New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves.

Our continued works on the chemical constituents of Ginkgo biloba (G. biloba) leaves has led to the isolation of two novel phenylbutenoids (1, 2), along with five previously unidentified terpene glycosides (3-7). Among them, compounds 1 and 2 represent unique (Z)-phenylbutenoids, 3-6 are megastigmane glycosides, and 7 is identified as a rare bilobanone glycoside (Fig. 1). This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from G. biloba. The chemical structures of these compounds were elucidated through extensive spectroscopic analysis, including HR-ESI-MS and various 1D and 2D NMR experiments. Furthermore, the absolute configurations of these molecules were determined using Mosher's method, ECD experiments, and Cu-Kα X-ray crystallographic analyses.

UPLC-Q-TOF/MS based metabolite profiling and quality marker constituents screening of root, stem and rhizome extracts of Ilex asprella.

OBJECTIVE: The root of Ilex asprella (RIA) is a popular plant resource for treating inflammation-related diseases. The purpose of this study was to identify the secondary metabolites, to compare anti-inflammatory effects and to determine the quality marker components among root, stem and rhizome sections of IA. METHODS: Chemical fingerprints of stem, root and rhizome of IA was determined by high performance liquid chromatography (HPLC). A reliable method using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for comprehensively determining the chemical constituents of the plants. Anti-inflammatory activities of IA and its ingredients were screened by in vivo mouse ear swelling and in vitro LPS-induced release of NO from RAW264.7 cells experiments. RESULTS: Root, stem and rhizome of IA have shown high similarity in chemical fingerprints. Totally 149 compounds were characterized in IA, including triterpenoids, triterpenoid saponins, phenolic acids and lignans. 44 of them were identified based on co-occurring Mass2Motifs, including 19 unreported ones, whilst 17 were tentatively confirmed by comparison with reference compounds. No significant anti-inflammatory activity difference among root, stem and rhizome parts of IA was found. Ilexsaponin B2, protocatechualdehyde, isochlorogenic acid B and quinic acid, were screened out as quality marker compounds in IA. CONCLUSION: A sensitive and rapid strategy was established to evaluate the differences on secondary metabolites of different parts of IA for the first time, and this study may contribute to the quality evaluation of medicinal herbs and provide theoretically data support for further analysis of different parts of IA.

Identification of chemical components and rat serum metabolites in Danggui Buxue decoction based on UPLC-Q-TOF-MS, the UNIFI platform and molecular networks.

Danggui Buxue Decoction (DBD), consisting of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (Huangqi, HQ) and Angelica sinensis (Oliv.) Diels (Danggui, DG), is a traditional Chinese medicine (TCM) formula with the function of tonifying Qi and promoting blood. In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively identify the chemical constituents in DBD and those entering into the rat serum after gastric perfusion. A combination of the UNIFI platform and Global Natural Product Social molecular networking (GNPS) was used to analyze the chemical composition of DBD. As a result, 207 compounds were unambiguously or tentatively identified including 60 flavonoids, 38 saponins, 35 organic acids, 26 phthalides, 12 phenylpropanoids, 11 amino acids and 25 others. Furthermore, a total of 80 compounds, including 29 prototype components and 51 exogenous metabolites, were detected in the serum of rats. Phase I reactions (oxidation, reduction, and hydration), phase II reactions (methylation, sulfation, and glucuronidation), and their combinations were the main metabolic pathways of DBD. The results provided fundamental information for further studying the pharmacological mechanisms of DBD, as well as its quality control research.

COIMMR: a computational framework to reveal the contribution of herbal ingredients against human cancer via immune microenvironment and metabolic reprogramming.

