## 1 Introduction  
The incidence of type 2 diabetes mellitus (T2 DM) has increased and is continuously rising worldwide. T2 DM is characterized by hyperglycemia resulting from insulin insufficiency, insulin resistance, or both. Diabetic condition is likely accompanied by obesity due to excessive food consumption and less daily activity. As a consequence, fat accumulation in adipose tissue leads to chronic inflammation and insulin resistance of these cells [1]. Adipocytes and their activated macrophages produce various pro-inflammatory cytokine factors, including tumor necrosis factor-alpha (TNF-\(\alpha\)), interleukin-\(\delta\) (IL-\(\delta\)), and interleukin-\(\delta\) (IL-\(\delta\)). These cytokines have paracrine effects to activate inflammatory pathways within insulin target cells, including the liver and muscle, causing systemic insulin resistance and hyperglycemia [2, 3]. Chronic hyperglycemia has been reported to increase levels of reactive oxygen species in \(\beta\)-cells and leads to toxic effects on the \(\beta\)-cell. A prolonged and excess cell workload induces \(\beta\)-cell dysfunction and failure, resulting in inadequate insulin compensation and finally leading to the development of T2 DM [4]. The obese adipocytes or high-fat diet induces chronic inflammation, which contribute to insulin resistance and leads to T2 DM [2]. Anti-inflammation and anti-insulin resistance have become the main targets for treatment of T2 DM.  
At present, about 40 medications are available to treat T2 DM. However, adverse effects and safety concerns of available hypoglycemic drugs are severe hypoglycemia, weight gain, infections, cancer, pancreatitis, and cardiovascular events. This complicates the treatment plan that usually lasts throughout the lifetime of diabetic patients who are also at high risk of cardiovascular disease [5]. Therefore, a new approach is needed to identify safe, effective, affordable, and low side effect agents, especially natural products for T2 DM treatment. Currently, medicinal plants are possible ways of treating diabetes. These include _Momordica charantia_ L., _Gymnema inodorum_, and _Carissa carandas_[6; 7; 8; 9]. _C. carandas_ fruits are rich in iron, vitamin C, antioxidants, and anthocyanins and are widely consumed as fresh or food-processing products [10]. Several anthocyanins are found in _C. carandas_ fruits, such as cyanidin-3-O-rhamoside, cyanidin-3-O-glucoside, cyanidin-3-O-galactoside, pelargonidin-3-O-glucose, peonidin-3-O-glucose, and malvidin-3-O-glucoside [10; 11; 12]. Previous studies suggest that the _C. carandas_ fruit has antioxidant, anti-inflammatory, and antidiabetic activities in rat models. A methanolic extract from _C. carandas_ fruits reduced oxidative stress in gentamicin-induced diabetic nephrotoxicity in rats [13]. In addition, a dried fruit methanolic extract showed significant inhibition of carrageenan-induced hind paw edema in rats [14]. Unripe _C. carandas_ fruits have been reported to effectively prevent T1 DM in rat models induced by alloxan [8]. Furthermore, _C. carandas_ fruit extracts demonstrate hypoglycemic activity in streptozotocin (STZ)-induced diabetic rats. It also promotes insulin secretion by closing the K\({}_{\text{ATP}}\) channels in \(\beta\)-cells of pancreatic islets [9]. However, the antidiabetic property of _C. carandas_, especially in T2 DM, remains to be clarified.  
This study aimed to investigate the treatment ability of _C. carandas_ extracts on inflammation in macrophages and insulin resistance in adipocytes and T2 DM rats. Lipopolysaccharide (LPS)-induced inflammation of RAW 264.7 macrophages and LPS-induced insulin resistance of 3T3-L1 adipocytes were studied by treatment with a _C. carandas_ extract as in the in vitro model. Furthermore, the in vivo model investigated _C. carandas_ extract treatment on T2 DM rats that had been fed a high-fat diet with streptozotocin (STZ).