An Integrated Lipidomics and Phenotype Study Reveals Protective Effect and Biochemical Mechanism of Traditionally Used Alisma orientale Juzepzuk in Chronic Kidney Disease

Abstract

Alisma orientale Juzepzuk (AO) is widely used for various diuretic and nephropathic treatments in traditional Chinese medicines (TCM). In a clinical setting, AO is used as both a lipid-lowering and tubular interstitial fibrosis agent. However, the mechanisms of AO for the treatment of renal interstitial fibrosis and abnormal lipid metabolism are not well-understood. In this study, pharmacological and UPLC-HDMS-based lipidomic approaches were employed to investigate the lipid-lowering and tubular interstitial fibrosis effect of AO on rats with adenine-induced chronic kidney disease (CKD). Rats with CKD showed increased serum levels of creatinine and urea, tubular damage, and tubular interstitial fibrosis. Moreover, multiple lipid species were identified in CKD rats. Among these lipids, polyunsaturated fatty acid, eicosapentaenoic acid, 8,9-epoxyeicosatrienoic acid, and docosahexaenoic acid levels were significantly decreased in CKD rats compared to control rats. In CKD rats, up-regulation of the NF-κB pathway may impair polyunsaturated fatty acid metabolism, causing renal fibrosis. In addition, CKD rats showed significantly decreased diglyceride levels and increased triglyceride levels compared to the control group. Pathway over-representation analysis demonstrated that 30 metabolic pathways were associated with lipid species. AO treatment suppressed up-regulation of inflammation, and partly restored the deregulation of polyunsaturated fatty acids and glycerolipids metabolism. Our results indicated that AO treatment attenuated renal fibrosis by down-regulating inflammation, and mitigating lipid metabolism in CKD rats. In conclusion, this study has identified the therapeutic lipid-lowering and anti-fibrosis effects of AO on CKD.

Discrimination of Different Parts of Saffron by Metabolomic‐Based Ultra‐Performance Liquid Chromatography Coupled with High‐Definition Mass Spectrometry

“…Metabolomics technique has been extensively applied to the study of TCM and natural products . In agreement with the holistic thinking of TCM, metabonomics has shown potential to reveal the biological foundation and mechanism of TCM …”

“…[37 -40] In agreement with the holistic thinking of TCM, metabonomics has shown potential to reveal the biological foundation and mechanism of TCM. [41][42][43][44][45][46][47] The crocin family is the particular ingredients that occur naturally in stigmas of saffron when compared with other parts. According to the pathway of crocin Figure 5), crocetin can be converted into glucosyl crocetin and finally transferred into crocin.…”

New insights into TGF-β/Smad signaling in tissue fibrosis

“…Alismatis rhizome (AR), as a well-known herb, exhibited lipid-lowing and renoprotective effects [104][105][106][107]. Our results indicated that AR treatment retarded renal fibrosis by downregulating inflammation and TGF-β1/Smad pathway in CKD rats [108]. Our further study demonstrated that alisol B 23-acetate treatment significantly amileriated podocytes and tubular epithelial cells by inhibiting activation of Wnt/βcatenin, oxidative stress and inflammation [109].…”

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Alismatis rhizome (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, exhibited diuretic, antihyperlipidemic, and renoprotective effects that were also confirmed by our previous studies . Our recent study demonstrated that triterpenoid was the main component of AR, and further study showed that the novel tetracyclic triterpenoid 25‐O‐methylalisol F inhibited EMT by suppressing the Wnt/β‐catenin signaling pathway as well as the phosphorylation of Smad3 signaling in both NRK‐52E and NRK‐49F cells (Figure and Table ).…”