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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]

A new phenolic compound oleiphenol (1), and a new dihydrochalcone oleifechalcone (2) along with seven known compounds (3-9) were isolated from the fruit shell of Camellia oleifera Abel. The planar structures of compounds 1 and 2 were determined on the basis of extensive spectroscopic analyses (IR, UV, NMR, and HR-ESI-MS) and comparison with literature data. The absolute configurations of the new structures were determined by ECD calculations and chemical methods. In addition, compounds 1-9 underwent a series of pharmacological activity tests, including cytotoxic, anti-inflammatory, anti-RSV and antioxidant activities. [ABSTRACT FROM AUTHOR]

Thirteen undescribed dimeric Erythrina alkaloids, named as erythrivarines A1–A13, were isolated from the barks of Erythrina variegata L. and. Their structures were determined on the basis of NMR, UV and mass spectral analyses. Dimeric Erythrina alkaloid with a C-8/8′ linkage in erythrivarine A1 was not yet reported. Representative dimers from titled plant were used to prove their occurrence as natural products by LC − MS detection. Additionally, simultaneous investigation enabled us to propose the natural property of seemingly artificial Erythrina alkaloid with acetonyl group. Thirteen undescribed dimeric Erythrina alkaloids were isolated. Dimeric Erythrina alkaloid with a C-8/8′ linkage in erythrivarine A1 is not yet reported. Representative dimers from titled plant were proved their occurrence as natural products by LC-MS detection, which enabled us to propose the natural property of seemingly artificial products with acetonyl group. [Display omitted] [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]

This study aimed to investigate the protective effect of Apocynum venetum leaf extract (AVLE) on an in vitro model of ischemia-reperfusion induced by oxygen and glucose deprivation (OGD) and further explored the possible mechanisms underlying protection. Cell injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage; cell viability was measured by XTT reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8, and -9 activation and Bcl-2/Bax protein expression were determined by Western blot analysis. We report that treatment with AVLE (5 and 50 µg/mL) effectively reduced neuronal cell death and relieved cell injury induced by OGD. Moreover, AVLE decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspase-3 and -8 and Bax, and inhibited the reduction of Bcl-2 expression. These findings indicate that AVLE protects against OGD-induced injury by inhibiting apoptosis in rat cortical neurons by down-regulating caspase-3 activation and modulating the Bcl-2/Bax ratio. La présente étude a eu pour but d'examiner l'effet protecteur d'un extrait de feuilles d'Apocynum venetum (AVLE) sur un modèle in vitro d'ischémie-reperfusion induite par la privation d'oxygène et de glucose (POG), et d'explorer les mécanismes de protection possibles. La lésion cellulaire a été évaluée par microscopie à contraste de phase et quantifiée par la mesure de la fuite de lactate déshydrogénase (LDH), et la viabilité cellulaire a été examinée par le test de réduction du XTT. L'apoptose neuronale a été déterminée par cytométrie de flux, et la microscopie électronique a été utilisée pour examiner les modifications morphologiques des neurones. L'activation des caspase-3, -8 et -9 et l'expression protéique de Bcl2/Bax ont été déterminées par transfert de Western. Le traitement par AVLE (5 et 50 µg/mL) a diminué efficacement la mort cellulaire neuronale et éliminé la lésion cellulaire induite par la POG. De plus, l'AVLE a diminué le pourcentage de neurones apoptotiques, éliminé la lésion morphologique neuronale, supprimé la surexpression de Bax et des caspase-3 et -8 actives, et inhibé la réduction de l'expression de Bcl-2. Ces résultats indiquent que l'AVLE assure une protection contre la lésion induite par la POG en inhibant l'apoptose dans les neurones corticaux des rats en régulant négativement l'activation de la caspase-3 et en modulant le rapport Bcl-2/Bax. [ABSTRACT FROM AUTHOR]

