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Hydroxysafflor yellow A (HSYA) from safflower (Carthamus tinctorius L.) possesses several medicinal properties. However, it is unknown whether HSYA is effective in the treatment of rheumatoid arthritis (RA). Hence, we investigated the effects of HSYA on the inflammation and synovial damage in rats with collagen-induced arthritis (CIA) by subjecting them to treatment with different doses of HSYA. Our results revealed that HSYA could significantly reduce paw swelling, pathological manifestations, and serum cytokine levels in rats with CIA. The HSYA-treated groups showed increased antioxidant enzyme activity in the serum and decreased expression of inflammatory mediators in the synovial tissues. Furthermore, HSYA treatment inhibited extracellular signal-regulated kinase (ERK) signalling pathway activation. Notably, the highest dose of HSYA (20 mg/kg) exhibited the best effects against RA symptoms. Therefore, our findings suggest that HSYA alleviates the inflammatory response and synovial damage in rats with CIA by inhibiting the ERK signalling pathway. • HSYA alleviated the inflammation and synovial damage in rats with CIA. • HSYA prevented oxidative stress in the blood and synovial tissues of rats with CIA. • HSYA may exert anti-RA effects by inhibiting the ERK signaling pathway. [ABSTRACT FROM AUTHOR]

• A novel method of combinatorics-based chemical characterization was proposed. • A total of 131 compounds were characterized from Marsdenia tenacissima. • PCA and OPLS-DA were applied to compare different parts of Marsdenia tenacissima. • Tenacissoside H was discovered as a differential component between stems and roots. • The DPPH-scavenging activity and α-glucosidase inhibitory activity were compared. Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima , it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima , are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima. Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima , respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima , but also provides a paradigm for the research of other similar medicinal plants. [ABSTRACT FROM AUTHOR]

As a traditional medicinal plant, Juglans mandshurica has been used for the treatment of cancer. Different organs of this plant showed anti-tumor activity in clinic and laboratory. Comparative identification of constituents in different plant organs is essential for investigation of the relationship between chemical constituents and pharmacological activities. For this aim, the roots, branches, and leaves of J. mandshurica were extracted with 50% v/v methanol and then subjected to ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry analysis conducted under low and high energy. As a result, we have to date identified 111 compounds consisting of 56 tannins, 29 flavonoids, 13 organic acids, 8 naphthalene derivatives, and 5 anthracenes. Five compounds, namely, diquercetin trihydroxy-truxinoyl-glucoside, two quercetin kaempferol dihydroxy-truxinoyl-glucosides, syringoyl-tri-galloyl- O-glucose, and dihydroxy-naphthalene syringoyl-glucoside, were tentatively identified as new compounds. Of the compounds identified, 76 were found in the root extract, 67 in the branch extract, and 37 in the leaf extract. Only six compounds including four organic acids and two tannins were found in all three extracts. We developed a rapid and sensitive ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry approach to identify multiple constituents of complex extracts without separation and ion selection. The results presented provide useful information on further research of the bioactive compounds of J. mandshurica. [ABSTRACT FROM AUTHOR]

In the present study, two new compounds, together with six known compounds, were isolated from rhizome ofAtractylodes macrocephalaKoidz by a series of silica gel, ODS column chromatography, and preparative HPLC. Their structures were characterized as atractylenolide II (1), atractylenolide I (2), biepiasterolid (3), isoatractylenolide I (4), atractylenolide III (5), 3β-acetoxyl atractylenolide I (6), (4E,6E,12E)-tetradeca-4,6,12-triene-8,10-diyne-13,14-triol (7), (3S,4E,6E,12E)-1-acetoxy-tetradeca-4,6,12-triene-8,10-diyne-3,14-diol (8) on the basis of 1D, 2D NMR, and circular dichroism analyses. Among them, compounds6and8were novel compounds. In addition, their neuroprotective activity against MPP+-induced SH-SY5Y cells was evaluated by MTT colorimetry. The results showed that all these compounds have definite protective effect on MPP+-induced SH-SY5Y cells. [ABSTRACT FROM PUBLISHER]

