Toxicity and Mechanism of Alkaloids in Sophorae Tonkinensis Radix et Rhizoma： A Review / 中国实验方剂学杂志

Sophorae Tonkinensis Radix et Rhizoma （STRER） is a commonly used Chinese medicine in clinical practice， which has the effects of clearing heat， removing the toxin， alleviating edema， and relieving sore throat. In recent years， the clinical reports of STRER-induced poisoning have gradually increased， with neurotoxicity and hepatotoxicity as the main characteristics of the acute attack. Timely treatment will lead to the good prognosis， but long-term or high-dose administration will cause irreversible damage. Therefore， the safety of clinical use of STRER should be highlighted. The chemical components in STRER mainly include alkaloids， flavonoids， triterpenoids， triterpenoid saponins， and polysaccharides， as well as small amounts of proteins， organic acids， and trace elements， where alkaloids both serve as the important material basis for the pharmacodynamic action and the main substances causing toxicity. The adverse events induced by STRER and its alkaloids include nerve injury, Hepatic injury, cardiovascular injury, kidney injury and reproductive injury， and gastrointestinal reaction. Quinolizidine alkaloids are the main toxic components， mainly including matrine， oxymatrine， cytisine， sophocarpine， oxysophocarpine， sophoridine， sophoramine， and lehmannine. Many studies have been carried out on the toxicity of different extracts and alkaloids of STRER in China and abroad， but there are no comprehensive and detailed reports on the toxicity mechanism of alkaloids in STRER. As a Chinese medicine， STRER is widely used. It's an urgent problem to clarify the material basis and mechanism of toxicity caused by STRER and reduce the toxicity for good clinical application. The present study reviewed the components of alkaloids， toxicity， and toxic mechanism of extracts and alkaloids in STRER to provide the basis for further development and clinical safe and effective application of STRER.

Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control.

Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3'-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family.

Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF.

Compression-induced programmed cell death of nucleus pulposus (NP) cells is an important contributor to intervertebral disc degeneration (IDD). Dynamin-related protein 1 (Drp1), a crucial mitochondrial fission protein, triggers programmed necrosis upon cellular injury. However, limited information is available about the role of Drp1 in compression-induced programmed necrosis of NP cells. In the present study, we found that compression resulted in upregulation and mitochondrial translocation of Drp1. Inhibition of Drp1 by siRNA or mitochondrial division inhibitor 1 (mdivi-1) effectively prevented the programmed necrosis of NP cells treated with compression. Furthermore, Drp1 promoted mitochondrial translocation of p53 and nuclear translocation of apoptosis-inducing factor (AIF) in compression-treated NP cells. Inhibition of p53 mitochondrial translocation by pifithrin-µ (PFT-µ) and silencing of AIF expression by siRNA significantly alleviated compression-induced NP cell programmed necrosis. These data indicates that Drp1 mediates compression-induced programmed necrosis of NP cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF.

[The index F and relative index Fr of chromatographic fingerprints].

AIM: The index F and relative index Fr of chromatographic fingerprints were firstly proposed to indicate how bountiful was the information in traditional Chinese medicines chromatographic fingerprints, how better was the separation effect, how high was the peak signal and how equal were the peak areas. METHODS: The index F and relative index Fr of chromatographic fingerprints were firstly applied to evaluate the chromatographic fingerprints results of traditional Chinese medicines determined by the reversed-phase high performance liquid chromatographic method and high performance capillary electrophoresis. RESULTS: The Shegan Kangbingdu injection and all its traditional Chinese medicines ingredients had been evaluated by F and Fr, so did for the HPLC fingerprints of Radix salviae miltiorrhizae reported in literature. As the same time, the F and Fr of the capillary electrophoresis fingerprints of Folium isatidis, Rhizoma belamcandae and compound liquorice tablets were successfully determined. As far as F was concerned, there was no evident difference between HPLC and capillary electrophoresis (CE), but the Fr values came from CE was usually a thousand times more than that from HPLC. CONCLUSION: The F and Fr can be applied to evaluate objectively, simply and thoroughly the chromatographic fingerprints.