Morus alba L. (Sangzhi) Alkaloids Promote Insulin Secretion, Restore Diabetic β-Cell Function by Preventing Dedifferentiation and Apoptosis

 Front. Pharmacol.,  Sec. Ethnopharmacology, 2022

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 KKAy 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 KKAy 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 KKAy 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 KKAy 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.

Evaluation of the neuroprotective and antidiabetic potential of phenol-rich extracts from virgin olive oils by in vitro assays

Food Research International, 106, 558-567, 2018

DOI: 10.1016/j.foodres.2018.01.026

In this work, phenol-rich extracts from ‘Cornicabra’ and ‘Picual’ virgin-olive oils (EVOOs) were examined, for the first time, to establish their capacity to inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (LOX)), major depressive disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: hMAO-A and hMAO-B respectively), and diabetes mellitus (DM) (α-glucosidase and α-amylase). ‘Cornicabra’ displayed the best inhibitory activity against all enzymes, when compared to ‘Picual’: BuChE (IC50 = 156 ± 4 and 308 ± 33 mg mL−1), LOX (IC50 = 26 ± 0.5 and 37 ± 3 mg mL−1), hMAO-A (IC50 = 20 ± 2 and 37 ± 0.2 mg mL−1), hMAO-B (IC50 = 131 ± 7 and 215 ± 13 mg mL−1) and α-glucosidase (IC50 = 154 ± 17 and 251 ± 31 mg mL−1), respectively. The behaviour observed can be associated with the higher content of secoiridoids, lignans and phenolic acids in ‘Cornicabra’ EVOO.