Flos Lonicerae Research Articles

Comparative analyses of the main active ingredients of Lonicerae japonicae flos and Lonicerae flos

Objective To compare the quality of Lonicerae flos and Lonicerae japonicae flos by determine the main active ingredients. Methods According to methods and standards of determination in Chinese Pharmacopoeia (2015 Edition), the content of chlorogenic acid , galuteolin , macranthoidin B and asperosaponin B in 50 batches of samples of Lonicerae japonicae flos and .Lonicerae flos were determined. Results For Lonicerae japonicae flos (Lonicera japonica Thunb.), the contents of galuteolin was higher, and chlorogenic acid was lower, less or no contain saponins. For the main species of Lonicerae flos (Lonicera macranthoides Hand. -Mazz. and Lonicera hypoglauca Miq.), the contents of chlorogenic acid and the sum of saponins were higher, less or no galuteolin. Conclusions The main active ingredients of Lonicerae japonicae flos and Lonicerae flos were different. The contents of saponins in some samples of Lonicerae japonicae flos were higher, so the test of saponin should be considered when its raw material for injection. Key words: Flos lonicerae japonicae; Flos lonicerae; Main active ingredients; Determination; Quality control

Screening and evaluation of commonly-used anti-influenza Chinese herbal medicines based on anti-neuraminidase activity

Anti-influenza Chinese herbal medicines (anti-flu CHMs) have advantages in preventing and treating influenza virus infection. Despite various data on antiviral activities of some anti-flu CHMs have been reported, most of them could not be compared using the standard evaluation methods for antiviral activity. This situation poses an obstacle to a wide application of anti-flu CHMs. Thus, it was necessary to develop an evaluation method to estimate antiviral activities of anti-flu CHMs. In the present study, we searched for anti-flu CHMs, based on clinic usage, to select study objects from commonly-used patented anti-flu Chinese medicines. Then, a neuraminidase-based bioassay, optimized and verified by HPLC method by our research group, was adopted to detect antiviral activities of selected 26 anti-flu CHMs. Finally, eight of these herbs, including Coptidis Rhizoma, Isatidis Folium, Lonicerae Flos, Scutellaria Radix, Cyrtomium Rhizome, Houttuynia Cordata, Gardeniae Fructus, and Chrysanthemi Indici Flos, were shown to have strong antiviral activities with half maximal inhibitory concentration (IC50) values being 2.02 to 6.78 mg·mL−1 (expressed as raw materials). In contrast, the IC50 value of positive control peramivir was 0.38 mg·mL−1. Considering the extract yields of CHMs, the active component in these herbs may have a stronger antiviral activity than peramivir, suggesting that these herbs could be further researched for active compounds. Moreover, the proposed neuraminidase-based bioassay was high-throughput and simple and could be used for evaluation and screening of anti-flu CHMs as well as for their quality control.

Anti-encystment and amoebicidal activity of Lonicera japonica Thunb. and its major constituent chlorogenic acid invitro.

To examine the acanthamoebicidal effects of ethyl acetate, aqueous and butanol fractions of dried flower buds of Lonicera japonica (L. japonica) Thunb. (Flos Lonicerae) invitro. Acanthamoeba triangularis isolates were obtained from environmental water samples and identified by PCR. They were exposed to ethyl acetate, water and butanol fractions of L.japonica Thunb. at concentrations ranging from 0.5mg/mL to 1.5mg/mL. The extracts were evaluated for growth inhibition at 24, 48 and 72h, respectively. Chlorogenic acid at a concentration of 1mg/mL was examined for inhibition of encystment. Ethyl acetate fraction at a concentration of 1.5mg/mL evoked a significant reduction of trophozoite viability by 48.9% after 24h, 49.2% after 48h and 33.7% after 72h chlorogenic acid, the major active constituent of L.japonica Thunb. at the concentration of 1mg/mL reduced the cysts/trophozoite ratio by 100% after 24h, 84.0% after 48h and 72.3% after 72h. This phenolic compound at concentration of 1mg/mL concurrent with 0.6% hydrogen peroxide inhibited hydrogen peroxide-induced encystment by 92.8% at 72h. Results obtained from this study show that ethyl acetate fraction at 1.5mg/mL is the most potent fraction of L.japonica Thunb. and its major constituent chlorogenic acid showed the remarkable inhibition of encystment at a concentration of 1mg/mL.

Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

Rapid identification of Lonicerae japonicae Flos and Lonicerae Flos by Fourier transform infrared (FT-IR) spectroscopy and two-dimensional correlation analysis

Lonicerae japonicae Flos (LJF) and Lonicerae Flos (LF) are widely-used herbs derived from several plants of the genus Lonicera with similar appearances. LF are usually misused or counterfeited as LJF for economically motivated adulteration. However, the saponins in LF may cause serious side-effects. In this research, the infrared spectroscopic tri-step identification approach is used to develop a simple and rapid method to discriminate LJF and LF to ensure the safety and efficacy of these herbal drugs. In the primary identification by Fourier transform infrared spectra, LJF and LF show different peaks near 1534, 1404, and 781 cm−1. In the secondary identification by the second derivative infrared spectra, LJF and LF show more different peaks near 1078, 1050, 988, 923, 855, 815, and 781 cm−1. In the tertiary identification by the two-dimensional correlation infrared spectra, the differences between LJF and LF are shown more remarkably and convincingly. The results show the potential of the infrared spectroscopic tri-step identification approach in the rapid identification of LJF and LF when the samples are too few to build a statistical recognition rule. This should be very helpful to ensure the quality, safety, and efficacy of LJF and LF for clinical applications.

Research progress on chemical constituents and their differences between Lonicerae Japonicae Flos and Lonicerae Flos

The dried flower buds or initial flowers of Lonicerae Japonicae Flos and Lonicerae Flos, which belong to different species of Lonicera or Caprifoliaceae, are usually taken to clear away heat and toxic material and treat the exopathogenic wind-heat. They are two different herbs, and due to various reasons, there are far more controversies. This paper reviews the research on the chemical constituents and their differences between Lonicerae Japonicae Flos and Lonicerae Flos. Both of them contain the similar chemical constituents, such as organic acids, flavonoids, triterpenoidal saponins, iridoids, volatile oils and trace elements. But there are also differences between them. The main differences：Lonicerae Japonicae Flos contains a wealth of iridoids and flavonoids, while Lonicerae Flos contains more kinds of triterpenoidal saponins; the content of chlorogenic acid in Lonicerae Flos is significantly higher than that of Lonicerae Japonicae Flos; the content of rutin, luteoloside,luteolin-7-O-β-D-galactoside and lonicerin in Lonicerae Japonicae Flos is much higher than that of Lonicerae Flos; the content of Fe and Ni in Lonicerae Japonicae Flos is higher, while the content of Mn is higher in Lonicerae Flos. Finally, main problems and suggestions on chemical composition between Lonicerae Japonicae Flos and Lonicerae Flos were also discussed.

Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for luteoloside detection in Flos Lonicerae Japonicae

Flos Lonicerae Japonicae (FLJ), the flower bud of Lonicera japonica Thunb. (Caprifoliaceae), is a widely used traditional Chinese medicine with various pharmacological activities. Luteoloside is a major active compound and a quality control marker of FLJ. Luteolin-7-O-glucuronide (LG), an analog of luteoloside, was conjugated with bovine serum albumin (BSA) and ovalbumin (OVA) to create the immunogen and coating antigen, respectively. A sensitive and specific monoclonal antibody (mAb), designated as mAb3A4, was generated with LG-BSA. To screen the authenticity and quality of FLJ, an indirect competitive enzyme-linked immunosorbent assay (icELISA) was established. The concentration of luteoloside producing 50% inhibition and the working range of the icELISA were 42.3 and 9.1-258.1μgL(-1), respectively. The icELISA showed cross-reactivity values of 2414, 402, 230, and <1% for LG, baicalin, scutellarin, and other analogs of luteoloside, respectively. The average recovery of luteoloside in the FLJ samples as determined by icELISA ranged from 83.0 to 112.5%. The luteoloside content was determined for different Lonicera herbal samples with icELISA, and the results were confirmed by high-performance liquid chromatography analysis. Thus, this icELISA is suitable for the quality assurance of FLJ samples. Graphical abstract Specific monoclonal antibody-based enzyme-linked immunosorbent assay for luteoloside.

