1. Introduction
The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide (Rosengren & Dikaiou, 2023). International Diabetes Federation reported that the number of T2DM patients will probably rise to 700 million by 2045 (Cucinotta et al., 2021). Obesity is a high-risk factor for T2DM, and there is a close link between the two conditions (Kojta, Chacinska & Blachnio-Zabielska, 2020). In support, the epidemiological survey has demonstrated that obese patients are more likely to develop T2DM (Lee, Park & Choi, 2022).
Insulin is a hypoglycemic hormone secreted under endogenous or exogenous stimulation, which helps to store energy as the form of lipid (Najjar, Caprio & Gastaldelli, 2023). Nowadays, insulin is losing its physiological significance in energy storage with abundant nutritional sources. Conversely, over-nutrition triggers insulin resistance (IR). Accumulating facts have evidenced that IR plays a pivotal role in obesity-induced T2DM (Samuel & Shulman, 2012). It has been recognized that obesity could weakens the metabolic functions of insulin in the liver, skeletal muscle and adipose tissues, induce triglyceride (TG) accumulation and β-cells failure, thereby leading to IR and finally T2DM (Kojta, Chacinska & Blachnio-Zabielska, 2020). Obese patients could deliver the risk of IR to the next generation as early as pregnant (Nicholas, Morrison, Rattanatray, Zhang, Ozanne & McMillen, 2016). Hence, relieving obesity-induced IR is one of the key therapeutic strategies to improve T2DM.
The most natural and successful approaches to cure IR and T2DM are changing unhealthy lifestyles, taking more exercise and keeping on a healthy diet, however, it is hard to maintain a healthy routine. Gastric bypass surgery or bariatric surgery could also reduce the blood glucose levels in diabetic patients, but it sacrifices caloric intake and bodyweight artificially (Sylow, Tokarz, Richter & Klip, 2021). Insulin sensitizers (biguanides and thiazolidinediones), nutrient absorption adjustment medicine (α-glucosidase inhibitors), insulin secretion-promoting medicine (sulfonylurea) and glucagon-like peptide-1 (GLP-1) agonists medicine are frequently used to improve T2DM. However, these medicines have limited efficacy and unsatisfied side effects (Bellary, Kyrou, Brown & Bailey, 2021; Perreault, Skyler & Rosenstock, 2021). For example, metformin, a first-line drug of biguanides, is forbidden to use in patients with advanced chronic kidney disease and liver disease. Sulfonylurea administration might cause hypoglycemia, weight gain, and cardiovascular disease exacerbation. Therefore, screening for natural medicines with potent efficacy and few side effects on obesity-induced T2DM are attracting great attention.
Diabetes mellitus (DM) is named “Xiao Ke” in traditional Chinese medicine (TCM), it is mandarin, for a general term of a series of symptoms including polydipsia, polyphagia, polyuria, emaciation, and sweet urine (Su, Hu, Tang, Tang & Huang, 2023). “Xiao Ke” was mentioned in the book “Su Wen • Tong Ping Xv Shi Lun(Plain Questions & General Comments )”, which explained that obesity was a major pathogenic factor in DM and guided the principles of medication in TCM for diabetes. As TCM, herbs, and nutraceuticals share a lot of similarities in their original materials, it makes sense to look for neoteric cures for diabetes-related disorders in these natural herbs and nutraceuticals (Fang et al., 2021).
As IR is a multi-factorial etiology disease with complex pathomechanism, single target therapy is limited for its prevention and treatment. Recently, natural products from herbs and nutraceuticals have shown unique characteristics as multi-component and multi-target in improving IR and T2DM efficiently, which attracts wide attention and favor (Law et al., 2022). An increasing number of researches have indicated that active constituents from herbs and nutraceuticals might ameliorate DM and its complications by improving metabolic abnormalities, inhibiting inflammation, reversing intestinal flora disorder and regulating miRNAs. For instance, resveratrol, berberine and curcumin have been proved to exert anti-diabetic effects through various mechanisms simultaneously (Kim, Chung & Song, 2019; Kunnumakkara et al., 2017; Xu et al., 2021).
The aim of the present review was to summary the effects of natural active constituents on IR (especially obesity-induced IR), as well as to explain and discuss the action mechanisms. This review will provide potential perspectives for the clinical treatment of IR and T2DM.