TET3 Contributes to Exercise-Induced Functional Axon Regeneration and Visual Restoration.

Axons have intrinsically poor regenerative capacity in the mature central nervous system (CNS), leading to permanent neurological impairments in individuals. There is growing evidence that exercise is a powerful physiological intervention that can obviously enhance cell rejuvenate capacity, but its molecular mechanisms that mediate the axonal regenerative benefits remain largely unclear. Using the eye as the CNS model, here it is first indicated that placing mice in an exercise stimulation environment induced DNA methylation patterns and transcriptomes of retinal ganglion cell, promoted axon regeneration after injury, and reversed vision loss in aged mice. These beneficial effects are dependent on the DNA demethylases TET3-mediated epigenetic effects, which increased the expression of genes associated with the regenerative growth programs, such as STAT3, Wnt5a, Klf6. Exercise training also shows with the improved mitochondrial and metabolic dysfunction in retinas and optic nerves via TET3. Collectively, these results suggested that the increased regenerative capacity induced by enhancing physical activity is mediated through epigenetic reprogramming in mouse model of optic nerve injury and in aged mouse. Understanding the molecular mechanism underlying exercise-dependent neuronal plasticity led to the identification of novel targets for ameliorating pathologies associated with etiologically diverse diseases.

The effect of olsalazine of chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt in BALB/c mice.

PURPOSE: To explore effect and mechanism of olsalazine of Chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt (DSS) in BALB/c mice. METHODS: The mouse model of ulcerative colitis was induced by free drinking of 3% (w/v) DSS aqueous solution for seven days. The mice were treated with olsalazine (0.6 g·kg-1) of Chinese generic drugs. The therapeutic effect of olsalazine on ulcerative colitis mice was evaluated by measuring disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS), and detected the expression levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1ß in serum and IL-7, IL-17, IL-22, epidermal growth factor (EGF), transforming growth factor ß1 (TGF-ß1) in colonic homogenate of mice. RESULTS: Olsalazine significantly increased the contents of IL-2, IL-10, IL-22, TGF and EGF in ulcerative colitis rats, and significantly decreased the scores of DAI, CMDI, HS and the contents in IL-7, IL-17, TNF-α, IL-1ß and IFN-γ when compared with the model group. It improved the degree of colonic lesion in ulcerative colitis mice. CONCLUSIONS: It was suggested that olsalazine has a therapeutic effect on ulcerative colitis induced by DSS in mice, and the mechanism may be related to the increase of IL-2, IL-10, IL-22, TGF, and EGF and the decrease of the expression of IL-7, IL-17, TNF-α, IL-1ß, and IFN-γ.

Panax Notoginseng polysaccharide stabilized gel-like Pickering emulsions: Stability and mechanism.

In this work, the polysaccharide from Panax Notoginseng (SPNP), a traditional herb in China, was used as an outstanding Pickering stabilizer to fabricate Pickering emulsions. The SPNP was characterized to be a porous network structure with a rough surface surrounded by some nanoparticles. Rheological measurement of the obtained Pickering emulsions demonstrated the formation of emulsion gels. Moreover, the emulsions exhibited excellent storage (14 days), pH (1.0-11.0), ionic strength (0-500 mM), and temperature (4-50 °C) stabilities. In addition, the Pickering emulsions showed a freeze-thaw stability, which is beneficial in food, cosmetic or biomedical applications when they may require freezing for storage and melting before use. Confocal laser scanning microscope (CLSM) and cryo-scanning electron microscopy (cryo-SEM) results showed that SPNPs effectively adsorbed at the oil-water interface by forming a compact three-dimensional (3D) network structure and multilayer anchoring on the surface of the emulsion droplets, thus inhibiting the droplet coalescence and flocculation. This study provides a kind of Pickering emulsions applicable in food, biomedical and cosmetic industries.

Formononetin Attenuates Renal Tubular Injury and Mitochondrial Damage in Diabetic Nephropathy Partly via Regulating Sirt1/PGC-1α Pathway.

