Growing evidence to demonstrate the majority of herbal products and secondary metabolites used in treating DM, the acting mechanisms are involved in the regulation of insulin signaling pathways, translocation of glucose transporter 4 (GLUT-4) transporter and/or activation the peroxisome proliferator-activated receptor γ (PPARγ). Several flavonoids suppress glucose absorption by inhibiting intestinal α-amylase and α-glucosidase17. Dietary polyphenols may impede α-amylase and α-glucosidase, hinder glucose absorption in the intestine by sodium-dependent glucose transporter 1 (SGLT1), stimulate insulin secretion and reduce hepatic glucose output. Furthermore, polyphenols may also activate insulin-dependent glucose uptake, activate 5' adenosine monophosphate-activated protein kinase (AMPK)18. AMPK would decrease gluconeogenesis and fatty acid synthesis and enhance catabolism, leading to body weight reduction and metabolic syndrome alleviation19.
Interestingly, a possible mechanism by which garlic, white onion, and purple onion exerts antidiabetic properties could be through the inhibitory effect on α-amylase and α-glucosidase coupled with their ability to prevent lipid peroxidation in the pancreas and heart, which validate their strong antioxidant properties20. Sulfur compounds including S-methylcysteine and flavonoids such as quercetin are mainly responsible for the hypoglycemic activity of A. cepa helping to decrease the levels of blood glucose, serum lipids, oxidative stress, and lipid peroxidation, as well as increasing antioxidant enzyme activity and insulin secretion9. Extracts of onion have been shown to have hypoglycemic and hypolipidemic effects by normalizing the activities of liver hexokinase, glucose 6-phosphatase, and HMG coenzyme-A reductase9. In preliminary clinical trials, patients with diabetes safely consumed slices of A. cepa, exhibiting sufficient hypoglycemic activity. In the future, further studies need to investigate and seek to confirm the hypoglycemic activities of A. cepa and its constituents and/or their synthetic analogs.
On the other side, while blood sugar levels are not adequately lowered, the medication metformin is typically recommended21. Metformin's efficacy reflects activation of AMP-activated kinase, which shows preliminary evidence that certain compounds in our study have similar activities but without the side effects associated with metformin. Other natural agents with the potential to treat and possibly prevent DM include extracts of bitter melon and cinnamon. Nutraceuticals featuring meaningful doses of combinations of these agents would likely have substantial diabetes-preventive efficacy, and presumably could be marketed legally as aids to good glucose tolerance and insulin sensitive22.
Crude extract of cinnamon showed the strongest anti-amylase activities that provide a prospective therapeutic approach for the management of DM23. Cinnamon contains derivatives, such as cinnamaldehyde, cinnamic acid, cinnamate, and numerous other components such as polyphenols and antioxidant, anti-inflammatory, antidiabetic, antimicrobial, and anticancer effects. Experimental studies have confirmed that C. cassia contains terpenoids, phenylpropanoids, glycosides etc. and many medicinal values including antitumor, anti-inflammatory, analgesic, anti-diabetic, anti-obesity, antibacterial, antiviral, cardiovascular protective, cytoprotective, neuroprotective, immunoregulatory effects, and anti-tyrosinase activity24. All cinnamon types showed potent species-specific effects on starch digestion enzyme activity inhibition. C. cassia was most effective against α-amylase and all tests strongly inhibited α-glucosidase when compared to acarbose25. Natural agents that slow carbohydrate absorption may mimic the protective effect of acarbose. Recently, many trials have investigated the beneficial effects of cinnamon for Alzheimer's disease, diabetes, arthritis, and arteriosclerosis.
Accumulatively experimental studies have demonstrated that tea has protective effects against DM and its complications via several underlined mechanisms, including augmenting insulin action, ameliorating insulin resistance, triggering insulin signaling pathway, protecting islet β-cells, scavenging free radicals, and diminishing inflammation26. Teas has polyphenols called catechins and the most abundant being the (-) epigallocatechin gallate and also contain other phenolic compounds such as gallic, caffeic, chlorogenic or cinnamic acids, quercetin, and proanthocyanidols27. Generally, tea is classified into six categories: white, green, yellow, oolong, black, and dark teas based on the process of fermentation degree28. In the present results exhibited Da Hong Pao tea, black tea had greater efficacy of anti-hyperglycemia. Remarkably, black tea has thousands of various biological compounds such as flavonoids (Thearubigins (TRs) and theaflavins (TFs) and catechins), phenolic acids (caffeic acid (CA), gallic acid (GA), chlorogenic acids (CGA) and cauramic acid (CA) that illustrated many promising pharmacological effects regarded as growth promoter, cardio-protector, potent cholesterol-lowering effect, and has antioxidant and antimicrobial effects, etc.29.
The previous literature has reported that natural compounds isolated from medical plants or Chinese herbs that reduce hyperglycemia in animals. Interestingly, they have some biological activities, which can treat or ameliorate diabetes e.g. catechin30 and quercetin31. Accordingly, these compounds could inhibit the activities of α-amylase and α-glucosidase and delay carbohydrate digestion. In docking results, we have shown that some of the chemical compounds isolated from cinnamon, purple onion, and tea had a better effect on the inhibition of α-amylase and α-glucosidase than that of the clinic drug. This in silico evidence is associated with in vivo diabetic mice tests. Interestingly, there are a large number of aforementioned phytochemicals with good pharmacological activity in the natural plants as the extract of onion, cinnamon, and tea mixture that can be applied to treat human diseases because of their anti-oxidation and anti-inflammation properties particularly for metabolic syndromes.
Some of oral anti-hyperglycemic drugs have been obtained from plants or have a microbial origin, such as galegine isolated from Galega officinalis, which has a great similarity to the antidiabetic drug metformin. Picnogenol, acarbose, miglitol, and voglibose are other antidiabetic products of natural origin32. A variety of herbs has been used in traditional medicine for the treatment of diabetes. Nevertheless, the natural compounds are more stable and have less side effects when compared to clinic drug33. Diet and plant derived products have also been tested in a number of preclinical and clinical trials34, 35. Since herbal medicine has been chosen as a monotherapy or an adjuvant to conventional therapeutics, thorough clinical trials and standardized herbal preparations are required to evaluate their efficacy, safety, tolerability, and underlined clinical recommendations3, 36–38.
The inhibitory activities of α-amylase and α-glucosidase; anti-hyperglycemia of purple onion, cinnamon, and tea mixture extracts when compared to the acarbose and metformin in OSTT and OGTT. A mixture extract (purple onion, cinnamon, and tea) has demonstrated remarkable antidiabetic activities and is further confirmed that they could preserve the active component in the regulation of AMPK, α-amylase, and α-glucosidase. Several compounds (Diallyl disulfide, Quercetin, Cinnamic acid, Cinnamic alcohol, Cinnamic aldehyde, Catechin, and Epigallocatechin gallate) in extracts of purple onion, cinnamon, and tea mixture have a notably inhibitory effect of diabetic molecules when compared with clinical drugs (acarbose, anti-α-amylase) and metformin, AMPK) via virtual screen.