Aim of the study: To investigate the neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides (GLPS) on cerebral ischemic injury in rats, and to explore the involved mechanisms. Materials and methods: Two models [middle cerebral artery occlusion (MCAO) in Sprague–Dawley (SD) rats and oxygen and glucose deprivation (OGD) in primary cultured rat cortical neurons] were employed to mimic ischemia–reperfusion (I/R) damage, in vivo and in vitro, respectively. Cerebral infarct area was measured by tetrazolium staining, and neurological functional deficits were assessed at 24h after I/R. Neuronal apoptosis was studied by Nissl staining and DNA fragmentation assay. Neuronal injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage, cell viability was measured by sodium 3′-1- (phenylaminocarbonyl)-3, 4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid (XTT) reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8 and -9 activation and Bcl-2, Bax protein expression were determined by western blot analysis. Results: Oral administration of GLPS (100, 200 and 400mg/kg) significantly reduced cerebral infarct area, attenuated neurological functional deficits, and reduced neuronal apoptosis in ischemic cortex. In OGD model, GLSP (0.1, 1 and 10μg/ml) effectively reduced neuronal cell death and relieved cell injury. Moreover, GLPS decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspases-3, -8 and -9 and Bax, and inhibited the reduction of Bcl-2 expression. Conclusions: Our findings indicate that GLPS protects against cerebral ischemic injury by inhibiting apoptosis by downregulating caspase-3 activation and modulating the Bcl-2/Bax ratio. [Copyright &y& Elsevier]

Objective. To systematically evaluate the efficacy and safety of XFZYD for coronary heart disease (CHD). Methods. A comprehensive literature search of randomized controlled trials using XFZYD for CHD was conducted in 10 electronic databases from their establishment to December 20, 2020. The researchers screened the relevant trials in NoteExpress, extracted the data in duplicate independently, assessed the risk of bias in the trials using the Cochrane collaboration tool, and then used Rev Man 5.3 for data analysis. Results. 30 trials with 3126 participants were included for meta-analysis. The results showed that the clinical effects of XFZYD and its combination with chemical drugs (CD) were 1.13 (RR; 1.13; 95% CI, 1.03 to 1.24) and 1.26 (RR; 1.26; 95% CI, 1.20 to 1.32) times those of CD, respectively. And, it could also improve electrocardiogram effect, which was 1.63 (RR; 1.63; 95% CI, 1.04 to 2.53) times that of CD. XFZYD could not only decrease duration of angina pectoris and improve vascular endothelial function but also obviously reduce the TCM syndrome score. When used in combination with CD, it could also lower AF, correct the dyslipidemia, and reduce the blood viscosity. Conclusion. These results demonstrated that XFZYD had great advantages in treating CHD with no obvious adverse reactions. Therefore, it is believed that XFZYD is more suitable for CHD patients with clinical indicators of dyslipidemia, high blood viscosity, or vascular endothelial dysfunction. This study is the first systematic review and meta-analysis with some unique ways, including its comprehensiveness, large-scale search, the novelty of findings, and transparent approach. [ABSTRACT FROM AUTHOR]

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (Tw HF). TG tablets are the representative Tw HF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG. • Tripterygium glycosides (TG) triggered significant testicular injury in mice. • Celastrol was the main toxic component of TG-induced toxicity to mouse spermatogonia GC-1 cell line. • TG and celastrol induced the autophagy of spermatogonia cells contributed to its testicular toxicity. [ABSTRACT FROM AUTHOR]

We investigated the neuroprotective effects of Apocynum venetum leaf extract (AVLE) on a rat model of cerebral ischemia-reperfusion injury and explored the underlying mechanisms. Rats were randomly divided into five groups: sham, ischemia-reperfusion, AVLE125, AVLE250, and AVLE500. Cerebral ischemia was induced by 1.5 h of occlusion of the middle cerebral artery. Cerebral infarct area was measured by tetrazolium staining at 24 and 72 h after reperfusion, and neurological function was evaluated at 24, 48 and 72 h after reperfusion. Pathological changes on the ultrastructure of the blood-brain barrier (BBB) were observed by transmission electron microscopy. BBB permeability was assessed by detecting leakage of Evan's blue (EB) dye in brain tissue. The expression and activities of matrix metalloproteinase (MMP)-9/-2 were measured by western blot analyses and gelatin zymography at 24 h after reperfusion. AVLE (500 mg/kg/day) significantly reduced cerebral infarct area, improved recovery of neurological function, relieved morphological damage to the BBB, reduced water content and EB leakage in the brain, and downregulated the expression and activities of MMP-9/-2. These findings suggest that AVLE protects against cerebral ischemia-reperfusion-induced injury by alleviating BBB disruption. This action may be due to its inhibitory effects on the expression and activities of MMP-9/-2. [ABSTRACT FROM AUTHOR]

