Berberine ameliorates erectile dysfunction in rats with streptozotocin‐induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways

Abstract

Background The population with diabetes mellitus‐induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. Objectives To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. Materials and methods Fifty male Sprague‐Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. Results Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine‐1‐phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine‐1‐phosphate was not significant. Moreover, mitogen‐activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFβ1, collagen I/IV, Bax/Bcl‐2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. Conclusions Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine‐1‐phosphate/S1PR2 and mitogen‐activated protein kinase pathways.

Efficacy and safety assessment of traditional Chinese medicine for erectile dysfunction: A meta‐analysis and trial sequential analysis

“…Preclinical trials indicated that TCM could improve erectile function by suppressing oxidative stress, curing vascular endothelial injury, inhibiting apoptosis, and anti-atherosclerotic effects. [25][26][27][28] Further research validates that TCM combined with tadalafil has significant efficacy in treating ED with no increase in side effects. 29 Accumulating research focuses on the efficacy of TCM on ED and a systematic evaluation of whether TCM is available as a complementary and alternative therapy is in need.…”

Effects of β-Nicotinamide Mononucleotide, Berberine, and Cordycepin on Lipid Droplet Content and Developmental Ability of Vitrified Bovine Oocytes

“…NMN can inhibit apoptosis by reducing the BAX/BCL2 ratio and blocking the cleavage of CASPASE-3 [19]. Similarly, BER reduces apoptosis by suppressing the expression of BAX, which is a pro-apoptotic marker gene, and promoting the expression of BCL2, which is a marker gene of anti-apoptosis [83]. Additionally, COR reduces apoptosis through inhibiting the pro-apoptotic IRE1-JNK pathway [65].…”

Study on the mechanism of aging-related erectile dysfunction based on bioinformatics and experimental verification

“…Fibrosis, resulting from diabetes and nerve damage, is also involved in the pathophysiological process of ED (7,25). The process of fibrosis has also been reported to be involved in aging-related ED (18,23).…”

“…As a first-line treatment for ED, the overall effective rate of the phosphodiesterase type 5 inhibitor (PDE5i) is about 87% (7). However, PDE5i is only effective in roughly 65.7% of patients with aging-related ED (8).…”