Immune evasion and metabolism reprogramming have been regarded as two vital hallmarks of the mechanism of carcinogenesis. Thus, targeting the immune microenvironment and the reprogrammed metabolic processes will aid in developing novel anti-cancer drugs. In recent decades, herbal medicine has been widely utilized to treat cancer through the modulation of the immune microenvironment and reprogrammed metabolic processes. However, labor-based herbal ingredient screening is time consuming, laborious and costly. Luckily, some computational approaches have been proposed to screen candidates for drug discovery rapidly. Yet, it has been challenging to develop methods to screen drug candidates exclusively targeting specific pathways, especially for herbal ingredients which exert anti-cancer effects by multiple targets, multiple pathways and synergistic ways. Meanwhile, currently employed approaches cannot quantify the contribution of the specific pathway to the overall curative effect of herbal ingredients. Hence, to address this problem, this study proposes a new computational framework to infer the contribution of the immune microenvironment and metabolic reprogramming (COIMMR) in herbal ingredients against human cancer and specifically screen herbal ingredients targeting the immune microenvironment and metabolic reprogramming. Finally, COIMMR was applied to identify isoliquiritigenin that specifically regulates the T cells in stomach adenocarcinoma and cephaelin hydrochloride that specifically targets metabolic reprogramming in low-grade glioma. The in silico results were further verified using in vitro experiments. Taken together, our approach opens new possibilities for repositioning drugs targeting immune and metabolic dysfunction in human cancer and provides new insights for drug development in other diseases. COIMMR is available at https://github.com/LYN2323/COIMMR.

Integrated transcriptomic and metabolomic profiles reveal the protective mechanism of modified Danggui Buxue decoction on radiation-induced leukopenia in mice.

Leukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs.

Cryptotanshinone alleviates radiation-induced lung fibrosis via modulation of gut microbiota and bile acid metabolism.

Cryptotanshinone (CPT), a major biological active ingredient extracted from root of Salvia miltiorrhiza (Danshen), has shown several pharmacological activities. However, the effect of CPT on radiation-induced lung fibrosis (RILF) is unknown. In this study, we explored the protective effects of CPT on RILF from gut-lung axis angle, specifically focusing on the bile acid (BA)-gut microbiota axis. We found that CPT could inhibit the process of epithelial mesenchymal transformation (EMT) and suppress inflammation to reduce the deposition of extracellular matrix in lung fibrosis in mice induced by radiation. In addition, 16S rDNA gene sequencing and BAs-targeted metabolomics analysis demonstrated that CPT could improve the dysbiosis of gut microbiota and BA metabolites in RILF mice. CPT significantly enriched the proportion of the beneficial genera Enterorhabdus and Akkermansia, and depleted that of Erysipelatoclostridium, which were correlated with increased intestinal levels of several farnesoid X receptor (FXR) natural agonists, such as deoxycholic acid and lithocholic acid, activating the FXR pathway. Taken together, these results suggested that CPT can regulate radiation-induced disruption of gut microbiota and BAs metabolism of mice, and reduce the radiation-induced lung inflammation and fibrosis. Thus, CPT may be a promising drug candidate for treating RILF.

Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice.

Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood. A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria. In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS. Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS. This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system.

Effects of processing on the efficacy and metabolites of Cistanche tubulosa using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Cistanche tubulosa (CT), a well-known traditional Chinese medicine, has always been processed with rice wine for the treatment of kidney-yang deficiency syndrome (KYDS) since time immemorial. To explore the effect of processing on the efficacy and metabolites of CT in vivo, a comprehensive method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was established for the analysis of the altered endogenous metabolites in response to the intervention of the raw and processed CT in KYDS model and the metabolites of the absorbed compounds in rats after gastric perfusion. It was shown that CT could improve KYDS, and the effect of the processed product was more significant. A total of 47 differential metabolites were identified in urine. Pathway analysis proved that purine metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were the main pathways. Furthermore, 53 prototypes and 48 metabolites have been detected in rats. This was the first systematic research focus on the metabolites of raw and processed CT in vivo, which could provide a scientific basis for explaining the increasing efficiency of the processed CT. Moreover, it provides a valuable strategy for analyzing the chemical components and metabolites of other TCM prescriptions.

Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control.

Euodiae Fructus, referred to as "Wuzhuyu" in Chinese, has been used as local and traditional herbal medicines in many regions, especially in China, Japan and Korea, for the treatment of gastrointestinal disorders, headache, emesis, aphtha, dermatophytosis, dysentery, etc. Substantial investigations into their chemical and pharmacological properties have been performed. Recently, interest in this plant has been focused on the different structural types of alkaloids like evodiamine, rutaecarpine, dehydroevodiamine and 1-methyl-2-undecyl-4(1H)-quinolone, which exhibit a wide range of pharmacological activities in preclinical models, such as anticancer, antibacterial, anti-inflammatory, anti-cardiovascular disease, etc. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional uses, phytochemistry, pharmacology of Euodiae Fructus together with the toxicology and quality control, and discusses the possible direction and scope for future research on this plant.

Multi-omics and network pharmacology study reveals the effects of Dengzhan Shengmai capsule against neuroinflammatory injury and thrombosis induced by ischemic stroke.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan Shengmai capsule (DZSM) is a traditional herb medicine used by Dai, an ethnic-minority community living in Xishuang banna tropical rainforest in Southwest of China. It was originally intended to treat disorders caused by insufficient brain function, characterized by gibberish, unresponsiveness, or confusion. Accumulating clinical evidences exhibited that it is effective on treating ischemic stroke (IS). However, the action of DZSM against IS needs to be further elucidated. AIM OF THE STUDY: To investigate the effect of DZSM and its active components against IS and the way of its action by multi-omics and network pharmacology. MATERIALS AND METHODS: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to investigate the effect of DZSM on the focal cerebral ischemia/reperfusion injury. An integrated strategy combining metabolomics, network pharmacology and transcriptomics was performed to systematically clarify the underlying mechanism of action of DZSM against IS. AutoDock Vina was applied to conduct molecular docking simulation for the binding between the potential active compounds and targets. Arachidonic acid (AA) induced platelet aggregation and lipopolysaccharide (LPS) stimulated microglial cells BV2 inflammation models were applied for the in vitro validation of effects of DZSM and its potential active compounds. RESULTS: In MCAO/R rats, DZSM could significantly reduce the infarct volume. Putative target prediction and functional enrichment analysis based on network pharmacological indicated that the key targets and the potential active compounds played important roles in DZSM's treatment to IS. The targets included four common genes (PTGS1, PTGS2, NFKB1 and NR1I2) and five key TFs (NFKB1, RELA, HIF1A, ESR1 and HDAC1), whilst 22 potential active compounds were identified. Molecular docking indicated that good binding affinity have been seen between those compounds and NR1I2, NFKB1, and RELA. Multi-omics study revealed that DZSM could regulate glutamate by influencing citrate cycle and glutamate involved pathways, and have showed neuroprotection activity and anti-inflammation activity by inhibiting NF-κB pathway. Neuroprotective effects of DZSM was validated by regulating of NF-κB signaling pathway and its downstream NO, TNF-α and IL-6 cytokines contributed to the activity of DZSM and its active compounds of scutellarin, quercetin 3-O-glucuronide, ginsenoside Rb1, schizandrol A and 3, 5-diCQA, whilst the antithrombotic activity of DZSM and its active compounds of schisanhenol, apigenin and schisantherin B were screened out by anti-platelet aggregation experiment. CONCLUSION: DZSM could against IS via regulating its downstream NO, TNF-α and IL-6 cytokines through NF-κB signaling pathway and alleviating thrombosis.

Vlasouliodes A-D, four new C30 dimeric sesquiterpenes exhibiting potential inhibition of MCF-7 cells from Vladimiria souliei.

