ReferenceID 1121
Aloperine protects beta-cells against streptozocin-induced injury to attenuate diabetes by targeting NOS1
Eur J Pharmacol
Type 1 diabetes (T1D) is a metabolic dysfunction characterized by the selective destruction of islet β-cells, with oxidative stress playing an essential role in the manifestation of this disease state. Aloperine (ALO) re
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- Reference Id
- 1121
- Evidence Id
- 17711
- Core Evidence Id
- 17711
- Source Reference Id
- 2218
- Herb2 Reference Id
- HBREF003015
- Subject Paper Key
- HBIN015319_34954231
- Pubmed Id
- 34954231
- Doi
- 10.1016/j.ejphar.2021.174721
- Paper Title
- Aloperine protects beta-cells against streptozocin-induced injury to attenuate diabetes by targeting NOS1
- Paper Abstract
- Type 1 diabetes (T1D) is a metabolic dysfunction characterized by the selective destruction of islet β-cells, with oxidative stress playing an essential role in the manifestation of this disease state. Aloperine (ALO) represents the main active alkaloid extracted from the traditional Chinese herbal Sophora alopecuroides L. and features outstanding antioxidative properties. In this study, T1D was induced by a single high dose streptozotocin (STZ, 150 mg/kg, intraperitoneal) in mice. Diabetic animals were intragastrically administered ALO at a dose of 50 mg/kg/day. Notably, treatment of ALO (50 mg/kg/day) for seven consecutive days could observably reverse the onset of diabetes induced by STZ accompanied by weight gain, lower blood glucose levels, and relief of β-cells damage. Our in vitro study further demonstrated that ALO protected β-cells from STZ/hydrogen peroxide-induced oxidative damage as manifested by increased expression of MnSOD and CAT. Furthermore, a network pharmacology study revealed that NOS1 represented the main target of ALO. Mechanistic studies subsequently showed that treatment of ALO increased the expression of NOS1, whereas NOS2 was decreased. Moreover, a docking study carried out suggested that ALO could fit into the binding pocket of human NOS1 and molecular dynamics simulation further validated this docking event. Collectively, the administration of ALO prior to diabetes could be a viable approach to the prevention of β-cell injury. This study may offer a novel potential herbal medicine against T1D and may further help improve the understanding of the underlying molecular mechanisms of ALO-mediated protection against oxidative stress.
- Journal
- Eur J Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; human
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Diabetic; Metabolic Dysfunction; Type 1 Diabetes; β-cell injury; Diabetes
- Paper Title Cn
- Paper Title En
- Aloperine protects beta-cells against streptozocin-induced injury to attenuate diabetes by targeting NOS1
- Bilingual Status
- semi_complete