1.Molecular design, structural analysis and bactericidal activity of derivatives of antimicrobial peptide buforin II.
Gang HAO ; Guowei LE ; Yonghui SHI ; Danya MA
Acta Pharmaceutica Sinica 2013;48(3):366-71
A novel peptide, named BF2-X, was designed based on the structure-activity analysis of an analogue of Buforin II, named BF2-A. The BF2-X was a hybrid peptide containing the N-terminal residues 5 to 13 of BF2-A and three repeats of the C-terminal regular alpha-helical motif RLLR, and the residues 8 valine were replaced by leucine. The results of bioinformatics analysis had showed that compared with BF2-A, the helicity, positive charge, hydrophobicity rate and C-terminal amphipathy of BF2-X had remarkably enhanced. Both peptides showed a random coil structure in an aqueous solution, while displaying a typical alpha-helical structure in 50% trifluoroethanol solution (a membrane mimic condition). BF2-X exhibited higher alpha-helical contents than BF2-A in hydrophobic environment. BF2-X displayed potent antimicrobial activities against a broad spectrum of microorganisms. And BF2-X showed stronger antimicrobial activities against bacteria tested than parent peptide BF2-A. These results suggest that the alpha-helical content was directly correlated with the enhanced antibacterial activity. Both peptides had no hemolytic action on mouse erythrocyte.
2.Effect of Pangshi Antai Zhixue Decoction on Th1/Th2 Balance in Decidua and Membrane of Spontaneous Abortion Rats with Heat Syndrome by Regulating p38 MAPK Signal Pathway
Liya MA ; Yuanyuan CAI ; Xuelin ZHANG ; Yitong YANG ; Mengyuan JIA ; Danya WANG ; Jingyi WANG ; Dawei ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(18):62-69
ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 (Th1)/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome, based on the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MethodAconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group, aspirin group (5.25 mg·kg-1), dydrogesterone group (3.02 mg·kg-1), Pangshi Antai Zhixue decoction high-dose (44 g·kg-1), medium-dose (22 g·kg-1), and low-dose (11 g·kg-1) groups, with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs, Once a day for 12 d. After 24 h of the last administration, blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of β-human chorionic gonadotropin (β-HCG), progesterone (P), estradiol (E2), γ interferon (IFN-γ), and interleukin-4 (IL-4) in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3, T-bet, p38 MAPK, and its phosphorylation in the decidual tissue. ResultAs compared with the normal group, the number of live births, the β-HCG, P, E2, and IL-4 in the serum, and the GATA3 protein expression in the decidual tissue in the model group were reduced (P<0.01), whereas the number and rate of miscarriages, IFN-γ in the serum, and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased (P<0.01). As compared with the model group, the number of live births, the β-HCG, P, E2, and IL-4 in the serum, and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased (P<0.01), whereas the number and rate of miscarriages, IFN-γ in the serum, and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced (P<0.01). As compared with the aspirin group, the P, E2, and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased (P<0.01), the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased (P<0.01), and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased (P<0.01). The number and rate of miscarriages, IFN-γ in the serum, and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased (P<0.05). Compared with the Pangshi Antai Zhixue decoction medium-dose group, the low-dose group, high-dose group, and dydrogesterone group showed increased number and rate of miscarriages (P<0.05), and the high-dose group and dydrogesterone group decreased the number of live birth (P<0.01). The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group, and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased (P<0.05). The β-HCG, P, and E2 in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group, dydrogesterone group, and aspirin group decreased (P<0.01), and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased (P<0.01). ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.