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Background: Cimicifugae Rhizoma, known in Chinese as Shengma, is a common medicinal material in traditional Chinese medicine (TCM), mainly used for treating wind-heat headaches, sore throat, uterine prolapse, and other diseases., Objectives: An approach using a combination of ultra-performance liquid chromatography (UPLC), MS, and multivariate chemometric methods was designed to assess the quality of Cimicifugae Rhizoma., Methods: All materials were crushed into powder and the powdered sample was dissolved in 70% aqueous methanol for sonication. Chemometric methods, including hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least-squares discriminant analysis (OPLS-DA), were adopted to classify and perform a comprehensive visualization study of Cimicifugae Rhizoma. The unsupervised recognition models of HCA and PCA obtained a preliminary classification and provided a basis for classification. In addition, we constructed a supervised OPLS-DA model and established a prediction set to further validate the explanatory power of the model for the variables and unknown samples., Results: Exploratory research found that the samples were divided into two groups, and the differences were related to appearance traits. The correct classification of the prediction set also demonstrated a strong predictive ability of the models for new samples. Subsequently, six chemical makers were characterized by UPLC-Q-Orbitrap-MS/MS, and the content of four components was determined. The results of the content determination revealed the distribution of representative chemical markers caffeic acid, ferulic acid, isoferulic acid, and cimifugin in two classes of samples., Conclusions: This strategy can provide a reference for assessing the quality of Cimicifugae Rhizoma, which is significant for the clinical practice and QC of Cimicifugae Rhizoma., Highlights: The HCA, PCA and OPLS-DA models visually classify Cimicifugae Rhizoma by appearance traits and obtain the chemical markers that influence the classification. The training and prediction sets were built to demonstrate the accuracy of the classification. Advanced UPLC-Q-Orbitrap-MS/MS technology provides powerful elucidation of critical chemical markers., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Polygonati Rhizoma has been a famous traditional Chinese medicine (TCM) for two thousand years. It is increasingly being used not just as a traditional herbal medicine but also as a popular functional food. In this study, qualitative and quantitative analysis of PR from three different origins were initially performed using chemical fingerprint and chemometrics methods. Hierarchical cluster analysis (HCA) and Principal component analysis (PCA) were used to classify 60 PR samples from three different origins. The results revealed that the PR samples fell into three clusters related to the origins. In addition, pairwise comparison of varying PR and obtaining chemical markers between different species through the establishment of partial least squares discriminant analysis. Finally, chemical markers 9,13 and 17 were identified by LC/MS as disporopsin, 5,7-dihydroxy-3-(4'-hydroxybenzyl)-6,8-dimethylchroman-4-one and (3R)-5,7-dihydroxy-3-(4'-hydroxybenzyl)-6-methylchroman-4-one or isomer, respectively. In conclusion, these methods can be applied to identify and distinguish the quality of PR with other original plants and provide novel ideas for evaluating herbal products used in TCM., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

In the processing field, there is a saying that "seed drugs be stir-fried". Bitter almond (BA) is a kind of seed Chinese medicine. BA need be used after being fried. To distinguish raw bitter almonds (RBA) from processed products and prove the rationality of "seed drugs be stir-fried", we analyzed the RBA and five processed products (scalded bitter almonds, fried bitter almonds, honey fried bitter almonds, bran fried bitter almonds, bitter almonds cream) using RP-HPLC fingerprints and chemometric methods. The similarity between RBA and processed products was 0.733∼0.995. Hierarchically clustered heatmap was used to evaluate the changes in components. Principal component analysis (PCA) was used for classification, and all samples are distinguished according to RBA and five processing methods. Six chemical markers were obtained by partial least squares discriminant analysis (PLS-DA). The content and degradation rate of amygdalin and β-glucosidase activity were determined. Compared with RBA, the content and degradation rate of amygdalin, and β-glucosidase activity were increased in bitter almonds cream. The content and degradation rate were decreased, and β-glucosidase was inactivated in other processed products. The above results showed that stir-frying had the best effect. The results showed that processing can ensure the stability of RBA quality, and the saying "seed drugs be stir-fried" is reasonable., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Panax Japonicus (PJ) is a widely used Chinese herbal medicine, functional food and tonic. However, its origin has a great influence on the quality of PJ, and with the