In Vitro Inhibition of Phytophthora nicotianae by Berberine and Associated Physiological and Transcriptomic Responses

Phytophthora nicotianae is a destructive plant-pathogenic oomycete. This study evaluated the in vitro inhibitory activity of berberine against strain ACCC 39210 and examined associated physiological and transcriptomic responses. Berberine inhibited mycelial growth, with an estimated EC50 of 42.1 μg/mL (95% CI: 7.66–76.55 μg/mL). Exposure to 42 and 200 μg/mL increased malondialdehyde (MDA) content and superoxide dismutase activity, while decreasing peroxidase activity, ATPase activity, and ATP content. Catalase activity only decreased significantly at 200 μg/mL. Conductivity measurements, propidium iodide staining, and microscopy provided evidence of cellular-envelope injury. Exploratory RNA-sequencing analysis using unadjusted p < 0.05 and |log2(fold change)| > 1 identified 1255 and 1417 candidate differentially expressed genes at 42 and 200 μg/mL, respectively. Functional annotations suggested changes in metabolism, transport, and stress responses. Quantitative reverse-transcription PCR showed concordant expression directions for eight selected genes, using the same biological samples and a single reference gene; this comparison did not provide independent biological validation. These findings associate berberine-mediated growth inhibition with cellular-envelope injury, altered antioxidant enzyme activities, reduced ATP availability, and transcriptional responses in one isolate. Causal mechanisms, efficacy in planta, crop safety, and sensitivity across isolates require further investigation.