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Medicinal food homology is referring to a group of food itself being considered as herbal medicine without a boundary of usage. Under the guidance of this food/medicine principle, the current study aims to develop anti-depressant from this food/medicine catalog. The herbal mixture of Sesami Semen Nigrum and Longan Arillus was evaluated in cultured PC12 rat pheochromocytoma cells, rat primary cortical neurons, and in chronic mild stress (CMS)-induced depressive rat model. The combination of two ethanolic extracts of Sesami Semen Nigrum and Longan Arillus in 1 : 1 ratio mimicked the function of nerve growth factor (NGF) and synergistically induced neurite outgrowth of PC12 cells. Besides, the expression and phosphorylation of tropomyosin receptor kinase A (TrkA) of the cultured cells were also elevated. This neurotrophic activity of herbal mixture was further supported by the increased expressions of biomarkers for neurogenesis and synaptogenesis in cortical neurons. Moreover, the depressed rats were soothed by the intake of herbal mixture, showing improved performance in behavior tests, as well as reversed levels of neurotransmitters and neurotrophic factors. Our results provide a new way to make full use of the current food/medicine resources, as to accelerate the development of therapeutics for depression. [ABSTRACT FROM AUTHOR]

Background: To promote herbal medicine depends largely on its quality. Chromatographic fingerprint is a frequent approach for quality assessment of herbs however with challenges on robust and reproducibility. To develop rapid, cheap and comprehensive measurements as complementary tools for herbal quality control are still urgently needed. Moreover, biological activities are essential for herbal quality, and should be taken into consideration with emphasized in quality control. Methods: In this research, HPLC fingerprint and delayed luminescence (DL, a rapid and systematic tool) were used to measure the rhubarb samples of multiple species. Statistics were explored to classify these rhubarb samples using data obtained from two analytic methods. In addition, DL properties were linked to specific chemical components which may reflect bioactivities of rhubarb using Spearman's rank correlation. Moreover, mice model was used to evaluate the cathartic effect between rhubarb samples stratifying by two analytic methods. Results: We found that there was no significant difference of chemical fingerprints and DL signals among the different species of medicinal rhubarb. However, our results show a high similarity between HPLC fingerprint analysis and DL measurements in classification of these rhubarb samples into two sub-groups. In addition, the two sub-groups of rhubarb samples that may have different cathartic activities. Conclusion: This approach provides new leads for development of herbal quality assessment based on bioactivity. In conclusion, integrated assessment by measuring HPLC fingerprint and DL with emphasized on bioactivity may provide novel strategy for herbal quality control. [ABSTRACT FROM AUTHOR]

Ginkgetin, a biflavone from Ginkgo biloba leaf, and resveratrol, a polyphenol found in grape and wine, are two phytochemicals being identified for its binding to vascular endothelial growth factor (VEGF): the binding, therefore, resulted in the alteration of the physiological roles of VEGF-mediated angiogenesis. The bindings of ginkgetin and resveratrol were proposed on different sites of VEGF, but both of them suppressed the angiogenic properties of VEGF. The suppressive activities of ginkgetin and resveratrol in VEGF-mediated angiogenesis were supported by several lines of evidence including (i) inhibiting the formation of sub-intestinal vessel in zebrafish embryos and microvascular sprouting in rat aortic ring; and (ii) suppressing the phosphorylations of VEGFR2, Akt, eNOS, and Erk as well as expressions of matrix metalloproteinases (MMPs), MMP-2, and MMP-9 in human umbilical vein endothelial cells (HUVECs). Here, we showed the synergy of ginkgetin and resveratrol in suppressing the VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation. The synergy of ginkgetin and resveratrol was further illustrated in HT-29 colon cancer xenograft nude mice. Ginkgetin and resveratrol, when applied together, exerted a synergistic anti-tumor effect of 5-fluorouracil with decreasing microvessel density of tumors. In parallel, the combination of ginkgetin and resveratrol synergistically relieved the 5-fluorouracil-induced inflammatory response by suppressing expressions of COX-2 and inflammatory cytokines. Thus, the anti-angiogenic roles of ginkgetin and/or resveratrol could provide effective therapeutic strategy in cancer, similar to that of Avastin, in suppressing the VEGF-mediated angiogenesis during cancer development. [ABSTRACT FROM AUTHOR]

