Comparative Metabolomic and Transcriptomic Analysis of Flavonoid Accumulation in the Zest and Pith of Guang Foshou at Green and Ripe Stages

Citrus medica 'Fingered' (known as Guang Foshou in Chinese) is a distinctive edible fruit and a traditional herbal medicine enriched with bioactive flavonoids. However, the spatiotemporal patterns of flavonoid accumulation in the zest and pith throughout fruit development remain poorly characterized. This study combined metabolomic and transcriptomic analyses to examine green and yellow fruits. Total flavonoid content increased significantly in the zest during fruit ripening, rising from 1.60 to 2.46 mg/g, whereas it remained relatively stable in the pith at approximately 2.2-2.3 mg/g. In the pith, flavanone glycosides, including hesperidin, neohesperidin, and naringin, accumulated progressively and are recognized for their cardioprotective and anti-inflammatory properties. In comparison, polymethoxylated flavones (nobiletin, tangeretin, and syringetin) accumulated in the zest, contributing to fruit coloration and showing well-known anti-inflammatory and anticancer activities. Transcriptomic analysis revealed that the flavonoid biosynthesis pathway involves core structural genes, including CHS, CHI, FLS, CYP75B2, FGT, and UFGT, which play crucial roles in regulating tissue-specific accumulation patterns. These results identify several potential quality markers, including diosmin, hesperidin, neohesperidin, naringin, nobiletin, tangeretin, and syringetin, and provide a scientific platform for medicinal quality control and molecular breeding of Guang Foshou.