Rhus coriaria (Sumac) Fruit Extract Enhances the Biocompatibility of a Propolis-Based Herbal Formulation for Oral...

We investigated the biocompatibility of a novel oral herbal formulation containing Rhus coriaria (sumac) extract plus propolis compared with a propolis-only formulation using zebrafish embryos. Zebrafish embryos (AB/AB strain) were exposed to 3,4-dichloroaniline (DCA), a propolis-only formulation, or a combined sumac-propolis formulation from 24 to 72 h post-fertilization. Biochemical endpoints-including lipid peroxidation (LPO), nitric oxide (NO), acetylcholinesterase (AChE), and superoxide dismutase (SOD)-were evaluated, while gene expression levels of fabp10a, cyp1a, vtg, bax, bcl2, gfap, erg, and igf2 were quantified using RT-PCR. Statistical analysis was performed using one-way ANOVA with a significance threshold of p < 0.05. DCA increased oxidative stress (LPO: p < 0.001; NO: p < 0.01) with reduced SOD (p < 0.01). The propolis-only formulation increased LPO (p < 0.01) and decreased SOD (p < 0.05) versus control, whereas the sumac + propolis formulation showed milder edema, normalized LPO and NO (both p < 0.05 vs. DCA), and increased SOD versus control (p < 0.05), DCA (p < 0.001), and propolis-only (p < 0.001); AChE was unchanged (p > 0.05). At the transcript level, DCA upregulated fabp10a/cyp1a/vtg (all p < 0.0001) and bax (p < 0.0001) while downregulating bcl2 (p < 0.001), erg (p < 0.0001), and igf2 (p < 0.01); these alterations were largely mitigated by the sumac + propolis formulation (vtg lower vs. DCA p < 0.0001 and vs. propolis-only p < 0.001; igf2 higher vs. DCA p < 0.001 and vs. propolis-only p < 0.01). Overall, incorporating sumac into a propolis-based formulation improved biocompatibility in zebrafish embryos, supporting further evaluation of this strategy for oral mucositis-oriented applications.