Biomolecular mechanisms of the reported Ashitaba (Angelica keiskei) compounds against type 2 diabetes mellitus identified using network pharmacology and molecular docking

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and/or a dysfunctional β-cells. In the Philippines, 3.7 million people were reported to have the disease in 2017 and at least 100 deaths are caused by diabetes-related complications daily. The goal of T2DM management is to maintain blood glucose at normal physiologic levels. While drugs like oral hypoglycemic agents and insulin are available, the use of herbal medicine by T2DM patients to treat the disease is prevalent. One of the most common herbal medicines used to alleviate the symptoms of T2DM is ashitaba (Angelica keiskei). In the Philippines, ashitaba is commonly marketed as a tea and over 50 ashitaba-containing preparations are registered under the Philippine FDA. Since T2DM is a chronic disorder, consumption of such herbal preparation can lead to possible drug-herb interaction that may alter the pharmacokinetics and pharmacodynamics of drugs used in the management of T2DM. Hence, insights on the biomolecular mechanisms of ashitaba against T2DM is essential to determine possible drug-herb interactions if any, or to rationalize its therapeutic use. Through network pharmacology and molecular docking, reported ashitaba compounds are found to target TNF-α, STAT3, p53, AKT1, HAT p300, PPAR-γ and COX-2 in T2DM. Because of these biomolecular mechanisms, consumption of ashitaba compounds can possibly synergize or antagonize the effects of drugs used in the management of T2DM if taken concomitantly.