Relationship between maceration and extraction yield in the production of Chinese herbal medicine

The relationship between maceration and extraction yield in the production of Chinese herbal medicine has been studied. There is a general belief that swelling of herb tissue by maceration enhances the extraction yield of a chemical marker in the afterward extraction; however, this may not be true in general. The extraction of chrysophanol from a seed grounded into powder, Semen Cassiae, served as an example to show how maceration enhances the extraction yield of a chemical marker. It is possibly due to the fact that there are so many water soluble substances like starch, sugar and protein in seeds. When water is used as the maceration solvent, it dissolves and removes the water soluble substances, and therefore increases the availability of chemical marker to be extracted by the mixture of ethanol and water. In some other cases, it was found that maceration had no effect on the extraction yield of chemical marker, like the extraction of danshesu from Radix Salviae Miltiorrhizae (herb of root) and peaonol from Cortex Moutan (herb of root bark). Also, chemical markers may decompose during maceration and extraction, such as extractions of pinoresinol diglucoside from Cortex Eucommiae (herb of stem bark) and chlorogenic acid from Flos Lonicerae (herb of flower), leading to a decrease of the extraction yield. Based on these experimental results, this study provides general considerations to evaluate if it is cost and time effective to carry out maceration in the production process of Chinese herbal medicine. These considerations include whether the chemical marker is stable during maceration, and whether any substance present in the herb would affect extraction and can be removed during maceration.

Spectrum-Effect Relationships Between Chemical Fingerprints and Antibacterial Effects of Lonicerae Japonicae Flos and Lonicerae Flos Base on UPLC and Microcalorimetry.

The traditional Chinese medicines Lonicerae Japonicae Flos (LJF, Jinyinhua in Chinese) and Lonicerae Flos (LF, Shanyinhua in Chinese) refer to the flower buds of five plants belonging to the Caprifoliaceae family. Until 2000, all of these were officially listed as a single item, LJF (Jinyinhua), in the Chinese Pharmacopoeia. However, there have recently been many academic controversies concerning the separation and combination of LJF and LF in administrative regulation. Till now there has been little work completed evaluating the relationships between biological activity and chemical properties among these drugs. Microcalorimetry and UPLC were used along with principal component analysis (PCA), hierarchical cluster analysis (HCA), and canonical correlation analysis (CCA) to investigate the relationships between the chemical ingredients and the antibacterial effects of LJF and LF. Using multivariate statistical analysis, LJF and LF could be initially separated according to their chemical fingerprints, and the antibacterial effects of the two herbal drugs were divided into two clusters. This result supports the disaggregation of LJF and LF by the Pharmacopoeia Committee. However, the sample of Lonicera fulvotomentosa Hsu et S. C. Cheng turned out to be an intermediate species, with similar antibacterial efficacy as LJF. The results of CCA indicated that chlorogenic acid and 3,4-Dicaffeoylquinic acid were the major components generating antibacterial effects. Furthermore, 3,4-Dicaffeoylquinic acid could be used as a new marker ingredient for quality control of LJF and LF.

Simultaneous Determination of 11 Components in Yinzhihuang Preparations and Their Constituent Herbs by High-Performance Liquid Chromatography with Diode Array Detector.

