Lactococcus lactis KR‐050L inhibit IL‐6/STAT3 activation

• Published in: Journal of applied microbiology 2017-05, Vol.122 (5), p.1412-1422
• Main Authors: Hwang, J.T., Jang, H.‐J., Kim, J.H., Park, C.S., Kim, Y., Lim, C.‐H., Lee, S.W., Rho, M.‐C.
• Format: Article
• Language: English
• Subjects: 2,5‐diketopipperazine; Activation; Biological Factors - chemistry; Biological Factors - isolation & purification; Biological Factors - pharmacology; Brassica - microbiology; Cell Line; Chromatography; Column chromatography; Commercialization; Culture; Functional foods & nutraceuticals; Gajuknamu kimchi; Humans; Hydroxyl groups; IL‐6; Inhibitors; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - genetics; Interleukin-6 - metabolism; Isometric; Kimchi; Lactic acid; Lactic acid bacteria; Lactococcus lactis; Lactococcus lactis - chemistry; Lactococcus lactis - genetics; Lactococcus lactis - isolation & purification; Lactococcus lactis - metabolism; Lactococcus lactis KR‐050L; Liquid chromatography; Medical treatment; Molecular Structure; NMR; Nuclear magnetic resonance; Phenylalanine; RNA, Ribosomal, 16S - genetics; rRNA 16S; STAT3; Stat3 protein; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Vegetables - microbiology
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/jam.13444

Aims The purpose of this study was to investigate IL‐6/STAT3 inhibitory activity using lactic acid bacteria (LABs) isolated from Gajuknamu kimchi. Methods and Results Six LABs were isolated from Gajuknamu kimchi and identified through 16S rRNA sequencing. Among them, the culture broth of Lactococcus lactis KR‐050L inhibited IL‐6‐induced STAT3 luciferase activity. Fifteen compounds were isolated from the EtOAc extract of culture broth though column chromatography and preparative high‐performance liquid chromatography, and they were identified as 2,5‐diketopipperazine structures by spectroscopic analyses (MS, 1H‐ and 13C‐NMR). They also showed inhibitory activities on IL‐6‐induced STAT3 activation, and showed the different in activity according to the presence of a phenylalanine residue, hydroxyl groups and isometric structure. Conclusions The six new LABs isolated from Gajuknamu kimchi, and Lc. lactis KR‐050L was selected as candidate IL‐6/STAT3 inhibitors. The activity levels of 15 2,5‐DKPs isolated from Lc. lactis KR‐050L were verified. Significance and Impact of the Study This study constitutes the first attempt to isolate various LABs from Gajuknamu kimchi and to discover IL‐6/STAT3 inhibitors in the EtOAc extract of Lc. lactis KR‐050L culture broth. Moreover, our data provide useful biochemical information regarding the commercialization of Lc. lactis isolated from Gajuknamu kimchi as an approach to use functional foods for the treatment of various diseases via IL‐6/STAT3 activation.