Abstract:
Culinary herbs and spices are widely used as a traditional medicine in the treatment of
diabetes and its complications, and there are several scientific studies in the literature supporting
the use of these medicinal plants. However, there is often a lack of knowledge on the bioactive
compounds of these herbs and spices and their mechanisms of action. The aim of this study was
to use inverse virtual screening to provide insights into the bioactive compounds of common
herbs and spices, and their potential molecular mechanisms of action in the treatment of diabetes.
In this study, a library of over 2300 compounds derived from 30 common herbs and spices were
screened in silico with the DIA-DB web server against 18 known diabetes drug targets. Over 900
compounds from the herbs and spices library were observed to have potential anti-diabetic activity
and liquorice, hops, fennel, rosemary, and fenugreek were observed to be particularly enriched
with potential anti-diabetic compounds. A large percentage of the compounds were observed to be
potential polypharmacological agents regulating three or more anti-diabetic drug targets and included
compounds such as achillin B from yarrow, asparasaponin I from fenugreek, bisdemethoxycurcumin
from turmeric, carlinoside from lemongrass, cinnamtannin B1 from cinnamon, crocin from sa ron
and glabridin from liquorice. The major targets identified for the herbs and spices compounds were
dipeptidyl peptidase-4 (DPP4), intestinal maltase-glucoamylase (MGAM), liver receptor homolog-1
(NR5A2), pancreatic alpha-amylase (AM2A), peroxisome proliferator-activated receptor alpha
(PPARA), protein tyrosine phosphatase non-receptor type 9 (PTPN9), and retinol binding protein-4
(RBP4) with over 250 compounds observed to be potential inhibitors of these particular protein
targets. Only bay leaves, liquorice and thyme were found to contain compounds that could potentially
regulate all 18 protein targets followed by black pepper, cumin, dill, hops and marjoram with 17
protein targets. In most cases more than one compound within a given plant could potentially regulate
a particular protein target. It was observed that through this multi-compound-multi target regulation
of these specific protein targets that the major anti-diabetic e ects of reduced hyperglycemia and
hyperlipidemia of the herbs and spices could be explained. The results of this study, taken together
with the known scientific literature, indicated that the anti-diabetic potential of common culinary
herbs and spices was the result of the collective action of more than one bioactive compound regulating
and restoring several dysregulated and interconnected diabetic biological processes.
