Rhus coriaria (Sumac) Fruit Extract Enhances the Biocompatibility of a Propolis-Based Herbal Formulation for Oral Mucositis: Biochemical and Gene Expression Analyses in Zebrafish Embryos

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.