A simple and sensitive liquid chromatography method with diode array detector was established for simultaneous determination of 11 components (geniposidic acid, chlorogenic acid, caffeic acid, geniposide, luteoloside, isochlorogenic acid C, baicalin, luteolin, wogonoside, baicalein and wogonin) in various commercial Yinzhihuang preparations and their herbs by optimizing the extraction, separation and analytical conditions. Eleven components were identified on the basis of their retention times and mass spectra. Chromatographic separation was performed on a C18 analytical column with a gradient elution of acetonitrile and 0.1% formic acid water solution at a flow rate of 1.0 mL/min. The linearity, precision and accuracy of the data obtained were acceptable. The method was used to analyze four Yinzhihuang preparations (powder, capsule, oral liquid and injection) and related herbs (Radix Scutellariae, Flos Lonicerae, Herba Artemisiae Scopariae and Fructus gardeniae). Results suggested that the optimized method could be considered as a good approach to control the quality of Yinzhihuang preparations and their herbs.

The effect of Flos Lonicerae Japonicae extract on gastro-intestinal motility function

Ethnopharmacological relevanceFlos Lonicerae Japonicae is a well-known herb of traditional Chinese medicine that has been used for heat-clearing, detoxification, anti-inflammation, throat pain and gastro-intestinal (GI) disorder. In order to verify the effect of Flos Lonicerae Japonicae on GI disorder, we investigated the prokinetic effect of GC-7101 on GI motility function. Materials and methodsGC-7101 is the standardized extract of Flos Lonicerae Japonicae. The contractile action of GC-7101 on feline esophageal smooth muscle cell (ESMC) was evaluated by measuring dispersed cell length. The isometric tension study was performed to investigate the effect of GC-7101 on feline lower esophageal sphincther (LES). The prokinetic effect of GC-7101 was investigated by gastric emptying (GE) and gastro-intestinal transit (GIT) in rats. ResultsGC-7101 produced concentration-dependent contractions in ESMCs. Pretreatment with 5-HT3 and 5-HT4 receptor blocker (ondansetron and GR113808) inhibited the contractile responses of the GC-7101-induced ESMCs. In isometric tension study, GC-7101 recovered the HCl-induced decreased tone of LES muscle strips. The treatment of GC-7101 enhanced the carbachol-induced contractile responses and the electric field stimulation (EFS)-induced on-contraction. The oral administration of GC-7101 not only significantly accelerated GE and GIT in normal rats but also recovered the delayed GE and GIT, and its effect was more potent than that of conventional prokinetics (e.g., domperidone, a dopamine-receptor antagonist, and mosapride, a 5-HT4-receptor agonist). ConclusionGC-7101 revealed a prokinetic effect through enhancing the contractile responses of ESMCs, tone increases, enhancing the carbarchol- or EFS-induced contractile responses of LES muscle strips, and the acceleration of GE and GIT. We have identified the significant potential of GC-7101 for the development of new prokinetic drugs through this study.

Ionic liquid-based ultrasound-assisted extraction and aqueous two-phase system for analysis of caffeoylquinic acids from Flos Lonicerae Japonicae

In this work, an ionic liquid-based ultrasonic-assisted extraction (ILUAE) method was developed to extract caffeoylquinic acids (CQAs) from Flos Lonicerae Japonicae (FLJ). ILUAE parameters were optimized by response surface methodology, including IL concentration, ultrasonic time, and liquid–solid ratio. Optimized ILUAE approach gained the highest extraction yields of 28.53, 18.21, 3.84mg/g for 3-O-caffeoylquinic acid (C1), 3,5-di-O-caffeoylquinic acid (C2), 3,4-di-O-caffeoylquinic acid (C3), respectively. C1–C3 are the three most abundant CQAs compounds in FLJ. The method showed comparable extraction yield and shorter extraction time compared with conventional extraction techniques. Subsequently, an aqueous two-phase system (ATPS) was applied in extraction solutions. Two trace CQAs, 5-O-caffeoylquinic acid (C4) and 4,5-di-O-caffeoylquinic acid (C5), were significantly enriched with signal to noise values increasing from less than 10 to higher than 1475. The results indicated that ILUAE and ATPS are efficient and environmentally-friendly sample extraction and enrichment techniques for CQAs from herbal medicines.

