。
{"title":"Eco-Friendly Capillary Electrophoresis for Enhanced Detection of Hydrophobic Flavonoids in Tangerine Peel Tea via Borate Complexation and Micellar Stacking.","authors":"Rong Xue, Yaxin Qin, Wei Gao, Yaping Zang, Yangbin Lv, Yaxin Cheng, Wenli Sun, Chu Chu","doi":"10.1002/pca.70007","DOIUrl":"10.1002/pca.70007","url":null,"abstract":"<p><strong>Introduction: </strong>Tangerine peel tea, a bioactive-rich plant beverage containing hydrophobic flavonoids (hesperidin, naringin, and neohesperidin), faces analytical challenges in quality control due to poor aqueous solubility.</p><p><strong>Objectives: </strong>In order to determine the hydrophobic flavonoids components in tangerine peel tea and evaluate its quality, this experiment was carried out.</p><p><strong>Method: </strong>An eco-friendly offline-online capillary electrophoresis stacking strategy integrating polyethylene glycol (PEG)-based aqueous biphasic extraction with borate complexation-assisted micelle-to-cyclodextrin stacking was developed. Critical parameters influencing separation, enrichment, and extraction efficiency were systematically optimized. The method was subsequently validated for accuracy, precision and green evaluation.</p><p><strong>Results: </strong>Following single-factor optimization, the online stacking parameters were defined as 90 mmol/L sodium tetraborate and 35% (v/v) methanol in the background solution, with injection times fixed at 40 s (SDS), 20 s (cyclodextrin), and 200 s (sample). Offline pretreatment employed a salt PEG sample aqueous biphasic system (ABS) for extraction. Under optimized conditions, the method demonstrated excellent linearity (r ≥ 0.998) and low detection limits (40-50 ng/mL), achieving a 723-fold sensitivity enhancement over conventional detection. Greenness assessment confirmed superior sustainability, and the method successfully quantified three hydrophobic targets (hesperidin, naringenin, and neohesperidin) in tangerine peel tea and spiked rat urine with high accuracy.</p><p><strong>Conclusion: </strong>The proposed strategy establishes a robust analytical platform for nutraceutical quality control, resolving critical challenges in quantifying poorly soluble bioactive compounds through optimized online stacking and aqueous biphasic extraction.</p>","PeriodicalId":20095,"journal":{"name":"Phytochemical Analysis","volume":" ","pages":"2011-2021"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}