ReferenceID 4878
Loganin and catalpol exert cooperative ameliorating effects on podocyte apoptosis upon diabetic nephropathy by targeting AGEs-RAGE signaling
Life Sci
BACKGROUND/AIMS: Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log)
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Record Fields
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- Reference Id
- 4878
- Evidence Id
- 21468
- Core Evidence Id
- 21468
- Source Reference Id
- 2997
- Herb2 Reference Id
- HBREF003794
- Subject Paper Key
- HBIN019909_32277978
- Pubmed Id
- 32277978
- Doi
- 10.1016/j.lfs.2020.117653
- Paper Title
- Loganin and catalpol exert cooperative ameliorating effects on podocyte apoptosis upon diabetic nephropathy by targeting AGEs-RAGE signaling
- Paper Abstract
- BACKGROUND/AIMS: Rehmanniae Radix (RR) and Cornus officinalis (CO) are a typical herbal pair used to treat diabetic nephropathy (DN) in clinical practice. DN can be effectively treated by catalpol (Cat) and loganin (Log), the main active components of RR and CO respectively, through combating apoptosis, oxidative stress and inflammation. Herein, a spontaneous DN and podocyte injury model induced by advanced glycation end products (AGEs), i.e. KK-Ay mice, was used to explore the cooperative effects of Log and Cat on DN and the mechanism targeting the AGEs-RAGE (receptor for AGE) pathway. METHODS AND KEY FINDINGS: Log and Cat alone or in combination mitigated diabetic symptoms, decreased the level of fasting blood glucose, and increased that of serum insulin. The two drugs alone or in combination protected renal function from damage, prevented extracellular matrix hyperplasia and glycogen deposition, as well as alleviated the loss of podocytes detected by histological assay and immunohistochemistry. Flow cytometry revealed that Log and Cat alone or in combination relieved the apoptosis of AGEs-induced podocytes in vitro. Silencing RAGE by RNA interference played a protective role in podocyte apoptosis, whereas overexpression of it worked oppositely. Western blot exhibited that Log and Cat alone or in combination inhibited the activation of RAGE/p38 MAPK/p65 NF-kappaB and RAGE/Nox4/p65 NF-kappaB pathways in podocytes. The inhibitory effects of drug combination were more evident than those of individual treatments. SIGNIFICANCE: Log and Cat cooperatively resisted the apoptosis of podocytes upon DN by targeting AGEs-RAGE and its downstream pathways p38 MAPK and Nox4.
- Journal
- Life Sci
- Publish Year
- 2020
- Experiment Subject
- mouse
- Experiment Type
- Cell Experiment
- Phenotype Related
- Diabetic Nephropathy; Dn And Podocyte Injury; Extracellular Matrix Hyperplasia
- Paper Title Cn
- Paper Title En
- Loganin and catalpol exert cooperative ameliorating effects on podocyte apoptosis upon diabetic nephropathy by targeting AGEs-RAGE signaling
- Bilingual Status
- semi_complete