butylidenephthalide and ferulic-acid

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Brain Edema; Cells, Cultured; Cerebrovascular Circulation; Coumaric Acids; Male; Mice, Inbred C57BL; Neurogenesis; Neurons; Neuroprotective Agents; Phthalic Anhydrides; Rats, Sprague-Dawley; Stroke; Stromal Cells; Vascular Endothelial Growth Factor A

Being a potential candidate for stroke treatment, bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) have been demonstrated to be able to enhance angiogenesis and proliferation of reactive astrocytes, which subsequently leads to the amelioration of neurological injury. Increasing evidence further indicates that combining BM-MSCs with certain agents, such as simvastatin, may improve therapeutic effects. Sodium ferulate (SF) and n-butylidenephthalide (BP), two main components of Radix Angelica Sinensis, are proven to be important regulators of stem cells in cell migration, differentiation, and pluripotency maintenance. This study aimed to investigate whether combining BM-MSCs with SF and BP had better therapeutic effect in the treatment of stroke, and the underlying molecular basis for the therapeutic effects was also investigated. The results showed that combination treatment notably reduced neurological injury after stroke and increased the expression of astrocyte-derived vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and von Willebrand factor-positive vascular density in the ischemic boundary zone as evaluated by immunofluorescence staining. After treatment with BM-MSCs plus SF and BP, astrocytes showed increased expression of VEGF and BDNF by upregulating protein kinase B/mammalian target of rapamycin (AKT/mTOR) expression in an oxygen- and glucose-deprived (OGD) environment. Human umbilical vein endothelial cells (HUVECs) incubated with the conditioned medium (CM) derived from OGD astrocytes treated with BM-MSCs plus SF and BP showed significantly increased migration and tube formation compared with those incubated with the CM derived from OGD astrocytes treated with BM-MSCs alone. These results demonstrate that combination treatment enhances the expression of astrocyte-derived VEGF and BDNF, which contribute to angiogenesis after cerebral ischemia, and the underlying mechanism is associated with activation of the astrocytic AKT/mTOR signaling pathway. Our study provides a potential therapeutic approach for ischemic stroke.

Topics: Animals; Astrocytes; Bone Marrow Cells; Brain Ischemia; Brain-Derived Neurotrophic Factor; Cells, Cultured; Coumaric Acids; Fluorescent Antibody Technique; Human Umbilical Vein Endothelial Cells; Humans; Male; Mesenchymal Stem Cells; Neovascularization, Physiologic; Phthalic Anhydrides; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Stroke; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A; von Willebrand Factor; Wound Healing

Studies have indicated that bone marrow stromal cell (BMSC) administration is a promising approach for stroke treatment. For our study, we chose sodium ferulate (SF) and n-butylidenephthalide (BP) combined with BMSC, and observed if the combination treatment possessed more significant effects on angiogenesis and neurogenesis post-stroke.. We established rat permanent middle cerebral artery occlusion (MCAo) model and evaluated ischemic volumes of MCAo, BMSC, SF + BP, Simvastatin + BMSC and SF + BP + BMSC groups with TTC staining on the 7th day after ischemia. Immunofluorescence staining of vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF), as well as immunohistochemistry staining of von Willebrand factor (vWF) and neuronal class III β-tubulin (Tuj1) were performed in ischemic boundary zone (IBZ), furthermore, to understand the mechanism, western blot was used to investigate AKT/mammalian target of rapamycin (mTOR) signal pathway in ischemic cortex. We also tested BMSC derived-VEGF and BDNF expressions by western blot assay in vitro.. SF + BP + BMSC group obviously decreased infarction zone, and elevated the expression of VEGF and the density and perimeter of vWF-vessels as same as Simvastatin + BMSC administration; moreover, its effects on BDNF and Tuj1 expressions were superior to Simvastatin + BMSC treatment in IBZ. Meanwhile, it showed that SF and BP combined with BMSC treatment notably up-regulated AKT/mTOR signal pathway compared with SF + BP group and BMSC alone post-stroke. Western blot results showed that SF and BP treatment could promote BMSCs to synthesize VEGF and BDNF in vitro.. We firstly demonstrate that SF and BP combined with BMSC can significantly improve angiogenesis and neurogenesis in IBZ following stroke. The therapeutic effects are associated with the enhancement of VEGF and BDNF expressions via activation of AKT/mTOR signal pathway. Furthermore, triggering BMSC paracrine function of SF and BP might contribute to amplifying the synergic effects of the combination treatment.