Mitochondrial abnormality is one of the main factors of tubular injury in diabetic nephropathy (DN). Formononetin (FMN), a novel isoflavonoid isolated from Astragalus membranaceus, has diverse pharmacological activities. However, the beneficial effects of FMN on renal tubular impairment and mitochondrial dysfunction in DN have yet to be studied. In this study, we performed in vivo tests in Streptozotocin (STZ) -induced diabetic rats to explore the therapeutic effects of FMN on DN. We demonstrated that FMN could ameliorate albuminuria and renal histopathology. FMN attenuated renal tubular cells apoptosis, mitochondrial fragmentation and restored expression of mitochondrial dynamics-associated proteins, such as Drp1, Fis1 and Mfn2, as well as apoptosis-related proteins, such as Bax, Bcl-2 and cleaved-caspase-3. Moreover, FMN upregulated the protein expression of Sirt1 and PGC-1α in diabetic kidneys. In vitro studies further demonstrated that FMN could inhibit high glucose-induced apoptosis of HK-2 cells. FMN also reduced the production of mitochondrial superoxide and alleviated mitochondrial membrane potential (MMP) loss. Furthermore, FMN partially restored the protein expression of Drp1, Fis1 and Mfn2, Bax, Bcl-2, cleaved-caspase-3, Sirt1 and PGC-1α in HK-2 cells exposure to high glucose. In conclusion, FMN could attenuate renal tubular injury and mitochondrial damage in DN partly by regulating Sirt1/PGC-1α pathway.

[Research progress of pesticide residues in traditional Chinese medicines].

The residue of the pesticides is closely related to the quality and safety of traditional Chinese medicines(TCMs) and has attracted widespread attention at home and abroad.This article analyzed the current status of pesticide residues in TCMs by summarizing the research results of recent years.At the same time,the methods for the detection of pesticide residues in TCMs were summarized,and the domestic and foreign pesticide residue limit standards for TCMs were compared,intending to provide reference and basis for the detection and control of pesticide residues in TCMs.

Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory deficits and cognitive decline. Amyloid-ß (Aß) deposition and cholinergic defect are widely thought to be the underlying mechanism of learning and memory impairment. Geniposide, which is the main active component of the traditional Chinese herbal Gardenia jasminoides Ellis, elicits neuroprotective effects by alleviating inflammation responses and oxidative damages. In this study, we investigated the protective effect of geniposide on levels of cholinergic markers, RAGE, RAGE-dependent signalling pathways and amyloid accumulation in the APPswe/PS1dE9 AD model mouse. Geniposide suppressed MAPK signaling over-activation mediated by Aß-RAGE interaction, resulting in reduced Aß accumulation and amelioration of cholinergic deficits in the cerebral hippocampus. Furthermore, geniposide inhibited the toxic effect of oligomeric Aß1-42 induced cholinergic deficit by increasing ChAT levels and activity but decreasing AChE activity in cultured primary hippocampal neurons. These results indicated that geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect.

Systematic Analysis of Long Noncoding RNAs in the Senescence-accelerated Mouse Prone 8 Brain Using RNA Sequencing.

Long noncoding RNAs (lncRNAs) may play an important role in Alzheimer's disease (AD) pathogenesis. However, despite considerable research in this area, the comprehensive and systematic understanding of lncRNAs in AD is still limited. The emergence of RNA sequencing provides a predictor and has incomparable advantage compared with other methods, including microarray. In this study, we identified lncRNAs in a 7-month-old mouse brain through deep RNA sequencing using the senescence-accelerated mouse prone 8 (SAMP8) and senescence-accelerated mouse resistant 1 (SAMR1) models. A total of 599,985,802 clean reads and 23,334 lncRNA transcripts were obtained. Then, we identified 97 significantly upregulated and 114 significantly downregulated lncRNA transcripts from all cases in SAMP8 mice relative to SAMR1 mice. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these significantly dysregulated lncRNAs were involved in regulating the development of AD from various angles, such as nerve growth factor term (GO: 1990089), mitogen-activated protein kinase signaling pathway, and AD pathway. Furthermore, the most probable AD-associated lncRNAs were predicted and listed in detail. Our study provided the systematic dissection of lncRNA profiling in SAMP8 mouse brain and accelerated the development of lncRNA biomarkers in AD. These attracting biomarkers could provide significant insights into AD therapy in the future.

Geniposide Protects Primary Cortical Neurons against Oligomeric Aß1-42-Induced Neurotoxicity through a Mitochondrial Pathway.

