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Background: Myocardial injury (MI) after acute ischemic stroke (AIS) poses a significant threat to patient prognosis. However, effective intervention strategies are currently lacking., Purpose: To elucidate the mechanism of MI after AIS and effects of Naoxintong capsule (NXT) therapy., Method: In vivo, after a rat model of middle cerebral artery occlusion (MCAO)-induced MI was established and assessed. NXT was administered prophylactically to evaluate its pharmacodynamic effects and mechanisms. In vitro, a noradrenaline (NA)-induced damage cell model was constructed. Subsequently, the NXT was applied to the cell models to examine its cardioprotective effects and potential mechanisms., Results: The in vivo findings revealed that following MCAO, there was a notable upregulation of TH expression in the rat brain, which subsequently triggered an increase in serum levels of various biomarkers, including AD, NA, AST, cTnT, CK-MB, and NT-proBNP. Histological analysis employing H&E staining and TUNEL assay disclosed significant pathological alterations and an escalation in apoptotic activity within the myocardial tissue. The myocardial tissue exhibited elevated levels of MDA alongside diminished CAT activity. Additionally, a marked increase in the Bax/Bcl-2 ratio, Cytochrome C release, and Caspase-3 activation was observed, all of which are indicative of heightened apoptotic activity. Administration of the NXT intervention successfully attenuated TH expression in the brains of rats subjected to MCAO, consequently leading to a reduction in circulating levels of catecholamines (CAs). NXT also exhibited significant efficacy at ameliorating cardiac oxidative stress and reducing apoptosis. In vitro, stimulation with NA led to an increase in ROS levels and calcium ion concentration in H9c2 cardiomyocytes. However, the administration of NXT has been found to effectively alleviate these adverse effects, thereby protecting H9c2 cardiomyocytes from the deleterious consequences of oxidative stress and calcium dyshomeostasis., Conclusion: Overall, this study has demonstrated that increased CAs synthesis in the brain after AIS in experimental rats led to a surge in circulating CAs, ultimately leading to MI. NXT can alleviate MI due to cerebral ischemia by increasing improving brain catecholamine synthesis, cardiac oxidative stress, and apoptosis., Competing Interests: Declaration of competing interest All authors have approved of the manuscript and agree with submission to your esteemed journal. We declare no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Lanbuzheng (Geum japonicum Thunb. var. chinense Bolle), a plant found in Southwest China, is a traditional Chinese medicine that promotes hematopoiesis and antioxidant functions. Many of its chemical constituents remain unknown, posing challenges both to understanding its pharmacological mechanisms and to conducting quality control research. In this work, ultra-high performance liquid chromatography coupled with quadrupole Exactive Orbitrap high-resolution mass spectroscopy was used for profiling the composition of Lanbuzheng. Using positive ion mass spectrometry data enriched from Lanbuzheng extract, feature-based molecular networking (FBMN) was constructed and associated with Mass2Motifs substructures using MS2LDA. Prediction and validation of unknown constituents of Lanbuzheng using a custom-built compound library, SIRIUS, and network annotation propagation, achieved a semi-automated annotation of the molecular network. Based on the custom-built library comprising 206 compounds and the FBMN clustering results, the constituents in Lanbuzheng primarily include tannins, triterpenes, flavonoids, and phenolics. Using only 65 pre-identified compounds as references, 210 unknown compounds were annotated in various polarity regions of Lanbuzheng. Results of the current work indicate that molecular networks enable the efficient annotation of compounds in complex systems, laying the groundwork for the preliminary identification of pharmacologically active constituents of Lanbuzheng., (© 2024 Wiley‐VCH GmbH.)

