Abstract
Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.
Highlights
In many Western countries, diabetes mellitus (DM) is the third largest chronic non-communicable disease, preceded only by cardiovascular disease and cancer
The pathogenesis of DM and the factors that contribute to this disease are complicated, hyperglycemia and inflammation are known to be central to the initiation and pathogenesis of Diabetic nephropathy (DN) [4]
We recently reported that MCL can selectively eradicate AML stem and progenitor cells and that its water-soluble form, DMAMCL, demonstrates excellent efficacy in the treatment of acute leukemia in mouse models [35]
Summary
In many Western countries, diabetes mellitus (DM) is the third largest chronic non-communicable disease, preceded only by cardiovascular disease and cancer. Diabetic nephropathy (DN), characterized by the angiopathy of capillaries in the kidney glomeruli, is one of the most common and serious chronic complications of DM. DN can cause chronic kidney failure and end-stage kidney disease and is the leading cause of premature death in young diabetic patients (those between 50 and 70 years old). Silymarin (milk thistle extract), an herb containing a mixture of anti-inflammatory components, has recently been shown to be effective in reducing proteinuria in patients with DN [3]. The pathogenesis of DM and the factors that contribute to this disease are complicated, hyperglycemia and inflammation are known to be central to the initiation and pathogenesis of DN [4] Combination therapy with ACE inhibitor drugs and angiotensin receptor blockers (ARBs) drugs may slow the progression of DN [1], according to Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), combination therapy may worsen major renal outcomes and may result in a decline in the glomerular filtration rate [2].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
