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The presence of hypertension (HTN) in type 2 diabetes mellitus (DM) is a common phenomenon in more than half of the diabetic patients. Since HTN constitutes a predictor of vascular complications and cardiovascular disease in type 2 DM patients, it is of significance to understand the molecular and cellular mechanisms of type 2 DM binding to HTN. This review attempts to understand the mechanism via the perspective of the metabolites. It reviewed the metabolic perturbations, the biological function of perturbated metabolites in two diseases, and the mechanism underlying metabolic perturbation that contributed to the connection of type 2 DM and HTN. DM-associated metabolic perturbations may be involved in the pathogenesis of HTN potentially in insulin, angiotensin II, sympathetic nervous system, and the energy reprogramming to address how perturbated metabolites in type 2 DM affect the pathogenesis of HTN. The recent integration of the metabolism field with microbiology and immunology may provide a wider perspective. Metabolism affects immune function and supports immune cell differentiation by the switch of energy. The diverse metabolites produced by bacteria modified the biological process in the inflammatory response of chronic metabolic diseases either. The rapidly evolving metabolomics has enabled to have a better understanding of the process of diseases, which is an important tool for providing some insight into the investigation of diseases mechanism. Metabolites served as direct modulators of biological processes were believed to assess the pathological mechanisms involved in diseases.

Hyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities., The early identification of metabolic disorders could improve or prevent overt disease. Here the authors show that the circulating concentration of hyocholic acid (HCA) species is decreased in the context of obesity and diabetes and increased after gastric bypass surgery in humans, and further that serum HCA species are predictive of metabolic outcomes in healthy individuals.

Background Rice vinegar (RV) and white vinegar (WV) as daily flavoring, have also used as accessory in traditional Chinese medicine processing. As we know, the promoting blood circulation efficiency could be enhanced when herbs processed by vinegar. Number of reports focused on health benefits derived by consumption of vinegar. However, few concerned the blood circulation bioactivity. Methods In this paper, a metabolomics guided strategy was proposed to elaborate on the chemical constituents’ variation of two kinds of vinegar. GC–MS coupled with multivariate statistical analysis were conducted to analyze the chemical components in RV and WV and discriminate these two kinds of vinegar. The anti-platelet activities in vitro were investigated by whole blood aggregometry platelet test. And the anticoagulant activities were monitored by the whole blood viscosity, plasma viscosity, packed cell volume, prothrombin time, and four coagulation tests (PT, TT, APTT, FIB) in vivo. Results Constituents of RV and WV were globally characterized and 33 potential biomarkers were identified. The contents of four potential alkaloid biomarkers increased with aging time prolonged in RV. RV and its alkaloids metabolites exhibited some anti-platelet effects in vitro and anticoagulant activities in vivo. WV failed to exhibit promoting effects. Conclusions Alkaloid metabolites were demonstrated to be the principal compounds contributing to discrimination and it increased with aging time prolonged in RV. RV exhibited the blood circulation bioactivity. The alkaloids of RV contributed to the blood circulation bioactivity.Graphical abstractThe diagram of metabolomics guided promoting blood circulation bioactivity compounds screening strategy Electronic supplementary material The online version of this article (doi:10.1186/s13065-017-0265-5) contains supplementary material, which is available to authorized users.

In-depth research on processing can promote the globalization of processed herbs. The purpose of this study is to propose an improved strategy for processing effect investigation. Frankincense and processed frankincense were used as research subjects. First, high-speed countercurrent chromatography (HSCCC) and preparation high-performance liquid chromatography (PHPLC) techniques were used for major compounds isolation and minor compounds concentration. Processed frankincense was subjected to two stepwise solvent systems, namely, n-hexane:ethanol:water (6:5:1) and n-hexane:methyl-acetate:acetonitrile:water (4:4:3:4), to yield 12 fractions, and 18 compounds were further separated. Second, a comprehensive metabolomic analysis conducted by ultrahigh-performance liquid-chromatography/electrospray-ionization mass spectrometry (UHPLC-Qtof-MS) coupled with multivariate statistics was performed to fully characterize the chemical components and discover the potential biomarkers between frankincense and processed frankincense. In total, 81 metabolites, including the 18 separated compounds, were selected as potential biomarkers between frankincense and processed frankincense among 153 detected compounds for their VIP values of greater than one. The tirucallane-type compounds and components with 9,11-dehydro structures clearly occurred at high levels in the processed frankincense, while lupine-type compounds and those with 11-keto structures were significantly higher in frankincense. Then, a network pharmacology model was constructed to decipher the potential mechanisms of processing. Intestinal absorption properties prediction indicated the possibility of processing-related absorption enhancement. A systematic analysis of the constructed networks showed that the C-T network was constructed with 18 potential biomarkers and 69 targets. TNF and IL-1β were among the top-ranked and were linked by 8 and 7 pathways, which were mainly involved in inflammation. The arachidonic acid metabolism pathway exhibited the highest number of target connections. Finally, the prediction was validated experimentally by an intestinal permeability and efficacy assay. The experiments provided convincing evidence that processed frankincense harbored stronger inhibition effects toward TNF-α-, IL-1β- and arachidonic acid-induced platelet aggregation. The processing procedure leads to changes of the chemical metabolites, which triggers the enhancement of absorption and cure efficiency. The global change of the metabolites, absorption and pharmacological effects of processing were depicted in a systematic manner.

