No abstract

Objective. Nephrotic syndrome (NS) is a common glomerular disease caused by a variety of causes and is the second most common kidney disease. Guizhi is the key drug of Wulingsan in the treatment of NS. However, the action mechanism remains unclear. In this study, network pharmacology and molecular docking were used to explore the underlying molecular mechanism of Guizhi in treating NS. Methods. The active components and targets of Guizhi were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Hitpick, SEA, and Swiss Target Prediction database. The targets related to NS were obtained from the DisGeNET, GeneCards, and OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, active component-target network was constructed using Cytoscape software. And the protein-protein interaction (PPI) network was drawn through the String database and Cytoscape software. Next, Gene Ontology (GO) and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. And overall network was constructed through Cytoscape. Finally, molecular docking was conducted using Autodock Vina. Results. According to the screening criteria, a total of 8 active compounds and 317 potential targets of Guizhi were chosen. Through the online database, 2125 NS-related targets were identified, and 93 overlapping targets were obtained. In active component-target network, beta-sitosterol, sitosterol, cinnamaldehyde, and peroxyergosterol were the important active components. In PPI network, VEGFA, MAPK3, SRC, PTGS2, and MAPK8 were the core targets. GO and KEGG analyses showed that the main pathways of Guizhi in treating NS involved VEGF, Toll-like receptor, and MAPK signaling pathway. In molecular docking, the active compounds of Guizhi had good affinity with the core targets. Conclusions. In this study, we preliminarily predicted the main active components, targets, and signaling pathways of Guizhi to treat NS, which could provide new ideas for further research on the protective mechanism and clinical application of Guizhi against NS.

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro and in vivo was performed to investigate the potential mechanisms of Guizhi to treat NS.Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the overall network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro and in vivo experiments were performed to verify the mechanism of Guizhi to treat NS.Results: 63 intersecting targets were obtained, and the top five key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the overall network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top five key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. In vitro experiment showed that, 24 urinary protein and renal function were increased in ADR group. To western blot, CA down regulated the protein expression of p-p38 MAPK in rats of adriamycin-induced nephropathy.Conclusion: CA might be the main active component of Guizhi to treat NS, and the underlying mechanism might mainly be achieved by inhibiting MAPK signaling pathway.

Objective. Cinnamaldehyde (CA) is the main active component of Guizhi (Cinnamomi ramulus) to ameliorate adriamycin- (ADR-) induced proteinuria in rats. However, the underlying mechanism of CA against proteinuria remains unclear. The aim of this study was to investigate the action mechanisms of CA to treat proteinuria. Methods. 13 rats were randomly selected from 78 SD rats as control group, and the other rats were injected with ADR (3 mg/kg/time) twice through tail vein on day 1 and day 8 for modeling. After modeling, the rats were randomly divided into 5 groups as follows: ADR group, ADR+CA low-dose group, ADR+CA middle-dose group, ADR+CA high-dose group and Benazepril group with 13 rats in each group. The urine of SD rats was collected for 24 h, urine protein, creatinine and urea nitrogen were detected, renal index was calculated, and HE staining and western blot were performed. Results. The 24 h urine volume and urine protein, renal function, and renal histopathology got worse significantly in the ADR group. To western blot, CA downregulated the protein expression of ACE and Ang-2 and upregulated the protein expression of ACE2 in RAS signaling pathway. Conclusion. The underlying action mechanism of CA to treat NS might mainly be achieved by regulating RAS signaling pathway.

Fan Hong Hua ( saffron) is a natural product that has long been used in food and dye industries and fortreating various disorders. Saffron has a long history of applications in traditional Chinese medicine, following its introduction to China in 1979. According to the theory of traditional Chinese medicine, saffron is sweet, slightly cold in nature and enters heart and liver meridians. Moreover, this spice can invigorate blood circulation, eliminate blood stasis, cool blood and eliminate heat toxins. Saffron has been used to treat asthma, phlegm, insomnia, Alzheimer's disease, depression, fright, shock, hemoptysis, heartburn, and pain. Among the almost 70 bioactive ingredients of saffron, major constituents of this herb include safranal, crocin, and crocetin, which are responsible for the unique taste and color of saffron. These ingredients have been investigated using modern pharmaceutical research methods as potential therapeutics to treat disorders such as Alzheimer's disease, cardiovascular diseases, cancer, digestive system disorders, ocular issues, and COVID-19 infections. However, focus and emphasis on understanding the pharmacological effects of saffron in treating diseases are required. This article briefly reviews the history, cultivation processes, different qualities properties, and traditional and modern applications of this unique herb.