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OBJECTIVE: Sakurasosaponin, a primary bioactive saponin from Aegiceras corniculatum, shows potential as an anti-cancer agent. However, there is a lack of information on its in vivo metabolism. This study aims to profile the in vivo metabolites of sakurasosaponin in rat feces, urine, and plasma after oral administration. An efficient strategy using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was developed, which combined metabolic prediction, multiple mass defects filtering, and highresolution extracted ion chromatograms for rapid and systematic analysis. METHODS: Firstly, a theoretical list of metabolites for sakurasosaponin was developed. This was done by considering the metabolic pathways of saponins. Next, the multiple mass defects filtering method was employed to identify potential metabolites in feces and urine, using the unique metabolites of sakurasosaponin as multiple mass defects filtering templates. Subsequently, a high-resolution extracted ion chromatogram was used to quickly determine the metabolites in rat plasma post-identification in feces and urine. Lastly, the analysis of accurate mass, typical neutral loss, and diagnostic ion of the candidate metabolites was carried out to confirm their structural elucidation, and metabolic pathways of sakurasosaponin in vivo were also proposed. RESULTS: In total, 30 metabolites were provisionally identified in feces, urine, and plasma. Analysis of metabolic pathways revealed isomerization, deglycosylation, oxidation, hydroxylation, sulfate conjugation, glucuronide conjugation, and other related reactions as the primary biotransformation reactions of sakurasosaponin in vivo. CONCLUSION: The findings demonstrate that the designed research strategy effectively minimizes matrix interference, prevents the omission of low-concentration metabolites, and serves as a foundation for the discovery of active metabolites of sakurasosaponin.
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The PI3K/AKT/GSK-3ß signaling pathway plays a pivotal role in numerous physiological and pathological processes, including cell proliferation, apoptosis, differentiation, and metabolic regulation. Aberrant activation of the PI3K/AKT pathway is intricately linked to development of tumor. GSK-3ß, belonging to the serine/threonine protein kinase family, is crucial in the pathogenesis of liver cancer. As a key rate-limiting enzyme in the glucose metabolism pathway, GSK-3ß significantly impacts the growth, proliferation, metastasis, and apoptosis of liver cancer cells. It is also implicated in chemotherapy resistance. Elevated expression of GSK-3ß diminishes the sensitivity of liver cancer cells to chemotherapeutic agents, thereby playing a substantial role in the development of drug resistance. Consequently, targeting of GSK-3ß, particularly within the PI3K/AKT signaling pathway, is regarded as a promising therapeutic strategy for liver cancer. The precise identification and subsequent modulation of this pathway represent a substantial potential for innovative clinical interventions in the management of liver cancer.
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Gnetum montanum Markgr. (Gnetaceae) is a commonly used traditional herbal medicine among the Yao ethnic group, with potential effects in preventing and treating tumors. However, the substance basis of its anti-tumor properties remains unclear. This study utilized ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to identify the chemical components of G. montanum extract (GME) and its absorbed prototypes in cynomolgus monkey plasma after oral administration. A total of 57 compounds were detected in the GME, with 14 compounds in positive ion mode and 43 compounds in negative ion mode. In the cynomolgus monkey plasma, 17 compounds were identified, with 3 compounds in positive ion mode and 14 compounds in negative ion mode. Subsequently, we utilized high content screening technology to investigate the anti-tumor effects of GME on colon cancer, lung cancer, breast cancer, gastric cancer, liver cancer, and esophageal cancer. We found that the GME exhibited significant proliferation inhibition on colon cancer cells SW480, with an IC50 value of 50.77⯵g/mL. Further research using component separation and pharmacological tracking revealed that the F2 component of the GME demonstrated notable anti-tumor effects. Through UPLC-MS identification, the chemical components in the F2 fraction were identified as pinoresinol diglucoside, (+)-pinoresinol-4-O-beta-D-glucopyranoside, ursolic acid, and gnetol. In conclusion, this study contributes to elucidating the anti-tumor pharmacological basis of GME and provides robust support for future drug design and development.
