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Background: Determination of batch-to-batch consistency of botanical drugs (BDs) has long been the bottleneck in quality evaluation primarily due to the chemical diversity inherent in BDs. This diversity presents an obstacle to achieving comprehensive standardization for BDs. Basically, a single detection mode likely leads to substandard analysis results as different classes of structures always possess distinct physicochemical properties. Whereas representing a workaround for multi-target standardization using multi-modal data, data processing for information from diverse sources is of great importance for the accuracy of classification. Methods: In this research, multi-modal data of 78 batches of Guhong injections (GHIs) consisting of 52 normal and 26 abnormal samples were acquired by employing HPLC-UV, -ELSD, and quantitative 1H NMR (q1HNMR), of which data obtained was then individually used for Pearson correlation coefficient (PCC) calculation and partial least square-discriminant analysis (PLS-DA). Then, a mid-level data fusion method with data containing qualitative and quantitative information to establish a support vector machine (SVM) model for evaluating the batch-to-batch consistency of GHIs. Results: The resulting outcomes showed that datasets from one detection mode (e.g., data from UV detectors only) are inadequate for accurately assessing the product's quality. The mid-level data fusion strategy for the quality evaluation enabled the classification of normal and abnormal batches of GHIs at 100% accuracy. Conclusions: A quality assessment strategy was successfully developed by leveraging a mid-level data fusion method for the batch-to-batch consistency evaluation of GHIs. This study highlights the promising utility of data from different detection modes for the quality evaluation of BDs. It also reminds manufacturers and researchers about the advantages of involving data fusion to handle multi-modal data. Especially when done jointly, this strategy can significantly increase the accuracy of product classification and serve as a capable tool for studies of other BDs. [ABSTRACT FROM AUTHOR]

Background: Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice. Methods: Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment. Results: Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days' treatment (p < 0.05). The oral mucositis score of NCE group was significantly higher than other groups (p < 0.05). The differences in histopathology scores between the NCE and other groups were statistically significant (p < 0.01). Conclusions: NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK. [ABSTRACT FROM AUTHOR]

Ten diterpenoids including three new abietanes (1–3) were isolated from the twigs and needles ofPodocarpus imbricatus, an endangered conifer growing in a Cantonese garden. The new structures were established by means of spectroscopic methods. Among the isolates, 3β-hydroxy-abieta-8,11,13-trien-7-one (5), decandrin G (6), and 7,15-pimaradien-18-oic acid (8) showed significant anti-neuroinflammatory activities by inhibiting the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells, with IC50values of 3.7, 11.1, and 4.5 μM, respectively. [ABSTRACT FROM PUBLISHER]

Three new oleanane-type triterpene saponins, namely licorice-saponin M3 (1), licorice-saponin N4 (2), and licorice-saponin O4 (3), an artificial product (4), as well as five known triterpene glucuronides (5–9), were isolated from the roots of Glycyrrhiza glabra L. Their structures were established using 1D and 2D NMR spectroscopy, mass spectrometry, and by comparison with spectroscopic data reported in the literature. The inhibitory effects of the selected compounds on neuraminidase were evaluated, and the preliminary structure–activity relationship was also predicted. [ABSTRACT FROM AUTHOR]

