Berberine ameliorates neonatal necrotizing enterocolitis by activating the phosphoinositide 3-kinase/protein kinase B signaling pathway

Fang, Chengzhi; Xie, Lili; Liu, Chunmei; Fu, Chunhua; Ye, Wei; Liu, Hong; Zhang, Binghong

doi:10.3892/etm.2018.5858

Cited by 15 publications

(26 citation statements)

References 27 publications

(30 reference statements)

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“…TLRs, cell transmembrane receptors of the natural immune system, are critical for pathogen resistance (24). Berberine has been demonstrated to effectively reduce inflammatory cytokine levels (25) and to attenuate NEC by inhibiting inflammation and apoptosis via the phosphatidylinositol 4,5-bisphosphate 3-kinase/RAC-α serine/threonine-protein kinase signaling pathway (26). The authors of the present study inferred that berberine may be effective at reducing the incidence and severity of NEC through its anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response

Peng

Shan

et al. 2018

Exp Ther Med

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Necrotizing enterocolitis (NEC) is a life-threatening disease that occurs in premature infants. The aim of the present study was to investigate the effects of berberine, an isoquinoline alkaloid mainly used to treat digestive diseases, in a rat model of NEC. NEC models were established in newborn rats via inhalation of N 2 for 90 sec every 4 h and oral administration of 4 mg/kg/day lipopolysaccharides on days 0 and 1. Berberine was administered via oral gavage. In the NEC model group, Toll-like receptor (TLR)4, nuclear factor NF-κB (NF-κB), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were upregulated. Symptoms of NEC in the berberine intervention group were significantly relieved, with a clear reduction in the incidence of NEC compared with the NEC group. TLR4, NF-κB, iNOS, TNF-α, IL-6 and IL-10 expression was decreased following berberine intervention. Furthermore, the expression of mucin-2 (MUC2) and RNA polymerase σ factor SigA (SIgA) were decreased in the NEC model group and increased following berberine intervention, when compared with the untreated group. It was also demonstrated that the incidence of NEC was reduced following berberine administration, possibly owing to changes in the inflammatory responses. The results of the current study support a potential therapeutic role of berberine for the treatment of NEC.

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Section: Discussionmentioning

confidence: 99%

Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response

Peng

Shan

et al. 2018

Exp Ther Med

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“…A previous study showed that the neonatal small intestine is prone to necrotizing enterocolitis (NEC), a severe acquired disease characterized by inflammation ( MohanKumar et al, 2019 ). However, these changes were notably reversed by treatment with berberine; the anti-inflammatory mechanism of berberine in this context may act via suppression of the PI3K/Akt pathway ( Fang et al, 2018 ). Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and are a major cause of postsurgical morbidity ( Tsai et al, 2018 ).…”

Section: Effects Of Berberine On Vascular Diseasesmentioning

confidence: 99%

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Peng

et al. 2021

Front. Pharmacol.

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Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Vascular diseases affecting vasculature in the heart, cerebrovascular disease, atherosclerosis, and diabetic complications have compromised quality of life for affected individuals and increase the burden on health care services. Berberine, a naturally occurring isoquinoline alkaloid form Rhizoma coptidis, is widely used in China as a folk medicine for its antibacterial and anti-inflammatory properties. Promisingly, an increasing number of studies have identified several cellular and molecular targets for berberine, indicating its potential as an alternative therapeutic strategy for vascular diseases, as well as providing novel evidence that supports the therapeutic potential of berberine to combat vascular diseases. The purpose of this review is to comprehensively and systematically describe the evidence for berberine as a therapeutic agent in vascular diseases, including its pharmacological effects, molecular mechanisms, and pharmacokinetics. According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity via the regulation of multiple signaling pathways, including AMP-activated protein kinase (AMPK), nuclear factor κB (NF-κB), mitogen-activated protein kinase silent information regulator 1 (SIRT-1), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), janus kinase 2 (JAK-2), Ca2+ channels, and endoplasmic reticulum stress. Moreover, we discuss the existing limitations of berberine in the treatment of vascular diseases, and give corresponding measures. In addition, we propose some research perspectives and challenges, and provide a solid evidence base from which further studies can excavate novel effective drugs from Chinese medicine monomers.

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“…17 Berberine also significantly inhibits the apoptosis of epithelial cells by downregulating the expressions of caspase-9 and caspase-3 in the mitochondrial apoptosis pathway. 46 These results indicate that MPLs alleviate LPS-induced intestinal cell necroptosis by regulating the secretion of Bcl-2 family and caspase family proteins.…”

Section: ■ Materials and Methodsmentioning

confidence: 83%

Prevention of Necrotizing Enterocolitis through Milk Polar Lipids Reducing Intestinal Epithelial Apoptosis

Yang

Zhang

Zhou

et al. 2020

J. Agric. Food Chem.

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Neonatal necrotizing enterocolitis (NEC) is a common and devastating disease. The objective of this research was to investigate the protective mechanisms of milk polar lipids (MPLs) on the attenuation of lipopolysaccharides (LPS)-induced intestinal inflammation and apoptosis. MPLs were extracted from buttermilk and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A neonatal NEC rat model was used to investigate the effects of MPLs on NEC and its underlying mechanisms. Hematoxylin−eosin (H&E) staining and terminal deoxynucleotidyl transferasemediated dUTP-biotin nick-end labeling (TUNEL) assay were used to observe intestinal morphological changes and intestinal epithelial cell apoptosis, which showed that MPLs could reduce NEC symptoms and intestinal apoptosis. The expressions of IL-6, IL-8, and TNF-α in the MPL group was significantly downregulated (P < 0.05), and the expression levels of IL-10 were significantly upregulated (P < 0.05). At the same time, MPLs also significantly reduced (P < 0.05) activation of the LPS-induced TLR4/NF-κB signaling pathway. Furthermore, MPLs inhibit apoptosis by reducing the expressions of Bax, caspase-9, and caspase-3 and by increasing the expression of Bcl-2. In conclusion, MPLs could reduce NEC symptoms in mice by inhibiting cell inflammation and protecting against intestinal apoptosis.

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Berberine ameliorates neonatal necrotizing enterocolitis by activating the phosphoinositide 3-kinase/protein kinase B signaling pathway

Cited by 15 publications

References 27 publications

Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response

Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

Prevention of Necrotizing Enterocolitis through Milk Polar Lipids Reducing Intestinal Epithelial Apoptosis

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