increasing demand for PJ, fake and inferior products, such as Panax Stipuleanatus (PS), often appear. The identification of the origin and authenticity of PJ is critical for ensuring the quality, safety and effectiveness of drugs., Objective: Proposing a strategy to identify the origin, authenticity, and quality of PJ using HPLC fingerprints, chemometrics, and network pharmacology., Methods: The chromatographic fingerprint method was established to analyze the origin and authenticity of PJ. Multiple chemometric methods were performed to analyze the fingerprints, including a Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA), and Counter Propagation Artificial Neural Network (CP-ANN). Finally, the network pharmacology method was used to construct the "active ingredient-target" network, predict and assist in analyzing potential Qmarkers in PJ., Results: Ward's method was used for the HCA. The results showed that PJ samples from different origins had significant regional differences and could be accurately distinguished from PS. The PCA classification results are consistent with the HCA classification results, further illustrating the model's accuracy. The CP-ANN model can analyze and predict PJ and PS and accurately obtain PJ and PS chemical markers to identify PJ and PS correctly. The network pharmacology of PJ was constructed, and three PJ Q-markers, namely, ginsenoside Ro, ginsenoside Rb1, and chikusetsu saponin Ⅳa, were identified, which lays a foundation for the establishment of PJ quality standards., Conclusion: This research provides a feasible platform for the quality evaluation of PJ in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The quality of the root bark of Morus alba L. (SBP) herbs currently circulating in the market is variable. In order to ensure clinical effectiveness, a high-performance liquid chromatography (HPLC) fingerprinting method combined with chemical pattern recognition should be established to control the quality of SBP herbs. The differences of 23 batches of SBP were analyzed by exploratory cluster analysis based on shared fingerprint peak data, and the results indicated that the processing method to remove the cork layer from SBP materials is an important influencing factor on SBP quality. Principal component analysis indicated that SBP samples with the cork layer removed can be clearly distinguished from samples without cork layer removal. The potential chemical markers (kuwanon G, morusin and oxyresveratrol) were screened by partial least squares discriminant analysis. Finally, the contents of the main components were determined, indicating that the processing method of SBP materials can affect content of bioactive ingredients and that cork layer removal leads to a more uniform chemometric profile. The HPLC-based chemometrics approach described here will support the development of quality standards in SBP products., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Danggui Buxue Decoction (DBT) is classical prescriptions, which contains two Traditional Chinese Medicines of Angelicae sinensis radix and Astragali radix. According to the preliminary work of our laboratory and numerous studies, it has been found that DBT has a therapeutic effect on diabetic nephropathy (DN). However, the mechanisms underlying its action remain unclear., Aim of the Study: The aim of this study was to evaluate the impact of DBT on kidney disease in diabetic mice and further explore its protective mechanism., Methods: DN mice model was induced by high-fat fodder and streptozotocin (STZ). Qualitative and quantitative analysis of 6 compounds in DBT was carried out by HPLC, including calycosin-7-glucoside, ferulic acid, ononin, calycosin, formononetin, and levostilide A. Hematoxylin-Eosin (HE) staining was used to determine the degree of kidney pathological damage. The UPLC-Q Exactive MS technique was used to analyze the lipids metabolism profile of kidneys samples and multiple statistical analysis methods were used to screen and identify biomarkers. Transcriptomics analyses were carried out using RNAseq. The possible molecular mechanism was unraveled by network pharmacology., Results: Thirty-one significantly altered lipid metabolites were identified in the model group comparing with the control group. DBT improved aberrant expression of several pathways related to lipidomics, including glycerophospholipid metabolism and sphingolipid metabolism. Comprehensive analysis indicated that DBT intervention reduced the content of Cers, phosphatidylethanolamines and phosphatidylcholines in mouse kidneys by downregulating the transcription level of Degs2 and Cers, reducing lipid accumulation and promoting Akt phosphorylation by upregulating the expression of Acers and Pdk1. Network pharmacology analysis showed that components in DBT, such as kaempferol, ferulic acid and astragaloside IV, could be responsible for the pharmacological activity of DN by regulating the AGE-RAGE, PI3K/Akt, MAPK and NF-κB signaling pathways in diabetic complications., Conclusions: These results showed that DBT may improve DN by affecting insulin resistance, chronic inflammation and lipid accumulation., (Copyright © 2021. Published by Elsevier B.V.)