In traditional Chinese medicine, the two commodity forms of Cassiae Semen Raw and Prepared Cassiae Semen, exert different clinical applications, in which Prepared Cassiae Semen is commonly used to treat liver and eye diseases. However, the material basis of Raw and Prepared Cassiae Semen remains unclear due to the limited studies on their overall composition and metabolism in vivo. In this study, an integrated analysis strategy based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry was established to systematically screen the prototype and metabolite constituents of Raw and Prepared Cassiae Semen. Automatic matching analysis of metabolites was performed on Compound Discoverer software based on the function of predicting metabolites. Using this strategy, a total of 77 compounds in Raw Cassiae Semen and 71 compounds in Prepared Cassiae Semen were identified. Furthermore, in vivo study, 46 prototype components and 104 metabolites from the Raw Cassiae Semen group and 41 prototype components and 87 metabolites from the Prepared Cassiae Semen group were unambiguously or preliminarily identified in mice (plasma, urine, feces, eye, and liver). This is the first study of chemical component analysis and in vivo metabolite profiling of Raw and Prepared Cassiae Semen., (© 2024 Wiley-VCH GmbH.)

Angong Niuhuang Pill (ANP) is a traditional Chinese medicine (TCM) formula with significant clinical efficacy in the treatment of stroke. Due to its complex composition, little attention has been directed toward the analysis of chemical composition and absorption characteristics of ANP. In this study, a reliable two-dimensional ultra-high-performance liquid chromatography (2D-UHPLC) coupled with quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS) method was established to characterize the chemical constituents in ANP as well as the prototype components and metabolites absorbed in plasma, urine, feces, and brain tissues after oral administration. The prototype components were identified by a high mass accuracy (within 5 ppm) and MS/MS data based on online, local, and ANP self-built databases. The metabolites were predicted and identified using Compound Discoverer metabolic platform. A total of 154 compounds mainly including 37 flavonoids, 35 alkaioids, 19 organic acid, 19 bile acid, 32 terpenoids and 12 others were identified in this way. In addition, 60 prototype components mainly including flavonoids, alkaioids, organic acid, terpenoids and 164 metabolites were confirmed or preliminarily identified in rats. The metabolic pathways phase I reaction (hydration, reduction, oxidation, demethylation, and hydroxylation) and phase II reaction (acetylation, stearyl conjugation, and methylation) for the absorbed constituents were explored and summarized. This is the first systematic and comprehensive chemical characterization in ANP and its metabolism in vivo by 2D-UHPLC-Q-Orbitrap HRMS. This approach provides an effective strategy for the characterization of compounds and metabolites in traditional Chinese medicine formulas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Pharbitidis Semen (the seeds of Ipomoea nil (L.) Roth or Ipomoea purpurea (L.) Roth), a popular traditional Chinese medicine, is also known as "Heichou" or "Baichou" (Chinese: , ). It can purge the bowels, promote diuresis, remove stagnated accumulation, and kill worms. It can be used for treating anasarca with constipation and oliguria; dyspnea and cough caused by retained fluid; abdominal pain because of intestinal parasitosis; ascariasis; and taeniasis., Aims: This review discusses the botany, ethnopharmacology, phytochemistry, pharmacological activities, toxicology, and quality control of Pharbitidis Semen, to obtain a complete understanding of its effects and provide a basis for further research and the development of new drugs., Materials and Methods: The literature on Pharbitidis Semen is mainly obtained from pharmacopoeias of different countries, masterpieces of traditional Chinese medicine, Master's and Ph.D. theses, and published articles obtained from literature retrieval websites, such as CNKI, PubMed, SciFinder, WanFang data, Web of Science, Springer, ScienceDirect, Wiley, ACS Publications, Taylor & Francis, J-STAGE, and Google Scholar. Its botany, ethnopharmacology, phytochemistry, pharmacological activities, toxicology, and quality control are discussed to understand its effects and provide a basis for further research., Results: Pharbitidis semen has been used ethnomedically in many tropical and subtropical countries as deobstruents, diuretics, and anthelmintics. About 170 chemical compounds, including terpenoids, phenylpropanoids, resin glycosides, fatty acids and other compounds, have been isolated. It has been reported to have different effects, including laxative, renal-protective, neuroprotective, insecticidal, antitumor, anti-inflammatory, and antioxidant. Moreover, a brief introduction to processing, toxicity, and quality control is provided., Conclusions: The traditional efficacy of Pharbitidis Semen in diarrhea has been confirmed, but its bioactive and toxic ingredients are not entirely clear. It is necessary to strengthen the research and