Mitochondrial dysfunction plays a key role in the progression of Alzheimer's disease (AD). The accumulation of amyloid-beta peptide (Aß) in the brains of AD patients is thought to be closely related to neuronal mitochondrial dysfunction and oxidative stress. Therefore, protecting mitochondria from Aß-induced neurotoxicity is an effective strategy for AD therapeutics. In a previous study, we found that geniposide, a pharmacologically active compound purified from gardenia fruit, has protective effects on oxidative stress and mitochondrial dysfunction in AD transgenic mouse models. However, whether geniposide has a protective effect on Aß-induced neuronal dysfunction remains unknown. In the present study, we demonstrate that geniposide protects cultured primary cortical neurons from Aß-mediated mitochondrial dysfunction by recovering ATP generation, mitochondrial membrane potential (MMP), and cytochrome c oxidase (CcO) and caspase 3/9 activity; by reducing ROS production and cytochrome c leakage; as well as by inhibiting apoptosis. These findings suggest that geniposide may attenuate Aß-induced neuronal injury by inhibiting mitochondrial dysfunction and oxidative stress.

Notoginsenoside R1 inhibits oxidized low-density lipoprotein induced inflammatory cytokines production in human endothelial EA.hy926 cells.

Notoginsenoside R1 (NG-R1), a unique and main active ingredient of Panax notoginseng, has been described to exhibit anti-inflammatory activity. However, its protective effects against oxidized low-density lipoprotein (oxLDL)-induced inflammatory injury in vascular endothelial cells have not been clarified. In the present study, we have evaluated the anti-inflammatory effects of NG-R1 on oxLDL-induced endothelial cells and its possible molecular mechanism of action. Our results showed that NG-R1 treatment significantly attenuated oxLDL-induced expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. These effects were accompanied with suppression of oxLDL-induced activation of NF-κB and Mitogen-activated protein kinases (MAPK). Moreover, NG-R1 also increased in Peroxisome proliferator-activated receptor γ (PPARγ) protein expression and transcription levels, and attenuated oxLDL-induced suppression of PPARγ expression. The inhibition of NG-R1 on oxLDL-induced TNF-α and IL-1ß productions can be reversed by PPARγ antagonist GW9662. In conclusion, these data suggested that NG-R1 could suppress oxLDL-induced inflammatory cytokines production via activating PPARγ, which subsequently inhibiting oxLDL-induced NF-κB and MAPK activation.

[Protective effects of notoginsenoside R1 against amyloid-ß (1-42) induced mitochondrial apopototic death in SH-SY5Y cells].

OBJECTIVE: To investigate the effects and underlying mechanism of notoginsenoside R1 on amyloid-ß (1-42) (Aß(1-42)) induced mitochondrial apoptotic death in SH-SY5Y cells. METHOD: Cell viability was assayed by MTT, apoptotic rates were analyzed with PI/Annexin V flow cytometry, Bax and Bcl-2 expression were detected with Western blotting, enzymatic activity of caspase-3, caspase-8 and caspase-9 were measured by ELISA assay. RESULT: The 6.25-100 nmol x L(-1) of notoginsenoside R1 attenuate Aß(1-42) induced apoptotic death of SH-SY5Y in dose dependent manner. The ratio of Bcl-2/Bax was elevated in SH-SY5Y with notoginsenoside R1 treatment. Caspase-3 and caspase-9 were activated with notoginsenoside R1 treatment while caspase-8 was not affected. CONCLUSION: Notoginsenoside R1 could protect SH-SY5Y cells from Aß(1-42) induced apoptosis via mitochondria related apoptotic pathway.

Protective Effect of Notoginsenoside R1 on an APP/PS1 Mouse Model of Alzheimer's Disease by Up-Regulating Insulin Degrading Enzyme and Inhibiting Aß Accumulation.