Citrus fruit is an important health-promoting food that is rich in dietary phenolic metabolites. Traditional Chinese medicines, such as Zhishi and Zhiqiao, come from young and immature fruits of Citrus cultivars. The preparation of diversified bioactive phenolic products and establishment of the corresponding quality control methodology are challenging and necessary. In the current study, four types of solid-phase extraction sorbents for the enrichment and clean-up of the phenolic matrix were evaluated. A solid-phase extraction column coated with Strata-X was finally used in the procedure. Twenty phenolic compounds were selected to evaluate the extraction performances of the sorbents using high-performance liquid chromatography analysis. Under the optimized conditions, good linearities were obtained with R2 more than 0.9996 for all analytes with LODs of 0.04-1.012 μg/g. Intra- and interday relative standard deviation values were less than 3%, and the recovery was equal to or higher than 90.02%. Compared to non-solid-phase extraction process, the content of total phenolic products was elevated 35.55-68.48% with solid-phase extraction. Finally, the developed and validated method was successfully applied to the discrimination of Zhishi samples from different species as well as Zhishi and Zhiqiao samples in different development stages.

The dried root of Salvia miltiorrhiza Bunge (Danshen in Chinese, ZHDS) is a very commonly used herbal medicine with purple flowers, and the dried root of S. miltiorrhiza Bge f. Alba (Baihua Danshen in Chinese, BHDS) with white flowers is a variety of ZHDS that is also used in clinics in some areas of China. Their authentication has always been a challenging task due to their similar morphological characteristics and ingredients. In the present study, an effective method for identifying BHDS and ZHDS based on multi-wavelength HPLC-fingerprinting chromatographic analysis and chemometric methodology was established. Peak-rich wavelengths (203, 270 and 281 nm) were combined to build a multi-wavelength fingerprint for each sample. Simultaneously, single-wavelength fingerprinting at 281 nm and content determination of nine active compounds were carried out. The results showed that a classification model between ZHDS and BHDS based on multi-wavelength fingerprint profiling was better than that on single-wavelength, and their discrimination became more feasible. The difference in components was not directly revealed, but latent information was revealed by PCA and PLS-DA. There were no significant differences in the contents of the nine main components (danshensu, caffeic acid, rosmarinic acid, lithospermic acid, salvianolic acid B, dihydrotanshinone I, cryptotanshinone, tanshinone I and tanshinone IIA). The results suggest that BHDS and ZHDS are chemically distinct and need to be evaluated for clinical applications.

Boswellic acids have long been considered the main bioactive components of frankincense, and many studies in vitro and in animals as well as several clinical studies have confirmed their various bioactivities. In particular, a large number of mechanistic studies have confirmed their anti-inflammatory and antitumor activities. However, not every boswellic acid exhibits a satisfactory pharmacological performance, which depends on the chemical structure and functional groups of the acid. To enhance the pharmacological values of boswellic acids, derivatization has been specifically applied with the aim of discovering more active derivatives of BAs. In addition, the preliminary pharmacokinetic studies of these compounds using various standard methods show their poor bioavailability in humans and rodents, which has led to questions of their pharmacological relevance and potentially limits their use in clinical practice and pharmaceutical development. To improve these effects, some approaches have shown some improvements in effectiveness, and the new formula compatibility approach is considered a very reasonable method for improving the bioavailability of boswellic acids.