identification of effective parts or natural active components of Pharbitidis Semen, clarify the molecular mechanism of its toxicity and change rule of endogenous substances to make Pharbitidis Semen better used in clinical practice. Additionally, the imperfect quality standard is also a challenge that must be solved urgently. The study of modern pharmacology has broadened the application of Pharbitidis Semen and provided ideas for better utilization of this resource., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Shengmai San Formula (SMS), composed of Ginseng Radix et Rhizoma, Ophiopogon Radix and Schisandra chinensis Fructus, was a famous formula in Tradition Chinese Medicine (TCM). With the expansion of clinical applications, SMS was developed to different dosage forms, including Shengmai Yin Oral liquid (SMY), Shengmai Capsule (SMC), Shengmai Granule (SMG), Shengmai Injection (SMI) and Dengzhan Shengmai Capsule (DZSMC). These above SMS-derived compound prescriptions (SSCPs) play an important role in the clinical treatment. This review is aimed to providing a comprehensive perspective of SSCP., Methods: The relevant literatures were collected from classical TCM books and a variety of databases, including PubMed, Google Scholar, Science Direct, Springer Link, Web of Science, China National Knowledge Infrastructure, and Wanfang Data., Results: The chemical constituents of SSCPs, arrived from the individual medicinal materials including Ginseng Radix et Rhizoma, Ophiopogon Radix, Schisandra chinensis Fructus, Erigerontis Herba, were firstly summarized respectively. Then the pharmacokinetics studies, quality control, and pharmacological properties of SSCPs were all reviewed. The active compounds, pharmacokinetics characterizes, quality control markers, the effects and mechanisms of pharmacology of the different dosage forms of SSCPs were summarized. Furthermore, the research deficiencies of SSCPs and an innovative research paradigm for Chinese materia medica (CMM) formula were proposed., Conclusions: SMS, as a famous CMM formula, has great values in drug research and in clinical treatment especially for cardiocerebrovascular diseases. This article firstly make a comprehensive and systematic review on SMS., Competing Interests: Declaration of Competing Interest All authors have approved of the manuscript and agree with submission to your esteemed journal. We declare no conflicts of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

A reliable method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to conduct a comprehensive analysis of the chemical constituents of Du-zhi pill (DZP) as well as their metabolites in rat plasma, urine and feces after gastric perfusion. The efficient on-line mass data acquisition modes combined the various off-line mass data mining strategy was applied. A full mass scan was performed, and then accurate MS/MS datasets were obtained through the use of a multiple mass defect filter (MMDF) and dynamic background subtraction (DBS)-dependent data acquisition method. Furthermore, post-acquisition data processing was conducted using various data-mining tools, including extracted ion chromatography (XIC), mass defect filtering (MDF), product ion filtering (PIF), and neutral loss filtering (NLF) (MetabolitePilot™). Finaly, a total of 176 compounds were identified or tentatively characterized in DZP. Moreover, a total of 233 components in vivo, which includes 92 prototype components and 141 metabolites, were unambiguously or tentatively identified in rat plasma, urine and feces. The metabolic pathways, including phase I reactions (hydroxylation, dehydroxylation and hydrogenation) and phase II reactions (acetylation, sulfation, glucuronidation and methylation), for the absorbed constituents, were explored and summarized. This is the first systematic study on the components of DZP and their metabolites in vivo. This study provide a valid analytical strategy for the characterization of chemical compounds and metabolites of TCM formulas. Moreover, an integrative strategy was proposed for the characterization and identification of chemical constituents and metabolites for additional TCM prescriptions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Farfarae Flos (FF; dried flower buds of Tussilago farfara L.), a widely used traditional Chinese medicine (TCM), is also known as "Kuandonghua" (Chinese: ). It has a wide range of pharmacological effects and has long been used to treat various respiratory conditions including cough, asthma, and acute or chronic bronchitis., Aims: This study reviews the current advances in the research on the botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology of Farfarae Flos. Prospects for future investigation and application of this herb are also discussed., Materials and Methods: Information on FF was collected from both published materials (such as ancient and modern books, Ph.D. and M. Sc. dissertations, monographs on medicinal plants, and pharmacopoeia) and electronic databases (such as CNKI, SciFinder, WanFang data, PubMed, ScienceDirect, Web of Science, Taylor&Francis, ACS Publications, Wiley, Springer, Europe PMC, EBSCOhost, J-STAGE, and Google