Background: Xin-Ke-Shu (XKS), a commonly used traditional Chinese medicine, has been clinically proven to be effective for treatment of acute myocardial ischemia (AMI). Numerous studies underscore the important role of fatty acid metabolism in the pathogenesis of AMI., Purpose: This study examined the relationship between free fatty acids (FFAs) and AMI and the contributions of individual herbs found in XKS to provide a basis for the study of the compatible principle of XKS., Methods: UFLC-MS/MS-based targeted metabolomics was performed to analyze the levels of 15 FFAs in the plasma and myocardium of isoproterenol (ISO)-induced AMI rats treated with XKS and the subtracted prescriptions of XKS. Electrocardiogram data, H&E staining, biochemical analysis and western blotting were assayed to illustrate the cardioprotection of XKS and its subtracted prescription in AMI. Correlation analysis was used to reveal the relationship between the levels of FFAs and overexpressed proteins/biochemical enzymes., Results: We found aberrant fatty acid metabolism in AMI rats. In both plasma and myocardium, the concentrations of most of quantified FFAs were significantly altered, whereas the concentrations of stearic acid and behenic acid were similar between the control and AMI groups. Correlation analysis revealed that palmitic acid, oleic acid, linoleic acid and arachidonic acid were potentially the most relevant FFAs to inflammatory and apoptotic proteins and CK-MB. Moreover, XKS effectively alleviated pathological alterations, FFA metabolism abnormity, inflammation and apoptosis found in the myocardium of AMI rats. Notably, the removal of Salvia miltiorrhiza and Pueraria lobata from XKS resulted in markedly regulation loss of cardioprotection during AMI, especially mediation loss of FFA metabolism. The other three herbs of XKS also played a role in improving AMI., Conclusion: Fatty acid metabolism aberrance occurred during AMI. S. miltiorrhiza and P. lobata play vital roles in the anti-inflammatory and anti-apoptotic action partially by regulating FFA levels. Our findings revealed potential novel clinical FFAs for predicting AMI and extended the insights into the compatible principle of XKS in which S. miltiorrhiza and P. lobata can potently modulate FFA metabolism., (Copyright © 2021. Published by Elsevier GmbH.)

