Magnolol effectively ameliorates diabetic peripheral neuropathy in mice.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes lacking efficient treatment. Magnolol (MG), a peroxisome proliferator-activated receptor γ (PPARγ) agonist, is a natural product derived from Magnolia officinalis and widely used to treat a variety of diseases as a traditional Chinese medicine and Japanese Kampo medicine. PURPOSE: Here, we aimed to investigate the potential of MG in ameliorating DPN-like pathology in mice and decipher the mechanism of MG in treating DPN. MATERIALS AND METHODS: 12-week-old male streptozotocin (STZ)-induced type 1 diabetic (T1DM) mice and 15-week-old male BKS Cg-m+/+Lepr db/J (db/db) type 2 diabetic mice (T2DM) were used as DPN mice. MG was administrated (i.p) daily for 4 weeks. Peripheral nerve functions of mice were evaluated by measuring mechanical response latency, thermal response latency and motor nerve conduction velocity (MNCV). The mechanisms underlying the amelioration of MG on DPN-like pathology were examined by qRT-PCR, western blot and immunohistochemistry assays, and verified in the DPN mice with PPARγ-specific knockdown in dorsal root ganglia (DRG) neuron and sciatic nerve tissues by injecting adeno-associated virus (AAV)8-PPARγ-RNAi. RESULTS: MG promoted DRG neuronal neurite outgrowth and effectively ameliorated neurological dysfunctions in both T1DM and T2DM diabetic mice, including improvement of paw withdrawal threshold, thermal response latency and MNCV. Additionally, MG promoted neurite outgrowth of DRG neurons, protected sciatic nerve myelin sheath structure, and ameliorated foot skin intraepidermal nerve fiber (IENF) density in DPN mice by targeting PPARγ. Mechanism research results indicated that MG improved mitochondrial dysfunction involving PPARγ/MKP-7/JNK/SIRT1/LKB1/AMPK/PGC-1α pathway in DRG neurons, repressed inflammation via PPARγ/NF-κB signaling and inhibited apoptosis through regulation of PPARγ-mediated Bcl-2 family proteins in DRG neurons and sciatic nerves. CONCLUSIONS: Our work has detailed the mechanism underlying the amelioration of PPARγ agonist on DPN-like pathology in mice with MG as a probe, and highlighted the potential of MG in the treatment of DPN.

Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Network pharmacology-based prediction of the active ingredients and mechanism of Shen Gui capsule for application to coronary heart disease.

BACKGROUND: Shen Gui capsule (SGC) is a new national drug in China that is widely used in clinical practice and has significant therapeutic effects on coronary heart disease (CHD). However, its active ingredients and mechanism of action for treating coronary heart disease remain unknown. Therefore, the purpose of this paper is to systematically explore the mechanism and efficacy of SGC in the "multicomponent-multitarget- multipathway" treatment for CHD using network pharmacology technology. METHODS: The potential active ingredients of SGC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened by pharmacokinetic parameters. Their possible targets were predicted using the TCMSP and DrugBank database. The CHD-related targets were identified from Comparative Toxicogenomics Database (CTD), UniProt, and PharmGKB database. The compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed by Gene Ontology (GO) and KEGG enrichment analysis using the Metascape platform. RESULTS: The 61 active ingredients of SGC were found to regulate neuroactive ligand-receptor interaction, fluid shear stress and atherosclerosis, estrogen signaling pathway and other pathways through 62 targets. SGC is involved in regulating the circulatory system, nervous system and immune system and other aspects of the body, and thus plays a significant role in the treatment of CHD and its complications, showing the mechanism of SGC's "multicomponent, multitarget, and multipathway" prevention and treatment of CHD. In addition, three predictive components were first found to have potential biological activity by this method. CONCLUSION: The studies we have performed successfully predict the effective components and potential targets of SGC in the prevention and treatment of CHD, which helped to systematically clarify its mechanism of action and provided a direction for future research on the modern mechanism of SGC in the treatment of CHD.

Effects of peanut meal extracts fermented by Bacillus natto on the growth performance, learning and memory skills and gut microbiota modulation in mice.