As our ongoing interest to search bioactive dimeric sesquiterpenes from the genus Vladimiria (Asteraceae), the plant of Vladimiria souliei was studied. Based on the repetitive chromatographic fractionation, a chemical investigation on the roots of Vladimiria souliei led to the isolation and the identification of four previously undescribed sesquiterpene dimers, vlasouliodes A-D (1-4). Their chemical structures were elucidated by comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR spectroscopic data. The absolute configurations of them were unambiguously established by the experimental and calculated ECD data. In the in vitro biological activity evaluation, 1 and 3 displayed pronounced inhibitory activity against human breast adenocarcinoma cell lines (MCF-7) with IC50 values of 17.12 ± 0.42 µM and 13.12 ± 0.10 µM, respectively. Additionally, treatment with 1 and 3 induced cell apoptosis in MCF-7 cells, down-regulated the expression of Caspase-3 and up-regulated the expression of Cleaved-caspase-3.

Integrated metabolomics and network pharmacology to reveal the therapeutic mechanism of Dingkun Pill on polycystic ovary syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP), a traditional Chinese medicine prescription, was modified from Bujing decoction and Xusijiangsheng pill by the imperial physician in the Qing dynasty (1700' s). It was believed to treat various gynecological diseases by nourishing qi and blood. Accumulating evidence indicates that it is effective in treating polycystic ovary syndrome (PCOS). However, the therapeutic efficacy and mechanism of action DKP against PCOS need to be further elucidated. AIM OF THE STUDY: To investigate the therapeutic effect and action mechanism of DKP against PCOS using an integrated approach of metabolomics and network pharmacology. MATERIALS AND METHODS: The rat model of PCOS was established by dehydroepiandrosterone. An integrated metabolomics and network pharmacology strategy was applied to systemically clarify the mechanism of DKP against PCOS. Theca cells were prepared to evaluate the effect of DKP and its ingredients on testosterone synthesis in vitro. RESULTS: The pharmacological experiments demonstrated that DKP could effectively convert the disordered estrous cyclicity, decrease the level of testosterone and the luteinizing hormone/follicle stimulating hormone ratio, and inhibit abnormal follicle formation in PCOS rats. By metabolomics analysis, 164 serum endogenous differential metabolites and 172 urine endogenous differential metabolites were tentatively identified. Steroid hormone biosynthesis and ovarian steroidogenesis were the most significantly impacted pathways. Based on network pharmacology and metabolomics studies, the ingredient-target-pathway network of DKP in the treatment of PCOS was constructed. Among the 10 key targets, CYP17A1, CYP19A1, STS, AR, ESR1, and MYC were closely involved in ovarian androgen synthesis. In theca cell-based assay of testosterone synthesis, DKP and its two active compounds (ligustilide and picrocrocin) showed inhibitory effects. CONCLUSION: DKP effectively improved symptoms in rats with dehydroepiandrosterone-induced PCOS. The mechanism of DKP in the treatment of PCOS is related to the CYP17A1 enzyme required for androgen synthesis.

Systematic analysis of chemical profiles of Sophorae tonkinensis Radix et Rhizoma in vitro and in vivo using UPLC-Q-TOF-MSE.

Sophorae tonkinensis Radix et Rhizoma (S. tonkinensis) has been recorded as a 'poisonous' Chinese herbal medicine in Chinese Pharmacopoeia 2020. The clinical reaction reports of S. tonkinensis indicated its neurotoxicity; however, there still exists dispute about its toxic substances. At present, no report is available on the blood and brain prototype research of S. tonkinensis. Most studies focused on alkaloids and less on other compounds. Moreover, the constituents absorbed into the blood and brain have been rarely investigated so far. This study established a rapid and efficient qualitative analysis method using UPLC-Q-TOF-MSE to characterize the ingredients of S. tonkinensis and those entering into the rat's body after oral administration. A total of 91 compounds were identified in S. tonkinensis, of which 28 were confirmed by the standards. In addition, 30 and 19 prototypes were also first identified in the rat's blood and brain, respectively. It was found that most flavonoids, except alkaloids, were detected in the rat's body and distributed in the cerebrospinal fluid, suggesting that flavonoids may be one of the important toxic or effective substances of S. tonkinensis. This finding provides new clues and data for clarifying the toxicity or efficacy of this medicinal plant.

