Preclinical pharmacokinetics of trigonelline using ultra‐performance liquid chromatography–tandem mass spectrometry and pharmacological studies targeting type 2 diabetes

Abstract

Trigonelline is a quaternary base alkaloid and zwitterionic complex that acts by affecting β‐cell regeneration and insulin secretion. Tr inhibits enzymatic activities, lowering the blood glucose and lipid levels due to which it is used in the treatment of co‐morbid diseases such as diabetes, Alzheimer's, etc. Herein, it was aimed to develop a bioanalytical method for estimation of Tr using ultra‐performance liquid chromatography–tandem mass spectrometry and explore the pharmacokinetic profile. The anti‐diabetic, antilipidemic efficacy studies of Tr in the high‐fat diet‐induced streptozotocin‐diabetic rat model was also explored. The separation of analyte was achieved with acetonitrile and 0.1% formic acid (20:80) with a flow of 0.4 mL/min. The ionization of the analyte was achieved in positive electrospray ionization mode with the precursor to product ion transitions of Tr (138.14 > 94), and Trigonelline D3 (143.19 > 97.13). The validated assay was effectively applied for the estimation of compartmental pharmacokinetic by using Phoenix WinNolin8.0 (Certera™, USA) and it was observed that the Tr follow two compartmental pharmacokinetic model. The experimental results also suggest that Tr distributed through the central compartment to the peripheral compartment and redistributed to the central compartment. In addition, Tr exhibited significant anti‐hyperglycemic and antihyperlipidemic efficacy against high‐fat diet‐induced streptozotocin‐induced type 2 diabetic rats.

A novel UPLC–MS/MS method for simultaneous quantification of trigonelline, 4‐hydroxyisoleucine, and diosgenin from Trigonella foenum‐graecum extract: Application to pharmacokinetic study in healthy and type 2 diabetic rats

“…The blood glucose level was measured after 72 h of STZ injection. Table 1 shows that a HFD with STZ resulted in a significant increase in fasted blood glucose level compared to normal rats and only HFD rats (Wadhwa et al, 2021).…”

Enhancing glycaemic control and promoting cardiovascular health: the therapeutic potential of Trigonella foenumgraecum in diabetic patients – a systematic review and meta-analysis

“…However, the current paradigm is shifted now to identify the potential phytoconstituents present in the fenugreek to report the exact mechanism exhibited by them 31 , 32 . Among the various phytoconstituents of fenugreek, 4 hydroxy isoleucine (4OHI) has been identified as a potential insulinotropic agent 33 , trigonelline has been reported as an insulin sensitizer 34 and diosgenin has been reported as the regenerator of pancreatic beta cells 35 . Furthermore, vitexin, isovitexin 36 and scopoletin 37 have been evaluated for their antidiabetic effects.…”

PEGylated Polymer–Lipid Hybrid Nanoparticles to Enhance In Vivo Exposure and Uptake of Repaglinide in Brain Cells to Treat Diabetes-Linked Neurodegenerative Disorders

“…The prepared sections were stained with hematoxylin and eosin stain (H&E), and hippocampal regions (dentate gyrus and cornus ammonis) were examined under a Zeiss microscope. The deteriorating neurons were evaluated in terms of percentage by using ImageJ software …”

“…The deteriorating neurons were evaluated in terms of percentage by using ImageJ software. 53 2.12. Statistical Analysis.…”