This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages. Metabolomics can capture a comprehensive analysis of small molecule metabolites and can provide a powerful approach to establish metabolic profiling, creating a bridge between genotype and phenotype. To further investigate the different metabolites in four closely-related Citrus TCMs, non-targeted metabolite profiling analysis was employed as an efficient technique to profile the primary and secondary metabolites. The results presented in this manuscript indicate that primary metabolites enable the discrimination of species, whereas secondary metabolites are associated with species and the ripening process. In addition, analysis of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages. Ultimately, this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses.

Additional file 1: Table S1. The content of TMPZ in RV and WV. Table S2. The peak area and the relative peak area value of four potential biomarkers in different aging period. Table S3. The levels and factors investigated in BBD. Figure S1. HPLC chromatogram of TMPZ. Figure S2. The results of bioactivity screening. Figure S3. Diagnostic efficacy evaluation using ROC curves of the four potential biomarker metabolites in two different vinegar. Figure S4. Trends of time-series analysis graphs of four potential biomarkers. (A) TMPZ (MAPE: 2.05853, MAD: 1.67627, fitted curve: Yt = 60.81+5.089xt); (B) Dihydroergotamine (MAPE: 1.63096, MAD: 0.15345, fitted curve: Yt = 6.726+0.7121xt); (C) Harmine (MAPE: 1.72704, MAD: 0.01711, fitted curve: Yt = 0.7764+0.05780xt); (D) 1,2,3,4-tetrahydroharmine (MAPE: 3.76071, MAD: 0.04998, fitted curve: Yt = 0.9695+0.0910xt). Figure S5. Response surfaces estimated from the full factorial design for the content of total alkaloids.

Frankincense resins are extensively used as natural remedies in regions ranging from North Africa to China. Triterpenoid metabolites from frankincense exhibit notable anti-inflammatory and anti-tumor properties. In the present paper, without the use of an isolation process, the fragmentation rules and NMR spectral characteristics of triterpenoid metabolites in frankincense are summarized through a coupling method using high performance liquid chromatography-diode array detection/electrospray ionization tandem mass spectrometry (HPLC-DAD/ESI-MSn) combined with HPLC-nuclear magnetic resonance (NMR) experiments. Based on this groundwork, a coupling strategy for the comprehensive metabolic profiling of active triterpenoid metabolites from enriched fractions of frankincense was developed. The proposed strategy may serve as a method for the holistic screening of bioactive metabolites in complex TCM samples.

Boswellic acids (BAs), as the main components of frankincense, exhibit notable anti-inflammatory properties. However, their pharmaceutical development has been severely limited by their poor oral bioavailability. Traditional Chinese medicinal processing, called Pao Zhi, is believed to improve bioavailability, yet the mechanism is still completely unclear. Previous research suggested that the bioavailability of a drug can be influenced by physical properties. This paper was designed to investigate the physical properties of frankincense and processed frankincense, including the surface morphology, particle size, polydispersity index (PDI), zeta potential (ZP), specific surface area, porosity, and viscosity. The differences in the intestinal absorption characteristics and equilibrium solubilities between frankincense and processed frankincense were determined by an ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UHPLC-TQ-MS) analysis method. The results showed that vinegar processing can alter the surface morphology, decrease the particle size and PDI, raise the absolute values of the ZP, specific surface area and porosity, and drop the viscosity of frankincense. Meanwhile, the rates of absorption and dissolution of the main BAs were increased after the processing of frankincense. The present study proves that the physical properties were changed after processing, in which case the bioavailability of frankincense was enhanced.

This study is to establish an HPLC fingerprint by HPLC-DAD method and simultaneous quantitative analysis of 17 components of 18 batches of Citrus aurantium and 10 batches of C. sinensis. The separation was performed on an Agilent Poroshell 120 SB-C₁₈ (4.6 mm×100 mm,2.7 μm) column with the gradient elution of methanol-0.1% formic acid water, the flow was 0.6 mL•min⁻¹. The detection wavelength was set at 318 nm. The column temperature was maintained at 30 ℃. The data calculation was performed with similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (Version 2004A) together with SIMCA-P 13.0 software to clarify the differential marker between these two different species of Aurantii Fructus Immaturus. This method has good precision stability and repeatability that could provide basis for quality control and evaluation of Aurantii Fructus Immaturus.

