PMID- 38015303 OWN - NLM STAT- Publisher LR - 20231128 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) DP - 2023 Nov 28 TI - Tauroursodeoxycholic Acid Inhibited Apoptosis and Oxidative Stress in H(2)O(2)-Induced BMSC Death via Modulating the Nrf-2 Signaling Pathway: the Therapeutic Implications in a Rat Model of Spinal Cord Injury. LID - 10.1007/s12035-023-03754-5 [doi] AB - Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining TUDCA with BMSC transplantation using an animal model of SCI. The results showed that TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally, TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy. CI - (c) 2023. The Author(s). FAU - Weng, Jiaxian AU - Weng J AD - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China. AD - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. AD - Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. FAU - Wang, Le AU - Wang L AD - Department of Spine Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, 510080, Guangdong, China. FAU - Wang, Kai AU - Wang K AD - Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. FAU - Su, Haitao AU - Su H AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, Department of Orthopedic Surgery,, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. FAU - Luo, Dan AU - Luo D AD - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, Department of Orthopedic Surgery,, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. FAU - Yang, Haimei AU - Yang H AD - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. AD - Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. FAU - Wen, Yaqian AU - Wen Y AD - Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. FAU - Wu, Qiduan AU - Wu Q AD - The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. wuqiduan@126.com. FAU - Li, Xing AU - Li X AUID- ORCID: 0000-0002-5676-8962 AD - Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. liqixi723@126.com. AD - Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. liqixi723@126.com. AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, Department of Orthopedic Surgery,, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. liqixi723@126.com. LA - eng GR - No. 82004384/Natural Science Foundation of China/ GR - No.82102583/Natural Science Foundation of China/ PT - Journal Article DEP - 20231128 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 SB - IM OTO - NOTNLM OT - Apoptosis OT - Bone marrow mesenchymal stem cells OT - Oxidative stress OT - Spinal cord injury OT - TUDCA EDAT- 2023/11/28 12:42 MHDA- 2023/11/28 12:42 CRDT- 2023/11/28 11:09 PHST- 2023/06/26 00:00 [received] PHST- 2023/10/28 00:00 [accepted] PHST- 2023/11/28 12:42 [medline] PHST- 2023/11/28 12:42 [pubmed] PHST- 2023/11/28 11:09 [entrez] AID - 10.1007/s12035-023-03754-5 [pii] AID - 10.1007/s12035-023-03754-5 [doi] PST - aheadofprint SO - Mol Neurobiol. 2023 Nov 28. doi: 10.1007/s12035-023-03754-5.