# GB5, a synergistic phytotherapy for type 2 diabetes mellitus management: an integrated polyherbal approach from phytochemical profiling to network pharmacology

## TL;DR

A new herbal therapy called GB5 shows promise in managing type 2 diabetes by targeting multiple issues like high blood sugar and inflammation.

## Contribution

GB5 is a standardized polyherbal formulation with demonstrated multi-target efficacy and mechanistic transparency for T2DM.

## Key findings

- GB5 exhibited strong antioxidant activity and inhibited carbohydrate-digesting enzymes effectively.
- GB5 improved glucose uptake and reduced lipid accumulation in adipocytes comparable to known drugs.
- Network pharmacology linked GB5 compounds to key diabetes-related pathways like PPARγ and AGE–RAGE.

## Abstract

Type 2 diabetes mellitus (T2DM) remains a global health burden characterized by insulin resistance, persistent hyperglycaemia, and chronic inflammation. Although single-target therapies effectively reduce glucose levels, they seldom address oxidative stress or adipocyte dysfunction. Polyherbal formulations (PHFs) harness synergistic phytochemicals for multimodal intervention; however, many lack mechanistic transparency owing to excessive inclusion of diverse botanical bioactives, suffer from non-standardized composition, and underexplore volatile antidiabetic constituents. Confronting these challenges, we developed Gluco Balance V (GB5), a cold-percolated ethanolic extract comprising equal proportions of bio-effective parts of Asparagus racemosus, Cyperus rotundus, Tinospora cordifolia, Terminalia arjuna, and Mimosa pudica. These botanicals were selected for complementary antidiabetic, antioxidant, and adiporegulatory activities documented in preclinical and clinical settings, indicating balanced, synergistic, and safe bioactivity.

GB5’s phytochemical composition was standardized using gas chromatography–mass spectrometry (GC–MS) fingerprinting. In vitro assays assessed 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging capacity, inhibition of carbohydrate-digesting enzymes (α-amylase, α-glucosidase), enzyme kinetics, and effects on glucose uptake (GU) and lipid accumulation (LA) in yeast and 3T3-L1 adipocytes. Computational network pharmacology, molecular docking, and pharmacokinetic analyses elucidated molecular targets and bioavailability. Statistical analyses employed robust dose-response modelling, analysis of variance with Dunnett’s T3 test, and t-tests with false discovery rate correction.

GC–MS identified 21 bioactive compounds, including phytol, fatty acids, and sterols, driving GB5’s therapeutic synergy. GB5 showed robust antioxidant activity (DPPH and NO; half-maximal inhibitory concentration (IC50) 88.6 and 74.8 µg/mL) and mixed-type inhibition of α-amylase and α-glucosidase (IC50 71.6 and 174 µg/mL). At sub-inhibitory doses, it outperformed ascorbic acid (ASA) and acarbose. In 3T3-L1 adipocytes, GB5 increased GU by 32.3% at 2.0 mg/mL, comparable to rosiglitazone, and reduced lipid accumulation by 18.6% (90% effective concentration (EC90) 0.742 mg/mL). Network pharmacology and molecular docking implicated peroxisome proliferator-activated receptor gamma (PPARγ), protein tyrosine phosphatase 1B (PTP1B), cyclooxygenase-2 (COX-2), and advanced glycation end-products–receptor for advanced glycation end-products (AGE–RAGE) pathways with 9,12-octadecadienoic acid and cholestan-3-ol, 2-methylene-, (3β,5α)- as key associates.

GB5’s multi-targeted efficacy against hyperglycaemia, oxidative stress, and adipocyte dysfunction positions it as a promising complementary therapy for T2DM, meriting further in vivo evaluation.

The online version contains supplementary material available at 10.1186/s12906-025-05192-3.