Topics: Animals; Brain Ischemia; Brain-Derived Neurotrophic Factor; Cell Shape; Cells, Cultured; Combined Modality Therapy; Coumaric Acids; Dose-Response Relationship, Drug; Flow Cytometry; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Models, Biological; Neovascularization, Physiologic; Neurogenesis; Phenotype; Phthalic Anhydrides; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Signal Transduction; Stroke; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A

To investigate the establishment and application methods of entropy-weight TOPSIS model in synthetical quality evaluation of traditional Chinese medicine with Angelica sinensis growing in Gansu Province as an example.. The contents of ferulic acid, 3-butylphthalide, Z-butylidenephthalide, Z-ligustilide, linolic acid, volatile oil, and ethanol soluble extractive were used as an evaluation index set. The weights of each evaluation index were determined by information entropy method. The entropyweight TOPSIS model was established to synthetically evaluate the quality of Angelica sinensis growing in Gansu Province by Euclid closeness degree.. The results based on established model were in line with the daodi meaning and the knowledge of clinical experience.. The established model was simple in calculation, objective, reliable, and can be applied to synthetical quality evaluation of traditional Chinese medicine.

Topics: 4-Butyrolactone; Angelica sinensis; Coumaric Acids; Drugs, Chinese Herbal; Entropy; Medicine, Chinese Traditional; Oils, Volatile; Phthalic Anhydrides

Ligusticum canbyi (J.M. Coult & Rose) is a medicinal understory forest species used in traditional rituals and ceremonies for spiritual enlightenment and improved mental health. Very little is known about the phytochemical complexity or diversity of L. canbyi tissues or extracts. The current study was undertaken to determine whether Ligusticum tissues and extracts contain specifically targeted biologically active phytochemicals such as: melatonin, serotonin, Z-ligustilide, E-3-butylidenephthalide, and ferulic acid and to investigate the untargeted phytochemical complexity of the entire L. canbyi metabolome. The results of these studies identified melatonin and serotonin in roots and shoots of L. canbyi and L. porteri. Z-ligustilide, E-butylidenephthalide, and ferulic acid were quantified in roots and shoots of L. canbyi. Metabolomic analysis detected approximately 34,000 compounds in each L. canbyi extract, and predictive analysis suggests the presence of more than 70 putative phthalide metabolites. The relative contribution of the known metabolites and the unknown markers to the antioxidant potential of root and shoot tissues were compared, and it was determined that the majority of the antioxidant capacity could be attributed to ferulic acid in the tissues. These data provide new understandings of the phytomedicinal composition and potential mechanisms of activity of L. canbyi extracts and tissues.

Topics: Antioxidants; Coumaric Acids; Drug Discovery; Indoles; Ligusticum; Melatonin; Metabolome; Metabolomics; Phthalic Anhydrides; Plant Roots; Plant Shoots; Serotonin

Pressurized liquid extraction, one of the most promising and recent sample preparation techniques, offers the advantages of reducing solvent consumption and allowing for automated sample handling. It is being exploited in diverse areas because of its distinct advantages. However, because the extraction is performed at elevated temperatures using PLE, thermal degradation could be a concern. Z-ligustilide, one of the biologically active components in Angelica sinensis, is an unstable compound, which decomposes rapidly at high temperature. In this study, we carried out a comparative study to evaluate PLE as a possible alternative to current extraction methods like Soxhlet and sonication for simultaneous extraction of Z-ligustilide, Z-butylidenephthalide and ferulic acid in A. sinensis. The operating parameters for PLE including extraction solvent, particle size, pressure, temperature, static extraction time, flush volume and numbers of extraction were optimized by using univariate approach coupled with central composite design (CCD) in order to obtain the highest extraction efficiency. Determination of Z-ligustilide, Z-butylidenephthalide and ferulic acid were carried out by means of high performance liquid chromatography with diode-array detector. The results showed that PLE was a simple, high efficient and automated method with lower solvent consumption compared to conventional extraction methods such as Soxhlet and sonication. PLE could be used for simultaneous extraction of Z-ligustilide, Z-butylidenephthalide and ferulic acid in A. sinensis.

Topics: 4-Butyrolactone; Algorithms; Angelica sinensis; Chromatography, High Pressure Liquid; Coumaric Acids; Particle Size; Phthalic Anhydrides; Pressure; Solvents; Temperature; Ultrasonics

To analyze the chemical components in Danggui (the roots of Angelica sinensis (Oliv.) Diel).. HPLC-MS/MS was used to identify the main components in Danggui. Furthermore, the MS fragmentation regularity of the phthalides was proposed. The mobile phase of HPLC consisted of 0.5% acetic acid in water and 0.5% acetic acid in acetonitrile, analytical column was Hypersil ODS2 (250 mm x 4.6 mm, 5 microm), flow rate 1.0 mL x min(-1), injected volume 2 microL. The ionization source was ESI in positive ion mode.. Ferulic acid, nine known phthalides and one unknown phthalide derivative were tentatively identified in chromatograms based on their MS data and the comparison of their UV spectra with those published in the literatures.. The structural information of phthalides was obtained via HPLC-MS/MS, which provides an accurate and fast method to identify the phthalides and provides more scientific information for quality control of Danggui.

Topics: 4-Butyrolactone; Angelica sinensis; Benzofurans; Chromatography, High Pressure Liquid; Coumaric Acids; Molecular Structure; Phthalic Anhydrides; Plant Roots; Plants, Medicinal; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization