Curcumin preconditioning enhances the neuroprotective effects of olfactory mucosa-derived mesenchymal stem cells on experimental intracerebral hemorrhage

Yan Huang; Jianyang Liu; Jialin He; Fengbo Tan; Ming Lu; Fulai Yuan; Xuelin Zhu; Lingyu Kong

doi:10.1016/j.heliyon.2023.e17874

Curcumin preconditioning enhances the neuroprotective effects of olfactory mucosa-derived mesenchymal stem cells on experimental intracerebral hemorrhage

Heliyon. 2023 Jul 3;9(7):e17874. doi: 10.1016/j.heliyon.2023.e17874. eCollection 2023 Jul.

Authors

Yan Huang^{1

2

3}, Jianyang Liu⁴, Jialin He⁴, Fengbo Tan^{5

6}, Ming Lu^{2

3}, Fulai Yuan^{7

6}, Xuelin Zhu^{8

6}, Lingyu Kong^{8

6}

Affiliations

¹ NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha, Hunan 410008, PR China.
² Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, PR China.
³ Hunan Provincial Key Laboratory of Neurorestoration, PR China.
⁴ Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, PR China.
⁵ Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
⁶ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
⁷ Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
⁸ Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.

Abstract

Oxidative stress is essential in brain injury after intracerebral hemorrhage (ICH). Ferroptosis, iron-dependent oxidative cell death, overwhelms the antioxidant system. Recently, Olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) hold great potential for treating ferroptosis-mediated oxidative brain damage after ICH. However, massive grafted cell death, possibly caused by a hostile host brain microenvironment, lessens the effectiveness of OM-MSCs. Therefore, it is necessary to develop strategies to upregulate the therapeutic efficacy of OM-MSCs in ICH. Curcumin, a well-established traditional herbal substance, has potent antioxidant property. In the present study, curcumin preconditioning might enhance the anti-oxidative activity of OM-MSCs, thereby augmenting the therapeutic efficacy of OM-MSCs in ICH. In vitro model of ICH, we demonstrated that curcumin-preconditioned OM-MSCs co-culture is more effective in attenuating the cell injury, oxidative stress, and ferroptosis of neuronal cells compared to the native OM-MSCs treatment. In vivo model of ICH, transplantation of curcumin-preconditioned OM-MSCs also showed better neuroprotective effects. Moreover, curcumin pretreatment promoted the survival of OM-MSCs under a conditioned medium from hemin-insulted neurons by improving the anti-oxidative capacities of OM-MSCs. Collectively, our investigation suggested that curcumin preconditioning effectively enhanced the survival and neuroprotective effects of OM-MSCs in the ICH model by upregulating the anti-oxidative capacities of OM-MSCs. Curcumin-preconditioned OM-MSCs might be taken as a novel therapeutic strategy for treating ICH.

Keywords: Curcumin; Ferroptosis; Intracerebral hemorrhage; Mesenchymal stem cells; Oxidative stress; Preconditioning.