Diabetic kidney disease (DKD) is a common and devastating complication in diabetic patients, which is recognized as a large and growing problem leading to
end-stage kidney disease. As dietary-mediated
therapies are gradually becoming more acceptable to patients with DKD, we planned to find active compounds on preventing DKD progression from dietary material. The present paper reports the renoprotective properties and underlying mechanisms of
ginsenoside compound K (CK), a major metabolite in serum after
oral administration of ginseng. CK supplementation for 16 weeks could improve urine microalbumin, the ratio of urinary
albumin/
creatinine and renal morphological abnormal changes in db/db mice. In addition, CK supplementation reshaped the gut microbiota by decreasing the contents of Bacteroides and Paraprevotella and increasing the contents of Lactobacillu and Akkermansia at the genus level, as well as reduced
histidine-derived microbial metabolite
imidazole propionate (
IMP) in the serum. We first found that
IMP played a significant role in the progression of DKD through activating
toll-like receptor 4 (TLR4). We also confirmed CK supplementation can down-regulate
IMP-induced
protein expression of the TLR4 signaling pathway in vivo and in vitro. This study suggests that dietary CK could offer a better health benefit in the early intervention of DKD. From a nutrition perspective, CK or dietary material containing CK can possibly be developed as new adjuvant
therapy products for DKD.