Royal jelly mediates fibrotic signaling, collagen cross-linking and cell proliferation in cardiac fibroblasts

• Published in: Biomedicine & pharmacotherapy Vol. 164; p. 114922
• Main Authors: Al-U’datt, Doa’a G.F., Alu’datt, Muhammad H., Tranchant, Carole C., Al-Dwairi, Ahmed, Al-shboul, Othman, Almajwal, Ali, Elsalem, Lina, Jaradat, Saied, Alzoubi, Karem H., Faleh, Belal G., Ahmed, Yaman B., Alqbelat, Jenan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.08.2023; Elsevier
• Subjects: Animals; bcl-2-Associated X Protein - metabolism; Bees; Bioactivity; Cardiac fibrosis; Cell Proliferation; Collagen - metabolism; Fatty Acids - metabolism; Fibroblasts; Fibrosis; Fibrotic markers; Rats; Royal jelly; Sonication; Fibrotic markers; Sonication; NS; CTGF; MRJP; α-SMA; BCL-2; Cardiac fibrosis; S; CCND1; Fibroblasts; RT-qPCR; TG2; TG1; Royal jelly; FN1; CX43; ECM; COL1A1; CVD; COL3A1; CCNE2; MMP-2; ROS; RJ; BAX; TGF-β1; Bioactivity; MMP-9
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114922

Royal jelly (RJ) is a multifunctional bee product with a unique composition and wide-ranging biological properties, including antioxidant, anti-inflammatory and antiproliferative activities. Still, little is known about the possible myocardial protective properties of RJ. Considering that sonication could enhance RJ bioactivity, this study aimed to assess the effects of non-sonicated (NS) and sonicated (S) RJ on fibrotic signaling, cell proliferation, and collagen production in cardiac fibroblasts. S-RJ was produced by ultrasonication at 20 kHz. Ventricular fibroblasts isolated from neonatal rats were cultured and treated with different concentrations of NS-RJ or S-RJ (0, 50, 100, 150, 200, and 250 µg/well). S-RJ significantly depressed the expression levels of transglutaminase 2 (TG2) mRNA across all the concentrations tested and was inversely associated with the expression of this profibrotic marker. S-RJ and NS-RJ displayed distinct dose-dependent effects on mRNA expression of several other profibrotic, proliferation, and apoptotic markers. Unlike NS-RJ, S-RJ elicited strong negative dose-dependent relationships with the expression of profibrotic markers (TG2, COL1A1, COL3A1, FN1, CTGF, MMP-2, α-SMA, TGF-β1, CX43, periostin), as well as proliferation (CCND1) and apoptotic (BAX, BAX/BCL-2) markers, indicating that RJ dose-response effects were significantly modified by sonification. NS-RJ and S-RJ increased the content of soluble collagen, while decreasing collagen cross-linking. Collectively, these findings show that S-RJ has a greater range of action than NS-RJ for downregulating the expression of biomarkers associated with cardiac fibrosis. Reduced biomarker expression and collagen cross-linkages upon cardiac fibroblast treatment with specific concentrations of S-RJ or NS-RJ suggests putative roles and mechanisms by which RJ may confer some protection against cardiac fibrosis. •Royal jelly (RJ) displayed antifibrogenic activity in cultured ventricular fibroblasts.•RJ administration reduced collagen cross-linking in fibroblasts.•RJ altered the expression of key profibrotic, proliferation, and apoptotic markers.•Sonication enhanced RJ bioactivity in downregulating cardiac fibrosis signaling.•Sonicated RJ also showed superior potential for reducing fibroblast proliferation.