Scholar)., Results: Approximately 175 chemical compounds, including terpenoids, organic acids, flavonoids, alkaloids, chromones, volatile oils, and other compounds, have been isolated from FF. This TCM has been reported to produce pharmacological effects on the respiratory, cardiovascular, and digestive systems, and exert antioxidant, anti-inflammatory, and neuroprotective activities. FF is safe in the traditional dose range, but the potential toxicity due to the emergence of pyrrolidine alkaloids needs to be paid more attention., Conclusions: FF is a commonly used TCM with pharmacological activities mainly on the respiratory system. This study suggests that the further expansion of the pharmacological effect of FF and in-depth study of its prescription need to be concerned about. The investigations of the role of more active substances and the pharmacokinetics of the hepatotoxic components of FF will help to maximize the therapeutic potential and promote its popularization and application. Meanwhile, it is important to pay attention to pursue research on the similarities and differences between the leaves and the flower buds to find their respective advantages and make rational use of T. farfara L., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Magnoliae Officinalis Cortex (the dried bark of Magnolia officinalis), a widely used traditional Chinese medicine, is also known as 'Houpo' (Chinese: ). Magnoliae Officinalis Cortex has a wide range of pharmacological effects and has been used to treat conditions such as abdominal distention, vomiting, diarrhea, food accumulation, Qi stagnation, constipation, phlegm and fluid retention and cough resulting from asthma., Aims of the Review: The present paper reviews advances in research relating to the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Magnoliae Officinalis Cortex. Prospects for future investigation and application of this herb are also discussed., Materials and Methods: Information on Magnoliae Officinalis Cortex was obtained from published materials, including ancient and modern books; PhD and MSc dissertations; monographs on medicinal plants; the pharmacopoeia of different countries and electronic databases, such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, AGRIS, Europe PMC, EBSCO host, CNKI, WanFang DATA, J-STAGE and Google Scholar., Results: More than 200 chemical compounds have been isolated from Magnoliae Officinalis Cortex, including lignans, phenylethanoid glycosides, phenolic glycosides, alkaloids, steroids and essential oils. The plant has been reported to have pharmacological effects on the digestive system, nervous system and cardiovascular and cerebrovascular systems, as well as antibacterial, anti-tumour, analgesic, anti-inflammatory and anti-oxidative effects., Conclusions: Magnoliae Officinalis Cortex is an essential traditional Chinese medicine with pharmacological activities that mainly affect the digestive system, nervous system and cardiovascular and cerebrovascular systems. This review summarises its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. These information suggest that we should focus on the development of new drugs related to Magnoliae Officinalis Cortex, including specific constituents, so that Magnoliae Officinalis Cortex can exert greater therapeutic potential. Meanwhile, it is important to pay attention to the rational use of Magnolia resources, avoiding over-harvesting which could lead to lack of resources. We should also pursue research on Magnolia substitutes and develop resources such as Magnoliae Officinalis Flos and Magnolia Leaf., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Amino acids (AAs) in cerebrospinal fluid (CSF) play a pivotal role in cerebral ischemia (CI). BuChang NaoXinTong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases., Methods: In order to investigate the therapeutic effects and pharmacological mechanisms of BNC on reversing CI from a system level, an amino acid-protein interaction imbalanced network of CI containing metabolites of AAs, key regulatory enzymes, and proteins was constructed for the first time. Furthermore, a novel method for detecting the ten AAs in CSF was developed by UPLC-QQQ-MS in an effort to validate the imbalanced networks and the therapeutic effects of BNC via analysis of metabolites., Results: Based on a middle cerebral artery occlusion (MCAO) rat model, the dynamic levels of amino acids in CSF 3, 6, 12, and 24 h after MCAO were analyzed. Up to 24 h, the accumulated nine AA biomarkers were found to significantly change in the MCAO group compared to the sham group and exhibited an obvious tendency for returning to baseline values after BNC treatment. In addition, based on the imbalanced network of CI, four key enzymes that regulate the generation of BNC-mediated AA biomarkers were selected and validated using an enzyme-linked immunosorbent assay and western blotting. Finally, aromatic-L-amino-acid decarboxylase (AADC) was found to be one of the putative targets for BNC-mediated protection against CI., Conclusion: This study provides new strategies to explore the mechanism of cerebral ischemia and help discover the potential mechanism of BNC.

