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Δευτέρα 3 Ιουνίου 2019

Natural Medicines

Rapid discovery and identification of the anti-inflammatory constituents in Zhi-Shi-Zhi-Zi-Chi-Tang

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Hai-Qiang WANG, Yun-Xiang ZHU, Yi-Ning LIU, Ruo-Liu WANG, Shu-Fang WANG

Abstract

The anti-inflammatory active ingredients of Zhi-Shi-Zhi-Zi-Chi-Tang (ZSZZCT), a traditional Chinese medicine formula, were predicted and identified using an approach based on activity index, LC-MS, semi-preparative LC and NMR. Firstly, the whole extract of ZSZZCT was analyzed using liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) and liquid chromatography - ion trap mass spectrometry (LC-IT-MS), 79 constituents were detected and 39 constituents were identified unambiguously or tentatively. Subsequently, the whole extract of the formula was separated into multiple components and the activity index method was used to calculate index values of the 79 constituents by integrating the chemical and pharmacological information of multiple components. Four polymethoxyl flavones were predicted as the major active constituents according to the activity index values. Furthermore, three polymethoxyl flavones were prepared using the strategy with semi-preparative LC guided by LC-MS, and their anti-inflammatory activities were validated. The results show that three polymethoxyl flavones with higher positive index values, i.e., 3, 5, 6, 7, 8, 3′, 4′-heptamethoxyflavone, 3-hydroxynobiletein and tangeretin had significant anti-inflammatory effects. In conclusion, the predicted results indicated that the activity index method is feasible for the accurate prediction of active constituents in TCM formulae.



New octadecanoid derivatives from the seeds of Ipomoea nil

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Xiu-Qing SONG, Jun-Sheng ZHANG, Shu-Juan YU, Jin-Hai YU, Hua ZHANG

Abstract

Four new octadecanoid derivatives (1–4) including a pair of enantiomers (1/2), along with 12 known analogues (5–16), were isolatedfrom the seeds of Ipomoea nil. Their structures were determined by detailed spectroscopic analyses and comparison with reported data of structurally related compounds, with the absolute configurations of 1 and 2 being assigned by an in situ dimolybdenum ECD method. Our bioassays revealed that these isolates did not show ABTS radical scavenging activity while 10 and 13 displayed better α-glucosidase inhibitory activity than the positive control acarbose (IC50 167.7 ± 1.55 μmol·L−1), with IC50 of 92.73 ± 3.12 and 11.39 ± 2.18μmol·L−1, respectively.



Jatrogricaine A: a new diterpenoid with a 5/6/6/4 carbon ring system from the stems of Jatropha podagrica

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Lin CHEN, Jia-Luo HUANG, Lei ZHANG, Hai-Yan TIAN, Sheng YIN

Abstract

Jatrogricaine A (1), a new diterpenoid possessing a 5/6/6/4 carbon ring system, together with eight known diterpenoids (2–9) were isolated from the stems of Jatropha podagrica. Their structures were elucidated by extensive spectroscopic methods and the absolute configuration of 1 was determined by single crystal X-ray diffraction analysis. All compounds were evaluated for their anti-inflammatory activities in vitro, and compound 3 showed significant inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells with an IC50 of 13.44 ± 0.28 μmol·L−1, being comparable to the positive control, quercetin (IC50 17.00 ± 2.10 μmol·L−1).



Eight new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Cheng-Yao MA, Jia-Hui LU, Xiang LI, Xiao LIU, Jian-Wei CHEN

Abstract

Eight new annonaceous acetogenins, squamotin A-D (1–4), annosquatin IV-V (5 and 6), muricin O (7) and squamosten B (8), together with four known ones (9–12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1–9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.



A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Yong-Li HUA, Qi MA, Zi-Wen YUAN, Xiao-Song ZHANG, Wan-Ling YAO, Peng JI, Jun-Jie HU, Yan-Ming WEI

Abstract

Danggui Buxue Tang (DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague-Dawley(SD) rats were randomly divided into 3 groups including control (NC, Saline), the DBT (at a dose of 8.10 g−1), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry (LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component-target protein interaction network and establish a component, protein and hub metabolite protein-protein interaction (PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-l-methionine, glycine, l-cysteine, arachidonic acid (AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.