In vivo and in vitro metabolism study of traditional Chinese medicine formula Dingkun Dan in rats by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study.

Simultaneous determination of five bioactive components of XiaoJin Capsule in normal and mammary gland hyperplasia rat plasma using LC-MS/MS and its application to a pharmacokinetic study.

XiaoJin Capsule (XJC) is a classic Traditional Chinese Medicine formula for clinical treatment of thyroid nodules, mammary gland hyperplasia and breast cancer. For the specification and rational application of XJC in the future, an accurate and specific LC-MS/MS method was developed and validated for quantitative determination of five components in rat plasma after oral administration of XJC. The collected plasma samples were extracted by protein precipitation with methanol-acetonitrile (1:3, v/v) mixture solvent and separated on a C18 column using a gradient elution system. Mass spectrometry was performed on a triple quadrupole mass spectrometer, and samples were detected in positive ionization and multiple reactions monitoring mode. The method was properly validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves showed good linearity (r2 > 0.9910) over their concentration ranges. The intra- and inter-day precisions (RSD) were within 11.0%, and the LLOQ was 0.1, 0.2, 0.5, 7.5 and 7.5 ng/ml for aconine, songorine, neoline, 3-acetyl-11-keto-ß-boswellic acid and 11-keto-ß-boswellic acid, respectively. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. This established method was successfully applied to a pharmacokinetics study of five compounds after oral administration of XJC to normal and mammary gland hyperplasia model rats.

Quantitative proteomics reveals Shexiang Baoxin Pill exerts cardioprotective effects by preserving energy metabolism in a rat model of myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Baoxin Pill (SBP) is a composite formula of traditional Chinese medicine used to treat cardiovascular disease (CVD) in the clinic. However, the mechanism of its therapeutic effect on CVD has not been clearly elucidated yet. AIM OF THE STUDY: The aim of this study was to investigate the potential cardioprotective mechanism of SBP in the treatment of myocardial infarction (MI) model rats by applying proteomic approach. MATERIALS AND METHODS: The rat model of MI was generated by ligating the left anterior descending coronary artery. Eighteen rats were randomly divided into three groups (n = 6 each): the MI group, MI group treated with SBP (SBP), and sham-operated group (SOG). Cardiac function in the experimental groups was assessed by echocardiography analyses after 15 days of treatment. A label-free quantitative proteomic approach was utilized to investigate the whole proteomes of heart tissues from the groups above on the day of the operation (Day 0) and 15 days later (Day 15). The differentially expressed proteins were subsequently analyzed with bioinformatic methods. Additionally, the expression levels of two promising proteins were validated by Western blotting. RESULTS: The echocardiography analyses showed that SBP treatment significantly preserved the cardiac function of MI rats. Additionally, quantitative proteomics identified 389 differentially expressed proteins, and 15 proteins were considered as logical candidates for explaining the cardioprotective effect of SBP. Bioinformatic analysis of these differentially expressed proteins revealed that the proteins involved in cellular mitochondrial energy metabolism processes, such as fatty acid beta-oxidation and aerobic respiration, were significantly regulated under SBP treatment, of which fatty acid-binding protein 3 (FABP3) and myoglobin (MB) were significantly downregulated in the MI model group compared with the SOG group and returned to the basal level with SBP treatment, confirmed by Western blotting. CONCLUSIONS: The results of our study suggest that the cardioprotective effects of SBP are achieved through the preservation of energy metabolism in the heart tissue of MI rats.

Chemical profiling of Honghua Xiaoyao tablet and simultaneous determination of its quality markers by liquid chromatography-tandem mass spectrometry combined with chemometrics methods.

