Rapid screening of hepatotoxic components in Uncariae Ramulus Cum Uncis based on "component-target-pathway" network.

As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.

Microstructures and Mechanical Properties of V-Modified Ti-Zr-Cu-Ni Filler Metals.

TA2 titanium alloy was brazed with Ti-Zr-Cu-Ni-V filler metals developed in a laboratory. The melting properties, the microstructures, phase compositions of filler metals and wettability, erosion properties, tensile properties of the brazed joint were studied in detail. The results show that with the increase of V content, the solidus-liquidus temperature of Ti-Zr-Cu-Ni-V filler metals increased, but the temperature difference basically remained unchanged, trace V element had a limited influence on the melting temperature range of Ti-Zr-Cu-Ni filler metals. The microstructure of Ti-Zr-Cu-Ni-1.5V filler metal was composed of Ti, Zr matrix, (Zr, Cu) solid solution and crystal phase. With the addition of V content, these phases containing V such as Ni3VZr2, NiV3, Ni2V in the molten filler metals increased. V was more inclined to combine with Ni to slow down the diffusion of Ni to titanium matrix. The wettability of filler metal with trace (≤0.5 wt.%) V to TA2 titanium alloy became worse, the wettability improved significantly with continuous increase of V content. The thickness of embrittlement layer and intergranular infiltration region decreased significantly by adding V. With the increase of V content, V could regulate the brazing interface reaction, more strengthened phases generated, which resulted the significant increase of the strength (302.72 MPa) and plasticity index (16.3%) of the brazed joint with Ti-Zr-Cu-Ni-1.5V filler metal.

Application of lipidomics strategy to explore aging-related biomarkers and potential anti-aging mechanisms of ginseng.

Aging often leads to an increase risk of age-related diseases, and the development of anti-aging drugs have become the trend and focus of the current scientific research. In this experiment, serum samples from healthy people of different ages were analyzed based on clinical lipidomics, and a total of 10 potential biomarkers in middle-aged and youth group, 20 biomarkers in the youth and the elderly group were obtained. Furthermore, dhSph and dhCer involved above may affect the aging process through sphingolipid metabolic pathway. As the first and rate-limiting step of catalyzing de novo sphingolipid pathway, SPT may play a key role in human anti-aging, which is revealed by lipidomics liposome tracer analysis. The potential active components in ginseng on SPT was further verified by molecular docking virtual screening and atomic force microscope. Four ingredients of ginseng may reduce the levels of metabolites dhSph and dhCer by inhibiting the activity of SPT, and play an anti-aging effect by affecting the sphingolipid metabolism pathway.A clinical trials registration number: ChiCTR1900026836.

Determination of Alkaloids and Flavonoids in Sophora flavescens by UHPLC-Q-TOF/MS.

This study is based on UHPLC-Q-TOF/MS and fragment ions to achieve classification and identification of alkaloids and flavonoids in Sophora flavescens. By reviewing the available and relevant literature, the mass fragmentation rules of alkaloids and flavonoids were summarized. 0.1% formic acid water (A) and acetonitrile (B) were used as mobile phases. 37 chemical constituents were identified, including 13 alkaloids and 24 flavonoids. This research method offers a complete strategy based on the fragmentation information of characteristic fragment ions and neutral loss obtained by MS/MS to characterize the chemical composition of Sophora flavescens.

ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery.

Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.