RSM-based optimization of antidiabetic multi-component formula and gastric simulation effect with promising implications for type-2 diabetes treatment

Postprandial blood glucose levels in diabetic patients can be controlled by inhibiting α-amylase-catalyzed starch hydrolysis in the gastrointestinal system. A common anti-diabetic drug acarbose functions through this mechanism. The drug has safety and cost challenges and therefore needs safer and cost-effective alternatives. Many herbs are used for the same purpose in the traditional healthcare system including Gymnema sylvestre (GS) and Holarrhena antidysenterica (HA). The current study aimed at discovering a combination of GS and HA with acarbose that is highly effective for α-amylase inhibitory activity (AIA). Efficient herbal extraction was done by an enzyme-aided ultrasound-assisted extraction (EA-UAE). The synergistic α-amylase inhibitory effect of GS and HA and GS, HA, and acarbose were studied with and without digestive simulation (DS). As per the results, in GS-HA formulation, the most effective ratio of GS and HA was 51 % and 49 %, respectively, that showed 73.49 % AIA, and in GS-HA-acarbose formulation, the ratio was GS 20 %, HA 20 % and acarbose 60 % that showed 96.11 % AIA. This formulation demonstrated AIA similar to the pure drug acarbose with IC50 values of 32.64 µg/mL and 45.14 µg/mL, respectively. The optimization models were supported by statistical analysis and validation experiments with minimal %RSDs (0.82–2.08). It is concluded that the discovered optimal combination of the herbs with acarbose has highly promising prospects for diabetes treatment. It is expected to be more cost-effective and safer than the pure drug and thus has the potential to be used as complementary medicine.