Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats

Abstract

Erectile dysfunction (ED) is one of the significant complications of diabetes mellitus (DM), and CASR plays an important role in cellular antiapoptosis and NO production in the vascular endothelium by activating PKC. The present study was aimed to investigate the efficacy of Leech and Centipede Granules (LCG) through the CaSR/PLC/PKC signaling. Fifty male Sprague-Dawley rats were treated with streptozotocin to induce the DM model. After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were administrated with LCG and U73122 for 4 weeks. Fasting blood glucose, body weight, insulin and glucagon levels were measured. Erectile function in rats was assessed by apomorphine. Serums were measured using enzyme-linked immunosorbent assay and flow cytometry, and penile tissues were harvested for histologic and the expression of related targets analyses. After treatment, fasting blood glucose, body weight, insulin, glucagon levels, and erectile function were significantly ameliorated in the LCG groups. The LOX-1, NOX, and EMPs concentrations were significantly decreased with LCG treatment. LCG also continuously increased NO and decreased ET-1 content in penile tissues. LCG and U73122 administration also improved penile fibrosis by significantly decreasing VCAM-1, ICAM-1, and CD62P. The data also showed that LCG reduced the apoptosis level in the penis. Furthermore, the inhibited activation of the CaSR/PLC/PKC pathway was observed in DMED rats with LCG treatment. Collectively, LCG significantly ameliorated erectile function of DMED rats via increased NO generation, inhibiting endothelial cells apoptosis and penile fibrosis, which might benefit from the suppression of CaSR/PLC/PKC pathway in DMED rats.

Combination of traditional Chinese medicine and PDE5i for diabetic erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials

“…Through animal experiments and cell biology experiments, we have preliminarily identi ed the mechanism of TCM. TCM is able to reduce the incidence of vascular endothelial injury and vascular protection 41,42 . It also has an effect on improving diabetic peripheral neuropathy, and improving peripheral nerve conduction velocity 43,44 .…”

Aberrant upregulation of CaSR promotes pathological new bone formation in ankylosing spondylitis

“…CaSR is reportedly linked to PLC via the heterotrimeric G protein isoforms Gq and mediates the downstream ERK1/2 pathway (Hannan et al , 2018a). PLC is a classic second massager of CaSR that is expressed in multiple organs, such as the parathyroid gland, vascular endothelium and vascular smooth muscle (Zhang et al , 2019; Ma et al , 2020). PLC protein mediates extracellular Ca 2+ signalling and downstream biological functions, including hormone secretion, apoptosis and wound repair (Milara et al , 2010; Hannan et al , 2018a; Ma et al , 2020).…”

“…PLC is a classic second massager of CaSR that is expressed in multiple organs, such as the parathyroid gland, vascular endothelium and vascular smooth muscle (Zhang et al , 2019; Ma et al , 2020). PLC protein mediates extracellular Ca 2+ signalling and downstream biological functions, including hormone secretion, apoptosis and wound repair (Milara et al , 2010; Hannan et al , 2018a; Ma et al , 2020). Moreover, the PLCγ/PKC signalling pathway mediates osteogenic differentiation in osteoblasts (Moenning et al , 2009).…”

N‐acetylcysteine improves diabetic associated erectile dysfunction in streptozotocin‐induced diabetic mice by inhibiting oxidative stress

“…It has been reported that increased oxidative activity and expression of inflammatory markers, such as endothelin‐1 (ET‐1) and intracellular adhesion molecule‐1 (ICAM‐1), are present in DMED patients. 9 , 10 Inflammation and oxidative stress due to chronic hyperglycaemia exert damaging effects upon the vasculature, nerves and NO, which then seriously impairs penile function. Such destructive effects involve a cascade of reactions, with the initial component being the formation of reactive oxygen species (ROS) resulting in increased NO scavenging.…”