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Unveiling Dragon's Blood Radiation Mitigation Mechanism: Identifying Key Targets and Bioactive Compounds with
Boyang Li1,2,3, Chu Han1,2, Han Zhang1,2,3
1School of Interdisciplinary Science, Beijing Institute of Technology, Beijing 100081, China.
Abstract:
Radiotherapy often causes severe and irreversible neural damage, including cognitive impairment and depression-like behaviors. Current mitigants are limited, with single-target molecules being ineffective and nanomedicines posing complexity and toxicity risks. Dragon's Blood (DB), a nontoxic, brown-red resin extracted from Dracaena cochinchinensis (Lour.) (S. C. Chen, China), possesses diverse pharmacological properties. Extensive studies demonstrated that the compounds in DB exhibit multiple therapeutic effects, including cardiovascular protection, promotion of blood circulation, and anti-inflammatory effect. Herein, DB's neuronal radiation mitigation effect and mechanism were investigated. In a whole-brain irradiation rat model, DB administration significantly alleviated radiation-induced anhedonia-like behavior, normalized calcium dyshomeostasis, restored mitochondrial membrane potential, mitigated dendritic spine loss, suppressed neuroinflammation (IL-1β and TNF-α), and preserved hippocampal cytoarchitecture. Brain tissue proteomics revealed 23 DB-modulated KEGG pathways, encompassing the glutamatergic/GABAergic synapse, synaptic plasticity, addiction-related pathways, calcium/cAMP signaling, and hormonal regulation. Ensemble analysis integrating proteomics, WGCNA, machine learning, and PPI pinpointed 24 DB radiation mitigation-related proteins. Among these, eight targets (Grin1, Gabra4, Grm2, Grm3, Grm7, Prkcb, Shank3, and Pak7) functioning via ligand-target interactions were dysregulated by radiation and restored by DB. Molecular docking identified three DB ingredients (socotrin-4'-ol, cinnabarone, and 2'-methoxysocotrin-5'-ol) interacted with all eight targets. Plasma proteomics further revealed radiation mitigation-related brain-enriched proteins (Mib1, Gucy1b1, Fkbp1a, Synj1, and Clasp2). PPI between these 5 plasma proteins and 24 brain proteins reveals DB's multitarget radiation mitigation effect on neurotransmission and synaptic regulation, neuroplasticity, and signaling transduction and cellular response. This work nominated DB and its key constituents as promising candidates for mitigating radiotherapy-induced neural injury.
Insights
Dragon's Blood (DB) effectively mitigates radiotherapy-induced neural damage by restoring synaptic function and reducing neuroinflammation. This study identifies key proteins and compounds in DB for treating radiation-induced brain injury.
Area of Science:
- Neuroscience
- Pharmacology
- Radiology
Background:
- Radiotherapy frequently causes severe, irreversible neural damage, leading to cognitive deficits and depression-like behaviors.
- Existing treatments for radiation-induced neural injury are limited, with single-target drugs showing ineffectiveness and nanomedicines presenting toxicity concerns.
Purpose of the Study:
- To investigate the neuroprotective effects of Dragon's Blood (DB) against radiation-induced neural damage.
- To elucidate the underlying molecular mechanisms of DB's radioprotective action.
Main Methods:
- Establishment of a whole-brain irradiation rat model.
- Administration of Dragon's Blood (DB) and assessment of behavioral, biochemical, and histological outcomes.
- Utilized brain tissue and plasma proteomics, Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and protein-protein interaction (PPI) analysis.
- Molecular docking was employed to identify interactions between DB compounds and target proteins.
Main Results:
- DB administration significantly alleviated radiation-induced anhedonia, normalized calcium homeostasis, restored mitochondrial function, and preserved hippocampal structure.
- DB suppressed neuroinflammation by reducing IL-1β and TNF-α levels.
- Proteomic analysis identified 24 key proteins and 23 modulated pathways, including synaptic function and signaling transduction, with eight specific targets restored by DB.
- Molecular docking confirmed interactions between three DB compounds and eight identified protein targets.
Conclusions:
- Dragon's Blood (DB) demonstrates significant efficacy in mitigating radiotherapy-induced neural injury through multitarget mechanisms.
- DB's active compounds show promise as therapeutic agents for preventing or treating radiation-induced neurological damage.
- This research highlights DB as a potential candidate for developing novel strategies against radiotherapy-induced brain complications.
