Multiomics approach towards the detoxification of cadmium in Fritillaria cirrhosa using citrulline and zinc oxide nanoparticles in Qinghai-Tibet's ecosystems.

The Qinghai-Tibet Plateau, a biodiversity hotspot with escalating cadmium (Cd) pollution, demands urgent strategies to safeguard its endemic medicinal plants. Fritillaria cirrhosa, a critically endangered alpine species endemic to this region, confronts severe survival challenges due to habitat constraints and Cd-contaminated soils, leading to collapse of intrinsic detoxification systems. This study demonstrates that foliar application of citrulline and zinc oxide nanoparticles orchestrate altitude-specific physiological and molecular adaptations to counteract Cd toxicity while preserving medicinal integrity. Both agents restored photosynthetic function (11.7 % and 11.1 % recovery in Fv/Fm) and suppressed oxidative damage, reducing H₂O₂ by 38.8 %/36.4 %, respectively. Citrulline uniquely amplified peroxidase activity by 333.7 %, synergizing with cell wall lignification to immobilize Cd in leaves (44.3 % reduction) and block uptake of bulb (88.4 % inhibition). Conversely, zinc oxide nanoparticles selectively enhanced catalase activity by 78.5 %, directly neutralizing ROS while reducing leaf Cd by 59.7 %. Ultrastructural analyses confirmed both treatments preserved thylakoid architecture and minimized plastoglobule formation. Integrated multiomics profiling revealed compartmentalized detoxification pathways: citrulline activated phenylpropanoid biosynthesis (PAL1 and 4CL2) for Cd sequestration via lignified cell walls, whereas zinc oxide nanoparticles upregulated starch-sucrose metabolism (INV and BGLX) to reinforce osmotic homeostasis. Both strategies converged on hormonal signaling and ABC transporter induction, elevating amino acids to chelate Cd. Remarkably, citrulline and zinc oxide nanoparticles boosted the peiminine by 69.22 % and 266.73 %, validating concurrent detoxification and phytochemical enhancement. Our findings establish the first evidence-based framework for precision phytoremediation in high-altitude medicinal plants, offering a solution for sustainable production of low-Cd medicinal resources in climate-sensitive zones.