Identification of potential targets of cinnamon for treatment against Alzheimer's disease-related GABAergic synaptic dysfunction using network pharmacology.

Cinnamon aqueous extract's active substance base remains unclear and its mechanisms, mainly the therapeutic target of anti-Alzheimer's disease (AD)-related GABAergic synaptic dysfunction, remain unclear. Here, 30 chemical components were identified in the aqueous extract of cinnamon using LC/MS; secondly, we explored the brain-targeting components of the aqueous extract of cinnamon, and 17 components had a good absorption due to the blood-brain barrier (BBB) limitation; thirdly, further clustering analysis of active ingredient targets by network pharmacology showed that the GABA pathway with GABRG2 as the core target was significantly enriched; then, we used prominent protein-protein interactions (PPI), relying on a protein-metabolite network, and identified the GABRA1, GABRB2 and GABRA5 as the closest targets to GABRG2; finally, the affinity between the target and its cognate active compound was predicted by molecular docking. In general, we screened five components, methyl cinnamate, propyl cinnamate, ( +)-procyanidin B2, procyanidin B1, and myristicin as the brain synapse-targeting active substances of cinnamon using a systematic strategy, and identified GABRA1, GABRB2, GABRA5 and GABRG2 as core therapeutic targets of cinnamon against Alzheimer's disease-related GABAergic synaptic dysfunction. Exploring the mechanism of cinnamon' activities through multi-components and multiple targets strategies promise to reduce the threat of single- target and symptom-based drug discovery failure.

Integrated network pharmacology and hepatic metabolomics to reveal the mechanism of Acanthopanax senticosus against major depressive disorder.

Objective: Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on major depressive disorder (MDD), but its mechanism is still unclear. The current study aimed to investigate the effect of ASH on MDD and potential therapeutic mechanisms. Materials and Methods: The chemical compound potential target network was predicted based on network pharmacology. Simultaneously, chronic unpredictable mild stress (CUMS) model mice were orally administrated ASH with three dosages (400, 200, and 100 mg/kg) for 6 weeks, and hepatic metabolomics based on gas chromatography-mass spectrometry (GC-MS) was carried out to identify differential metabolites and related metabolic pathways. Next, the integrated analysis of metabolomics and network pharmacology was applied to find the key target. Finally, molecular docking technology was employed to define the combination of the key target and the corresponding compounds. Results: A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. Finally, DAO, MAOA, MAOB, GAA, HK1, and PYGM were verified bounding well to their corresponding compounds including isofraxidin, eleutheroside B1, eleutheroside C, quercetin, kaempferol, and acacetin. Conclusion: Based on these results, it was implied that the potential mechanism of ASH on MDD was related to the regulation of metabolism of several excitatory amino acids and carbohydrates, as well as the expression of DAO, MAOA, MAOB, GAA, HK1, and PYGM.

Emerging application of metabolomics on Chinese herbal medicine for depressive disorder.

Depressive disorder is a kind of emotional disorder that is mainly manifested with spontaneous and persistent low mood. Its etiology is complex and still not fully understood. Metabolomics, an important part of system biology characterized by its integrity and systematicness, analyzes endogenous metabolites of small molecules in vivo and examines the metabolic status of the organism. It is widely used in the field of disease research for its unique advantage in the disease molecular marker discovering Due to fewer adverse reactions and high safety, Chinese herbal medicine (CHM) has great advantages in the treatment of chronic diseases including depression. Metabolomics has been gradually applied to the efficacy evaluation of CHM in treatment of depression and the metabolomics analysis exhibits a systemic metabolic shift in amino acids (such as alanine, glutamic acid, valine, etc.), organic acids (lactic acid, citric acid, stearic acid, palmitic acid, etc.), and sugars, amines, etc. These differential metabolites are mainly involved in energy metabolism, amino acid metabolism, lipid metabolism, etc. In this review, we have exemplified the study of CHM in animals or clinics on the depression, and revealed that CHM treatment has significantly changed the metabolic disorders associated with depression, promoting metabolic network reorganization through restoring of key metabolites, and metabolic pathways, which may be the main mechanism basis of CHM's treatment on depression. Besides, we further envisioned the future application of metabolomics in the study of CHM treatment of depression.

[Ginkgo biloba extract 50 inhibited beta-amyloid-induced oxidative stress in rats' hippocampal neurons: an experimental study].

OBJECTIVE To study the in vitro effect and mechanism of Ginkgo biloba Extract 50 (GBE50) for inhibiting beta-amyloid (Abeta)-induced oxidative stress in rats' hippocampal neurons. METHODS: The primary hippocampal neurons were cultured in vitro and divided into 4 groups, i. e. the normal control group (Ctrl), the Abeta group, the propanediol control group (PDO), and the six GBE50 concentrations groups (5, 10, 25, 50, 100, and 200 microg/mL). Excepted the Ctrl group, neurons were induced to oxidative stress by 20 gmolLAbeta25-35. The MTT and fluorescent probes labeling were used to observe the effect of GBE50 with different concentrations on the cell viability and the generation of intracellular reactive oxygen species (ROS) in neurons. Furthermore, Western blot was used to detect the cytoplasmic/total cytochrome C (Cyto C) ratio and total intracytoplasmal Cyto C, and the effect of the expression of oxidative stress-related protein Cyto C and activated Caspase-3 in three GBE50 concentrations groups (25, 50, and 100 microg/mL). RESULTS: Compared with the Ctrl group, the cell vitality was obviously lowered and intracellular ROS generation significantly increased after induction of 20 micromol/L Abeta25-35 (both P < 0.05). Compared with the Abeta group, the cell vitality was evidently improved after treated with different GBE50 doses. Except for 10 microg/mL, the cell vitality could be obviously elevated along with increased drug concentrations (P < 0.05). Meanwhile, the intracellular ROS generation decreased significantly in each GBE50 dose groups (P < 0.05). Abeta could increase the cytoplasmic/total Cyto C ratio and enhance the activated Caspase-3 expression significantly (P < 0.05). Compared with the Abeta group, among the three concentrations of GBE50, the Cyto C ratio was obviously lowered in the 100 microg/mL GBE50 group (P < 0.05), and the expression of activated Caspase-3 significantly decreased in 50 microg/mL and 100 microg/mL GBE50 groups (P < 0.05). CONCLUSIONS: 20 micromol/L Abeta25-35 could induce the generation of intracellular ROS in hippocampal neurons. GBE50 could inhibit Abeta induced intracellular oxidative stress of neurons through lowering the cytoplasmic/total Cyto C ratio and inhibiting the activation of apoptosis protein Caspase-3 expression.