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Antineoplásicos Fitogênicos , Macaca fascicularis , Extratos Vegetais , Animais , Administração Oral , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/sangue , Humanos , Linhagem Celular Tumoral , Masculino , Proliferação de Células/efeitos dos fármacos , Espectrometria de Massas/métodos , Feminino , Espectrometria de Massas em Tandem/métodosRESUMO
Diabetic cardiomyopathy (DCM) is a specific heart condition in diabetic patients, which is a major cause of heart failure and significantly affects quality of life. DCM is manifested as abnormal cardiac structure and function in the absence of ischaemic or hypertensive heart disease in individuals with diabetes. Although the development of DCM involves multiple pathological mechanisms, mitochondrial dysfunction is considered to play a crucial role. The regulatory mechanisms of mitochondrial dysfunction mainly include mitochondrial dynamics, oxidative stress, calcium handling, uncoupling, biogenesis, mitophagy, and insulin signaling. Targeting mitochondrial function in the treatment of DCM has attracted increasing attention. Studies have shown that plant secondary metabolites contribute to improving mitochondrial function and alleviating the development of DCM. This review outlines the role of mitochondrial dysfunction in the pathogenesis of DCM and discusses the regulatory mechanism for mitochondrial dysfunction. In addition, it also summarizes treatment strategies based on plant secondary metabolites. These strategies targeting the treatment of mitochondrial dysfunction may help prevent and treat DCM.
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It is well-known that the hepatotoxicity of drugs can significantly influence their clinical use. Despite their effective therapeutic efficacy, many drugs are severely limited in clinical applications due to significant hepatotoxicity. In response, researchers have created several machine learning-based hepatotoxicity prediction models for use in drug discovery and development. Researchers aim to predict the potential hepatotoxicity of drugs to enhance their utility. However, current hepatotoxicity prediction models often suffer from being unverified, and they fail to capture the detailed toxicological structures of predicted hepatotoxic compounds. Using the 56 chemical constituents of Gardenia jasminoides as examples, we validated the trained hepatotoxicity prediction model through literature reviews, principal component analysis (PCA), and structural comparison methods. Ultimately, we successfully developed a model with strong predictive performance and conducted visual validation. Interestingly, we discovered that the predicted hepatotoxic chemical constituents of Gardenia possess both toxic and therapeutic effects, which are likely dose-dependent. This discovery greatly contributes to our understanding of the dual nature of drug-induced hepatotoxicity.
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ETHNOPHARMACOLOGICAL RELEVANCE: Lablab Semen Album (lablab), the white and dried mature fruit of Lablab purpureus in the Lablab genus of the Fabaceae family, is a renowned traditional medicinal herb with a long history of use in China. In Chinese medicine, lablab is often combined with other drugs to treat conditions such as weak spleen and stomach, loss of appetite, loose stools, excessive leucorrhoea, summer dampness and diarrhea, chest tightness, and abdominal distension. MATERIALS AND METHODS: Comprehensive information on lablab was gathered from databases including Web of Science, Science Direct, Google Scholar, Springer, PubMed, CNKI, Wanfang, and ancient materia medica. RESULTS: Lablab, a member of the lentil family, thrives in warm and humid climates, and is distributed across tropical and subtropical regions worldwide. Traditionally, lablab is used to treat various ailments, such as spleen and stomach weakness, loss of appetite, and diarrhea. Phytochemical analyses reveal that lablab is a rich source of triterpenoid saponins, glucosides, volatile components, polysaccharides, and amino acids. Lablab extracts exhibit diverse biological activities, including hypolipidemic, hypoglycemic, immunomodulatory, antioxidant, hepatoprotective, antitumoral, antiviral properties, and more. Besides its medicinal applications, lablab is extensively used in the food industry due to its high nutrient content. Additionally, the quality of lablab can be regulated by determining the levels of key chemical components pivotal to its medicinal effects, ensuring the herb's overall quality. CONCLUSION: Lablab is a promising medicinal and edible plant ingredient with diverse pharmacological effects, making it a valuable ingredient for food, pharmaceuticals, and animal husbandry. However, it has inherent toxicity if not properly prepared. Additionally, some traditional uses and pharmacological activities lack scientific validation due to incomplete methods, unclear results, and insufficient clinical data. Thus, further in vivo and in vitro studies on its pharmacology, pharmacokinetics, and toxicology, along with clinical efficacy evaluations, are needed to ensure lablab's safety and effectiveness. As an important traditional Chinese medicine, lablab deserves more attention.
