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. 2024 Sep-Oct;18(5):15579883241277423.
doi: 10.1177/15579883241277423.

Mechanisms of Xuefu Zhuyu Tang in the Treatment of Diabetic Erectile Dysfunction in Rats Through the Regulation of Vascular Endothelial Function by CaSR/PLC/PKC and MEK/ERK/RSK Pathways

Xiao Li  1 , Mingzhao Zhang  1 , Junlong Feng  2 , Jisheng Wang  2 , Kaifeng Wang  3 , Baojun Ju  1 , Xiangyu Wang  1 , Guoming Pang  1   3
Affiliations

Mechanisms of Xuefu Zhuyu Tang in the Treatment of Diabetic Erectile Dysfunction in Rats Through the Regulation of Vascular Endothelial Function by CaSR/PLC/PKC and MEK/ERK/RSK Pathways

Xiao Li et al. Am J Mens Health. 2024 Sep-Oct.

Abstract

Xuefu zhuyu Tang (XFZYT) is a classic formula used for promoting blood circulation and resolving blood stasis in Traditional Chinese Medicine. Clinical data have indicated that XFZYT plays a significant therapeutic role in diabetes-induced erectile dysfunction (DIED) disease, but the underlying mechanism remains elusive. Male Sprague-Dawley (SD) rats were randomly categorized into normal, model, and treatment groups. The diabetic rat model was established via intraperitoneal injection of streptozotocin. DIED rats were screened using apomorphine, and the number of erections was measured after 8 weeks of XFZYT treatment. Serum nitric oxide (NO) and endothelin-1 levels as well as penile tissue structure alterations were assessed by hematoxylin-eosin staining and electron microscopy. CaSR/PLC/PKC and MEK/ERK/RSK pathway-related proteins in the penile tissue were detected by western blotting (WB) analysis and polymerase chain reaction (PCR). Compared with the blank group, the model group rats showed a significant decrease in weight and erectile function. The pathological damage in the penile tissues of the model rats was indicated by a significantly decreased serum NO level and an increased endothelin-1 content. After treatment with XFZYT, the protein expression of CaSR, PLCβ1, PKCβ, MEK1, ERK1, and RSK1 in the penile tissue was significantly increased. Overall, the treatment group showed significant improvements in the evaluated indexes. In conclusion, this study revealed that XFZYT improves erectile function in diabetic rats, and the underlying mechanism might be linked with the regulation of CaSR/PLC/PKC and related molecules of the MEK/ERK/RSK pathway, which promotes the vascular endothelial diastolic effect.

Keywords: herbal; protein pathway; sexual dysfunction; vascular endothelial function.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Overall Process Based on Biological Network Research and Animal Experiments
Figure 2.
Figure 2.
The Body Weight and Blood Glucose in Rats From the C, M, and T Groups Data are expressed as the mean ± SEM. Independent sample t-tests were employed for comparison between the two groups. Differences with p < .05 were considered statistically significant. *p< .05,the M group versus the C group; #p< .05, the T group versus the M group.
Figure 3.
Figure 3.
The NO and ET-1 Levels in Rats From the C, M, and T Groups Data are expressed as the mean ± SEM. Independent sample t-tests were employed for comparison between the two groups. Differences with p < .05 were considered statistically significant. *p < .05, the M group versus the C group; #p < .05, the T group versus the M group.
Figure 4.
Figure 4.
(A) and (B) HE Staining of Penile Tissue of Rats From the C, M, and T Groups (×20 and ×40). (a) In the C group: the muscle and collagen fibers were neatly arranged, and the blood sinusoids were structurally intact, containing a small number of erythrocytes (Arrow ①②);(b) In the M group: the broken muscle fibers, collagen fibers were twisted into strips, and the blood sinusoids were reduced (Arrow ③④); (c) In the T group: there were still breaks in the smooth muscle fibers, but the collagen fibers and blood sinusoids were restored (Arrow ⑤⑥). Figure (C) and (D) Ultrastructure of penile tissue of rats from the C, M, and T Groups (×4,000 and ×8,000)
Figure 5.
Figure 5.
(A) to (F) The Expression Levels of Six Proteins (CaSR, PLCβ1, PKCβ, MEK1, ERK1, and RSK1) in Rats From the C, M, and T Groups Determined Using Western Blotting. (G) Electrophoretogram of Six Proteins (CaSR, PLCβ1, PKCβ, MEK1, ERK1, and RSK1) in Rats From the C, M, and T Groups Data are expressed as the mean ± SEM. Independent sample t-tests were employed for comparison between the two groups. differences with p < .05 were considered statistically significant. *p < .05, the M group versus the C group; #p < .05, the T group versus the M group.
Figure 6.
Figure 6.
(A) to (F) The mRNA Expression Levels of Six Proteins (CaSR, PLCβ1, PKCβ, MEK1, ERK1, and RSK1) in Rats From the C, M, and T Groups Determined Using RT-qPCR Data are expressed as the mean ± SEM. Independent sample t-tests were employed for comparison between the two groups. differences with p < .05 were considered statistically significant. *p < .05, the M group versus the C group; #p < .05, the T group versus the M group.
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