Abstract: Two new α-pinene derivatives (1–2) were isolated from the aerial parts of Angelica sinensis. Their structures were determined by spectroscopic and chemical methods to be 6β,9-dihydroxy-(+)-α-pinene (1) and 9-hydroxy-(+)-α-pinene-6β-O-D-glucoside (2). In the anticoagulative assay, compounds 1 and 2 exhibited weak antithrombin activity and strong antiplatelet aggregation activity in vitro. [Copyright &y& Elsevier]

Based on the notion of traditional Chinese medicine, the theory of invigorating the circulation of blood is a prominent treatment for cancer in clinic. Therefore, Salvia miltiorrhiza Bunge, as a representative of Chinese medicine of invigorating the circulation of blood, has been proved to be an effective medicinal herb for treating cancer. To clarify the anti-cancer effect of Salvia miltiorrhiza Bunge aqueous extract (SMAE) on colorectal cancer (CRC) and investigate whether the therapeutic effect of SMAE was mediated by attenuating the infiltration of tumor-associated macrophages (TAMs) into the tumor microenvironment (TME). High-performance liquid chromatography (HPLC) was used for determined the main compounds of SMAE. MC38 cells were subcutaneously injected into the mice to establish the mouse model of CRC. Tumor growth curve was detected by tumor volume measurement. The model group received distilled water irrigation once a day. SMAE-treated group received 5 g/kg or 10 g/kg SMAE once a day. Anti-PD-L1 treated group received 5 mg/kg anti-PD-L1 once every three days. Protein expression of Cox2 and PD-L1 was determined by Western blot assay. The secretion levels of PGE2, IL-1β, IL-6, MCP-1, and GM-CSF were evaluated through ELISA. The mRNA expression of CSF1 , CCL2 , CXCL1 , CXCL2 , and CXCL3 was measured by using RT-qPCR. Staining of Ki67, TUNEL and Caspase3 was used to investigate cell proliferation and apoptosis. Immunohistochemical staining was used to determine CD8+ T cell distribution. H&E staining was used to confirm histopathological changes. The expressions of F4/80 and CD68 were measured by flow cytometry to identify macrophages in tumors and lymph nodes. The number of CD8+ T cells and the expression of PD-1, IFN-γ, and Granzyme B (GZMB) were determined by flow cytometry. SMAE significantly retarded the growth of MC38 mouse colorectal cancer. SMAE strikingly inhibited the expression of Cox2 and impaired the secretion of PGE2 in tumors, contributing to the attenuated intra-tumoral infiltration of TAMs via Cox2/PGE2 cascade. Meanwhile, SMAE augmented anti-tumor immunity by the elevated proportion of IFN-γ+ CD8+ T cells and GZMB+ CD8+ T cells, which decreased the tumor load. Furthermore, the combination of SMAE and anti-PD-L1 showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in MC38 xenograft model. SMAE attenuated the infiltration of TAMs into tumors and synergized with anti-PD-L1 to treat CRC via modulating Cox2/PGE2 cascade. SMAE inhibited the Cox2-mediated release of PGE2 and thus reshaped the tumor inflammatory microenvironment, resulting in the attenuated infiltration of TAMs while elevated the infiltration and killing function of CD8+ T cells. [Display omitted] • SMAE delayed tumor progression through modulating Cox2/PGE2 cascade in the mouse CRC model. • SMAE inhibited inflammation levels and hindered the infiltration of TAMs into the TME. • SMAE enhanced the infiltration and function of CD8+ T cells. • SMAE and PD-L1 blockade produced the synergistic anti-cancer impact in the mouse CRC model. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance : Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. Aim of the study : This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). Materials and methods : Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. Results : Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus , Romboutsia , Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. Conclusion : Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia , Akkermansia and UCG_005 and water channels of AQP1 and AQP3. [Display omitted] • For constipation relief, Sennoside A should be used at regular dose for less than 7 days. • Sennoside A exerts the laxative effect by regulating gut microbiota and aquaporins. • The optimal time is obtained through a comprehensive analysis of fecal index, intestinal histopathology, gut microbiota and aquaporins. [ABSTRACT FROM AUTHOR]

