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Ethnopharmacological relevance Notopterygium incisum Ting ex H.T. Chang, known in Chinese as ‘Qianghuo’ is a traditional Chinese medicinal herb with the rhizome and roots associated with meridians of the kidney and urinary bladder. It is pungent, bitter and warm in nature. It has been used over the years to disperse cold, prevent painful obstructions from wind, damp and warm pain. It has also been used with other herbs to treat wind-cold exterior syndrome and wind-cold-damp bi-syndromes and has been known to grow well in regions of high altitude such as Gansu, Tibet etc. The aim of the review This systematic review focuses on the ethnopharmacological uses of this herb, including recent advances on the phytochemical and pharmacological study of N. incisum. Recent analytical methods developed for the quantitative and qualitative determination of constituents in this herb have also been reviewed. Additionally, future trends and prospects in the study of this herb have been proposed. Materials and method Various literature and electronic databases such as Pubmed, Science Direct, Springer, Wiley etc were searched and data obtained. Other online academic libraries such as Google Scholar and ethnopharmacological literature were searched systematically for more information on the herb. Results This review focuses on the ethnopharmacological uses of N. incisum and also the various chemical constituents present in the herb and their various therapeutic effects such as analgesic, anti-inflammatory, anti-cancer and antioxidants effects. Analytical methods developed for the quantitative and qualitative determination of various compounds in this herb were further reviewed. Conclusion In this paper, we have reviewed various researches conducted on N. incisum especially in areas of its ethnopharmacological use, phytochemicals, pharmacology and developed analytical methods. This herb has been used over the years in treating headache, rheumatoid arthritis, cold, diaphoretic etc, prompting many types of research into identifying which compounds are responsible for these activities and their mechanism of action. More research is needed in the area of pharmacokinetics and toxicology to give further information on the clinical use and control the quality of the herb.

Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe drugs, namely, omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) to study the potential influences of NXT on the activities of CYP enzymes and assessed the pharmacokinetics effect of NXT on metoprolol tartrate in rat plasma. The study showed that AUC(0–24) and AUC(0–∞) of midazolam (CYP3A4) in NXT coadministration group (283.7 ± 65.2 h·ng·mL−1 and 292.0 ± 75.1 h·ng·mL−1 in group B; 295.7 ± 62.7 h·ng·mL−1 and 299.5 ± 60.0 h·ng·mL−1 in group C) were significantly decreased as compared to another group (416.8 ± 82.3 h·ng·mL−1 and 424.9 ± 77.9 h·ng·mL−1 in group A), while that of dextromethorphan (CYP2D6) showed an opposite tendency (540.7 ± 119.7 h·ng·mL−1 and 595.3 ± 122.2 h·ng·mL−1 in group A, 760.6 ± 184.9 h·ng·mL−1 and 788.7 ± 211.0 h·ng·mL−1 in group B, and 734.3 ± 118.5 h·ng·mL−1 and 757.2 ± 105.4 h·ng·mL−1 in group C). Moreover, NXT preadministration can enhance the metabolism of metoprolol tartrate and reduce the metabolism of O-demethylmetoprolol. The results indicated that NXT had potential effects in inducing CYP3A4 and inhibiting CYP2D6 in the metabolism of metoprolol tartrate. It suggests that patients who coadministered NXT and metoprolol tartrate should be advised of potential herb-drug interactions (HDIs) to reduce therapeutic failure or accelerated toxicity of conventional drug treatment.

An in-capillary 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-CE-the DAD (in-capillary DPPH-CE-DAD) combined with reversed-electrode polarity stacking mode has been developed to screen and quantify the active antioxidant components of Cuscuta chinensis Lam. The operation parameters were optimized with regard to the pH and concentration of buffer solution, SDS, β-CDs, organic modifier, as well as separation voltage and temperature. Six antioxidants including chlorogenic acid, p-coumaric acid, rutin, hyperin, isoquercitrin, and astragalin were screened and the total antioxidant activity of the complex matrix was successfully evaluated based on the decreased peak area of DPPH by the established DPPH-CE-DAD method. Sensitivity was enhanced under reversed-electrode polarity stacking mode and 10- to 31-fold of magnitude improvement in detection sensitivity for each analyte was attained. The results demonstrated that the newly established in-capillary DPPH-CE-DAD method combined with reversed-electrode polarity stacking mode could integrate sample concentration, the oxidizing reaction, separation, and detection into one capillary to fully automate the system. It was considered a suitable technique for the separation, screening, and determination of trace antioxidants in natural products.

