Curr Mol Pharmacol. , 2021., Sep 2. doi: 10.2174/1874467214666210902121337.

Anti-Diabetic Effects of Isolated Lipids from Natural Sources through Modulation of Angiogenesis.

Sajadimajd S Khosravifar M Bahrami G.

Abstract

Background: Aberrant angiogenesis plays a fateful role in the development of diabetes and diabetic complications. Lipids, as a diverse group of biomacromolecules, are able to relieve diabetes through the modulation of angiogenesis. Objective: Owing to the present remarkable anti-diabetic effects with no or few side effects of lipids, the aim of this study was to assess the state-of-the-art research on anti-diabetic effects of lipids via the modulation of angiogenesis. Methods: To study the effects of lipids in diabetes via modulation of angiogenesis, we have searched the electronic databases including Scopus, PubMed, and Cochrane. Results: The promising anti-diabetic effects of lipids were reported in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (FO) were reported to significantly induce neovasculogenesis in high glucose (HG)-mediated endothelial progenitor cells (EPCs) neovasculogenic dysfunction in type 2 diabetic mice. Linoleic acid, mono-epoxy-tocotrienol-α (MeT3α), and ginsenoside Rg1 facilitate wound closure and vessel formation. N-Palmitoylethanolamine (PEA), α-linolenic acid (ALA), omega-3 (ω3) lipids from flaxseed (FS) oil, ω-3 polyunsaturated fatty acids (PUFA), lipoic acid, taurine, and zeaxanthin (Zx) are effective in diabetic retinopathy via suppression of angiogenesis. Lysophosphatidic acid, alkyl-glycerophosphate, crocin, arjunolic acid, α-lipoic acid, and FS oil are involved in the management of diabetes and its cardiac complications. Furthermore, in two clinical trials, R-(+)-lipoic acid (RLA) in combination with hyperbaric oxygenation therapy (HBOT) for treatment of chronic wound healing in DM patients, as well as supplementation with DHA plus antioxidants along with intravitreal ranibizumab were investigated for its effects on diabetic macular edema. Conclusion: Proof-of-concept studies presented here seem to well shed light on the anti-diabetic effects of lipids via modulation of angiogenesis.

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Key Points

The majority of research on the health benefits of the phytochemicals from flax seeds have focused on the fraction from the bound, lignan macromolecule complex whereas the unbound polar fraction has received far less attention. In a total valorization strategy based on cracking-type recovery, however, this fraction may be recovered after the extraction of the omega-3-rich oil and before the extraction, combined with hydrolysis, allowing for the recovery of the components from the lignan macromolecule complex, including the well-known lignan secoisolariciresinol diglucoside (SDG). Therefore, the present study aimed to valorize the free polar fraction of the flaxseeds, which also contain polyphenols, by investigating their composition, antidiabetic, antihyperglycemic, and antihyperlipidemic activities in an alloxan-induced diabetic mouse model, and their anti-inflammatory activity in Wistar rats.

 

This work highlighted the antihyperglycemic and antihyperlipidemic effects of the free polar extract in managing the diabetic status of the experimental animals. The anti-inflammatory activity may also contribute to resolving the complications of diabetes. The extract demonstrated an excellent effect, indicating that the polyphenol fraction of flaxseed represents a potent source of phytochemicals that may be used to manage diabetes and its complications. This study demonstrates that the compounds retained in cold-pressed flaxseed (or linseed) cakes, produced as a by-product following oil extraction, are also of primary interest. The polar free fraction of the flaxseed containing these polyphenols could be further optimized to develop new formulations and phytomedicine.