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Etnofarmacologia , Controle de Qualidade , Humanos , Animais , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , FitoterapiaRESUMO
OBJECTIVE: This study aimed to improve the efficiency of pharmacotherapy for CNS diseases by optimizing the ability of drug molecules to penetrate the Blood-Brain Barrier (BBB). METHODS: We established qualitative and quantitative databases of the ADME properties of drugs and derived characteristic features of compounds with efficient BBB penetration. Using these insights, we developed four machine learning models to predict a drug's BBB permeability by assessing ADME properties and molecular topology. We then validated the models using the B3DB database. For acyclovir and ceftriaxone, we modified the Hydrogen Bond Donors and Acceptors, and evaluated the BBB permeability using the predictive model. RESULTS: The machine learning models performed well in predicting BBB permeability on both internal and external validation sets. Reducing the number of Hydrogen Bond Donors and Acceptors generally improves BBB permeability. Modification only enhanced BBB penetration in the case of acyclovir and not ceftriaxone. CONCLUSIONS: The machine learning models developed can accurately predict BBB permeability, and many drug molecules are likely to have increased BBB penetration if the number of Hydrogen Bond Donors and Acceptors are reduced. These findings suggest that molecular modifications can enhance the efficacy of CNS drugs and provide practical strategies for drug design and development. This is particularly relevant for improving drug penetration of the BBB.
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Aciclovir , Barreira Hematoencefálica , Aprendizado de Máquina , Permeabilidade , Barreira Hematoencefálica/metabolismo , Humanos , Aciclovir/farmacocinética , Ligação de Hidrogênio , Ceftriaxona/farmacocinética , Fármacos do Sistema Nervoso Central/farmacocinética , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/metabolismo , Desenho de FármacosRESUMO
OBJECTIVE: This study aims to explore the impact of ADME on the Oral Bioavailability (OB) of drugs and to construct a machine learning model for OB prediction. The model is then applied to predict the OB of modified berberine and atenolol molecules to obtain structures with higher OB. METHODS: Initially, a drug OB database was established, and corresponding ADME characteristics were obtained. The relationship between ADME and OB was analyzed using machine learning, with Morgan fingerprints serving as molecular descriptors. Compounds from the database were input into Random Forest, XGBoost, CatBoost, and LightGBM machine learning models to train the OB 7prediction model and evaluate its performance. Subsequently, berberine and atenolol were modified using Chemdraw software with ten different substituents for mono-substitution, and chlorine atoms for a full range of double substitutions. The modified molecular structures were converted into the same format as the training set for OB prediction. The predicted OB values of the modified structures of berberine and atenolol were compared. RESULTS: An OB database of 386 drugs was obtained. It was found that smaller molecular weight and a higher number of rotatable bonds (ten or less) could potentially lead to higher OB. The four machine learning models were evaluated using MSE, R2 score, MAE, and MFE as metrics, with Random Forest performing the best. The models' predictions for the test set were particularly accurate when OB ranged from 30% to 90%. After mono-substitution and double substitution of berberine and atenolol, the OB of both drugs was significantly improved. CONCLUSIONS: This study found that some ADME properties of molecules do not have an absolute impact on OB. The database played a decisive role in the process of the machine learning OB prediction model, and the performance of the model was evaluated based on predictions within a range of strong generalization ability. In most cases, mono-substitution and double substitution were beneficial for enhancing the OB of berberine and atenolol. In summary, this study successfully constructed a machine learning regression prediction model that can accurately predict drug OB, which can guide drug design to achieve higher OB to some extent.
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Atenolol , Berberina , Disponibilidade Biológica , Aprendizado de Máquina , SoftwareRESUMO
Objective: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. Results: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. Conclusion: Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.
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Tumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour's microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation-an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour's inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1ß), transforming growth factor-beta (TGF-ß), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin's novel model of "state-target differentiation" and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state â phlegm state â stagnation state â deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy-a harmonious integration of state identification, target recognition, and simultaneous regulation-aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice.
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As a neurodegenerative disease, Alzheimer's disease (AD) is characterized by synaptic loss, extracellular plaques of amyloid accumulation, hyperphosphorylation of tau, and neuroinflammation. Various biological processes are affected by epitranscriptomic modifications, which regulate the metabolism of mRNA in cells and regulate the expression of genes. In response to changes in m6A modification levels, the nervous system becomes dysfunctional and plays a significant role in the development of Alzheimer's disease. As a result of recent research, this paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of AD. In addition, the article discusses recent research techniques related to animal models of m6A and AD. Furthermore, it discusses the possibility of studying the pathogenesis of AD at the level of the epitranscriptome, identifying early diagnostic markers, and screening for effective treatment options.