Context: Recent research has demonstrated that vitexin exhibits a prominent first-pass effect. In this light, it is necessary to investigate the causes of this distinct first-pass effect. Objective: The aim of this study was to evaluate hepatic, gastric, and intestinal first-pass effects of vitexin in rats and, furthermore, to investigate the role of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) in the absorption and secretion of vitexin in the duodenum. Materials and methods: Vitexin was infused into rats intravenously, intraportally, intraduodenally, and intragastrically (30 mg/kg) . In addition, verapamil (50 mg/kg), a common substrate/inhibitor of P-gp and CYP3A, was also instilled with vitexin into the duodenum to investigate the regulatory action of P-gp and CYP3A. The plasma concentrations of vitexin were measured by the HPLC method using hesperidin as an internal standard. Results: The hepatic, gastric, and intestinal first-pass effects of vitexin in rats were 5.2%, 31.3%, and 94.1%, respectively. In addition, the total area under the plasma concentration-time curve from zero to infinity (AUC) of the vitexin plus verapamil group and of the normal saline group was 44.9 and 39.8 μgċ min/mL, respectively. Discussion and conclusion: The intestinal first-pass effect of vitexin was considerable, and gastric and hepatic first-pass effects also contribute to the low absolute oral bioavailability of vitexin. The AUC of the vitexin plus verapamil group was slightly higher than that of the vitexin plus normal saline group (by approximately 1.13-fold), suggesting that verapamil does not play an important role in the absorption and secretion of vitexin. [ABSTRACT FROM AUTHOR]

• Proposal of a novel concept of lead chemome for drug discovery. • Development of a practical and efficient strategy to discover lead chemome. • Establishment of natural chromatogram-effect correlation (NCEC) based on traditional Chinese medicines. • Establishment of natural structure-effect correlation (NSEC) based on natural products. • Integration of NCEC and NSEC to screen active compounds for the first time. Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC 50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC 50 values. The structure–activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei ". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants. [ABSTRACT FROM AUTHOR]

• A novel strategy to discover selective enzyme inhibitors was proposed. • A total of 136 compounds were identified from five citrus herbs. • Selective α-glucosidase/acetylcholinesterases inhibitors were discovered. • The direct connection between citrus herbs and biological targets were established. • The opposite structure-activity relationships on different targets were observed. The lack of direct connection between traditional herbal medicines and multiple biological targets is a bottleneck in herbal research and quality evaluation. To solve this problem, a strategy for the discovery of active ingredients from function-similar herbal medicines based on multiple biological targets was proposed in this article. The technical route includes chromatographic separation, mass spectrometry analysis, enzymatic activity detection, pharmacophore analysis and molecular docking. Five citrus herbs of Citri Reticulatae Pericarpium (CRP), Citri Exocarpium Rubrum (CER), Citri Grandis Exocarpium (CGE), Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) were used as the research objects. A total of 136 chemical components were identified from above five herbs based on LC-Q-TOF-MS/MS and database matching. The extracts of the five herbs showed obvious inhibitory effects on α-glucosidase and acetylcholinesterase in a concentration-dependent manner. Interestingly, the different types of components in the herbs exhibited selectivity for different targets: flavanone glycosides are effective on α-glucosidase but ineffective on acetylcholinesterase; polymethoxyflavonoids are effective on acetylcholinesterase but ineffective on α-glucosidase. Furthermore, we found for the first time that the components in citrus herbs exhibit opposite structure-activity relationships on the above two targets. For example, the methoxy group can enhance the activity of compounds on acetylcholinesterase but weaken the activity of compounds on α-glucosidase. The selective action is a supplement to the "multi-components, multi-targets" system of herbal medicines. Pharmacophore analysis and molecular docking were applied to explore the interaction between active ingredients and biological targets from the perspective of ligands and receptors, respectively. By combining the above multiple technologies, a strong connection among herbal medicines, chemical components and multiple biological targets was established. This work not only helps to understand the similar function of citrus herbs for the treatment of diabetes and Alzheimer's disease, but also provides selective lead compounds for the development of related drugs. This strategy is also helpful to improve the quality evaluation of citrus herbs from the perspective of biological activity. [ABSTRACT FROM AUTHOR]

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3–16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright. [ABSTRACT FROM AUTHOR]