Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury

Wu, Weiqiang; Chen, Xin; Chen, Yaxing; Wang, Jie; Zhang, Hongyan; Fei, Ni; Chengmin, Ling; Feng, Chengjian; Yuan, Jianmin; Lin, Jiangkai

doi:10.1007/s10571-020-01018-7

Cited by 9 publications

(7 citation statements)

References 49 publications

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“…Figure 1 also reveals the interconnections between degenerative/regenerative extrinsic mechanisms and oxidative stress post-SCI. [341]. It has also been shown that intrathecal administration of curcumin can improve the functional recovery post-SCI through the spinal cord-NSPCs (SC-NSPCs) by increasing the expression of SC-NSPCs and decreasing the activity of reactive astrogliosis (GFAP) and lesion cavities [342].…”

Section: Extrinsic Molecular Mechanisms Of Regeneration Post-sci: Therapeutic Approaches To Polyphenolsmentioning

confidence: 99%

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Fakhri

Abbaszadeh

Moradi

et al. 2022

Oxidative Medicine and Cellular Longevity

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Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross-linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant-derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post-SCI complications.

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Section: Extrinsic Molecular Mechanisms Of Regeneration Post-sci: Therapeutic Approaches To Polyphenolsmentioning

confidence: 99%

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Fakhri

Abbaszadeh

Moradi

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Indeed, the fact that Cur possesses pleiotropic activity could be attributed to their activation and protection effects on MSCs [ 31 , 32 ]. Several studies have confirmed that Cur is involved in regulating the immunomodulatory capabilities; the differential potential of MSCs to different cell lineages (neurocyte, chondrocyte, adipocyte, and osteoblast), and in multiple signaling mechanisms is involved in this process [ 28 , 31 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway

Deng

Ouyang

et al. 2021

IJMS

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Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

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“…Curcumin (St. Louis, MO, Lot: C1386) was administered via intraperitoneal injection, and 100 mg of curcumin was dissolved in 1 mL dimethyl sulfoxide (DMSO) and 0.5 mL saline [25]. The first injection was administered immediately after MCAO and then injections were performed once every 24 h for 3 d. To treat cells, a dose of 4 μmol/L curcumin was selected.…”

Section: Administration Of the Reagents And The Huc-mscsmentioning

confidence: 99%

“…The clinical-grade hUC-MSCs were supplied by Chongqing Guolian Stem Cell Technology Co., Ltd. The cells were suspended in mesenchymal stem cell basal medium (MSCBM) supplemented with 5% Ultra-GROTM-Advanced (AventaCell, HPCFDCRL05) [25]. Fluorescence-activated cell sorting (FACS) analysis for hUC-MSC-specific markers (CD73, CD90, and CD105) and hematopoietic stem cell-specific markers (CD34, CD45, and HLA-DR) were performed to identify the immunophenotype.…”

Section: Culture and Identification Of Huc-mscsmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3β/β-TrCP/Nrf2 axis

Huang

Wang

et al. 2023

J Neuroinflammation

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Background Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. Methods Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3β activator sodium nitroprusside (SNP), GSK3β inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3β/β-TrCP/Nrf2 pathway protein. Results Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3β, inhibited the β-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3β and β-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3β inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3β inhibition with TDZD-8 restricted β-TrCP nucleus accumulation, which facilitated Nrf2 expression. Conclusions We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3β/β-TrCP/Nrf2 axis and an improved neurological function after AIS.

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Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury

Cited by 9 publications

References 49 publications

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway

Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3β/β-TrCP/Nrf2 axis

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