Neuroinflammation is known as a key player in a variety of neurodegenerative and/or neurological diseases. Brain Toll-like receptors (TLRs) are leading elements in the initiation and progression of neuroinflammation and the development of different neuronal diseases. Furthermore, TLR activation is one of the most important elements in the induction of insulin resistance in different organs such as the central nervous system. Involvement of insulin signaling dysregulation and insulin resistance are also shown to contribute to the pathology of neurological diseases. Considering the important roles of TLRs in neuroinflammation and central insulin resistance and the effects of these processes in the initiation and progression of neurodegenerative and neurological diseases, here we are going to review current knowledge about the potential crosstalk between TLRs and insulin signaling pathways in neuroinflammatory disorders of the central nervous system.
Ficus deltoidea Jack (Moraceae) leaf extract is used as an antidiabetic in traditional medicine. Its widespread usage is reflected by the available preparations in the present commercial market. The efficacy of other Ficus species has not been entirely satisfactory and many antidiabetic herbs have demonstrated poor safety profiles. This study examined hypoglycemic and toxicity profiles of F. deltoidea leaf extract in rodent models. Extracts of dried powdered leaves were obtained using methanol solution, n-hexane, chloroform, and n-butanol. These extracts were orally administered to rodents. Their blood glucose and insulin levels, acute and subchronic toxicity, biochemical and histological profiles of liver and kidney were determined. Methanol extract exhibited blood glucose lowering activity in mildly insulin resistant diabetic rats as well as in normoglycemic mice unlike hydrophilic butanol subextract which only expressed its activity in normoglycemic mice. Methanol extract could contain both insulin receptor sensitization and secretagogue constituents. Different from toxic chloroform and hexane subextracts, hydrophilic methanol extract gave zero percent mortality up to 6400 mg/kg in 14 days. It did not induce liver and kidney toxicity upon four-week consumption at 200 mg/kg. The methanol extract possessed mixed antidiabetic actions and exhibited a low level of oral toxicity.
The molecular basis of the anti-diabetic properties of camel milk reported in many studies and the exact active agent are still elusive. Recent studies have reported effects of camel whey proteins (CWP) and their hydrolysates (CWPH) on the activities of dipeptidyl peptidase IV (DPP-IV) and the human insulin receptor (hIR). In this study, CWPH were generated, screened for DPP-IV binding in silico and inhibitory activity in vitro, and processed for peptide identification. Furthermore, pharmacological action of intact CWP and their selected hydrolysates on hIR activity and signaling and on glucose uptake were investigated in cell lines. Results showed inhibition of DPP-IV by CWP and CWPH and their positive action on hIR activation and glucose uptake. Interestingly, the combination of CWP or CWPH with insulin revealed a positive allosteric modulation of hIR that was drastically reduced by the competitive hIR antagonist. Our data reveal for the first time the profiling and pharmacological actions of CWP and their derived peptides fractions on hIR and their pathways involved in glucose homeostasis. This sheds more light on the anti-diabetic properties of camel milk by providing the molecular basis for the potential use of camel milk in the management of diabetes.