Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of gut-liver axis.

BACKGROUND: Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses. Nevertheless, the underlying molecular mechanisms largely remained elusive. AIM: To determine the hepatoprotective effects of SHE on ethanol-triggered liver damage and further elucidate its potential mechanisms. METHODS: In the present study, the Sprague-Dawley rats were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without SHE (300 and 600 mg/kg/d bw) for 8 weeks. The levels of serum biomarkers (ALT, AST and LDH) and LPS were detected by biochemical assay kits and endotoxin detection LAL kit, respectively. The histopathological changes of liver and intestinal tissues were observed by hematoxylin and eosin (H&E) staining and Transmission electron microscope (TEM). The expressions of CD14, TLR4, MyD88, NF-κB, Iκ-B, P-Iκ-B and TNF-α in liver, and ZO-1 and occludin in intestine were determined by western blot. The faecal microbial composition was determined by16S rRNA Gene Sequencing Analysis. RESULTS: Biochemical and histopathological analysis revealed that SHE significantly alleviated the lipid deposition and inflammation response in liver induced by ethanol. SHE remarkably inhibited the TLR4 pathway and its downstream inflammatory mediators, and up-regulated the expressions of ZO-1 and occludin in the intestine. The further investigations suggested SHE dramatically reversed ethanol-induced alterations in the intestinal microbial flora and decreased the generation of gut-derived endotoxin. CONCLUSION: In summary, SHE probably modulated abnormalities of gut-liver axis and inhibited TLR4-associated inflammatory mediators activation to exert its hepatoprotective properties. These findings suggested that SHE as a traditional therapeutic options which may play an essential role in protecting against the chronic ethanol-triggered liver injury.

Quercetin Reduces Cortical GABAergic Transmission and Alleviates MK-801-Induced Hyperactivity.

An imbalance between neuronal excitation and inhibition represents a core feature in multiple neuropsychiatry disorders, necessitating the development of novel strategies to calibrate the excitatory-inhibitory balance of therapeutics. Here we identify a natural compound quercetin that reduces prefrontal cortical GABAergic transmission and alleviates the hyperactivity induced by glutamatergic N-methyl-d-aspartate receptor antagonist MK-801. Quercetin markedly reduced the GABA-activated currents in a noncompetitive manner in cultured cortical neurons, and moderately inhibited spontaneous and electrically-evoked GABAergic inhibitory postsynaptic current in mouse prefrontal cortical slices. Notably, systemic and prefrontal-specific delivery of quercetin reduced basal locomotor activity in addition to alleviated the MK-801-induced hyperactivity. The effects of quercetin were not exclusively dependent on α5-subunit-containing A type GABA receptors (GABAARs), as viral-mediated, region-specific genetic knockdown of the α5-subunit in prefrontal cortex improved the MK-801-evoked psychotic symptom but reserved the pharmacological responsivity to quercetin. Both interventions together completely normalized the locomotor activity. Together, quercetin as a negative allosteric GABAAR modulator exerted antipsychotic activity, facilitating further therapeutic development for the excitatory-inhibitory imbalance disorders.

Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury.

Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have infrequently been reported thus far. In the present study, C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and triglyceride deposition induced by chronic alcohol exposure. In addition, DMY dramatically attenuated the alcohol-triggered elevation of the level of inflammatory cytokines and partially recovered hepatic pathological changes. Notably, DMY remarkably modified aberrant expression of CYP2E1, Keap-1 and HO-1 in the liver and simultaneously ameliorated disordered nuclear localization of NF-κB and Nrf2 to exert its hepatoprotective effects. Further mechanistic exploration suggested that DMY activated Nrf2, possibly mediated through the autophagy pathway. Analysis of the crosstalk among p62, Keap-1 and Nrf2 demonstrated that the p62 upregulation caused by DMY contributes to a positive feedback loop in Nrf2 activation. In summary, DMY likely modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and the inflammatory response in the pathological progression of ALD.

[Analysis of different forms Linderae Radix based on HPLC and NIRS fingerprints].

Three different forms of Linderae Radix were evaluated by HPLC combined with NIRS fingerprint. The Linderae Radix was divided into three forms, including spindle root, straight root and old root. The HPLC fingerprints were developed, and then cluster analysis was performed using the SPSS software. The near-infrared spectra of Linderae Radix was collected, and then established the discriminant analysis model. The similarity values of the spindle root and straight root all were above 0.990, while the similarity value of the old root was less than 0.850. Two forms of Linderae Radix were obviously divided into three parts by the NIRS model and Cluster analysis. The results of HPLC and FT-NIR analysis showed the quality of Linderae Radix old root was different from the spindle root and straight root. The combined use of the two methods could identify different forms of Linderae Radix quickly and accurately.

[Rapid Identification of Fresh-cut and Sulphur Fumigation Processed Fritillaria thunbergii Bulb Slices Based on Near-infrared Spectroscopy].

OBJECTIVE: A rapid identification model of the fresh-cut and sulphur fumigation processed Fritillaria thunbergii bulb slices was developed by near-infrared spectroscopy (NIR) with chemometrics method. METHODS: 186 batches of Fritillaria thunbergii bulb slices were collected from the two main producing areas Ningbo and Pan'an in Zhejiang Province, and the near-infrared spectrums were gathered to establish the qualitative identification model by discriminant analysis. RESULTS: The identification model was developed by choosing the spectrum of 9,881.46-4,119.20 cm(-1) and "MSC + spectrum + Ns" to the original spectral preprocessing, and then was verified by prediction set, with 100% identify accuracy. CONCLUSION: The rapid identification model of the fresh-cut and sulphur fumigation processed Fritillaria thunbergii bulb slices by NIR is feasible and efficient.

[Rapid identification of crude and sweated dipsaci radix based on near-infrared spectroscopy combined with principal component analysis-mahalanobis distance].

In order to discriminate the crude and sweated Dipsaci Radix correctly and rapidly, the crude and sweated Dipsaci Radix were scanned by the NIR spectrometer, and an identifying model was developed by near infrared spectroscopy combined with principal component-Mahalanobis distance pattern recognition method. The pretreated spectra data of 129 crude samples and 86 sweated ones were analyzed through principal component analysis (PCA). The identifying model was developed by choosing the spectrum for 9 881.46-4 119.20 cm(-1) and "SNV + spectrum + S-G" to the original spectral preprocessing with 14 principal components, and then was verified by prediction set, identifying with 100% accuracy. The rapid identification model of the crude and sweated Dipsaci Radix by NIR is feasible and efficient, and could be used as an assistant means for identifying the crude and sweated Dipsaci Radix.

[Effect of polysaccharides in crude and processed Cornus officinalis on the immunologic function of mice with immunosuppression induced].

OBJECTIVE: To investigate the effect of polysaccharides in crude and processed Cornus officinalis on the immunologic function of mice with immunosuppression induced. METHODS: The immunosuppressed mice were induced by Cyclophosphamide. Non-specific immune function was determined by cleaning carbon particle method. Humoral immunity was determined by serum haemolysin formation method. Cellular immunity was determined by proliferation and transformation of spleen lymphocyte method. RESULTS: The polysaccharides in crude and processed Cornus officinalis both markedly increased the carbon particle clearance index K, phagocytic index alpha, serum HC50 and proliferation and transformation of spleen lymphocyte,and the polysaccharides in processed Cornus officinalis was better than the crude one. CONCLUSION: The polysaccharides in crude and processed Cornus officinalis have an enhanced effect on non-specific immunity, specific humoral immunity and specific cellular immunity in immunodeppressed mice, and after being processed with wine, the action of polysaccharides increased markedly.