PMID- 37517821 OWN - NLM STAT- MEDLINE DCOM- 20230801 LR - 20230801 IS - 1875-5364 (Electronic) IS - 1875-5364 (Linking) VI - 21 IP - 7 DP - 2023 Jul TI - Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-kappaB/Bcl-2 pathway. PG - 540-550 LID - S1875-5364(23)60445-5 [pii] LID - 10.1016/S1875-5364(23)60445-5 [doi] AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1(G93A)-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-kappaB) signaling pathway by reducing the phosphorylation of p65 and IkappaBalpha. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-kappaB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1(G93A)-NSC34 cells through suppressing the NF-kappaB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract). CI - Copyright (c) 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved. FAU - Huang, Yu AU - Huang Y AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Labortory of Stem Cell Clinical Research, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Yang, Huili AU - Yang H AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Yang, Biying AU - Yang B AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Zheng, Yu AU - Zheng Y AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Hou, Xiaomei AU - Hou X AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Chen, Guiling AU - Chen G AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Labortory of Stem Cell Clinical Research, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Zhang, Wenqi AU - Zhang W AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - Zeng, Xiang AU - Zeng X AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Labortory of Stem Cell Clinical Research, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. FAU - DU, Baoxin AU - DU B AD - Labortory of Stem Cell Clinical Reaearch, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Labortory of Stem Cell Biology and Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, China. Electronic address: dbx.dr@163.com. LA - eng PT - Journal Article PL - China TA - Chin J Nat Med JT - Chinese journal of natural medicines JID - 101504416 RN - 0 (NF-kappa B) RN - PJ788634QY (ginsenoside Rg1) RN - 0 (Ginsenosides) RN - 0 (Culture Media, Conditioned) RN - EC 1.15.1.1 (Superoxide Dismutase-1) SB - IM MH - Humans MH - NF-kappa B/genetics/metabolism MH - *Ginsenosides/pharmacology MH - *Amyotrophic Lateral Sclerosis/drug therapy/genetics MH - Culture Media, Conditioned/pharmacology MH - Superoxide Dismutase-1 MH - *Neurodegenerative Diseases MH - Neurons/metabolism MH - Apoptosis OTO - NOTNLM OT - Amyotrophic lateral sclerosis OT - Apoptosis OT - Conditioned medium OT - Ginsenoside-Rg1 OT - Umbilical cord mesenchymal stem cells EDAT- 2023/07/31 00:41 MHDA- 2023/08/01 06:44 CRDT- 2023/07/30 20:55 PHST- 2023/02/06 00:00 [received] PHST- 2023/08/01 06:44 [medline] PHST- 2023/07/31 00:41 [pubmed] PHST- 2023/07/30 20:55 [entrez] AID - S1875-5364(23)60445-5 [pii] AID - 10.1016/S1875-5364(23)60445-5 [doi] PST - ppublish SO - Chin J Nat Med. 2023 Jul;21(7):540-550. doi: 10.1016/S1875-5364(23)60445-5.