PMID- 38181531 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240204 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 124 DP - 2024 Feb TI - Pharmacological effects of biologically synthesized ginsenoside CK-rich preparation (AceCK40) on the colitis symptoms in DSS-induced Caco-2 cells and C57BL mice. PG - 155301 LID - S0944-7113(23)00659-1 [pii] LID - 10.1016/j.phymed.2023.155301 [doi] AB - BACKGROUND: Despite the notable pharmacological potential of natural ginsenosides, their industrial application is hindered by low oral bioavailability. Recent research centers on the production of less-glycosylated minor ginsenosides. PURPOSE: This study aimed to explore the effect of a biologically synthesized ginsenoside CK-rich minor ginsenoside complex (AceCK40), on ameliorating colitis using DSS-induced colitis models in vitro and in vivo. METHODS: The ginsenoside composition of AceCK40 was determined by HPLC-ELSD and UHPLC-MS/MS analyses. In vitro colitis model was established using dextran sodium sulfate (DSS)-induced Caco-2 intestinal epithelial model. For in vivo experiments, DSS-induced severe colitis mouse model was established. RESULTS: In DSS-stimulated Caco-2 cells, AceCK40 downregulated mitogen-activated protein kinase (MAPK) activation (p < 0.05), inhibited monocyte chemoattractant protein-1 (MCP-1) production (p < 0.05), and enhanced MUC2 expression (p < 0.05), mediated via signaling pathway regulation. Daily AceCK40 administration at doses of 10 and 30 mg/kg/day was well tolerated by DSS-induced severe colitis mice. These doses led to significant alleviation of disease activity index score (> 36.0% decrease, p < 0.05), increased luminal immunoglobulin (Ig)G (> 37.6% increase, p < 0.001) and IgA (> 33.8% increase, p < 0.001), lowered interleukin (IL)-6 (> 65.7% decrease, p < 0.01) and MCP-1 (> 116.2% decrease, p < 0.05), as well as elevated serum IgA (> 51.4% increase, p < 0.001) and lowered serum IL-6 (112.3% decrease at 30 mg/kg, p < 0.001). Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining revealed that DSS-mediated thickening of the muscular externa, extensive submucosal edema, crypt distortion, and decreased mucin droplets were significantly alleviated by AceCK40 administration. Additionally, daily administration of AceCK40 led to significant recovery of colonic tight junctions damaged by DSS through the elevation in the expression of adhesion molecules, including occludin, E-cadherin, and N-cadherin. CONCLUSION: This study presents the initial evidence elucidating the anti-colitis effects of AceCK40 and its underlying mechanism of action through sequential in vitro and in vivo systems employing DSS stimulation. Our findings provide valuable fundamental data for the utilization of AceCK40 in the development of novel anti-colitis candidates. CI - Copyright (c) 2023. Published by Elsevier GmbH. FAU - Kim, Hoon AU - Kim H AD - Department of Food and Nutrition, Chung-Ang University, Anseong 17546, South Korea. FAU - Jeong, Eun-Jin AU - Jeong EJ AD - Department of Integrated Biomedical and Life Sciences, Korea University, Seoul 02841, South Korea. FAU - Hwang, Byungdoo AU - Hwang B AD - Department of Food and Nutrition, Chung-Ang University, Anseong 17546, South Korea. FAU - Lee, Hak-Dong AU - Lee HD AD - Department of Plant Science and Technology, Chung-Ang University, Anseong 17546, South Korea. FAU - Lee, Sanghyun AU - Lee S AD - Department of Plant Science and Technology, Chung-Ang University, Anseong 17546, South Korea. FAU - Jang, Mi AU - Jang M AD - The Food Industry Promotional Agency of Korea, Iksan, South Korea. FAU - Yeo, Kwangeun AU - Yeo K AD - The Food Industry Promotional Agency of Korea, Iksan, South Korea. FAU - Shin, Yunjeong AU - Shin Y AD - The Food Industry Promotional Agency of Korea, Iksan, South Korea. FAU - Park, Sanghoon AU - Park S AD - The Food Industry Promotional Agency of Korea, Iksan, South Korea. FAU - Lim, Wan Taek AU - Lim WT AD - Research Institute, AceEMzyme, Anseong, South Korea. FAU - Kim, Woo Jung AU - Kim WJ AD - Biocenter, Gyeonggido Business and Science Accelerator, Suwon 16229, South Korea. FAU - Moon, Sung-Kwon AU - Moon SK AD - Department of Food and Nutrition, Chung-Ang University, Anseong 17546, South Korea. Electronic address: sumoon66@cau.ac.kr. LA - eng PT - Journal Article DEP - 20231218 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - A9RLM212CY (ginsenoside M1) RN - 0 (Ginsenosides) RN - 0 (Immunoglobulin A) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Humans MH - Mice MH - Animals MH - *Ginsenosides/metabolism MH - Caco-2 Cells MH - Mice, Inbred C57BL MH - Tandem Mass Spectrometry MH - *Colitis/chemically induced/drug therapy/metabolism MH - Colon MH - Immunoglobulin A/metabolism/pharmacology/therapeutic use MH - Dextran Sulfate/adverse effects MH - Disease Models, Animal MH - Intestinal Mucosa/metabolism OTO - NOTNLM OT - Enzymatic bioconversion OT - Inflammatory bowel disease OT - Inflammatory cytokine OT - Intestinal barrier OT - Minor ginsenoside OT - Synthetic biology COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/06 10:41 MHDA- 2024/01/29 06:44 CRDT- 2024/01/05 18:06 PHST- 2023/08/28 00:00 [received] PHST- 2023/11/13 00:00 [revised] PHST- 2023/12/17 00:00 [accepted] PHST- 2024/01/29 06:44 [medline] PHST- 2024/01/06 10:41 [pubmed] PHST- 2024/01/05 18:06 [entrez] AID - S0944-7113(23)00659-1 [pii] AID - 10.1016/j.phymed.2023.155301 [doi] PST - ppublish SO - Phytomedicine. 2024 Feb;124:155301. doi: 10.1016/j.phymed.2023.155301. Epub 2023 Dec 18.