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Aquaporins (AQPs) are a family of transmembrane proteins expressed in various organ systems. Many studies have shown that the abnormal expression of AQPs is associated with gastrointestinal, skin, liver, kidneys, edema, cancer, and other diseases. The majority of AQPs are expressed in the digestive system and have important implications for the physiopathology of the gastrointestinal tract as well as other tissues and organs. AQP regulators can prevent and treat most gastrointestinal-related diseases, such as colorectal cancer, gastric ulcer, and gastric cancer. Although recent studies have proposed clinically relevant AQP-targeted therapies, such as the development of AQP inhibitors, clinical trials are still lacking and there are many difficulties. Traditional Chinese medicine (TCM) has been used in China for thousands of years to prevent, treat and diagnose diseases, and is under the guidance of Chinese medicine (CM) theory. Herein, we review the latest research on the regulation of AQPs by TCMs and their active components, including Rhei Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Salviae miltiorrhizae Radix et Rhizoma, Poria, Astragali radix, and another 26 TCMs, as well as active components, which include the active components include anthraquinones, saponins, polysaccharides, and flavonoid glycosides. Through our review and discussion of numerous studies, we attempt to explore the regulatory effects of TCMs and their active components on AQP expression in the corresponding parts of the body in terms of the Triple Energizer concept in Chinese medicine defined as "upper energizer, middle energizer, and lower energizer,"so as to offer unique opportunities for the development of AQP-related therapeutic drugs for digestive system diseases.
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Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, ß-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".
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In recent years, activation of thermal transient receptor potential (TRP) ion channels at a range of temperatures has received widespread attention as a target for traditional Chinese medicine (TCM) to regulate body temperature and relieve pain. Discovery of transient receptor potential vanilloid 1 (TRPV1) was awarded a Nobel Prize, reflecting the importance of these channels. Here, the regulatory effects of TCMs and their active ingredients on TRP ion channels are reviewed, and future directions for research on the cold, hot, warm, cool, and neutral natures of TCMs are considered. In herbs with cold, hot, warm, cool, and neutral natures, we found 29 TCMs with regulatory effects on TRP ion channels, including Cinnamomi Cortex, Capsici Fructus, Rhei Radix et Rhizoma, Macleayae cordatae Herba, Menthae Haplocalycis Herba, and Rhodiolae Crenulatae Radix et Rhizoma. Although some progress has been made in understanding the regulation of TRP ion channels by TCMs and their ingredients, the molecular mechanism by which TCMs have this effect remains to be further studied. We hope this review will provide a reference for further research on the cold, hot, warm, cool, and neutral natures of TCMs.
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Tetrandrine (Tet), derived from the traditional Chinese herb Fangji, is a class of natural alkaloids with the structure of bisbenzylisoquinoline, which has a wide range of physiological activities and significant pharmacfological effects. However, studies and clinical applications have revealed a series of drawbacks such as its poor water solubility, low bioavailability, and the fact that it can be toxic to humans. The results of many researchers have confirmed that chemical structural modifications and nanocarrier delivery can address the limited application of Tet and improve its efficacy. In this paper, we summarize the anti-tumor efficacy and mechanism of action, anti-inflammatory efficacy and mechanism of action, and clinical applications of Tet, and describe the progress of Tet based on chemical structure modification and nanocarrier delivery, aiming to explore more diverse structures to improve the pharmacological activity of Tet and provide ideas to meet clinical needs.
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The species of Camellia nitidissima Chi (CC) and C. euphlebia Merr. ex Sealy (CE) are two most important plant sources for commercialized herbal tea (Jinhuacha) worldwide. However, some other species of camellia genus are also sold as alternatives in market due to the great commercial value. In this study, the similarity and difference of CC and CE as well as C.insularis (CI) are comprehensively compared both in chemistry and pharmacology. Based on the ultraperformance liquid chromatography coupled with a hybrid quadrupole orthogonal time-of-flight mass spectrometer(UPLC-QTOF-MS) analysis, a sequential-optimization based new statistical model has been developed by combining the untargeted metabolomics and fingerprint analyses, and successfully applied for chemical pattern recognition and discrimination of three yellow camellias species. The results indicated that CC, CE and CI could be well discriminated with the optimized chemical combination including quercetin-3-O-rhamnoside (C2), okicamelliaside (C4), Kaempferol 7-O-rhamnoside (C6), Corymboside (C9), asiatic acid-glc-rha-xyl (C11) and 3'-methy-4'-glucoside-ellagic acid (C14). Moreover, the 30 % ethanolic extracts of yellow camellias species presented the optimal activities on anti-inflammation/anti-oxidation in LPS-stimulated Raw264.7 macrophages dose-dependently. The averaged 50 % inhibitory concentrations (IC50) on NO production were 754.68 ± 50.96, 1182.39 ± 22.10, 1527.83 ± 106.24 µg(herb)/mL, and ROS production were 311.70 ± 26.57, 332.64 ± 25.46, 917.60 ± 41.36 µg(herb)/mL for CC, CE and CI, respectively. The results indicated a certain similarity of CC and CE, as well as their significant difference from CI.