Notoginsenoside R1 (NTR1) is the main active ingredient of the well-known traditional Chinese herbal medicine Panax notoginseng, the root of Panax notoginseng (Burk.) F. H. Chen. Studies demonstrated that NTR1 may have some neuronal protective effects. Alzheimer's disease (AD) is a neurodegenerative disease characterized by ß -amyloid protein (Aß) deposition, neurofibrillary tangle formation and neuronal loss. This study was designed to explore the protective effect of NTR1 on an APP/PS1 double-transgenic mouse model of AD and investigate the possible mechanism. The 3-month-old mice were fed with 5 mg/(kg•d), 25 mg/(kg•d) NTR1 or vehicle via oral gavage for 3 months and changes in behavior, neuropathology, and amyloid pathology were investigated. The mice with NTR1 treatment showed significant amelioration in the cognitive function and increased choline acetyl transferase expression, as compared to the vehicle treated mice. NTR1 treatment inhibited Aß accumulation and increased insulin degrading enzyme expression in both APP/PS1 mice and N2a-APP695sw cells, suggesting that of NTR1 may exert its protective effects through the enhancement of the Aß degradation. Furthermore, our data showed that the increased level of peroxisome proliferator-activated receptor γ (PPARγ) and the up-regulation of insulin degrading enzyme induced by NTR1 were inhibited by administration of GW9662 (a PPARγ antagonist), indicating that the effect of NTR1 was mediated, at least in part, by PPARγ. Thus, our findings provide the evidences that NTR1 has protective effect on AD mouse model and NTR1 may be a potential candidate for AD treatment.

Pharmacokinetics and brain distribution differences of baicalin in rat underlying the effect of Panax notoginsenosides after intravenous administration.

Baicalin (BA) is the most well-known flavonoid present in Radix Scutellariae. The aim of this study was to explore whether the pharmacokinetic behavior of BA in rat brain can be affected by Panax notoginsenosides (PNS), and to assess the possible mechanism for the observed effects. Specific HPLC and HPLC/MS/MS methods were developed and validated for the determination of BA in the rat plasma and brain using carbamazepine as an internal standard. BA was found to enter rat brain quickly after a single intravenous dose. When co-administered with PNS, clearance (CL) of BA from rat plasma decreased by 50.00%, while the area under the curve AUC0-t and AUC0-∞ increased 94.69% and 87.68%, respectively. On the other hand, some pharmacokinetic parameters of BA in rat brain had obvious differences after PNS was administered, such as an increase in Tmax from 5 min to 15 min, an increase in AUC0-t and AUC0-∞ by 42.75% and 29.39%, respectively, as well as a decrease in CL by 27.95%. Together, these results indicate that PNS can decrease the elimination rate of BA from rat plasma, promote the penetration of BA into rat brain, increase the concentration and slow down the elimination of BA from rat brain. The data provide important information that compatibility with PNS can promote the consequent effects of BA for the treatment of encephalopathy.

[Advance in studies of Panax notoginseng saponins on pharmacological mechanism of nervous system disease].

The pharmacological mechaisms of Panax notoginseng saponins on nervous system diseases (Alzheimer's disease, Parkinson's disease, ischermic cerebral apoplexy and depressive disorder) , including panax notoginseng saponins, protoparaxotriol saponins, panasadiol saponins, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Re and notoginsenoside R1 were summarized to analyze the study hotspots and potential advantages (such as estrogen-like effect) of notoginsenoside's pharmacological actions, provide reference for further pharmacological studies and new ideas for clinical treatment of nervous system diseases and drug studies and development.

[Restricting factors and countermeasures of Yunnan traditional Chinese medicine industry development].

This paper summarizes the current situation and restricting factors of the Yunnan traditional Chinese medicine industry. With further analysis comparing, the research puts forward some suggestions and strategic countermeasures to promote the development of the Yunnan traditional Chinese medicine industry.

Inhibition of advanced glycation end product formation by Pu-erh tea ameliorates progression of experimental diabetic nephropathy.

Accumulation of advanced glycation end products (AGEs) has been implicated in the development of diabetic nephropathy. We investigated the effects of Pu-erh tea on AGE accumulation associated with diabetic nephropathy. Although it did not affect blood glucose levels and insulin sensitivy, Pu-erh tea treatment for 8 weeks attenuated the increases in urinary albumin, serum creatinine, and mesangial matrix in db/db mice. We found that Pu-erh tea prevented diabetes-induced accumulation of AGEs and led to a decreased level of receptor for AGE expression in glomeruli. Both production and clearance of carbonyl compounds, the main precursor of AGE formation, were probably attenuated by Pu-erh tea in vivo independent of glyoxalase I expression. In vitro, HPLC assay demonstrated Pu-erh tea could trap methylglyoxal in a dose-dependent manner. Our study raises the possibility that inhibition of AGE formation by carbonyl trapping is a promising approach to prevent or arrest the progression of diabetic complications.

Chemical fingerprinting of Gardenia jasminoides fruit using direct sample introduction and gas chromatography with mass spectrometry detection.

