1. Herbal formula LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut‐liver axis in Zucker diabetic fatty rats
- Author
-
You Wu, Tonghua Liu, Mei Li, Wei Liu, Lingling Qin, Lei Ding, Yu-Li Hu, and Lili Wu
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Lipopolysaccharide ,ved/biology.organism_classification_rank.species ,T2DM ,Gut flora ,Pharmacology ,traditional Chinese medicine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Crocus sativus ,medicine ,Animals ,Hypoglycemic Agents ,Medicine, Chinese Traditional ,toll‐like receptor signalling pathway ,gut microbiota ,Fatty acid metabolism ,biology ,Plant Extracts ,ved/biology ,Toll-Like Receptors ,lipopolysaccharide ,Original Articles ,Cell Biology ,Edgeworthia gardneri ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Rats ,Rats, Zucker ,030104 developmental biology ,Liver ,chemistry ,Mechanism of action ,Hyperglycemia ,030220 oncology & carcinogenesis ,gut‐liver axis ,TLR4 ,Molecular Medicine ,Original Article ,medicine.symptom ,transcriptome ,Dysbiosis ,Drugs, Chinese Herbal - Abstract
LLKL, a new traditional Chinese medicine formula containing Edgeworthia gardneri (Wall.) Meisn., Sibiraea angustata and Crocus sativus L. (saffron), was designed to ameliorate type 2 diabetes mellitus. Despite the therapeutic benefits of LLKL, its underlying mechanisms remain elusive. This study evaluated the LLKL anti‐diabetic efficacy and its effect on gut microbiota to elucidate its mechanism of action in Zucker diabetic fatty rats. We found that administration of different LLKL concentrations (4.68, 2.34 and 1.17 g/kg/d) improved several diabetic parameters after a 6‐week treatment. Moreover, LLKL modulated gut microbiota dysbiosis, increased the expression of occluding and maintained intestinal epithelial homeostasis, leading to a reduction in LPS, TNF‐α and IL‐6 levels. Hepatic transcriptomic analysis showed that the Toll‐like receptor signalling pathway was markedly enriched by LLKL treatment. RT‐qPCR results validated that LLKL treatment decreased the expressions of TLR4, MyD88 and CTSK. Furthermore, a gene set enrichment analysis indicated that LLKL enhanced the insulin signalling pathway and inhibited glycerolipid metabolism and fatty acid metabolism, which were verified by the liver biochemical analysis. These findings demonstrate that LLKL ameliorates hyperglycaemia, modulates the gut microbiota and regulates the gut‐liver axis, which might contribute to its anti‐diabetic effect.
- Published
- 2020
- Full Text
- View/download PDF