Fuzi Lizhong pill (FLP) is used to treat gastritis, and the monarch drug of it is Aconiti Lateralis Radix Praeparata (Fuzi, aconite roots) which is a toxic herbal medicine. To better control the safety and quality of FLP, an effective method to analyze the contents of 16 toxic and bioactive components using rapid resolution liquid chromatography-tandem triple-quadrupole mass spectrometer was established. The 16 constituents included aconine, mesaconine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, adenosine, liquiritin, liquiritigenin, glycyrrhizic acid, isoliquiritigenin, 6-gingerol, atractylenolide III, atractylenolide I, atractylenolide II and glycyrrhetic acid. Ideal separation was performed using gradient elution in 13 min by optimized conditions. All the isomerides were isolated to baseline. The improved method with a polarity switch in contiguous time segments could analyze the five types of components, including polar and nonpolar compounds, without decreasing sensitivity. The proposed method was fully validated. The results revealed that contents of six alkaloids from Fuzi were significantly different among the samples. Using the established method and multivariate statistical method, the quality consistency of two dosage forms of FLP from different companies were analyzed. The optimized method could be used for the quality control of FLP and investigate index compound variation between two dosage forms.

Citrus fruit is an important health-promoting food that is rich in dietary phenolic metabolites. Traditional Chinese medicines, such as Zhishi and Zhiqiao, come from young and immature fruits of Citrus cultivars. The preparation of diversified bioactive phenolic products and establishment of the corresponding quality control methodology are challenging and necessary. In the current study, four types of solid-phase extraction sorbents for the enrichment and clean-up of the phenolic matrix were evaluated. A solid-phase extraction column coated with Strata-X was finally used in the procedure. Twenty phenolic compounds were selected to evaluate the extraction performances of the sorbents using high-performance liquid chromatography analysis. Under the optimized conditions, good linearities were obtained with R

Single standard to determine multi-components (SSDMC) method has been accepted as an efficient technique for the quality control of Traditional Chinese medicines (TCMs), especially for overcoming the shortage of reference standards. HPLC-UV methods have been applied to establish SSDMC method for quantitative analysis in several plant medicines and Chinese patent medicines, however, no LC-MS methods have been used. The purpose of this study is to put forward an improved strategy for the choice of single marker in SSDMC using rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry (RRLC-QqQ-MS). Five different Panax genus plants, recorded in the Chinese Pharmacopeia 2015 edition, were used as research subjects. An improved SSDMC strategy for simultaneous characterization and determination of 18 bioactive saponins in five Panax plants was put forward, and which was validated to be more superior. Then, it was fully investigated with respect to linearity, LODs, LOQs, precision and accuracy. Coupling with multivariate statistical analysis, the established and validated SSDMC strategy could be successively used in discrimination of the five Panax genus plants.

In this paper, an HPLC-QqQ-MS method for determination of 5 different ginsenosides of Panax japonica collected from different cultivated geographic regions was established. The separation was performed on a Zorbax XDB-C₁₈ (4.6 mm×100 mm, 1.8 μm) column with the gradient elution of acetonitrile (contained 0.1% formic acid)-0.1% formic acid water. The flow rate was 0.5 mL•min⁻¹. The colunm temperature was maintained at 30 ℃. The analytes were detected using electrospray ionization (ESI) in multiple reaction monitoring (MRM) modes. Reaction selected ions were 203.2 for ginsenoside Re, 202.9 for ginsenoside Rg₁, 365.0 for ginsenoside Rf, 789.1 for ginsenoside Rd, 360.9 for ginsenoside Ro. Ginsenosides Re, ginsenosides Rg₁, ginsenosides Rf, ginsenosides Rd, ginsenosides Ro had good linearity in the ranges of 3.33-66.60 μg (r=0.999 1),2.83-56.54 μg (r=0.999 2), 0.32-6.51 μg (r=0.999 2), 12.55-251.00 μg (r=0.999 3), 0.85-16.90 μg (r=0.999 5), respectively. The results of recovery were among 100.8% to 104.6%, and the values of RSD were blow 3.0%. This method is simple, reliable and accurate, and can provide basis for P. japonica basic research.