A rapid, rugged, and inexpensive approach is described to develop chemical fingerprints of volatile and semivolatile fractions in herbal medicine. The method is based on the combination of direct sample introduction and gas chromatography (GC) analysis with mass spectrometry detection. In comparison with routine methods, the proposed approach provides the most informative fingerprint and does not demand time-consuming extraction, pretreatment, and cleanup procedures. The approach was applied to establish the GC fingerprint of gardenia fruit (Gardenia jasminoides Ellis), in which 39 components were identified. With the help of principal components analysis, the obtained fingerprint could reveal the variation in and within different herb samples as affected by season and developmental state (wild or cultivated). The results indicated that the proposed approach could serve as a rapid, simple, and effective technique for the quality control of herbal medicines.

[Application of HPLC/ELSD fingerprint and constellation graphical clustering method applied to evaluate the quality of Qingkailing injection].

AIM: To evaluate the quality of Qingkailing injections effectively, and to develop a credible method for the quality control of traditional Chinese medicine. METHODS: Fingerprints of 18 Qingkailing injection samples from various manufacturers were obtained by HPLC/ELSD, and quality evaluation was performed by constellation graphical clustering method. RESULTS: HPLC/ELSD and constellation graphical clustering method properly revealed the quality information apparently and accurately. CONCLUSION: It was an apparent, credible and efficient method for quality evaluation of Chinese medicines.

[Simultaneous determination of five groups of components in qingkailing injection by high performance liquid chromatography with photo diode array detector and evaporative light scattering detector].

A method was established for the simultaneous quantification of nine components of five different structural types in Qingkailing injection. High performance liquid chromatography coupled with a photo diode array detector and an evaporative light scattering detector (HPLC-DAD-ELSD) was employed in the determination. Four monitoring wavelengths of 240, 254, 280 and 330 nm were set to determine nucleosides (uridine and adenosine), iridoid glucoside (geniposide), flavone glycoside (baicalin) and organic acids (chlorogenic acid and caffeic acid) respectively, and a combined evaporative light scattering detector was used to detect three steroid compounds (cholic acid, ursodesoxycholic acid and hyodeoxycholic acid). The proposed method permitted the simultaneous separation and determination of five groups of compounds in Qingkailing injection, and acceptable validation results of the precision, repeatability, stability and accuracy tests were achieved. The method was applied to the analysis of 19 Qingkailing injection samples from three different plants, and the results indicated that the method could be used as a convenient and reliable method in the multi-component determination and quality control of traditional Chinese medicines.

Simultaneous determination of major bioactive components in Qingkailing injection by high-performance liquid chromatography with evaporative light scattering detection.

High-performance liquid chromatography with evaporative light scattering detection (HPLC/ELSD) was established for simultaneous determination of seven major bioactive components of Qingkailing injection including adenosine, geniposide, chlorogenic acid, baicalin, ursodeoxycholic acid, cholic acid, and hyodeoxycholic acid. The proposed method was applied to analyze ten various Qingkailing injections and produced data with acceptable linearity, repeatability, precision and accuracy having a limit of detection (LOD) of 10-50 ng. In comparison with UV detection, HPLC/ELSD permits the determination of non-chromophoric compounds without prior derivatization, and shows good compatibility to the multi-components of complex analytes. The proposed method is a useful alternative for routine analysis in the quality control of traditional Chinese medicine.

An approach to develop two-dimensional fingerprint for the quality control of Qingkailing injection by high-performance liquid chromatography with diode array detection.

An approach was proposed to develop two-dimensional fingerprint (2D fingerprint) by means of principal component analysis (PCA) of high-performance liquid chromatography with diode array detection (HPLC/DAD) data. The approach was applied to establish 2D fingerprints of various Qingkailing injections which were produced by different manufacturers and procedures. In comparison with common one-dimensional fingerprint (ID fingerprint) at fixed wavelength, 2D fingerprint compiled additional spectral data and was hence more informative. Principal component analysis of the 2D fingerprint data was performed in this study, and it led to an accurate classification of various samples on their manufacturers and procedures. The quality of Qingkailing samples was further evaluated by similarity measures and the same results were achieved. For comparison, four conventional ID fingerprints were also applied to the quality assessment for the same samples. Finally, we demonstrated that 2D fingerprint was a more powerful tool to characterize the quality of samples, and could be used to comprehensively conduct the quality control of traditional Chinese medicines.