Curcumin ameliorates traumatic brain injury via C1ql3-mediated microglia M2 polarization.

Purpose: Curcumin can regulate the polarization of microglia and alleviate traumatic brain injury (TBI). However, its detailed action mechanism on downregulating Complement 1q-like-3 protein (C1ql3) in TBI is less reported. The purpose of this study is to explore the role and mechanism of curcumin-regulated C1ql3 in TBI.

Method: GSE23639 dataset was used to acquire gene data for microglia. C57BL/6 J wild-type (WT) mice were subjected to establish a controlled cortical impact model of TBI. The effects of curcumin (200 mg/kg) on the brain injury, inflammatory cytokine levels, microglia polarization, and C1ql3 protein expression in mice and BV-2 cells were detected by H&E staining, qRT-PCR, immunofluorescence, and Western blot, respectively. The effects of curcumin (5, 10, 20 μmol/L) and lipopolysaccharides (LPS, 1 µg/mL) on the viability of BV-2 cells were determined by MTT assay. After the transfection of C1ql3 overexpression plasmid, C1ql3 expression, IL-1β and IL-6 levels, and the number of CD16/32 and CD206 cells were determined by qRT-PCR, ELISA and flow cytometry, respectively.

Result: C1ql3 expression was down-regulated in microglia after the curcumin treatment. Curcumin treatment could alleviate the TBI-induced brain injury in mice, reduce IL-1β and IL-6 levels, promote M2 polarization of microglia, and decrease C1ql3 protein expression. For BV-2 cells, curcumin treatment had no significant toxic effect on cell viability, but reversed the effect of LPS on cells, while C1ql3 overexpression counteracted the effect of curcumin.

Conclusion: Curcumin induces M2 microglia polarization through down-regulating C1ql3 expression, which may become a new treatment method for TBI.

Availability Of Data And Materials: The analyzed data sets generated during the study are available from the corresponding author on reasonable request.