Jatrorrhizine ameliorates Schwann cell myelination via inhibiting HDAC3 ability to recruit Atxn2l for regulating the NRG1‐ErbB2‐PI3K‐AKT pathway in diabetic peripheral neuropathy mice

Abstract

Diabetic peripheral neuropathy (DPN) is a chronic complication associated with nerve dysfunction and uncontrolled hyperglycemia. Unfortunately, due to its complicated etiology, there has been no successful therapy for DPN. Our research recently revealed that jatrorrhizine (JAT), one of the active constituents of Rhizoma Coptidis, remarkably ameliorated DPN. This work highlighted the potential mechanism through which JAT relieves DPN using db/db mice. The results indicated that JAT treatment significantly decreased the threshold for thermal and mechanical stimuli and increased nerve conduction velocity. Histopathological analysis revealed that JAT significantly increased the number of sciatic nerve fibers and axons, myelin thickness, and axonal diameters. Additionally, JAT markedly elevated the expression of myelination‐associated proteins (MBP, MPZ, and Pmp22). The screening of histone deacetylases (HDAC) determined that histone deacetylase 3 (HDAC3) is an excellent target for JAT‐induced myelination enhancement. Liquid chromatography–mass spectrometry—(MS)/MS and coimmunoprecipitation analyses further confirmed that HDAC3 antagonizes the NRG1‐ErbB2‐PI3K‐AKT signaling axis by interacting with Atxn2l to augment SCs myelination. Thus, JAT ameliorates SCs myelination in DPN mice via inhibiting the recruitment of Atxn2l by HDAC3 to regulate the NRG1‐ErbB2‐PI3K‐AKT pathway.

Advances of traditional Chinese medicine preclinical mechanisms and clinical studies on diabetic peripheral neuropathy

“…In addition, Gong et al. ( 2023 ) found that JAT offers more protection against DPN than other flavonoid alkaloids. After the treatment of JAT (50, 100 and 200 mg/kg) in db/db mice for eight consecutive weeks, it significantly improved the general physiological functions and nerve morphology.…”

Berberine ameliorates contrast‐induced acute kidney injury by regulating HDAC4‐FoxO3a axis‐induced autophagy: In vivo and in vitro

“…Recent studies have shown that epigenetics plays an important role in the pathogenesis of several diseases (Zhang, Guan, et al, 2020). Acetylation is an epigenetic modification commonly affected by histone acetyltransferases (HATs) and histone deacetylases (HDACs), of which histone deacetylase 4 (HDAC4) has been widely studied because it mediates the physiological and pathological processes of several acute and chronic kidney diseases (Gong et al, 2023; Liu et al, 2022). In diabetic nephropathy (DN), high glucose (HG) leads to nephrin deacetylation and ubiquitination by inducing HDAC4 expression, which in turn leads to podocyte damage and renal dysfunction (Tung et al, 2018).…”