Berberine-mediated bidirectional regulation of MIL-101(Fe-Cu) nanozyme: A novel probe-free colorimetric strategy for alkaloid sensing and its biological application.

The development of simple, probe-free colorimetric methods for bioactive alkaloid detection remains highly desirable. Herein, a MIL-101(Fe-Cu) bimetallic MOF nanozyme-based colorimetric platform was developed by exploiting the concentration-dependent bidirectional regulation of nanozyme activity by berberine (BBR). The MIL-101(Fe-Cu) exhibited prominent peroxidase-like activity, which was unexpectedly regulated by BBR in a bidirectional manner: activity was enhanced at low BBR concentrations but suppressed at high concentrations. This unique response enabled a dual-range linear detection (0.005-30 μM and 40-90 μM) with a detection limit of 0.0031 μM. The platform exhibited excellent selectivity against common interferents and structurally related alkaloids. Satisfactory recoveries (93.3-123.0%) were obtained in Coptidis Rhizoma extract (CRE), and the results were in good agreement with those of the standard HPLC method. The optimized BBR/nanozyme combination also demonstrated synergistic anti-inflammatory and antioxidant effects. This work provides a natural-product-mediated strategy for designing responsive nanozyme-based analytical platforms with potential therapeutic applications.