Study on the effect and mechanism of Zhenzhu Tongluo pills in treating diabetic peripheral neuropathy injury.

BACKGROUND: As a traditional Mongolian medicine, Zhenzhu Tongluo pills has played a good neuroprotective function in clinic. However, the key mechanisms by which it works are poorly studied. OBJECTIVES: To study the effect and mechanism of Zhenzhu Tongluo pills in treating diabetic peripheral neuropathy injury. METHODS: Diabetic peripheral neuropathy model was established by injecting STZ into rats. Physiological, behavioral, morphological and functional analyses were used to evaluate that the overall therapeutic effect of rats, ELISA, qRT-PCR, Western blot, immunohistochemical staining, HE staining and TUNEL staining were used to further study the related mechanism. RESULTS: Zhenzhu Tongluo pills can significantly improve the physiological changes, behavioral abnormalities, structural and functional damage in diabetic peripheral neuropathy rats, which may be related to the anti-inflammatory and anti-apoptotic effects that realized by regulating PI3K/AKT, MAPK, NF-κB signaling pathways. CONCLUSIONS: Zhenzhu Tongluo pills has neuroprotective effect, and anti-inflammatory and anti-apoptosis may be the important way of its function.

Study on the mechanism of Shenkang injection in the treatment of chronic renal failure based on the strategy of "Network pharmacology-Molecular docking-Key target validation".

OBJECTIVE: To explore the potential mechanism of Shenkang injection (SKI) in the treatment of chronic renal failure based on network pharmacology and molecular docking technology, and to verify the core targets and key pathways by using the renal failure model. METHODS: The active components and targets of Shenkang injection were retrieved by TCMSP database, and the disease related targets were obtained by OMIM, GeneCards and other databases. Then, the intersection was obtained, and were imported into String database for PPI analysis. After further screening of core targets, GO and KEGG analysis were performed. Autodock software was used to predict the molecular docking and binding ability of the selected active ingredients and core targets. Chronic renal failure (CRF) model was established by adenine induction in rats, and the pathological observation of renal tissues was conducted. Meanwhile, the effects of Shenkang injection and its active components on core targets and pathways of renal tissues were verified. RESULTS: The results of network pharmacology showed that the main components of Shenkang injection might be hydroxysafflor yellow A (HSYA)、tanshinol、rheum emodin、Astragaloside IV. Through enrichment analysis of core targets, it was found that Shenkang injection may play an anti-chronic renal failure effect through PI3K-Akt signaling pathway. Molecular docking results showed that the above pharmacodynamic components had strong binding ability with the target proteins PI3K and Akt. The results of animal experiments showed that renal function indexes of Shenkang injection group and pharmacodynamic component group were significantly improved compared with model group. HE staining results showed that the pathological status of the kidney was significantly improved in SKI and pharmacodynamic component treatment groups. Immunohistochemical results showed that the renal fibrosis status was significantly reduced in SKI and pharmacodynamic component treatment groups. q-RTPCR and WB results showed that the expression levels of PI3K and Akt were significantly decreased in the treatment groups (P< 0.05). CONCLUSIONS: Shenkang injection may inhibit PI3K-Akt signaling pathway to play an anti-chronic renal failure role through the pharmacodynamic component hydroxysafflor yellow A (HSYA), tanshinol, rheum emodin, Astragaloside IV.

ATP selection in a random peptide library consisting of prebiotic amino acids.

Based upon many theoretical findings on protein evolution, we proposed a ligand-selection model for the origin of proteins, in which the most ancient proteins originated from ATP selection in a pool of random peptides. To test this ligand-selection model, we constructed a random peptide library consisting of 15 types of prebiotic amino acids and then used cDNA display to perform six rounds of in vitro selection with ATP. By means of next-generation sequencing, the most prevalent sequence was defined. Biochemical and biophysical characterization of the selected peptide showed that it was stable and foldable and had ATP-hydrolysis activity as well.

Phthalide Anions in Organic Synthesis. A Direct Total Synthesis of Furomollugin.

Furomollugin was synthesized in three steps from commercially available starting materials using phthalide annulation chemistry.

Synthetic approach to the psoracorylifols.

Core analogs of the psoracorylifols were generated by a five-step route from 2,2-dimethyl-4-cyanobutanal.