Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.12.20.572649

Mechanism of action of Buqing Granule against Diabetic retinopathy based on network pharmacology and animal experiments

Yang, Y.·Yuan, L.·Li, X.·Liu, Q.·Jiang, W.·Jiao, T.·Li, J.·Ye, M.·Niu, Y.·Nan, Y.
View original source ↗Export metadata ↓

Abstract

ObjectiveFor this study, network pharmacology and animal experiments were used together to get a better idea of how BQKL works at the molecular level to treat DR. MethodsIn this study, we obtained the relevant action target information of BQKL from the TCMSP and also combined the GeneCards, OMIM, TTD, and PharmGKB databases with the GEO database to obtain the relevant target information of DR. The intersection of these targets was determined using a Venn diagram to identify the target of action for the treatment of DR with BQKL. The target proteins of BQKL for DR were then uploaded to the String database. The resultant data were imported into Cytoscape 3.9.0 to construct PPI networks and identify key targets of action. The DAVID database was used to do a GO and KEGG pathway enrichment analysis of target genes for treating DR with BQKL. Molecular docking was performed to validate the core action targets with the core compounds of BQKL. In addition, we induced DR production in rats by a high-fat, high-sugar diet and intraperitoneal injection of STZ and validated the results obtained from the network pharmacological analysis by changes in body weight and blood glucose, serum levels of biochemical markers, HE staining, immunohistochemistry, qRT-PCR, and Western blot experiments in rats. ResultsIn this study, quercetin, kaempferol, {beta}-sitosterol, lignanserin, and stigmasterol were identified as the key components, TP53, AKT1, JUN, CASPASE3, MAPK3, and MAPK1 as the key targets, and PI3K-Akt, AGE-RAGE, and MAPK signaling pathways as the main pathways involved. The results of animal experiments showed that BQKL could not only effectively reduce the degree of blood glucose, blood lipids, and oxidative damage in diabetic rats but also slow down the development process of DR. At the same time, it can significantly up-regulate the expression of AKT1, MAPK1, and MAPK3 and down-regulate the expression of CASPASE3, c-JUN, and TP53 in retinal tissue. ConclusionBQKL ameliorates oxidative stress, apoptosis, and inflammation due to hyperglycemia-related stress by regulating key targets of CASPASE3, AKT1, c-JUN, TP53, MAPK1, and MAPK3, thereby delaying the onset and progression of DR.

Explore related subjects

molecular biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yang, Y., Yuan, L., Li, X., Liu, Q., Jiang, W., Jiao, T., Li, J., Ye, M., Niu, Y., Nan, Y.. 2023-12-23. Mechanism of action of Buqing Granule against Diabetic retinopathy based on network pharmacology and animal experiments. https://doi.org/10.1101/2023.12.20.572649

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Single-AAV-mediated cardiomyocyte-specific adenine base editing ameliorates cardiac hypertrophy in vivo

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, frequently accompanied by cardiac hypercontractility, diastolic dysfunction, heart failure and sudden cardiac death. The disease is predominantly caused by pathogenic variants in genes encoding sarcomeric proteins and current therapeutic strategies largely focus on symptom management. Adeno-associated virus-based (AAV) delivery of base editing tools has emerged as an alternative strategy that acts directly on the genetic cause of disease. However, canonical SpCas9-based editors are too large to package into a single-AAV vector which mandates dual-AAV approaches that require higher overall vector doses with elevated toxicity risk and increased manufacturing costs. Here, we report the development and application of a single vector approach for cardiomyocyte-specific adenine base editing to correct a Dutch founder mutation in MYBPC3 (c.2827C>T, p.Arg943Ter) that causes HCM. We systematically compared compact base editors in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and selected the most efficient configuration, which reversed disease-associated hypercontractility in engineered human myocardium (EHM). To fit the editor/guide construct in a single-AAV vector, we screened a library of rationally designed small chimeric promoters and identified 6C2 to effectively drive expression in hiPSC-CMs and cardiac tissue of both mice and non-human primates (NHP) with exceptional specificity. Delivered in a single next-generation cardiotropic AAV capsid, we achieved therapeutic correction in an HCM mouse model at doses 20-fold below published dual-AAV cardiomyopathy base editing approaches. These results establish cardiomyocyte-specific, single vector-mediated base editing as a viable therapeutic strategy for inherited cardiomyopathies.

molecular biology↗
bioRxiv2026

Engineered Miniature ParTasR Enables Efficient PAMless Genome Editing

TIGR-Tas system holds great promise for genome-engineering applications owing to its compact size and PAMless targeting capability. However, its low editing efficiency in mammalian cells severely limits its broader utility. Here, we engineered a highly active variant of ParTasR, termed eTasR, through structure-guided rational design of ParTasR combined with fusion to the exonuclease TREX2. eTasR increased mammalian editing efficiency from the original 4.29% to 48.94% with an average 26.52-fold increase, significantly surpassing the efficiency of SpRY, a reported version of PAM-free nuclease. More importantly, single-AAV delivery enabled efficient Hpd disruption in vivo, resulting in robust phenotypic rescue. Thus, eTasR provides a compact, PAMless and highly efficient platform for genome editing and therapeutic applications.

molecular biology↗
bioRxiv2026

Enhancing pancreatic islet cell survival via NMDAR antagonist-driven ROR1 activation as revealed by phosphoproteomics

NMDA receptors (NMDARs) control function and survival not only of neurons, but also of insulin-producing pancreatic beta cells. Since insufficient insulin secretion and beta cell death are key events during diabetes development, targeting NMDARs offers a therapeutic approach. Specifically, the NMDAR antagonist dextrorphan (DXO) increases glucose-stimulated insulin secretion in clinical trials. Furthermore, treatment with DXO or optimized DXO derivatives prevents pancreatic islet cell death upon diabetogenic insults. Nonetheless, the signaling pathways induced by NMDAR inhibition are poorly understood. Here, we use complementary approaches, phosphoproteomics and tyrosine kinase profiling, to demonstrate that DXO and its derivatives rapidly regulate multiple intracellular signaling clusters, including mTOR and ERK signaling, in pancreatic islets. Notably, mTOR inhibition, but not ERK inhibition, is sufficient to negate DXO's protective effects. Further, we show that activation of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) is a universal event upon NMDAR inhibition in islets. Simultaneous knockdown of Ror1/ROR1 and its paralogue Ror2/ROR2 compromises the viability of both mouse and human islets, highlighting the ROR1/2 signaling axis as a promising avenue for enhancing beta cell survival.

molecular biology↗