Li, S.-y. | Search bioRxiv

bioRxiv2025

Metabolite Profiling of Epimedium sagittatum Bee Pollen: Identified Bioactive Flavonoids with Multi-Disease Functional Food Potential

Epimedium sagittatum bee pollen (EBP) is a bee pollen product of a medicinal plant, but its chemical characteristics remain unclear. In this study, EBP was systematically characterized by biochemical analysis and UPLC-MS/MS, using Brassica rapa bee pollen (BBP), Camellia sinensis bee pollen (CBP), and Epimedium leaves for compari-son. A total of 1,073 secondary metabolites were identified in EBP, mainly flavonoids (330, 30.8%) and phenolic acids (165, 15.3%). EBP showed the highest total flavonoid content among the three bee pollen types (4.75 mg/g) and was clearly separated from BBP and CBP in multivariate analysis. EBP contained 19 unique metabolites, fewer than CBP (271), but these included several high-content flavonoid compounds, such as cacticin, brassicin, and tricetin-4'-methyl ether-3'-{beta}-D-glucoside. Differential metabolite analysis identified 449 and 1,085 metabolites that differed between EBP and BBP, re-spectively, with flavonoid compounds forming the main differential class. Among the shared differential metabolites, 45 flavonoids were consistently higher in EBP, in-cluding kaempferol, tamarixetin, and sinensetin. Network pharmacology screening further suggested that flavonoid metabolites, especially kaempferol, tamarixetin, and sinensetin, deserve particular attention in future studies of EBP. Compared with Epimedium leaves, characteristic leaf flavonoids such as icariin and epimedins A-C were present at very low levels or were not detected in EBP. Overall, EBP is charac-terized by a distinct, relatively concentrated flavonoid chemical profile, distinct from both common commercial bee pollens and Epimedium medicinal tissues. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/679240v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@1587d35org.highwire.dtl.DTLVardef@8461d6org.highwire.dtl.DTLVardef@1336149org.highwire.dtl.DTLVardef@381ae8_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2018

Jagged1/Notch2 Controls Kidney Fibrosis via Tfam-mediated Metabolic Reprogramming

While Notch signaling has been proposed to play a key role in fibrosis, the direct molecular pathways targeted by Notch signaling and the precise ligand and receptor pair that are responsible for kidney disease remain poorly defined.\n\nIn this study, we found that JAG1 and NOTCH2 showed the strongest correlation with the degree of interstitial fibrosis in a genome wide expression analysis of a large cohort of human kidney samples. RNA sequencing analysis of kidneys of mice with folic acid nephropathy, unilateral ureteral obstruction, or APOL1-associated kidney disease indicated that Jag1 and Notch2 levels were higher in all analyzed kidney fibrosis models. Mice with tubule-specific deletion of Jag1 or Notch2 (Kspcre/Jag1flox/flox, and Kspcre/Notch2flox/flox) had no kidney-specific alterations at baseline, but showed protection from folic acid induced kidney fibrosis. Tubule-specific genetic deletion of Notch1 and global knock-out of Notch3 had no effect on fibrosis. In vitro chromatin immunoprecipitation experiments and genome-wide expression studies identified the mitochondrial transcription factor A (Tfam) as a direct Notch target. Re-expression of Tfam in tubule cells prevented Notch-induced metabolic and profibrotic reprogramming. Kidney tubule specific deletion of Tfam resulted in perinatal lethality.\n\nIn summary, Jag1/Notch2 plays a key role in kidney fibrosis development by regulating Tfam expression and metabolic reprogramming.

pathology↗