The extract of Belamcanda chinensis (L.) leaves (BCLE) is a traditional Chinese herbal medicine for the treatment of hyperglycemia in Hainan province, South China. In this study, the effects of BCLE on obese diabetes were investigated using the KK-A y mice. The component F2 of BCLE alleviate hyperglycemia and insulin resistance, as indicated by decreased levels of FBG, AUC, GSP, LDH and insulin. High levels of hepatic G6Pase and PEPCK in KK-A y mice were markedly attenuated by F2. The inhibitory effect of F2 on GSK-3β and the enhancement effect on liver glycogen demonstrated that F2 could significantly inhibit hepatic gluconeogenesis and glycogen accumulation. The higher PPAR γ showed F2 may prevent insulin resistance by PI3K signal transduction pathway. In addition, the component F1 of BCLE prevented cell degeneration and reduced pathological tissue injury in pancreas tissue. These findings suggest that F2 exhibited high hypoglycemic activities and could be explored as possible therapeutic agents for type 2 diabetes mellitus., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

A strategy combining chemical UPLC-MS profiling and multivariate classification techniques has been used for the comparison of raw and processed Aconiti Lateralis Radix. UPLC-MS was used to identify 18 characteristic compounds, which were selected for discrimination of the raw and two processed products (Heishunpian and Baifupian). Chemometric analyses, including the combination of a heat map and hierarchical cluster analysis (HCA) and principal component analysis (PCA), were used to visualize the discrimination of raw and two processed products. HCA and PCA provided a clear discrimination of raw Aconiti Lateralis Radix, Heishunpian and Baifupian. Finally, the counter-propagation artificial neural network (CP-ANN) was applied to confirm the results of HCA, PCA and to explore the effect of 18 compounds on samples differentiation and the rationality of processing. The results showed that this strategy could be successfully used for comparison of raw and two processed products of Aconiti Lateralis Radix, which could be used as a general procedure to compare herbal medicines and related processed products to elaborate the rationality of processing from the perspective of chemical composition., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: Xin-Ke-Shu (XKS), a patent medicine consisting of five commonly used traditional Chinese herbs, is used for the treatment of coronary heart diseases. A previous study showed that XKS has protective effects for ameliorating myocardial ischemia/reperfusion (I/R) injury., Purpose: This study was aimed to deeply understand the mechanisms and compatible principle of XKS against hypoxia/reoxygenation (H/R) injury and the contribution of each single herb to the efficacy of XKS., Methods: An H/R model in H9c2 cardiomyocytes was applied to mimic I/R injury observed in vivo. The cell viability, the levels of LDH, MDA, SOD, and apoptosis were determined to evaluate the cardioprotection of XKS and its subtracted formula (knocked out one herb) in H/R injury. Cell metabolomics, combined with western blot analysis, was performed to uncover the inert molecular mechanism of XKS against H/R injury., Results: Significant protective effects of XKS against oxidative stress and apoptosis induced by H/R injury were found in the pharmacodynamic evaluation. Moreover, the metabolic profile deviation of the H/R group from the control group was mainly ascribed to thirteen metabolites involved in four aberrant pathways, in which sphingolipid metabolism was revealed as the most relevant pathway involved in H/R injury (impact > 0.1). Notably, the accumulation of phytosphingosine (VIP = 5.84) was considered the most likely characteristic in H/R injury, which is well known to promote the opening of the mitochondrial permeability transition pore (mPTP) and activate cell apoptosis. Furthermore, XKS ameliorated all the abnormalities of the metabolic network in response to H/R injury. In agreement with this, a western blot analysis showed that XKS markedly regulated the over-expression of CaMK II and cleaved caspase-3. However, the subtracted formula showed no significant difference in comparison with the XKS group on protecting H/R injury except for QDS (subtracted Dan-Shen from XKS)., Conclusion: The roots of Salvia miltiorrhiza Bge. (Dan-Shen) play an important role in the regulation of Ca 2+ overloading, oxidative stress and apoptosis in H/R injury. Our study enabled information from holistic cell metabolomics to be used for mechanism and compatibility rule elucidations of TCMs., (Copyright © 2018. Published by Elsevier GmbH.)

Phellodendri Chinensis Cortex (PCC) and Phellodendri Amurensis Cortex (PAC) are increasingly being used as traditional herbal medicines, but they are often mistaken for each other. In this study, the fingerprints of PCC from six different geographical sources were obtained by high-performance liquid chromatography, and multivariate chemometric methods were used for comprehensive analysis. Two unsupervised pattern recognition models (principal component analysis and hierarchical cluster analysis) and a supervised pattern recognition model (partial least squares discriminant analysis) were established on the basis of the chemical composition and physical traits of PCC and PAC. PCC and PAC were found to be distinguishable by these methods. The PCC category was divisible into two categories, one with more crude cork and a maximum thickness of ~1.5 mm, and the other with less net crude cork and a maximum thickness of 0.5 mm. According to the model established by partial least squares discriminant analysis (PLS-DA), the important chemical marker berberine hydrochloride was obtained and analyzed quantitatively. From these results combined with chemometric and content analyses, the preliminary classification standards for phellodendron were established as three grades: superior, first-order and mixed. Compared with the traditional identification methods of thin layer chromatography identification and microscopic identification, our method for quality evaluation is relatively simple. It provides a basis and reference for identification of PCC and enables establishment of grade standards. It also could be applied in quality control for compound preparations containing PCC.

