Development And Evaluation Of Polyherbal Nanoparticle Formulation For Anti-Diabetic Efficacy

Abstract

Gymnema sylvestre, Tinospora cordifolia and Trigonella foenum-graecum are medicinal plants historically acclaimed to have diabetes preventing and treating properties. The three herbs were processed to extract active phytomolecules which were loaded into the nanoparticle formulation in Tablet form, referred to as polyherbal nanoparticle-loaded tablet formulation. The formulation was screened for pancreatic α-amylase inhibition in vitro, and antidiabetic efficacy was evaluated in STZ-induced diabetic rats. The isolated herbal compounds included kaempferol-3-O-sophoroside from G. sylvestre, berberine from T. cordifolia and bioactive alkaloidal compound from T. foenum-graecum. Nanoparticles of these phytochemicals were formulated using β-cyclodextrin and the solvent evaporation technique; an optimized preparation (~571 nm size, ~66% entrapment) was obtained. Fine powder and nanoparticle-loaded tablets also exhibited the desirable pharmaceutical properties and sustained in vitro release of berberine for 12 h. In-vitro α-amylase inhibition was found to be the maximum for ethanol extract of G. sylvestre, followed by aqueous extract of T. cordifolia and chloroform extract of T. foenum-graecum (44.13 ± 0.65%, 51.02 ± 1.20%, 37.86 ± 0.78% at 100 µg/mL, respectively). Each of the individual compounds (100 mg/kg) was efficacious for reducing fasting plasma glucose in STZ-diabetic animals (e.g. Compound 1 dropped from 299.3 ± 3.9 mg/dL in diabetic controls to 113.7 ± 4.9 mg/dL on Day 28). Nanoparticle tablet (30 mg/kg p.o.) brought further significant reduction in the glucose (101.2 ± 1.8 mg/dL) than an equivalent herbal capsule (140.3 ± 2.7 mg/dL) and approached the efficacy of glibenclamide (94.0 ± 4.1 mg/dL) on Day 28. This polyherbal nanoparticle system therefore exhibited synergistic glucose management at a dose that was lower than that of the individual phytochemicals. These findings proved that encapsulation of combination of anti-diabetic phytoconstitutents could increase and extend their blood glucose lowering action. The polyherbal nanoparticle-loaded tablet holds potential as a new anti-diabetic nutraceutical and deserves additional clinical study.