The dried roots of Euphorbia kansui T.N. Liou ex T.P. Wang have been traditionally used for edema in China. However, the severe toxicity caused by Euphorbia kansui has seriously restricted its clinical application. Therefore, in order to study the material basis of the toxicity attenuation effect of processing with vinegar, a rapid, sensitive, validated and reliable UPLC–MS/MS method was developed to determine twelve compounds in ethyl acetate extracts of Euphorbia kansui before and after fry-baked with vinegar simultaneously. Meanwhile, the study of their toxic effect on zebrafish was conducted. Chromatographic separation was accomplished on Waters BEH C 18 UPLC column. 0.3% formic acid in water and acetonitrile were used as mobile phase with a flow rate of 0.40 mL/min and a temperature at 30 °C. The analysis was performed in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). Furthermore, the toxic research results indicated that the toxicity of Euphorbia kansui was decreased after vinegar-processed, which might because of the increase in the content of 5- O -benzoyl-20-deoxyingenol and the decrease in the contents of the remaining terpenoids in ethyl acetate extracts of Euphorbia kansui fry-baked with vinegar. This study demonstrated that the method used is a powerful approach to determine the content of twelve compounds that responsible for the toxic effect of Euphorbia kansui at the same instant. And provided the experimental evidence for the rationale behind the reduction of toxicity. [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]

Scutellarin, which is extracted from the dried plant of Erigeron breviscapus, has been reported to protect the neural injury against excitotoxicity induced by ischemia. However, there are a few studies on the protective effects of scutellarein, which is the main metabolite of scutellarin in vivo. Thus, this study investigated the neuroprotective effects of scutellarein on cerebral ischemia/reperfusion in rats by bilateral common carotid artery occlusion (BCCAO) model, through the analysis of endogenous amino acids using HILIC-MS/MS, and evaluation of Ca2+ concentration together with Ca2+-ATPase activity. The results showed that scutellarein having good protective effects on cerebral ischemia/reperfusion might by decreasing the excitatory amino acids, increasing the inhibitory amino acids, lowing intracellular Ca2+ level, and improving Ca2+-ATPase activity, which suggested that scutellarein might be a promising potent agent for the therapy of ischemic cerebrovascular disease. [ABSTRACT FROM AUTHOR]

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: 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]

Abstract: Two new pentacyclic triterpenes and eight known pentacyclic triterpenes were isolated from the petroleum ether extract of Liquidambaris Resina. The structural elucidation of these compounds was determined by spectroscopic data interpretation. Their cytotoxic and antiplatelet aggregation activities were examined to find potent cytotoxic and antiplatelet aggregation compounds from natural resources. The results showed that 3-keto oleane triterpenes had strong cytotoxicity against MDA-MB-435S cancer cells and that 28-carboxyl oleane triterpenes possessed significant inhibition of platelet aggregation induced by ADP. [Copyright &y& Elsevier]

Abstract: Aim of the study: This present study was carried out to evaluate the anti-inflammatory and analgesic effects of 85% ethanol extract (EE) of Commiphora myrrha and its different fractions partitioned with petroleum ether extract (EPE), ethyl acetate extract (EEA), n-butanol extract (EBu), and the water extract (ECY). Moreover, the chemical constituents in EPE were analyzed and identified by UPLC–QTOF/MS/MS. Materials and methods: The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin. In addition, we determined the levels of PGE2 in the edema paw. While the analgesic activity was examined against thermally and chemically induced nociceptive pain in mice, using the acetic acid and hot-plate test methods. The effects of the administration of dolantin or indomethacin were also studied for references. The components in EPE were analyzed by the ultra-performance liquid chromatography coupled with mass spectrum. Results: In the anti-inflammatory test, EE inhibited the development of paw swelling induced by formalin significantly. The pharmacological activities of the petroleum ether fraction (EPE) were stronger than the EE extract and other fractions at the dose of 100mg/kg, and furthermore significantly decreased the levels of inflammatory factor PGE2 in the edema paw tissue at the fourth hour after formalin injection. It has been also shown that the ethanol extract (EE) significantly reduced acetic acid-induced writhing response in mice at the dose of 200mg/kg, and 100mg/kg. The petroleum ether fraction (EPE) showed significant analgesic activity in the model at the dose of 100mg/kg (p <0.01), and the ethyl acetate fraction (EEA) exhibited less analgesic activity (p <0.05). All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. The UPLC–MS/MS chromatogram analysis of EPE stated that EPE contains the ingredients of sesquiterpenes, diterpenes, and diterpenic acids. Moreover, seven main compounds were identified. Conclusion: These data demonstrated that the EE and EPE posses analgesic and anti-inflammatory activities and may support the fact the traditional application of this herb in treating various diseases associated with inflammatory pain. [Copyright &y& Elsevier]