Myocardial infarction (MI) occurs during a sustained insufficient blood supply to the heart, eventually leading to myocardial necrosis. Xin-Ke-Shu tablet (XKS) is a prescription herbal compound and a patented medicine extensively used in the clinical treatment of coronary heart disease (CHD). To understand the molecular mechanism of the XKS action against MI in detail, it is necessary to investigate the altered metabolome and related pathways coincident with clinical features. In this study, tissue-targeted metabonomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) were developed to explore the metabolic changes associated with XKS treatment in the heart tissue of rats with MI induced by a left anterior descending coronary artery ligation (LAD). The metabolic disorder induced by LAD was alleviated after low-dose XKS (LD) and intermediate-dose XKS (MD) treatment. XKS modulated six perturbed metabolic pathways. Among them, inhibition of Ca 2+ overload and dysfunction of fatty acid β-oxidation-related metabolic pathways likely underlie the therapeutic effects of XKS against MI. In agreement with its observed effect on metabolite perturbation, XKS reversed the over-expression of the four key proteins, long-chain acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyl transferase-1 (CPT1B), calcium/calmodulin-dependent kinase II (CaMKII), and phospholipase A2IIA (PLA2IIA). Both metabolite and protein changes suggested that XKS exerts its therapeutic effect on metabolic perturbations in LAD-induced MI mainly by inhibiting the Ca 2+ overload and fatty acid β-oxidation dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this work, a strategy was proposed to discriminate Polygoni Multiflori Radix (PMR) and its adulterant (Cynanchi Auriculati Radix, CAR). Ultra-high performance liquid chromatography (UHPLC) fingerprints were established to analyze samples containing PMR, CAR and mixtures simultaneously. Multivariate classification methods were applied to analyze the obtained UHPLC fingerprints, including principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), soft independent modeling of class analogy (SIMCA), support vector machine discriminant analysis (SVMDA) and counter-propagation artificial neural network (CP-ANN). A plot of PCA score showed that PMR and CAR samples belonged to separate clusters (PMR class and CAR class), and samples of mixtures were located near PMR or CAR classes. Analysis by PLS-DA, SVMDA and CP-ANN performed well for recognition and prediction in terms of PMR and CAR samples. Moreover, the PLS-DA method performed best in the detection of adulterated samples, even if the adulterant was about 25%., (Copyright © 2017 John Wiley & Sons, Ltd.)

Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection. At first, the stability of HSYA in solution and in a Xuebijing injection was investigated, then the mechanisms of the increased stability of HSYA in the XBJ injection were investigated to provide useful information on clinical safety. HSYA stability was investigated as a function of pH and temperature in aqueous solution and an XBJ injection, following the guidelines from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Products were identified by UPLC-MS/MS. HSYA reaction followed first-order kinetics under all conditions. The half-life of HSYA in XBJ was almost 40 times longer than in aqueous solution. The activation energies of HSYA reaction in aqueous solution and XBJ were calculated to be 78.53 and 92.90 kJ∙mol -1 by using Arrhenius equation. The results indicated that HSYA was more stable in XBJ than in aqueous solution. Two products were identified and the mechanism was intra-molecular nucleophilic substitution. The excellent stability of HSYA in XBJ injection partly due to the micelles formed in the injection. The study may provide clues for compatibility in TCM prescription and also provide useful information for further preparation technology research of HSYA and assessment of clinical safety of XBJ., Competing Interests: The authors declare no conflict of interest.