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Antioxidantes , Camellia , Anti-Inflamatórios/farmacologia , Antioxidantes/análise , Antioxidantes/farmacologia , Cromatografia Líquida , Metabolômica/métodosRESUMO
In this study, we proposed an integrated analytical strategy for the rapid and comprehensive discovery of a specific class of secoiridoid glycosides from a Yao medicine, Jasminum pentaneurum Hand.-Mazz. The strategy fully took advantage of the accuracy of ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry, and the efficiency of diagnostic ion filtering and neutral loss filtering. Twenty-four secoiridoid glycosides, including three known ones and 21 unreported ones, were rapidly discovered and characterized based on the detail analysis of their mass spectrometry data. Particularly, 10-syringicoyl-ligustroside (18) was isolated under the guidance of mass spectrometry analysis. Its chemical structure was elucidated on the basis of extensive spectroscopic data analysis, and absolute configuration was further elucidated by comparison of its experimental and electronic circular dichroism spectra. Furthermore, the mass spectrometry data of 18 was analyzed and the corresponding results indicated that its fragment pathway was fully consistent with the applied diagnostic ion filtering and neutral loss filtering rules, and thus the precision and efficiency of the integrated strategy were validated. The result demonstrated that the proposed integrated strategy could serve as a rapid, accurate, and comprehensive targeted components discovery method to effectively screen out those ingredients of interest from the complex herbal medicines.
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Medicamentos de Ervas Chinesas , Jasminum , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Medicamentos de Ervas Chinesas/análise , Glicosídeos Iridoides/análise , Espectrometria de Massas em Tandem/métodosRESUMO
AIMS: In this study, we aim to establish an integrated research strategy for the rapid chemical profiling of Compound Huanggen Granules (CHG) and absorbed prototypes in plasma by integrating the UHPLC-Q-TOF-MSE method and data post-processing strategy, to provide some valuable research basis for the further studies on the quality control, pharmacokinetics and pharmacodynamics of CHG. BACKGROUND: Compound Huanggen Granules (CHG), a traditional Chinese medicine (TCM) hospital preparation, has long been used in clinical practice for the prevention and treatment of liver fibrosis. However, due to the lack of in vitro chemical and in vivo metabolism studies, its pharmacodynamic material basis is still unrevealed. OBJECTIVE: To simplify the mass data post-processing process and enhance the structural identification efficiency by reducing the possibility of false positive, and rapidly identify the absorbed prototypes in plasma after oral administration of CHG. METHODS: An analytical strategy integrating ultra high-performance liquid chromatography coupled with quadrupletime- of-flight mass spectrometry (UHPLC-Q-TOF-MSE, E represents collision energy) method and data postprocessing strategy based on a self-built in-house components database was established and utilized for the rapid characterization of the multi-constituents of CHG and prototypes in cynomolgus monkey plasma after oral administration. RESULTS: As a result, a total of 81 compounds, including 14 phenolic acids, 6 coumarins, 25 flavonoids, 5 anthraquinones, 5 phenylpropanoids, 15 triterpenoid saponins, and 11 others, were plausibly or unambiguously identified based on their accurate masses, and MS/MS fragment pathways analysis, and also by comparison of retention time and MS data with reference standards. In the in vivo study, according to the extracted ion chromatograms (EICs) of identified components, 34 absorbed prototypical components were rapidly identified in cynomolgus monkey plasma after oral administration. CONCLUSION: It was demonstrated that the data post-processing strategy applied in this study could greatly simplify the data post-processing process and enhance the structural identification efficiency by reducing the possibility of false positives, and the results obtained might be helpful for further studies on the quality control, pharmacokinetics and pharmacodynamics of CHG.
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Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem , Animais , Macaca fascicularisRESUMO
Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and ß-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.