A rapid, sensitive and selective high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of four phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and ferulic acid) and seven alkaloids (berberine, epiberberine, coptisine, magnoflorine, berberubine, palmatine and jatrorrhizine) in rat plasma. After mixing with the internal standards tetrahydropalmatine (IS1) and rosmarinic acid (IS2), plasma samples were pretreated by protein precipitation using acetonitrile. The HPLC analysis was performed on an Agilent Eclipse plus C18 (4.6 mm×100 mm, 1.8 μm) column with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL min(-1). The detection was accomplished for the analytes and internal standards using positive electrospray ionization for the alkaloids and negative electrospray ionization for the phenolic acids in multiple-reaction monitoring mode. The method showed a good linearity over a wide concentration range (r(2)>0.99). The lower limit of quantification of seven alkaloids was lower than 2 ng mL(-1) and that of four phenolic acids was less than 20 ng mL(-1). The developed method was applied to the pharmacokinetic study of 11 components after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet in rats.

Columbianadin and its metabolite columbianetin exhibited the anti-inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid-liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.

Periplocin is a cardiac glycoside and has been used widely in the clinic for its cardiotonic, anti-inflammatory and anti-tumor effects. Although it is taken frequently by oral administration in the clinic, there have been no reports demonstrating that periplocin could be detected in vivo after an oral administration, so there is an urgen need to determine the characteristics of periplocin in vivo after oral administration. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated to identify and quantify periplocin and its two metabolites in rat tissue after a single dosage of perplocin at 50 mg/kg. The results demonstrated that periplocin and its two metabolites were detected in all of the selected tissues; periplocin could reach peak concentration quickly after administration, while periplocymarin and periplogenin reached maximum concentration > 4.83 h after administration. The tissue distribution of analytes tended to be mostly in the liver, and higher analyte concentrations were found in the heart, liver, spleen, lung and kidney, but a small amount of chemical constituents was distributed into the brain. The consequences obtained using this method might provide a meaningful insight for clinical investigations and applications.

Ardisia japonica is a well-known traditional Chinese medicinal herb used as a diuretic, for treating cough and for stopping uterine bleeding. A simple, sensitive, and reliable LC-MS/MS method was developed to determine six active compounds in rat plasma and this method was further applied to the pharmacokinetic study of these compounds after oral administration of Ardisia japonica extract. Acetonitrile was used to precipitate the protein in the plasma samples. Using acetonitrile and formic acid aqueous solution (0.05%) as the mobile phase, the separation of the six compounds and internal standards was achieved at a flow rate of 300 μL min−1 on an Eclipse plus C18 column at an elution time of 16 min. A tandem mass spectrometer having an electrospray ionization (ESI) source was used in the detection of the analytes and internal standards using multiple reactions monitoring (MRM) in the negative ionization mode. The LLOQ was 2, 2, 4, 2, 1, and 0.4 ng mL−1 for gallic acid, bergenin, epicatechin, epicatechin gallate, isoquercitrin, and quercetin-3-rhamnoside, respectively. The validated method was applied to the pharmacokinetic study of gallic acid, bergenin, and quercetin-3-rhamnoside in rat plasma after oral administration of A. japonica extract to rats.

