Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and induces anti-oxidative stress and anti-inflammatory effects via the MAPK pathway

Abstract

Esculin is a derivative of coumarin, which is also an active ingredient of ash bark, and has antibacterial, anti-inflammatory, anti‑allergy and skin protective effects. The underlying mechanism and protective effects of esculin on cognitive impairment in experimental diabetic nephropathy (DN) was investigated in the present study. Male C57BL/6J 6‑week‑old mice were injected intravenously with a single dose of streptozotocin (STZ; 30 mg/kg). At 2 weeks after the STZ injection, mice received intravenous injection with 5, 10 or 20 mg/kg esculin for 2 weeks. In the present study, the results of the Morris water maze test demonstrated that esculin significantly improved behavior and recognition memory in STZ‑induced diabetic rats. Furthermore, treatment of STZ‑induced diabetic rats with esculin significantly inhibited tumor necrosis factor‑α, interleukin‑6, malondialdehyde, monocyte chemoattractant protein‑1 and intracellular adhesion molecule‑1 activity levels, and increased the activity of superoxide dismutase, in the kidney, which was determined by ELISA. In addition, esculin treatment significantly suppressed the renal protein expression of activator protein 1, phosphorylated (p)‑p38 mitogen activated protein kinase (MAPK) and p‑c‑Jun N‑terminal kinase, and increased p‑extracellular signal regulated kinase 1/2 protein expression, in STZ‑induced diabetic rats, as determined by western blotting. These results indicate that esculin may ameliorate cognitive impairment in experimental DN, and exert anti‑oxidative stress and anti‑inflammatory effects, via the MAPK signaling pathway. Thus, it may serve as a potential target for cognitive impairment of DN in the future.

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…In a rat model of colon carcinogenesis, esculin mitigated oxidative stress, DNA damage, and tumorigenesis [140]. Additionally, esculin showed wide pharmacological activities against different diseases, such as cognitive impairment in experimental diabetic nephropathy where it exhibited a strong anti-inflammatory activity marked by the suppressed p38 MAPK and JNK [142]. In models of streptozotocin-induced renal damage in diabetic mice [143], cold-restrained stress and pylorus ligation-induced ulcer [144], ethanol-induced gastric lesion [145], and LPS/D-galactosamine-induced acute liver injury [146], esculin significantly ameliorated inflammation evidenced by the suppressed TNF-α, IL-1β, and MPO.…”

An integrated chemical analysis and network pharmacology approach to identify quality markers of Actinidia eriantha Benth radix on gastric cancer

“…Rutin and catechins are flavonoids and are widely used in cancer research 39,40 . Coumarins, including aesculin, esculetin, and 5,7‐dihydroxytryptophenone, also have anti‐inflammatory and anti‐tumour effects 41–43 . Protocatechuic, ferulic, and syringic acids are phenolic acids with anti‐inflammatory and anti‐oxidant activities 44–47 .…”

Dietary Coumarins

“…Osthol (10) attenuated cellular imbalance, blurry fringes of hepatic sinusoid and extensive vacuolization due to hepatocellular lipid accumulation, and reduced inflammatory infiltration in the pancreas. Esculin (18) ameliorated cognitive improvement in experimental diabetic nephropathy, mediated through its anti-inflammatory and antioxidant actions (Song et al 2018). Earlier, Kang et al (2014) reported the protective effect of this compound on streptozotocin-induced renal damage in diabetic mice.…”