Polyphenolic Composition and Multifunctional Biological Properties of Raspberry Leaves: Variation Among Cultivar-Specific Samples

Despite increasing interest in raspberry leaves (Rubus idaeus L.) as a source of bioactive compounds, comparative information linking their phenolic composition to multiple biological properties remains limited. This study compared the polyphenolic profiles and biological properties of leaves from seven raspberry cultivars representing Rubus idaeus L. and Rubus occidentalis L., grown under identical environmental conditions. Phenolic compounds were characterized by UPLC–Q/TOF-MS, while antioxidant capacity, α-amylase and α-glucosidase-inhibitory activities, inhibition of COX-1 and COX-2, and effects on colorectal cancer cell viability were evaluated. A total of 37 phenolic compounds were identified or tentatively characterized, with flavan-3-ols and procyanidins representing the quantitatively predominant phenolic group, followed by flavonols. Considerable variation in both phenolic composition and biological responses was observed among the cultivar-specific composite samples. Red-fruited samples generally showed higher antioxidant capacity, whereas α-amylase- and α-glucosidase-inhibitory activities varied among the samples. In contrast, the strongest COX-1 and COX-2 inhibition was observed for the yellow-fruited Poranna Rosa sample. Effects on colorectal cancer cell viability also varied among the samples, with the red-fruited samples generally producing greater reductions in LOVO, LOVO-DX, and SW48 cell viability. Exploratory Spearman correlation analysis using exact permutation-based p-values followed by FDR correction showed that flavan-3-ol and total polyphenol concentrations were positively associated with ABTS and FRAP antioxidant capacity and inversely associated with LOVO, LOVO-DX and SW48 cell viability at 600 μg/mL. No FDR-significant associations were observed for carbohydrate-hydrolyzing enzyme or COX inhibition. Overall, these results demonstrate substantial variation in the phenolic composition and biological properties among the analyzed raspberry leaf samples analyzed. Because the species, cultivar identity, and fruit color group cannot be separated within the present experimental design, the observed differences should not be independently attributed to genotype or fruit color. These findings support further investigation of raspberry leaves as sources of bioactive phenolic compounds for potential food and nutraceutical applications.