Discovering marker components of traditional Chinese medicine formulas is challenging because of the hundreds of components they inherently contain. This study first proposed a reliable and validated method for the comprehensive profiling of chemical constituents in Honghua Xiaoyao tablet by using high-performance liquid chromatography coupled with mass spectrometry. After searching within the in-house library, a total of 55 constituents were unambiguously characterized or tentatively identified through reference standards and by comparing mass spectrometry data with literature values. Quantitative analysis of 14 compounds, which were selected as the quality marker components based on a serum pharmacochemistry study, has been performed by triple-quardrupole mass spectrometry technique. Multiple chemometric methods, including principal components analysis and hierarchical cluster analysis, were subsequently used to analyze the quantitative results, classify samples from three manufacturers, and distinguish the analytical markers. In method validation results, 14 quality marker compounds have shown good linearity (R2 ≥ 0.9965) with a relative wide concentration range and acceptable recovery at 98.39-102.46%. The proposed approach provides the chemical evidence for revealing the material basis of Honghua Xiaoyao tablet, and establishes a reliable statistical analysis-based strategy of quality marker investigation for controlling its quality.

Herba Cistanche (Rou Cong Rong): A Review of Its Phytochemistry and Pharmacology.

Herba Cistanche, known as Rou Cong Rong in Chinese, is a very valuable Chinese herbal medicine that has been recorded in the Chinese Pharmacopoeia. Rou Cong Rong has been extensively used in clinical practice in traditional herbal formulations and has also been widely used as a health food supplement for a long time in Asian countries such as China and Japan. There are many bioactive compounds in Rou Cong Rong, the most important of which are phenylethanoid glycosides. This article summarizes the up-to-date information regarding the phytochemistry, pharmacology, processing, toxicity and safety of Rou Cong Rong to reveal its pharmacodynamic basis and potential therapeutic effects, which could be of great value for its use in future research.

Triterpenoid saponins from the roots of Psammosilene tunicoides.

Seven oleanane-type triterpenoid saponins, tunicosaponins B-D (1-3), F-I (4-7), along with eight known triterpenoid saponins (8-15), were isolated from the roots of Psammosilene tunicoides. The structures of compounds 1-7 were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and chemical methods. Triterpene glycosides have been considered as major active constituents of P. tunicoides. This work provides a more complete insight into the saponin constituents of P. tunicoides.

Identification and characterization of chemical constituents in Dengzhan Shengmai Capsule and their metabolites in rat plasma by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Dengzhan Shengmai Capsule (DZSMC) is a traditional Chinese medicine (TCM) formula with remarkable clinical effect in the treatment of stroke sequelae. Exploring the components of DZSMC and detecting the absorbed prototype constituents and metabolites in blood are of great significance to clarify the effective substances of this prescription. Here, a reliable method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for the comprehensive analysis of chemical constituents of DZSMC and their metabolites in rat plasma after gastric perfusion. Two acquisition modes, including MSE mode and Fast DDA mode, were performed for acquiring more precursor ions and cleaner precursor-product ions background during the study of constituents of DZSMC. As a result, a total of 125 constituents were unambiguously characterized or tentatively identified. For the first time, a total of 92 components, including 44 prototype components and 48 metabolites were unambiguously or tentatively identified in rat plasma. The metabolic pathways included phase I reactions (hydration, hydrogenation, oxidation, demethylation and hydroxylation) and phase II reactions (conjugation with glucuronide, sulfate and methyl). Furthermore, the metabolites from caffeic acid and scutellarin were characterized and validated by phase II metabolic reactions in vitro, which could be established as a simulated in vivo environment of metabolites identification and verification of TCM formula. It is the first systematic study on metabolism of DZSMC in vivo and could also provide a valid analytical strategy for characterization of the chemical compounds and metabolites of TCM formula.