Additional file 2: Table S2. Alkaloids, coumarins, limonoids, carotenoids and phenolic acids isolated from Citrus species. The table summarized alkaloids, coumarins, limonoids, carotenoids and phenolic acids from Citrus species including C. aurantifolia, C. aurantium, C. bergamia, C. canaliculata, C. clementina, C. grandis, C. hassaku, C. junos, C. kinokuni, C. leiocarpa, C. limon, C. limonimedica, C. maxima, C. microcarpa, C. myrtifolia, C. paradisi,, C. reticulate,C. sinensis, C. tachibana and C. unshiu.

Quinochalcones, quinone-containing chalcones, belong to the flavonoid family and have attracted increasing popularity in Western countries in the last decade due to their pharmacological activities. This review describes four types of naturally occurring quinochalcones and summarizes their different pharmacological activities, including anti-cerebral ischemia, anti-tumor, and anti-infection activities. In addition, the pharmacological activities and relevant structure-activity relationships of synthetic quinochalcones are also reviewed.

Background Citrus fruits are widely used as food and or for medicinal purposes, and they contain a host of active substances that contribute to health. The immature fruits of Citrus sinensis Osbeck and its cultivars (CS), C. junos Sieb. ex Tanaka (CJ), C. aurantium L. and its cultivars (CA) and Poncirus trifoliate Raf. (PT) are the most commonly used medicinal herbs in Traditional Chinese Medicine, called Zhishi. And their mature fruits can be used as food. Results In this study, the essential oils of four different Zhishi species were extracted by steam distillation and detected using gas chromatography- mass spectrometry (GC-MS). A total of 39 volatiles from the four species were tentatively identified. The limonene was the most abundant amongst the four species. Principal component analysis (PCA) of essential oils showed a clear separation of volatiles among CS, CJ and PT. However, CA could not be separated from these three species. Additionally, the volatiles accounting for the variations among the widely separated species were characterized through their corresponding loading weight. Conclusion Sesquiterpenes were identified as characteristic markers for PT. The content of some monoterpenes could be as taxonomic markers between CS and CJ. This work is of great importance for the evaluation and authentication of Zhishi samples through essential oils.

Background Rhodiola plants are used as a natural remedy in the western world and as a traditional herbal medicine in China, and are valued for their ability to enhance human resistance to stress or fatigue and to promote longevity. Due to the morphological similarities among different species, the identification of the genus remains somewhat controversial, which may affect their safety and effectiveness in clinical use. Results In this paper, 47 Rhodiola samples of seven species were collected from thirteen local provinces of China. They were identified by their morphological characteristics and genetic and phytochemical taxonomies. Eight bioactive chemotaxonomic markers from four chemical classes (phenylpropanoids, phenylethanol derivatives, flavonoids and phenolic acids) were determined to evaluate and distinguish the chemotaxonomy of Rhodiola samples using an HPLC-DAD/UV method. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to compare the two classification methods between genetic and phytochemical taxonomy. Conclusions The established chemotaxonomic classification could be effectively used for Rhodiola species identification.

Citrus fruits, which are cultivated worldwide, have been recognized as some of the most high-consumption fruits in terms of energy, nutrients and health supplements. What is more, a number of these fruits have been used as traditional medicinal herbs to cure diseases in several Asian countries. Numerous studies have focused on Citrus secondary metabolites as well as bioactivities and have been intended to develop new chemotherapeutic or complementary medicine in recent decades. Citrus-derived secondary metabolites, including flavonoids, alkaloids, limonoids, coumarins, carotenoids, phenolic acids and essential oils, are of vital importance to human health due to their active properties. These characteristics include anti-oxidative, anti-inflammatory, anti-cancer, as well as cardiovascular protective effects, neuroprotective effects, etc. This review summarizes the global distribution and taxonomy, numerous secondary metabolites and bioactivities of Citrus fruits to provide a reference for further study. Flavonoids as characteristic bioactive metabolites in Citrus fruits are mainly introduced. Electronic supplementary material The online version of this article (doi:10.1186/s13065-015-0145-9) contains supplementary material, which is available to authorized users.

The resinous metabolites commonly known as frankincense or olibanum are produced by trees of the genus Boswellia and have attracted increasing popularity in Western countries in the last decade for their various pharmacological activities. This review described the pharmacological specific details mainly on anti-inflammatory, anti-carcinogenic, anti-bacterial and apoptosis-regulating activities of individual triterpenoid together with the relevant mechanism. In addition, species-characterizing triterpenic markers with the methods for their detection, bioavailability, safety and other significant properties were reviewed for further research.