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ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM). The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man (OMIM). The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets, and STRING was adopted to build a protein-protein interaction (PPI) network. DAVID was used for gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin, and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor (TNF)-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained, of which ceramide, 6'-O-β-D-glucosylgentiopicroside, cerebroside, oleuropein, sphingomyelin, and cholesterol ferulate did not meet the screening conditions. Therefore, a total of 14 active ingredients were finally screened out, and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect, which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process, positive regulation of RNA polymerase Ⅱ promoter transcription, inflammatory response, protein synthesis, osteoclast differentiation, TNF signaling pathway, signaling pathways in cancer, mammalian target of rapamycin (mTOR) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H2O2-induced oxidative damage (P<0.05, P<0.01) and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide (LPS)-induced inflammation (P<0.05). ConclusionBased on the network pharmacology method, the mechanism of the multi-component, multi-target and multi-pathway treatment of OA by antler antler was explained, and the anti-inflammatory and antioxidant activities of antler antler were confirmed, which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.
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Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.
Assuntos
Medicamentos de Ervas Chinesas , Farmacocinética , Flavonoides , Farmacocinética , Scutellaria baicalensisRESUMO
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm) or normal saline as control (larger than 2000 nm). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.