Small molecules isolated from herbal medicines (HMs) were identified as the potential neuraminidase inhibitors which are effective in influenza prevention and treatment. Unfortunately, current available screen methods of small molecules isolated from HMs are inefficient and insensitive. Here a novel Ultra Performance Liquid Chromatography coupled with diode-array detectors and auto-fraction collector / time-of-flight mass spectrometry (UPLC-DAD-FC/Q-TOF-MS) screening method with high efficiency was developed and validated to separate, collect, enrich, identify and quantify potential neuraminidase inhibitors from Radix Scutellariae. The results showed that 26 components with neuraminidase inhibitory activity were identified from Radix Scutellariae extracts. It was also found that the influence of origins on the quality of RS was more than that of cultivated time on the basis of the concentration of the effective components. These results brought novel insights into quality evaluation of Radix Scutellariae. It was demonstrated that new activity-integrated strategy was a suitable technique for the identification, screening and determination of potential neuraminidase inhibitors in herbal medicine and will provide novel potential strategies in other drug screening from herbal medicine.

A sensitive, reliable and validated LC-MS/MS method was developed to determine the presence of eight flavonoids (catechin, typhaneoside, isorhamnetin-3-O-neohesperidoside, astragalin, isorhamnetin-3-O-β-d-glucoside, naringenin, kaempferol and isorhamnetin) in rat plasma. Puerarin was selected as the internal standard. Precipitation of the protein method with acetonitrile was used to extract these flavonoids from the rat plasma samples. The analysis was carried out on an Eclipse plus C18 column (4.6 mm×100mm, 1.8μm) when acetonitrile and formic acid aqueous solution (0.1%) was used as the mobile phase at a flow rate of 0.3mLmin-1. A tandem mass spectrometer having an electrospray ionization (ESI) source was used to detect eight flavonoids using multiple reaction monitoring (MRM) in the negative ionization mode. The LLOQs for catechin, typhaneoside, isorhamnetin-3-O-neohesperidoside, astragalin, isorhamnetin-3-O-β-d-glucoside, naringenin, kaempferol and isorhamnetin are 4, 4, 4, 0.8, 1, 0.4, 2 and 0.2ngmL-1, respectively. The precision, accuracy and recovery were all within acceptable limits and the analytes were stable in plasma for all conditions tested. The method was successfully applied to pharmacokinetic study of four flavonoids in rat plasma after administering Pollen Typhae extract orally to rats.

A sensitive, specific, reproducible and optimized high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the determination of bergapten in rat plasma was established and applied to the pharmacokinetic and bioavailability study in rat after oral and intravenous administration of bergapten. The method was also successfully applied to the excretion study of bergapten after an oral administration of bergapten at a dose of 15 mg kg−1 to rats. The sample preparation was achieved using liquid–liquid extraction. Isoimperatorin was used as the internal standard (IS). The analytes were detected by using fluorescence detection at an excitation and emission wavelength of 288 and 478 nm, respectively. Using aqueous formic acid (0.1 %, v/v) and acetonitrile as the mobile phase, the chromatographic separation was achieved on a Hedera™ ODS column at a flow rate of 1 mL min−1. The lower limit of quantitation (LLOQ) of bergapten was 2 ng mL−1. The HPLC-FLD method was successfully applied to the pharmacokinetic, bioavailability and excretion study of bergapten in rats.Graphical abstractAn high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the pharmacokinetic and bioavailability study in rat after administration of bergapten.

Traditional Chinese medicine (TCM) has been used for the treatment of many complex diseases. However, the bioactive components are always undefined. In this study, a bioactivity-based method was developed and validated to screen lipase inhibitors and evaluate the effects of processing on the lipase inhibitory activity of TCM by ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC). The results showed that bothPolygonum multiflorumand processedP. multiflorumextracts had inhibitory effect against lipase with IC50values of 38.84 μg/mL and 190.6 μg/mL, respectively. Stilbenes, phenolic acid, flavonoids, and anthraquinones were considered to be the potential lipase inhibitors. Eleven potential lipase inhibitors were simultaneously determined by UHPLC. Principal component analysis (PCA) was employed in exploring the effects of processing time on lipase inhibitory activity ofP. multiflorum. Compared with conventional methods, a bioactivity-based method could quantitatively analyze lipase inhibitory activity of individual constituent and provide the total lipase inhibitory activity of the samples. The results demonstrated that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and powerful tool for screening and identifying lipase inhibitors from traditional Chinese medicines.