Discovery and Current Status of Evaluation System of Bioavailability and Related Pharmaceutical Technologies for Traditional Chinese Medicines--Flos Lonicerae Japonicae--Fructus Forsythiae Herb Couples as an Example.

Traditional Chinese medicines (TCMs) have attracted extensive interest throughout the world due to their long history of health protection and disease control, and the internalization of TCM preparations or patented drugs has been considered a wind vane in the process of TCM modernization. However, multi-target effects, caused by multiple components in TCMs, hinder not only the construction of the quality evaluation system (bioavailability), but also the application of pharmaceutical technologies, which results in the poor efficacy in clinical practice. This review describes the methods in the literature as well as in our thoughts about how to identify the marker components, establish the evaluation system of bioavailability, and improve the bioavailability in TCM preparations. We expect that the current study will be positive and informative.

Discovery of Anti-inflammatory Ingredients in Chinese Herbal Formula Kouyanqing Granule based on Relevance Analysis between Chemical Characters and Biological Effects.

Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson’s correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role.

High-performance liquid chromatography with photodiode array detection and chemometrics method for the analysis of multiple components in the traditional Chinese medicine Shuanghuanglian oral liquid.

Shuanghuanlian oral liquid, a traditional Chinese medicine preparation, is a mixture of three herbs (Flos Lonicerae, Radix Scutellariae and Fructus Forsythiae). In this study, the quantitative analysis of three main active compounds, chlorogenic acid, forsythin and baicalin in samples from different manufacturers was performed rapidly by high-performance liquid chromatography coupled with photodiode array detection followed by Contour Projection coupled to stepwise regression treatment of the obtained three-dimensional spectra in which the partial overlap between adjacent target components existed. The method was validated for linearity (R>0.9940), precision (RSD<1.25%), recovery (92.20-102.50%), limit of detection (0.01-0.02 μg/mL) and limit of quantification (0.03-0.07 μg/mL). The results indicated that the combination of the three-dimensional spectra of traditional Chinese medicine and Contour Projection-stepwise regression offered an accurate, simple, low-cost and eco-friendly way for the rapid quantitative analysis of Shuanghuanlian oral liquid samples.

Rapid quantitative analysis of adulterant Lonicera species in preparations of Lonicerae Japonicae Flos

Lonicerae Japonicae Flos is often adulterated with Lonicerae Flos, which is derived from the other four Lonicera species, in both the crude drug and Lonicerae Japonicae Flos preparations. We proposed a methodology for the quantitative analysis of adulterant Lonicerae Flos in Lonicerae Japonicae Flos preparations. Taking macranthoidins A, B, dipsacoside B (saponins), sweroside (iridoids), and luteolin-7-O-d-glucoside (flavonoids) as markers, a method of ultra high performance liquid chromatography with triple quadrupole mass spectrometry was employed to determine their amounts in Lonicerae Flos, Lonicerae Japonicae Flos, and Lonicerae Japonicae Flos preparations. The proportion of adulterant Lonicerae Flos in Lonicerae Japonicae Flos preparations was estimated based on the saponin contents of Lonicerae Japonicae Flos and Lonicerae Flos. All analytes separated under isocratic elution in 12 min with acceptable linearity, precision, repeatability, and accuracy. Lonicerae Japonicae Flos was easily distinguished from Lonicerae Flos by the total amount of saponins (0.067 and > 45.8 mg/g for Lonicerae Japonicae Flos and Lonicerae Flos, respectively). Eighteen of twenty one Lonicerae Japonicae Flos preparation samples were adulterated with Lonicerae Flos in proportions of 11.3-100%. The developed ultra high performance liquid chromatography with triple quadrupole mass spectrometry method could be used for the identification of Lonicerae Japonicae Flos and the four species of Lonicerae Flos and for the analysis of Lonicerae Japonicae Flos preparations adulterated with Lonicerae Flos.

