Berberine promotes the viability of random skin flaps via the PI3K/Akt/eNOS signaling pathway

Chen, Jianpeng; Jiang, Zhikai; Liu, Xuao; Wang, Kaitao; Fan, Weijian; Chen, Tingxiang; Li, Zhijie; Lin, Dingsheng

doi:10.1002/ptr.7621

Cited by 15 publications

(7 citation statements)

References 61 publications

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“…eNOS is an enzyme that catalyzes the production of nitric oxide (NO) ( Guo et al, 2023 ). NO, as a potent vasodilator, can improve blood flow, reduce vascular inflammation, and inhibit apoptosis ( Chen et al, 2023 ). Apoptosis is one of the key factors leading to neuronal death in patients with IS ( Liu et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

β-asarone induces viability and angiogenesis and suppresses apoptosis of human vascular endothelial cells after ischemic stroke by upregulating vascular endothelial growth factor A

Sun,

Wu,

Lan

et al. 2024

PeerJ

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Ischemic stroke (IS) is a disease with a high mortality and disability rate worldwide, and its incidence is increasing per year. Angiogenesis after IS improves blood supply to ischemic areas, accelerating neurological recovery. β-asarone has been reported to exhibit a significant protective effect against hypoxia injury. The ability of β-asarone to improve IS injury by inducing angiogenesis has not been distinctly clarified. The experimental rats were induced with middle cerebral artery occlusion (MCAO), and oxygen-glucose deprivation (OGD) model cells were constructed using human microvascular endothelial cell line (HMEC-1) cells. Cerebral infarction and pathological damage were first determined via triphenyl tetrazolium chloride (TTC) and hematoxylin and eosin (H&E) staining. Then, cell viability, apoptosis, and angiogenesis were assessed by utilizing cell counting kit-8 (CCK-8), flow cytometry, spheroid-based angiogenesis, and tube formation assays in OGD HMEC-1 cells. Besides, angiogenesis and other related proteins were identified with western blot. The study confirms that β-asarone, like nimodipine, can ameliorate cerebral infarction and pathological damage. β-asarone can also upregulate vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) and induce phosphorylation of p38. Besides, the study proves that β-asarone can protect against IS injury by increasing the expression of VEGFA. In vitro experiments affirmed that β-asarone can induce viability and suppress apoptosis in OGD-mediated HMEC-1 cells and promote angiogenesis of OGD HMEC-1 cells by upregulating VEGFA. This establishes the potential for β-asarone to be a latent drug for IS therapy.

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Section: Discussionmentioning

confidence: 99%

β-asarone induces viability and angiogenesis and suppresses apoptosis of human vascular endothelial cells after ischemic stroke by upregulating vascular endothelial growth factor A

Sun,

Wu,

Lan

et al. 2024

PeerJ

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“…So, we determined whether PB2 induced the downregulation of the apoptotic process in the dermis of the random‐pattern skin flaps and accelerated flap survival. In previous studies, the expression of Bax, BCL2, and C‐caspase3 was used to identify the levels of programmed cell death (Chen et al, 2023). However, in this study, the expression levels of Bax and C‐caspase3 were not effectively inhibited in mouse skin flaps following PB2 administration, nor was the expression level of BCL2 significantly elevated (Figure S1a,b).…”

Section: Discussionmentioning

confidence: 99%

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random‐pattern skin flap survival

Zhu

et al. 2023

Phytotherapy Research

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Random‐pattern skin flaps have been widely used in the reconstruction of damaged tissues. Ischemia–reperfusion injury occurring in the distal regions of the flap is a common issue, which often leads to flap necrosis and restricts its clinical applications. Procyanidin B2 (PB2), a naturally occurring flavonoid in large quantities in various fruits, has been demonstrated to exhibit several significant pharmacological properties. However, the effect of PB2 on flap viability is not clearly known. Here, using Western blot analysis, immunohistochemistry, and immunofluorescence staining, we observed that PB2 significantly reduced oxidative stress and inflammation and enhanced angiogenesis. Mechanically, we provided evidence for the first time that the beneficial effects of PB2 occur through the activation of the Sirt1/Nrf2 signaling pathway. Moreover, co‐administration of PB2 and EX527, a selective inhibitor of Sirt1, resulted in down‐regulation of the expression of Sirt1, Nrf2, and downstream antioxidants. In summary, our study showed that PB2 might be a novel therapeutic strategy for improving the survival of random‐pattern skin flaps.

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“…AKT1 is present in all tissues and prevents apoptosis, leading to the induction of cell proliferation (Jafari et al, 2019). AKT promotes angiogenesis by regulating certain angiogenesis‐related genes, such as mitogen activated protein kinase (Braicu et al, 2019), heat shock protein 90 (Nagaraju et al, 2015), VEGF, epidermal growth factor receptor (Lo et al, 2007), nitric oxide synthase (Chen et al, 2023), and platelet‐derived growth factor (Xiao et al, 2017). AKT exerts its effects by promoting cell growth and preventing apoptosis primarily through two methods.…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine promotes the survival of the random skin flap via the PI3K/AKT signaling pathway

Wang,

Deng,

Yang

et al. 2023

Phytotherapy Research

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Flaps are mainly used for wound repair. However, postoperative ischemic necrosis of the distal flap is a major problem, which needs to be addressed urgently. We evaluated whether tetrandrine, a compound found in traditional Chinese medicine, can prolong the survival rate of random skin flaps. Thirty‐six rats were randomly divided into control, low‐dose tetrandrine (25 mg/kg/day), and high‐dose tetrandrine (60 mg/kg/day) groups. On postoperative Day 7, the flap survival and average survival area were determined. After the rats were sacrificed, the levels of angiogenesis, apoptosis, and inflammation in the flap tissue were detected with immunology and molecular biology analyses. Tetrandrine increased vascular endothelial growth factor and Bcl‐2 expression, in turn promoting angiogenesis and anti‐apoptotic processes, respectively. Additionally, tetrandrine decreased the expression of Bax, which is associated with the induction of apoptosis, and also decreased inflammation in the flap tissue. Tetrandrine improved the survival rate of random flaps by promoting angiogenesis, inhibiting apoptosis, and reducing inflammation in the flap tissue through the modulation of the PI3K/AKT signaling pathway.

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Berberine promotes the viability of random skin flaps via the PI3K/Akt/eNOS signaling pathway

Cited by 15 publications

References 61 publications

β-asarone induces viability and angiogenesis and suppresses apoptosis of human vascular endothelial cells after ischemic stroke by upregulating vascular endothelial growth factor A

β-asarone induces viability and angiogenesis and suppresses apoptosis of human vascular endothelial cells after ischemic stroke by upregulating vascular endothelial growth factor A

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random‐pattern skin flap survival

Tetrandrine promotes the survival of the random skin flap via the PI3K/AKT signaling pathway

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