Ethnopharmacological Relevance: Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury., Aims of the Review: This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed., Materials and Methods: The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI., Results: More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc., Conclusions: Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Buchang Naoxintong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. However, the therapeutic effects and mechanisms are not yet well understood., Materials and Methods: In this study, a UPLC/TOF-MS-based metabolomic study was conducted to explore potential biomarkers that will increase our understanding of cerebral ischemia and to assess the integral efficacy of BNC in a middle cerebral artery occlusion (MCAO) rat model. Plasma metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis., Results: Clear separations were observed between the sham, MCAO and BNC-treated groups. We identified 28 biomarkers in the MCAO rats using variable importance for the projections (VIP) values (VIP>1) and a t-test (P<0.05). The identified biomarkers were mainly related to disturbances in monoamine neurotransmitter metabolism, amino acid metabolism, energy metabolism and lipid metabolism. Moreover, a correlation network diagram of the plasma biomarkers perturbed by MCAO was constructed. Some biomarkers, such as glutamine, PE (17:0), LysoPE (20:1), LysoPE (24:0), and the ratios of LysoPE (24:1) to LysoPE (24:0), LysoPE (24:2) to LysoPE (24:0), showed obvious changes and a tendency for returning to baseline values in BNC-treated MCAO rats. In addition, MCAO rats receiving BNC treatment had improved neurological deficits and reduced cerebral infarct size demonstrating the therapeutic potential of BNC for treating cerebral ischemia., Conclusion: This study provides a useful approach for exploring the mechanism of MCAO-induced cerebral ischemia and evaluating the efficacy of BNC., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics.

Objective: To establish a HPLC method for the simultaneous determination of 4 major components in semen cassiae obtusifoline and provide valuable data for quality control of semen cassiae obtusifoline., Method: Kromasil 100-5 C18 column (4.6 mm x 250 mm, 5 microm). Eluted with water: acetonitrile: tetramethylene oxide: glacial acetic acid (100: 23: 5:1). Detecte at 278 nm. The flow rate was 1.0 mL x min(-1)., Result: Four compositions were separated well. Good linearies were obtained within the range of 0.274-1.37 microg, 0.153-0.765 microg, 0.302-1.51 microg and 0.052-0.26 microg for rubrofusarin gentiobioside, casside, aurantio-obtusin-6-O-beta-D- glucopyranoside, casside B respectively. The average recoveries were 100.9% (RSD 1.8%),101.2% (RSD 1.2%), 99.40% (RSD 2.2%), 100.5% (RSD 1.6%)., Conclusion: The method is accurate, reliable and convenient. It can be used to control the quality of semen cassiae obtusifoline and its products.

Objective: To study on the feasibility of cutting process of fresh Angelica sinensis., Method: Qualitative and quantitative chemical analysis methods were used to evaluate the quality of different cutting processed A. sinensis., Result: The contents of ligustilide and ferulic acid in the fresh cutting processed were both lower than the traditional cutting process, and the similarity of fingerprints of two different cutting processed A. sinensis were basically above 90%., Conclusion: The method of cutting process of fresh A. sinensis was not suitable apparently, and the effect on clinical application of these two different cutting processed A. sinensis need more study.