Involvement of mitochondrial apoptotic pathway and MAPKs/NF-κ B inflammatory pathway in the neuroprotective effect of atractylenolide III in corticosterone-induced PC12 cells

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Wen-Xia GONG, Yu-Zhi ZHOU, Xue-Mei QIN, Guan-Hua DU

Abstract

Atractylenolide III (ATL-III), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-III on corticosterone injured rat phaeochromocytoma (PC12) cells. Our results demonstrate that ATL-III increases cell viability and reduces the release of lactate dehydrogenase (LDH). The results suggest that ATL-III protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca2+ overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-ΚB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-III protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-III may serve as a therapeutic agent in the treatment of depression.



Astragalus membranaceus improves therapeutic efficacy of asthmatic children by regulating the balance of Treg/Th17 cells

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Wei WANG, Qing-Bin LIU, Wei JING

Abstract

Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission were divided into two combination group (control group, the combination of budesonide and terbutaline) and A. membranaceus group (treatment group, the combination of budesonide, terbutaline and A. membranaceus). The therapeutic results were compared between two groups after 3-month therapy. Porcine peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by using density gradient centrifugation on percoll. The levels of FoxP3, EGF-β, IL-17 and IL-23 from PBMCs and serum IgE were measured. The relative percentage of Treg/Th17 cells was determined using flow cytometry. The main components of A. membranaceus were calycosin-7-O-glucoside, isoquercitrin, ononin, calycosin, quercetin, genistein, kaempferol, isorhamnetin and formononetin, all of which may contribute to asthma therapy. Lung function was significantly improved in the treatment group when compared with a control group (P < 0.05). The efficacy in preventing the occurrence of childhood asthma was higher in the treatment group than the control group (P < 0.05). The levels of IgE, IL-17 and IL-23 were reduced significantly in the treatment group when compared with the control group, while the levels of FoxP3 and TGF-β were increased in the treatment group when compared with the control group (P < 0.05). A. membranaceus increased the percentage of Treg cells and reduced the percentage of Th17 cells. A. membranaceus is potential natural product for improving the therapeutic efficacy of combination therapy of budesonide and terbutaline for the children with asthma remission by modulating the balance of Treg/Th17 cells.



Roles of integrin in tumor development and the target inhibitors

Publication date: April 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 4

Author(s): Zhao-He LI, You ZHOU, You-Xiang DING, Qing-Long GUO, Li ZHAO

Abstract

Integrin is a large family of cell adhesion molecules (CAMs) which involves in the interaction of cells/cells and cells/ extracellular matrix (ECM) to mediate cell proliferation, differentiation, adhesion, migration, etc. In recent years, aberrant expression of integrin has been clearly found in many tumor studies, indicating that integrin is closely related to tumor formation and development. Meanwhile, it has effects on tumor cell differentiation, cell migration, proliferation and tumor neovascularization. The study of drugs targeting integrins is of great significance for the clinical treatment of tumors. Because of its important role in tumorigenesis and development, integrin has become a promising target for the treatment of cancer. This review summarizes the role of integrin in tumor development and the current state of integrin inhibitors to provide a valuable reference for subsequent research.



Quantification of Panax notoginseng saponins metabolites in rat plasma with in vivo gut microbiota-mediated biotransformation by HPLC-MS/MS

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Yin-Ping GUO, Man-Yun CHEN, Li SHAO, Wei ZHANG, Tai RAO, Hong-Hao ZHOU, Wei-Hua HUANG

Abstract

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.



Two new nimbolinin- and trichilin-class limonoids isolated from the fruits of Melia azedarach

Publication date: March 2019

Source: Chinese Journal of Natural Medicines, Volume 17, Issue 3

Author(s): Lu QIU, Li HENG, Rong XU, Jun LUO, Yi LI

Abstract

Two new furan fragment isomerized limonoids, meliazedalides A and B (compounds 1 and 2), were isolated from the fruits of Melia azedarach Linn.. Their chemical structures were elucidated on the basis of HR-ESI-MS and 1D and 2D NMR data, which belonged to nimbolinin- and trichilin-class, respectively. Compound 2 exhibited weak inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with IC50 being 37.41 μmol·L−1.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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