ReferenceID 871
Morus alba L. (Sangzhi) Alkaloids Promote Insulin Secretion, Restore Diabetic β-Cell Function by Preventing Dedifferentiation and Apoptosis
Front Pharmacol
Background: Morus alba L. (Sangzhi) alkaloids (SZ-A), extracted from the Chinese herb Morus alba L. (mulberry twig), have been shown to ameliorate hyperglycemia in type 2 diabetes and have been approved for diabetes trea
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- Reference Id
- 871
- Evidence Id
- 17461
- Core Evidence Id
- 17461
- Source Reference Id
- 1737
- Herb2 Reference Id
- HBREF002534
- Subject Paper Key
- HERB004837_35308210
- Pubmed Id
- 35308210
- Doi
- 10.3389/fphar.2022.841981
- Paper Title
- Morus alba L. (Sangzhi) Alkaloids Promote Insulin Secretion, Restore Diabetic β-Cell Function by Preventing Dedifferentiation and Apoptosis
- Paper Abstract
- Background: Morus alba L. (Sangzhi) alkaloids (SZ-A), extracted from the Chinese herb Morus alba L. (mulberry twig), have been shown to ameliorate hyperglycemia in type 2 diabetes and have been approved for diabetes treatment in the clinic. However, their versatile pharmacologic effects and regulatory mechanisms are not yet completely understood. Purpose: This study explored the protective effects of SZ-A on islet β cells and the underlying mechanism. Methods: Type 2 diabetic KKA y mice were orally administered SZ-A (100 or 200 mg/kg, once daily) for 11 weeks, and oral glucose tolerance, insulin tolerance, intraperitoneal glucose tolerance and hyperglycemia clamp tests were carried out to evaluate the potency of SZ-A in vivo . The morphology and β-cell dedifferentiation marker of KKA y mouse islets were detected via immunofluorescence. The effect of SZ-A on glucose-stimulated insulin secretion was investigated in both the islet β-cell line MIN6 and mouse primary islets. Potential regulatory signals and pathways in insulin secretion were explored, and cell proliferation assays and apoptosis TUNEL staining were performed on SZ-A-treated MIN6 cells. Results: SZ-A alleviated hyperglycemia and glucose intolerance in type 2 diabetic KKA y mice and improved the function and morphology of diabetic islets. In both MIN6 cells and primary islets, SZ-A promoted insulin secretion. At a normal glucose level, SZ-A decreased AMPKα phosphorylation, and at high glucose, SZ-A augmented the cytosolic calcium concentration. Additionally, SZ-A downregulated the β-cell dedifferentiation marker ALDH1A3 and upregulated β-cell identifying genes, such as Ins1 , Ins2 , Nkx2.2 and Pax4 in KKA y mice islets. At the same time, SZ-A attenuated glucolipotoxicity-induced apoptosis in MIN6 cells, and inhibited Erk1/2 phosphorylation and caspase 3 activity. The major active fractions of SZ-A, namely DNJ, FAG and DAB, participated in the above regulatory effects. Conclusion: Our findings suggest that SZ-A promotes insulin secretion in islet β cells and ameliorates β-cell dysfunction and mass reduction under diabetic conditions both in vivo and in vitro , providing additional supportive evidence for the clinical application of SZ-A.
- Journal
- Front Pharmacol
- Publish Year
- 2022
- Experiment Subject
- mouse; islet β-cell line min6; kka y mouse islets; min6 cells; mulberry; sz-a-treated min6 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Glucose Intolerance; Hyperglycemia; Type 2 Diabetic Kka; β-cell dysfunction; Diabetic; Type 2 Diabetes; Diabetes
- Paper Title Cn
- Paper Title En
- Morus alba L. (Sangzhi) Alkaloids Promote Insulin Secretion, Restore Diabetic β-Cell Function by Preventing Dedifferentiation and Apoptosis
- Bilingual Status
- semi_complete