Variation of essential oil content and antioxidant activity of Lonicera species in different sites of China

Flos Lonicerae (FL) was widely planted in China as a kind of pharmaceutical resource. In our research, the variations in content and antioxidant activity of essential oil of FL from five different sites of China were investigated. The results revealed that the essential oil content of samples varied over the range of 0.288± 0.015% to 0.387±0.016%. The essential oil antioxidant activity of samples were also determined by scavenging activity against 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS), ferric reducing/antioxidant power (FRAP) test and β-carotene-linoleic acid bleaching test. The results indicated that the sample from Shaoyang showed better antioxidant activity than the others. And the β-carotene-linoleic acid bleaching activity could reach 92.31%, when the concentration of the sample from Shaoyang was 4mg/mL, indicating that the sample from Shaoyang possessed excellent antioxidant activity. The chemical compositions of the essential oil were finally identified by GC–MS, and more than 20 compounds were identified. Principal component analysis was also performed to investigate the difference of the essential oil samples.

A strategy for comprehensive identification of sequential constituents using ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap mass spectrometer, application study on chlorogenic acids in Flos Lonicerae Japonicae

The analytical methodologies for evaluation of multi-component system in traditional Chinese medicines (TCMs) have been inadequate or unacceptable. As a result, the unclarity of multi-component hinders the sufficient interpretation of their bioactivities. In this paper, an ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap (UPLC–LTQ–Orbitrap)-based strategy focused on the comprehensive identification of TCM sequential constituents was developed. The strategy was characterized by molecular design, multiple ion monitoring (MIM), targeted database hits and mass spectral trees similarity filter (MTSF), and even more isomerism discrimination. It was successfully applied in the HRMS data-acquisition and processing of chlorogenic acids (CGAs) in Flos Lonicerae Japonicae (FLJ), and a total of 115 chromatographic peaks attributed to 18 categories were characterized, allowing a comprehensive revelation of CGAs in FLJ for the first time. This demonstrated that MIM based on molecular design could improve the efficiency to trigger MS/MS fragmentation reactions. Targeted database hits and MTSF searching greatly facilitated the processing of extremely large information data. Besides, the introduction of diagnostic product ions (DPIs) discrimination, ClogP analysis, and molecular simulation, raised the efficiency and accuracy to characterize sequential constituents especially position and geometric isomers. In conclusion, the results expanded our understanding on CGAs in FLJ, and the strategy could be exemplary for future research on the comprehensive identification of sequential constituents in TCMs. Meanwhile, it may propose a novel idea for analyzing sequential constituents, and is promising for quality control and evaluation of TCMs.

Chemistry and pharmacology of the herb pair Flos Lonicerae japonicae-Forsythiae fructus.

The Chinese medicine herb pair Flos Lonicerae japonicae (FLJ) and Forsythiae fructus (FF), is a representative heat-clearing (qing re) and detoxifying (jie du) combination that exhibits many pharmacological activities, including antibacterial, antiviral, antitumor, anti-inflammatory, and antioxidant effects. Extensive phytochemical studies have identified a series of bioactive compounds, such as chlorogenic acid from FLJ and forsythoside A from FF. This article provides a comprehensive review on the chemical and pharmacological principles of the traditional functions of FLJ-FF, and sheds light on further developments of this herb pair.

Change of chemical composition in Flos lonicerae: An investigation of herbal processing (PAO ZHI) using NMR spectroscopy

Change of chemical composition in Flos lonicerae: An investigation of herbal processing (PAO ZHI) using NMR spectroscopy