Table 1.

Molecular mechanisms of action and clinical studies of medicinal plants (Allium sativum, Momordica charantia, Hibiscus sabdariffa L., Zingiber officinale, and Vitamins (C, D, and E) in the management of DM.

Medicinal Plants & Vitamins	Mechanisms of Action	Clinical Studies
Allium Sativum	Allium Sativum plays a role in the treatment of diabetes by enhancing the gene expression of caspase 3 and caspase 9, reducing IL-1β, IL-6, and TNF-α level and increasing IFN-γ in vitro and in vivo [101].	A double-blind clinical trial in diabetic patients demonstrated garlic intake at a dose of 750 mg three times per day for 12 weeks had potential effects for treating diabetes by reducing fasting glucose blood levels through the decrease in hemoglobin A1c (HbA1C) [102].
Vitamin C	Vitamin C enhances the immune system by stimulating IFN production and lymphocyte proliferation, enhancing neutrophil phagocytic capability [103]. Vitamin C intake regulates fasting blood glucose (FBG) and glycosylated hemoglobin A1c (HbA1C) and improves insulin resistance [104,105].	More clinical trials are needed to confirm whether Vitamin C shows promise as an effective therapeutic agent for diabetes mellitus.
Momordica charantia	Momordica charantia exerts its hypoglycemic effect through multiple mechanisms of action including the stimulation or inhibition of the key enzymes of hexose monophosphate pathways. It can stimulate key enzymes of the hexose monophosphate pathway, inhibit glucose uptake by the intestine, increase the utilization of peripheral and skeletal muscle glucose, inhibit gluconeogenesis and adipocytes differentiation, and normalize the islet βcells [39,106,107,108].	Clinical trials are needed (clinical studies of Momordica charantia for the treatment of diabetes have been sparse and sporadic).
Hibiscus sabdariffa	The mechanism of action of Hibiscus sabdariffa is based on the strong ability to delay the digestion of complex sugars into simple sugars, reduce the absorption of simple sugar, and lower total blood glucose [109,110].	Clinical trials are needed.
Vitamin D	Studies showed that Vitamin D promotes the conversion of proinsulin to insulin, increases insulin output, and enhances insulin action through the regulation of the calcium pool [81,82].	A randomized control double-blind intervention study noted a significant improvement of insulin sensitivity in diabetic patients supplementing 4000 IU of Vitamin D for 6 months compared to placebo [84].
Vitamin E	Animal models and human studies have demonstrated that vitamin E intake blocks LDL lipid peroxidation, prevents the oxidative stress linked to T2DM-associated abnormal metabolic patterns (hyperglycemia, dyslipidemia, and elevated levels of FFAs), and, subsequently, attenuates cytokine gene expression.	A recent report evaluated the effects of a combination of Vitamin C (1000 mg/day) and vitamin E (400 IU/day) for four weeks on insulin sensitivity in untrained and trained healthy young men and concluded that such supplement may preclude the exercise-induced amelioration of insulin resistance in humans [111].
Zingiber Officinale	Diabetic patients who took 2 g of ginger for 2 months revealed a reduction in insulin, homeostasis model assessment (HOMA), and low-density lipoprotein (LDL), with no impact on fasting plasma glucose (FPG), HbA1C, total cholesterol, and HDL levels [112].	A double-blinded placebo-controlled randomized clinical trial conducted on two groups of patients with type 2 diabetes reported that ginger powder improved glycemic indices as well as TAC and PON-1 activity in patients [64]. However, more clinical trials are needed to shed light on the effectiveness of ginger in human subjects with diabetes.