Preclinical Research Baogan Yihao (BGYH) is a traditional Chinese herbal medicine for the treatment of chronic liver diseases. In this study, the effects of BGYH on dimethylnitrosamine (DMN)-induced liver fibrosis were investigated using a rat model. BGYH alleviate liver damage, as indicated by decreased levels of AST, ALT, γ-GT, and AKP. BGYH also prevented collagen deposition and reduced pathological tissue injury in liver tissue. In fibrosis, high levels of α-SMA and TGF-β in liver tissue were markedly attenuated by BGYH. The inhibitory effect of BGYH on HSC-T6 proliferation demonstrated that BGYH exhibited significant hepatoprotective and antifibrogenic effects on DMN-induced liver injury. These findings suggest that BGYH may have therapeutic potential in the prevention and therapy of liver fibrosis. Drug Dev Res 78 : 155-163, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Xue-Zhi-Ning (XZN) is a widely used traditional Chinese medicine formula to treat hyperlipidemia. Recently, cyclodextrins (CDs) have been extensively used to minimize problems relative to medicine bioavailability, such as low solubility and poor stability. The objective of this study was to determine the associated-extraction efficiency of various CDs in XZN. Three various type CDs were evaluated, including native CDs (α-CD, β-CD), hydrophilic CD derivatives (HP-β-CD and Me-β-CD), and ionic CD derivatives (SBE-β-CD and CM-β-CD). An ultra high-performance liquid chromatography (UHPLC) fingerprint was applied to determine the components in CD extracts and original aqueous extract (OAE). A counterpropagation artificial neural network (CP-ANN) was used to analyze the components in different extracts and compare the selective extraction of various CDs. Extraction efficiencies of the various CDs in terms of extracted components follow the ranking, ionic CD derivatives>hydrophilic CD derivatives>native CDs>OAE. Besides, different types of CDs have their own selective extraction and ionic CD derivatives present the strongest associated-extraction efficiency. Antioxidant potentials of various extracts were evaluated by determining the inhibition of spontaneous, H2O2-induced, CCl4-induced and Fe(2+)/ascorbic acid-induced lipid peroxidation (LPO) and analyzing the scavenging capacity for DPPH and hydroxyl radicals. The order of extraction efficiencies of the various CDs relative to antioxidant activities is as follows: SBE-β-CD>CM-β-CD>HP-β-CD>Me-β-CD>β-CD>α-CD. It can be demonstrated that all of the CDs studied increase the extraction efficiency and that ionic CD derivatives (SBE-β-CD and CM-β-CD) present the highest extraction capability in terms of amount extracted and antioxidant activities of extracts., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To optimize the vinegar processing technique of Euphorbia pekinensis., Method: The test was designed by using orthogonal table L9 (3(4)). The factors were vinegar amount, proportion of vinegar and water and duration and degree of heating. An aggregative weighted method was used to optimize processing technology of E. pekinensis with content of euphol, extract of ethanol, extract of water and appearance and section were used as evaluative indicators., Result: The optimal processing of E. pekinensis was identified as adding the mixture of 30 g vinegar and 270 g water to 100 g herbs, mixing evenly and softening, cooking until exhaustion under slow fire, taking out and drying to degree 6-7, and then cutting into thick slices., Conclusion: The study defines parameters of the processing technique of E. pekinensis. The quality of E. pekinensis is stable and controllable under the technical conditions.

Objective: To optimize the stir-baking with vinegar technology for Curcumae Radix., Method: The intrinsic quality (the content of Curcumin) and traditional outward appearance were chosen as indexes. The best technology was determined by orthogonal test L9 (3(4)). The factors of the moistening time, stir-baking temperature and stir-baking time were investigated., Result: The optimal technology was as follows: the quantity of vinegar was 10%, the moistening time was 10 min, the stir-baking temperature was 130 degrees C and the stir-baking time was 10 min., Conclusion: The optimal stir-baking with vinegar technology for Curcumae Radix is reasonable, which can be used to guide the standardized production of Curcumae Radix stir-baked with vinegar.