Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease(PD).Dioscin,a bioactive steroidal saponin,shows various activities.However,its effects and mechanisms against PD are limited.In this study,dioscin dramatically alleviated neuroinflammation and oxidative stress,and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus,Streptococcus,Bacteroides and Lactobacillus genera,which further inhibited bile salt hydrolase(BSH)activity and blocked bile acid(BA)deconjugation.Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent.In addition,non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis.Moreover,targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid,tauroursodeoxycholic acid,taurodeoxycholic acid and bmuricholic acid in feces and serum.In addition,ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice.Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5(TGR5),glucagon-like peptide-1 receptor(GLP-1R),GLP-1,superoxide dismutase(SOD),and down-regulated NADPH oxidases 2(NOX2)and nuclear factor-kappaB(NF-kB)levels.Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice,suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

Recent advance in natural plant products for treatment of dry eye disease

Dry eye disease(DED),a chronic multifactorial illness of the ocular surface with itching,burning,irritation,eye fatigue and ocular inflammation,may result in potential damage,such as cornea and conjunctiva,and even decreased vision.With the global prevalence of DED on the rise,it is crucial to find treatment options with minimal side effects.Natural plant products have shown promise in alleviating DED symptoms and may serve as a potential approach for its treatment.However,their application as instilled drugs is limited by solubility,stability and biological barriers.This review summarizes recent studies(published in the last 5 years)on natural plant products and their derivatives for the treatment of DED,focusing on efficacy,mechanism,drug delivery systems.Meanwhile,their shortcomings are also discussed.By exploring these aspects,we find polyphenol,flavonoid and others natural plant products can effectively improve or treat DED by different mechanisms,and suitable delivery system and structural modification can enhance their therapeutic effect,suggesting they are likely to become candidates for the treatment of DED.

Role of estrogen in angiogenesis in cardiovascular diseases

The formation of new blood vessels from existing ones is a major process of angiogenesis and it is most effective in the vascular systems。 The physiological process like hypoxia inducible factors involved in the regeneration of damaged tissues varies within the vascular systems in the endothelium and could be limited due to some major angiogenic growth factors like vascular endothelial growth factor, fibroblast growth factors and epidermal growth factor among others which bring about this cellular vascular regrowth。 These physiological processes leading to cellular vascular regrowth could be a major function for the treatment of cardiovascular diseases such as ischemia and atherosclerosis。 Estrogens are one of the known factors within the cellular mechanisms that could initiate repairs to the damaged vascular tissues, since estrogens are known inducers of angiogenesis leading to this cellular regrowth。 Research has also shown that this cellular regrowth is induced by vascular angiogenic growth factors via the estrogen receptors。 In this review we will attempt to summarize the main angiogenic growth factors involved in these physiological processes leading to angiogenesis and possible new mechanisms that could lead to this vascular regrowth。 And also we will try to summarize some reports on the effect of estrogen on these physiological processes leading to angiogenesis in cardiovascular diseases。

Niaoduqing granules inhibits TGF-β1-induced epithelial-mesenchymal transition in human renal tubular epithelial HK-2 cells

Objective Chronic renal failure(CRF)is a worldwide public health burden.Niaoduqing granules(NDQ)is widely used for CRF treatment in China.However,the underlying mechanism of NDQ is not fully studied.This study is aimed to investigate whether NDQ ameliorate CRF by inhibiting transforming growth factor-β1(TGF-β1)-induced EMT in human renal tubular epithelial HK-2 cells.Methods 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide assay and colony formation assay were used to investigate the cytotoxicity of NDQ in HK-2 cells.Morphological changes of HK-2 cells after TGF-β1 or/and NDQ treatment were observed under a microscope.Wound-healing,migration and invasion assays were performed to determine the cell movement,migratory and invasive abilities,respectively.Western blot analysis was carried out to examine the protein levels of TGF-βreceptor I(TβRI)and epithelial-mesenchymal transition(EMT)-associated factors.Fluorescence confocal microscopy was applied to observe the organization of filamentous actin.Results NDQ suppressed TβRI expression dose-dependently.NDQ inhibited TGF-β1-stimulated EMT in HK-2 cells,supported by the evidences that NDQ prevented morphology change,attenuated cell migration and invasion,downregulated EMT factors and reorganized filamentous actin distribution in TGF-β1-stimulated HK-2 cells.Conclusions NDQ attenuates chronic renal failure which may be associated with inhibition of TβRI expression and EMT process.

