Combining transcriptomic analysis and network pharmacology to explore the mechanism by which Shaofu Zhuyu decoction improves diabetes mellitus erectile dysfunction

Mao, Yinhui; Sun, Jian; Wang, Zhuo; Yang, Liu; Sun, Jilei; Wei, Zhitao; Wang, Mingxing; Yang, Yong

doi:10.1016/j.phymed.2023.155006

Cited by 11 publications

(2 citation statements)

References 42 publications

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“…After 7-day adaptive feeding, 12 rats were randomly selected to induce a type 1 DM model. According to the previous research 39 , 40 , the 12 rats were intraperitoneally injected with STZ (60 mg/kg; #S0130, Sigma, USA), dissolved in cold citrate buffer (pH 4.5; 0.1 M). Moreover, six normal rats were used as controls (control group), which were treated with the equal volume of odium citrate buffer via intraperitoneal injection.…”

Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps promote erectile dysfunction in rats with diabetes mellitus by enhancing NLRP3-mediated pyroptosis

Xu,

Ren,

Zou

et al. 2024

Sci Rep

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Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum.

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Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps promote erectile dysfunction in rats with diabetes mellitus by enhancing NLRP3-mediated pyroptosis

Xu,

Ren,

Zou

et al. 2024

Sci Rep

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show abstract

“…Numerous studies have shown that serum levels of proinflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-6, are elevated in ED patients and rats [3,4]. In addition, stressful conditions such as cold stimulation, unhealthy diet, and stress can induce an inflammatory response in the body, contributing to fibrosis in penile tissue, which in turn leads to ED [5,6].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of RIP1/RIP3 Necroptosis Pathway Promote Erectile Function in Cold-Stressed Rat Model

Yang,

Niu,

Zhu

et al. 2024

Andrologia

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Cold stimulation is the most common stressor in cold regions. Continuous cold stimulation can cause a series of pathophysiological changes in the body, such as aggregated neutrophils, macrophage activation, and increased inflammatory factors, which is also a risk factor for erectile function impairment. In addition, necroptosis is an important form of programmed cell death. However, the mechanisms of necroptosis in erectile function impairment due to cold stimulation have been very poorly studied. Therefore, we explored the mechanism of tumor necrosis factor-α (TNF-α)-mediated receptor interacting protein kinase 1 (RIP1)/receptor interacting protein kinase 3 (RIP3) necroptosis pathway on erectile function among cold-stressed rats. First, we established a cold-stressed rat model using cold stimulation and selected those rats that had developed erectile function impairment. Then, we used Necrostatin-1 (RIP1 specific inhibitor, Nec-1), Etanercept (TNF-α inhibitor, Ent), and Sildenafil (Sil) to intervene for 14 days and subsequently assessed their erectile function by apomorphine test and sexual behavioural test. Lastly, we performed various molecular studies and histopathological analyses of penile tissues collected from these rats after the experiments. We found that erectile function was impaired in cold-stressed rats, with increased penile tissue fibrosis and elevated levels of TNF-α and necroptosis. Contrastingly, intervention with Nec-1 and Ent restored erectile function, reduced penile tissue fibrosis, and decreased TNF-α and necroptosis levels, consistent with the results of intervention with Sil. Based on these results, we confirmed that the TNF-α-mediated RIP1/RIP3 necroptosis pathway was significantly altered in cold-stressed rats. In conclusion, inhibition of the TNF-α-mediated RIP1/RIP3 necroptosis pathway improved erectile function, suggesting that the specific downstream mechanisms need to be further explored.

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Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K/AKT/eNOS signaling pathway

Mao,

Zha,

Zang

et al. 2024

Biomedicine & Pharmacotherapy

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Combining transcriptomic analysis and network pharmacology to explore the mechanism by which Shaofu Zhuyu decoction improves diabetes mellitus erectile dysfunction

Cited by 11 publications

References 42 publications

Neutrophil extracellular traps promote erectile dysfunction in rats with diabetes mellitus by enhancing NLRP3-mediated pyroptosis

Neutrophil extracellular traps promote erectile dysfunction in rats with diabetes mellitus by enhancing NLRP3-mediated pyroptosis

Inhibition of RIP1/RIP3 Necroptosis Pathway Promote Erectile Function in Cold-Stressed Rat Model

Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K/AKT/eNOS signaling pathway

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