Abstract: The present study was the first time to investigate the effects of celastrol, derived from Trypterygium wilfordii Hook F. (“Thunder of God Vine”), a traditional Chinese medicine plant, on the metabolism of model probe substrates of CYP isoforms, CYP1A2, CYP2C11, CYP2D6, CYP2E1 and CYP3A2, which are important in the metabolism of a variety of xenobiotics. The effects of celastrol on CYP1A2 (phenacetin O-deethylase), CYP2C11 (tolbutamide 4-hydroxylase), CYP2D6 (dextromethorphan O-demethylation), CYP2E1 (chlorzoxazone 6-hydroxylase) and CYP3A2 (testosterone 6β-hydroxylase) activities were investigated using rat liver microsomes. HPLC-DAD was used to measure the model substrates and metabolites. Inhibition of rat CYP isoforms (IC50) by celastrol in potency order was CYP2C11 (10.2μM)>CYP3A2 (23.2μM)>CYP1A2 (52.8μM)>CYP2E1 (74.2μM)>CYP2D6 (76.4μM). Enzyme kinetic studies showed that the celastrol was not only a competitive inhibitor of CYP1A2 and 2C11, but also a mixed-type inhibitor of CYP3A2, with K i of 39.2μM, 7.05μM and 14.2μM, respectively. The data indicate that celastrol inhibited the metabolism of CYP1A2, 2C and 3A substrates in rat liver in vitro with a different mode of inhibition. These in vitro studies of celastrol with CYP isoforms may be helpful for the development and application of celastrol as a promising anti-cancer agent. Further systematic studies in humans in vitro and in vivo are needed to identify the interactions of celastrol with cytochrome P450s. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Xiang–Fu–Si–Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats. Materials and methods: Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC–MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration–time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA). Results: There were statistically significant differences (P<0.05) in C max, T max, AUC 0−t , AUC 0−∞ , MRT 0−t , MRT 0−∞ and CL/F between normal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C Spleen>C Liver>C Kidney>C Uterus>C Heart>C Lung>C Ovary>C Brain>C Thymus, C M-60min>C M-120min>C M-30min>C C-60min>C C-120 min>C C-30 min. The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats׳ tissues at different time points had significant difference (P<0.05). Conclusions: This study was the first report about pharmacokinetic and tissue distribution investigation in dysmenorrheal symptom animals. The results indicated that berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine have higher uptake and slower elimination in the rats with dysmenorrheal syndrome, which suggests that the rate and extent of drug metabolism were altered in dysmenorrheal syndrome rats. And the results also demonstrated that berberine, protopine and tetrahydropalmatine in normal and dysmenorrheal symptom rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in dysmenorrheal symptom animals. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance:: Abelmoschus manihot (L.) Medik. var. manihot is one of the most commonly used Chinese medicines and has played an important role in treating chronic glomerulonephritis and diabetic nephropathy. Aim of the study:: Metabolites identification of traditional Chinese medicine (TCM) is a complex and time-consuming process due to the complicity of TCM and subsequent large number of detected ions. In this paper, UPLC–MS combined with pattern recognition analysis approach were used to simplify and quicken the identification of the metabolites of Abelmoschus Manihot. Materials and methods:: Rat urine samples were collected before (as control sample) and after Abelmoschus Manihot administration. Pattern recognition analysis method was used to differentiate components between Abelmoschus Manihot-treated group and its controlled comparison. These components could be considered as Abelmoschus Manihot-related metabolites in vivo. Results:: LC–MS based metabolomics could be an advanced tool to help us find metabolites with regards to its capacity of processing large datasets, differentiating and classifying of sample groups, as well as its indiscriminative nature of biomarker and metabolite identification. Using this method, seven metabolites were identified, which are flavonoid aglycone glucuronidation, sulfatation, and methylation metabolites. Conclusion:: Our results showed that UPLC–MS based- pattern recognition analysis approach can be used to quickly identify Abelmoschus Manihot related metabolites in biological fluids. Furthermore, this work demonstrates the potential application of combining the UPLC–MS approach with the metabolomics approach in identifying the metabolites of TCM. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Hypericum perforatum (St. John''s wort) is an important anti-depressant herb used in clinic and commonly prescribed for mild depression. Hyperoside is one of the major components of H. perforatum and is also detected in many plant species such as Abelmoschus manihot, Black Currant, Rosa agrestis, Apocynum venetum and Nelumbo nucifera. Aim of the study: As the hyperoside showed CNS (central nervous system) protective activity (e.g. anti-depressant-like effect), the possibility of hyperoside or its metabolites to reach CNS should be investigated. Moreover, the pharmacokinetics profile of hyperoside or its metabolites in rat brain should be studied for further elucidating the mechanism of hyperoside action on CNS. Material and Methods: A simple method for simultaneous determination of unbound hyperoside and its metabolite 3′-O-methyl-hyperoside in rat brain was developed by using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS) and microdialysis technique. This method was applied for pharmacokinetics study of hyperoside and 3′-O-methyl-hyperoside in rat brain after intragastric (i.g.) and intraperitoneally (i.p.) administration of hyperoside in vivo. Results: Results showed that neither hyperoside nor its metabolites were detected in rat brain after i.g. administration but both compounds could be detected after i.p. administration. Considering the activity of hyperoside through both i.g. and i.p. administration, our results imply that the active components of hyperoside in vivo might be different. Therefore, further studies are needed to identify the active components of hyperoside in vivo through these two different routes. Moreover, non-oral administration route (e.g., i.p.) should be further investigated and be explored to obtain higher bioavailability and better activity for hyperoside. Our results also showed that the real existing form of hyperoside in rat brain were hyperoside and its methylated metabolite with maximum concentration to be 63.78ng/mL and 24.66ng/mL after 20mg/kg i.p. administration, respectively. Therefore, a more reasonable concentration of hyperoside should be considered in in vitro assay to reflect the real situation of hyperoside concentration in vivo. Conclusion: Due to the wide use of herbal remedies containing hyperoside, our investigation will contribute to further clarifying the action of this substance. Moreover, this method will be applied for clinical pharmacokinetics study of hyperoside and its metabolite as well as herbs that contain hyperoside. [Copyright &y& Elsevier]

Abstract: A new coumestan, named glycyrurol, and nine phenolic compounds were isolated from the ethyl acetate extract of the roots and rhizomes of Glycyrrhiza uralensis. Their structures were elucidated based on spectroscopic analysis and literature data, and anticoagulative assay found significant antithrombotic activity of compounds 4, 8 and 10. [Copyright &y& Elsevier]