Heat-Clearing Chinese Medicines in Lipopolysaccharide-Induced Inflammation

Lipopolysaccharide(LPS)-induced inflammation causes massive threatening diseases,such as sepsis,acute lung injury and multiple organ dysfunction syndrome.Efficient treatment to prevent inflammation is crucial in LPS-induced inflammatory diseases.Heat-clearing Chinese medicines(CMs)have been used to ameliorate LPS-induced inflammation in China for centuries.Heat-clearing CMs regulate inflammatory pathways,thereby inhibiting the release of inflammatory factors.This review aimed to introduce promising heat-clearing CMs countering LPS-induced inflammation in the last 5 years,exploring the underlying molecular mechanisms.

Gene Expression Profiling of the Proliferative Effect of Periplocin on Mouse Cardiac Microvascular Endothelial Cells

Objective： Periplocin is an active digitalis-like component from Cortex Periplocae, which has been widely used in the treatment of heart diseases in China for many years. According to the recommendations on the cardiovascular effect of periplocin from in vivo experiments, subsequent in vitro experiments are greatly needed for the global assessment of periplocin. The objective of this study is to investigate the cell proliferation effect and the mechanism of periplocin on endothelial cells. Methods： The proliferative activity of periplocin （0.4, 2, 10, 50, 250 pmol/L; 6, 12, 24, 48, 72 h） was investigated by a comparison with the well-reported cardiac glycoside, ouabain, on mouse cardiac microvascular endothelial cells （CMEC）. 3-（4,5-dimethylthiazolyl）- 2,5-diphenyltetrazolium bromide （MTT）, lactate dehydrogenase （LDH） and 5-bromo-2-deoxyuridine （BrdU） assays were used to evaluate cell proliferation and viability. Subsequently, cDNA microarray experiments were performed on periplocin- （50 pmol/L） and ouabain- （50 pmol/L） treated cells, and data was analyzed by ArrayTrack software. Results： Periplocin could increase cell viability to a level lower than ouabain in the MIF analysis, but decrease LDH release simultaneously. The BrdU incorporation assay showed an increase in cell proliferation with 2-50 μmol/L periplocin. Genes related to protein serine/threonine kinase were the most significantly enriched in the 160 genes identified in periplocin versus the control. In the 165 genes regulated by periplocin versus ouabain, GTP-binding was the most altered term. Conclusions： The results demonstrated the proliferation action of periplocin on CMEC. Meanwhile, its lower cytotoxicity compared to ouabain provides a new insight into the treatment of heart failure.

Effects of drying process of Yuanzhi (Radix Palygalae) on its bioactive ingredients

OBJECTIVE: To study the effects of the drying processing in terms operational parameters on the bioactive constituents of six Yuanzhi(Radix Palygalae)samples across China.METHODS: Six Yuanzhi(Radix Palygalae) samples were investigated using thermogravimetry analysis. The heating courses were set in two ways: thetemperature-programmed process from room temperature to 150℃,and the constant-temperature course at 50℃, 70℃ and 90℃.RESULTS: The peak temperature of six Yuanzhi(Radix Palygalae) samples ranged from 78℃ to 88℃.The mass loss rate ofYuanzhi(Radix Palygalae) alcohol-soluble extract was significantly increased when heated at 90℃. Four types of bioactive ingredients were detected in volatile oils of Yuanzhi(Radix Palygalae) sample from Shanxi province by Gas Chromatography-mass spectrometry analysis. Fourier Transform Infrared Spectroscopy results showed that the drying temperature exerted a great influence on types and amount of ingredients of Yuanzhi(Radix Palygalae). The kinetic study showed that the constant-temperature drying process ofYuanzhi Radix Palygalae) samples could be well described by the Page Model, especially for the drying process at 50℃, in which R2and SD values were more than 0.98 and less than 0.04, respectively. The drying constant k of three Yuanzhi(Radix Palygalae) samples from Shanxi, Gansu and Shaanxi provinces in China was corresponding to the Arrhenius equation, and their activation energies were28.07, 25.38 and 21.48 kJ/mol, respectively.CONCLUSION: The drying process of Yuanzhi(Radix Palygalae) was very important for bioactive ingredients improvement in Yuanzhi(Radix Palygalae). Temperature was a thermodynamic property significantly affecting the process.

Realgar(α-As_(4)S_(4))Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes(MDS).Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes,inducing gene silencing.Realgar(α-As_(4)S_(4))is a traditional medicine used for the treatment of various diseases in the ancient time.Realgar was reported to have efficacy for acute promyelocytic leukemia(APL).It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS.This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS,as well as the species and metabolisms of arsenic in vivo.