Curcumae L ongae R hizoma (CLR) is a safe natural herbal medicine, and which has been widely used for centuries as functional food and health products, but its effects on angiogenesis and related underlying mechanism remain unclear. The abnormal angiogenesis is closely related with various diseases, and therefore the precise control of angiogenesis is of great importance. The well-known angiogenic factor, vascular endothelial growth factor (VEGF), mediates angiogenesis and induces multiple signalling pathways via binding to VEGF receptor (VEGFR). The attenuation of VEGF-triggered angiogenic-related signalling pathways may relieve various diseases through suppression of angiogenesis. Here, we aimed to elucidate that CLR extract could exert striking anti-angiogenic activities both in vitro and in vivo. The viability of human umbilical vascular endothelial cell (HUVEC) was examined by LDH and MTT assays. Migrative and invasive ability of the endothelial cells were independently evaluated by wound healing and transwell assays. The activities of CLR extract on in vitro angiogenesis was tested by tube formation assay. In vivo vascularization was determined by using zebrafish embryo model in the present of CLR extract. Western blotting was applied to determine the phosphorylated levels of VEGFR2, PI3K, AKT and eNOS. Besides, the levels of nitric oxide (NO) and reactive oxygen species (ROS) were separately evaluated by Griess assay and 2′7′-dichlorofluorescein diacetate reaction. In addition, the cell migrative ability of cancer cell was estimated by using cultured human colon carcinoma cells (HT-29 cell line), and immunofluorescence assay was applied to evaluate the effect of CLR extract on nuclear translocation of NF-κB p65 subunit in the VEGF-treated HT-29 cultures. CLR extract significantly suppressed a series of VEGF-mediated angiogenic responses, including endothelial cell proliferation, migration, invasion, and tube formation. Moreover, CLR extract reduced in vivo sub-intestinal vessel formation in zebrafish embryo model. Mechanistically, the extract of CLR attenuated the VEGF-triggered signalling, as demonstrated by decreased level of phosphorylated VEGFR2 and subsequently inactivated its downstream regulators, e.g. phospho-PI3K, phospho-AKT and phospho-eNOS. The production of NO and formation of ROS were markedly inhibited in HUVECs. Furthermore, CLR extract suppressed cell migration and NF-κB translocation in cultured HT-29 cells. These preclinical findings demonstrate that the extract of CLR remarkably attenuates angiogenesis and which has great potential as a natural drug candidate with excellent anti-angiogenic activity. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Kai-xin-san (KXS), composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, is a famous Chinese medicinal formula applied for treating stress-related psychiatric disease with the symptoms such as depression, forgetfulness and dizziness. Dependent on the symptom differentiation of patients, the composition ratio of KXS was varied and one ratio of 3:2:2:3 was widely applied. However, its molecular mechanism has seldom been investigated. Purpose We aimed to reveal the action mechanism of KXS on anti-depression on synaptic protein regulation in both in vivo and in vitro models. Study design/methods Firstly, the anti-depression effect of KXS was evaluated on a chronic mild stress induced depressive animal model and the mRNA expressions of various synaptic proteins in hippocampus of the depressive rat brains were determined. Then, KXS with different ratios as well as single herb were further evaluated on rat primary cultured hippocampus neurons and the possible signaling pathway was explored. Results Intra-gastric administration of a chemically standardized KXS for only 6 h significantly alleviated the CUMS-induced depressive symptoms displayed by enhanced sucrose consumption and this effect was maintained after daily treatment for seven days. Simultaneously, the mRNA expressions of various synaptic proteins in hippocampus were regulated. Among these synaptic proteins, synaptotagmin (pre-synaptic marker) and post synaptic density protein (post-synaptic marker), with the higher altered magnitude on animal model, were further evaluated on rat primary cultured hippocampus neurons. After neuronal cultures treated with three ratios of KXS at the early and late stages of its life episode, the expression levels of synaptotagmin and PSD95 were both enhanced dramatically via stimulating cAMP dependent pathway. However, different ratio exerted different efficacy. The ratio with higher amounts of Ginseng Radix et Rhizoma and Polygalae Radix showed better effect in early life episode while higher amounts of Acori Tatarinowii Rhizoma and Poria behaved better in late life episode. The contribution of single herb on expressions of synaptic proteins was also evaluated. Conclusions KXS was beneficial for synaptogenesis by inducing synaptic protein expressions, which might account for its anti-depression effect. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Kai-Xin-San, an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for major depression disorders for thousands of years. However, its molecular mechanism has not clearly been investigated. Aim of the study We aimed to reveal the action mechanism of KXS on anti-depression on inducing neuronal differentiation on PC12 cells. Materials and methods A chemically standardized water extract of KXS was applied onto cultured PC12 cells in determining its effect on neurotransmitter regulation enzymes and neurite outgrowth. Results Single KXS treatment showed obvious changes in the expression of neurofilament and neurotransmitter regulation enzymes, which in parallel to treatment of nerve growth factor (NGF). Although KXS by itself did not show significant inductive effect on neurite outgrowth of PC12 cells, KXS could potentiate the NGF induced neurite outgrowth. Among the three ratios, K-652 showed the most powerful effect and cAMP-dependent pathway might play the major role. Conclusions KXS might exert the anti-depressant-like action of be inducing neuronal differentiation, which supported the clinically usage of this decoction. [ABSTRACT FROM AUTHOR]

Danggui Buxue Decoction (DBD), as a classical Chinese medicine prescription, is composed of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5, and it has been used clinically in treating anemia for hundreds of years. The aim of this study was to explore the treatment mechanisms of DBD in anemia rats from the perspective of thymus and spleen. In this study, a successful hemorrhagic anemia model was established, and metabolomics (UPLC-QTOF-MS/MS) and proteomics (label-free approach) together with bioinformatics (Gene Ontology analysis and Reactome pathway enrichment), correlation analysis (pearson correlation matrix) and joint pathway analysis (MetaboAnalyst) were employed to discover the underlying mechanisms of DBD. DBD had a significant blood enrichment effect on hemorrhagic anemia rats. Metabolomics and proteomics results showed that DBD regulated a total of 10 metabolites (lysophosphatidylcholines, etc.) and 41 proteins (myeloperoxidase, etc.) in thymus, and 9 metabolites (L-methionine, etc.) and 24 proteins (transferrin, etc.) in spleen. With GO analysis and Reactome pathway enrichment, DBD mainly improved anti-oxidative stress ability of thymocyte and accelerated oxidative phosphorylation to provide ATP for splenocyte. Phenotype key indexes were strongly and positively associated with most of the differential proteins and metabolites, especially nucleosides, amino acids, Fabp4, Decr1 and Ndufs3. 14 pathways in thymus and 9 pathways in spleen were obtained through joint pathway analysis, in addition, the most influential pathway in thymus was arachidonic acid metabolism, while in spleen was the biosynthesis of phenylalanine, tyrosine and tryptophan. Furthermore, DBD was validated to up-regulate Mpo, Hbb and Cp levels and down-regulate Ca2+ level in thymus, as well as up-regulate Fabp4, Ndufs3, Tf, Decr1 and ATP levels in spleen. DBD might enhance thymus function mainly by reducing excessive lipid metabolism and intracellular Ca2+ level, and promote ATP production in spleen to provide energy. Image 1 [ABSTRACT FROM AUTHOR]