Recent studies have demonstrated that the nutritional properties of peanut meal (PM) can be improved after being fermented. The assessment of fermented PM has been reported to be limited to various physical and chemical evaluations in vitro. In the present study, PM was fermented by Bacillus natto to explore the effects of fermented PM extract (FE) on growth performance, learning and memory ability and intestinal microflora in mice. Ninety newly weaned male Kunming (KM) mice were randomly divided into seven groups: normal group (n 20), low-dose FE group (n 10), middle-dose FE group (MFE) (n 10), high-dose FE group (HFE) (n 20), unfermented extraction group (n 10), model group (10) and natural recovery group (10). Learning and memory skills were performed by the Morris water maze (MWM) test, and the variation in gut microbiota (GM) composition was assessed by 16S rDNA amplicon sequencing. The results show that HFE remarkably improved the growth performance in mice. In the MWM test, escape latency was shortened in both MFE and HFE groups, while the percentage of time, distance in target quadrant and the number crossing over the platform were significantly increased in the HFE group. Moreover, the FE played a preventive role in the dysbacteriosis of mice induced by antibiotic and increased the richness and species evenness of GM in mice.

Data-Dependent Acquisition and Database-Driven Efficient Peak Annotation for the Comprehensive Profiling and Characterization of the Multicomponents from Compound Xueshuantong Capsule by UHPLC/IM-QTOF-MS.

The state of the art ion mobility quadrupole time of flight (IM-QTOF) mass spectrometer coupled with ultra-high performance liquid chromatography (UHPLC) can offer four-dimensional information supporting the comprehensive multicomponent characterization of traditional Chinese medicine (TCM). Compound Xueshuantong Capsule (CXC) is a four-component Chinese patent medicine prescribed to treat ophthalmic disease and angina. However, research systematically elucidating its chemical composition is not available. An approach was established by integrating reversed-phase UHPLC separation, IM-QTOF-MS operating in both the negative and positive electrospray ionization modes, and a "Component Knockout" strategy. An in-house ginsenoside library and the incorporated TCM library of UNIFITM drove automated peak annotation. With the aid of 85 reference compounds, we could separate and characterize 230 components from CXC, including 155 ginsenosides, six astragalosides, 16 phenolic acids, 16 tanshinones, 13 flavonoids, six iridoids, ten phenylpropanoid, and eight others. Major components of CXC were from the monarch drug, Notoginseng Radix et Rhizoma. This study first clarifies the chemical complexity of CXC and the results obtained can assist to unveil the bioactive components and improve its quality control.

Isolation and purification of a novel antimicrobial peptide from Porphyra yezoensis.

We aimed to isolate antimicrobial peptides from Porphyra yezoensis. Enzymatic hydrolysate of P. yezoensis was purified by ultrafiltration, molecular sieve chromatography, and ion exchange chromatography sequentially. A novel peptide with strong antimicrobial activity against Staphylococcus aureus was isolated and the amino acid sequence was identified to be Thr-Pro-Asp-Ser-Glu-Ala-Leu (TPDSEAL). Physical and chemical properties and antimicrobial activity of the peptide were determined. The antimicrobial mechanism was studied. The antimicrobial activity of TPDSEAL kept stable under acidic or basic conditions, high temperature, and ultraviolet radiation. The antimicrobial mechanism of antimicrobial peptides may damage the cell wall and membrane, and enhance the permeability of cells, which leads to the outflow of intracellular substances and death of bacteria. This study provides novel insight into the preparation of marine-derived antimicrobial peptides. PRACTICAL APPLICATIONS: Antimicrobial peptides, which act as defensive weapons against microbes, have been broadly used as food additives in food industry. Due to the limited amount of natural antimicrobial peptides in organisms and the high cost of chemical synthesis, producing novel natural antimicrobial peptides with bioengineering methods has become an urgent task. In the present study, we prepared a novel antimicrobial peptide from pepsin-digested hydrolysate of Porphyra yezoensis using ultrafiltration, molecular sieve chromatography, ion exchange chromatography, and mass spectrometry analysis. A novel peptide with strong antimicrobial activity against Staphylococcus aureus was isolated and the amino acid sequence was identified to be Thr-Pro-Asp-Ser-Glu-Ala-Leu (TPDSEAL). The identified peptide exhibits great stability under acidic or basic conditions, high temperature, and ultraviolet radiation. Mechanism revealed that TPDSEAL treatment may damage the cell wall and membrane, enhance the permeability of cells, and lead to the death of bacteria. Our study provides the novel insight into the preparation of marine-derived antimicrobial peptides.