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. 2021 Dec;59(1):547-556.
doi: 10.1080/13880209.2021.1920621.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology

Ji-Sheng Wang  1   2 , Jun-Long Feng  1   2 , Heng-Heng Dai  1   2 , Zi-Long Chen  1   2 , Xiao Li  3 , Bing-Hao Bao  1   2 , Sheng Deng  1   2 , Fan-Chao Meng  1   2 , Qi Zhao  1   2 , Hong-Sheng Xu  1   2 , Bin Wang  2 , Hai-Song Li  2
Affiliations

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology

Ji-Sheng Wang et al. Pharm Biol. 2021 Dec.

Abstract

Context: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects.

Objective: Explore mechanistic details of ABR + SV treatment against DMED.

Materials and methods: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 μg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA.

Results: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03).

Conclusion: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

Keywords: Endocrine diseases; biological network; penis; traditional Chinese medicine.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
(a) Intersection of ABR + SV targets, diabetes mellitus targets, and erectile dysfunction targets; (b) PPI network built by Cytoscape (3.7.1); (c) PPI network processed by Cytoscape (3.7.1) plug-in (cytohubba).
Figure 2.
Figure 2.
The network construction for herbal compound-target-disease.
Figure 3.
Figure 3.
Analyses of pathway enrichment using GO and KEGG databases.
Figure 4.
Figure 4.
(a) The body weight in rats from the C, M, and T groups; (b) The blood glucose in rats from the C, M, and T groups; (c) The insulin in rats from the C, M, and T groups; (d. The glucagon 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 < 0.05 were considered statistically significant. #p< 0.05, the M group vs. the C group; *p < 0.05, the T group vs. the M group.
Figure 5
Figure 5
(a) H&E staining of the penile tissue of rats from the C, M, and T groups (×400). (i) In the C group: The trabeculae and blood sinuses were distributed evenly, and some red blood cells (RBCs) were in the sinus space, many smooth-muscle cells were in blood-containing sinus trabeculae. (Arrow ①②); (ii) In the M group: The number of blood-containing sinuses in the cavernous body was reduced significantly and its distribution was disordered, the density of endothelial cells and smooth muscle cells was decreased, and the number of collagen fibres was increased. (Arrow ③④); (iii) In the T group: the distribution of blood-containing sinuses was more regular than that in group M, the density of endothelial cells was increased, the number of collagen fibres was decreased, and RBCs were seen in some blood-containing sinuses. (Arrow ⑤⑥); (b) Ultrastructure of penile tissue of rats from the C, M, and T groups (×5000). (i) In the C group: the blood vessels of were normal, the morphology and structure of endothelial cells were basically normal, the nucleus was regular, the endothelial cells were closely connected, mitochondria and endoplasmic reticulum were observed in endothelial cells. (Arrow ①②); (ii) In the M group: Endothelial cells swelled, endothelial cell junction disappeared, endothelial cell mitochondria swelled and endoplasmic reticulum expanded. (Arrow ③④); (iii) In the T group: The blood vessels were normal, the morphology and structure of endothelial cells were basically normal, the endothelial cells were tightly connected, and mitochondria were seen in endothelial cells (Arrow ⑤⑥).
Figure 6.
Figure 6.
(a) Electrophoretogram of five proteins (CASP3, VEGFA, eNOS, ACE, and ALB) in rats from the C, M, and T groups. (b–f) The expression levels of five proteins (CASP3, VEGFA, eNOS, ACE, and ALB) in rats from the C, M, and T groups were determined using western blotting. Data are expressed as the mean ± SEM. Independent sample t-tests were employed for comparison between the two groups. Differences with p < 0.05 were considered statistically significant. #p < 0.05, the M group vs. the C group; *p < 0.05, the T group vs. the M group.
Figure 7.
Figure 7.
(a–e) The mRNA expression levels of five proteins (CASP3, VEGFA, eNOS, ACE, and ALB) 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 < 0.05 were considered statistically significant. #p < 0.05, the M group vs. the C group; *p < 0.05, the T group vs. the M group.
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Grants and funding

This study was funded by the National Natural Science Foundation of China (Grant No. 81704086).