Bioactive Potential of Post-Distillation Residue of Clinopodium albanicum (Griseb. ex K. Malý) Melnikov: Phytochemical Profiling, Antioxidant and Antimicrobial Activities with Molecular Docking Insights.

The valorization of post-distillation by-products represents a key strategy within circular economy frameworks, particularly for medicinal and aromatic plants of the Lamiaceae family. This study investigates, for the first time, the chemical composition and biological potential of the liquid residue obtained after hydrodistillation of Clinopodium albanicum (Griseb. ex K.Malý) Melnikov, an endemic Balkan species. Untargeted LC-HRMS/MS analysis revealed a complex metabolomic profile dominated by hydroxycinnamic acid derivatives, including caffeoylquinic acids, alongside a diverse flavonoid fraction comprising quercetin, kaempferol, apigenin, and acacetin derivatives. The presence of sugars and organic acids further indicated a broad metabolic composition. The evaporated liquid residual extract exhibited strong antioxidant activity (DPPH: 32.54, ABTS: 27.80, FRAP: 35.95 mmol GAE/100 mg). Pronounced antibacterial activity was observed against both Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, MRSA, Listeria monocytogenes, Escherichia coli, and Pseudomonas aeruginosa (MICs 0.5-1 mg/mL). Additionally, the extract demonstrated antifungal activity against Candida auris and Candida parapsilosis, as well as strong antibiofilm effects against P. aeruginosa (up to 95.52% inhibition). Molecular docking supported these findings, revealing strong binding affinities of key phenolics toward the bacterial targets FabI and D-Ala-D-Ala ligase. Overall, the results highlight the potential of this by-product for nutraceutical and pharmaceutical applications.