2.1.3. Effect of CLL on Leptin, α-Amylase, Plasma Glucose, Insulin Levels, and Insulin Resistance

Obese rats are also reported to exhibit increment in the plasma levels of plasma glucose, insulin, insulin resistance, leptin, and α-amylase [22]. A significant elevation in plasma levels of glucose (1.5-fold increase), insulin (two-fold increase), and insulin resistance (three-fold increase) was noted in obese rats compared to normal rats.

Oral administration of Orly and CLL improved plasma levels of glucose (89.9 and 80 mg/dL, respectively), insulin (10.1 and 9.4 μg/L, respectively), and insulin resistance (2.2 and 1.9, respectively) with different degrees (Figure 1C,G, Table 1). Obese rats exhibited significantly elevated levels of plasma leptin, a key hormone in the control of food intake and body weight and a target in obesity management [23,24] (two-fold increase) comparable to those in normal rats. Orly and CLL significantly reduced plasma levels of leptin (21.1 and 18.0 ng/mL, respectively) compared to obese control (24.1 ng/mL). Another drug target in obesity is the inhibition of the digestive enzyme α-amylase [25]. In this study, significant increase in α-amylase activity in obese rats (15.3 U/L) was dramatically reduced upon administration of both Orly and CLL (13.7 and 12.4 U/L, respectively) (Figure 1C, Table 1). Hence, CLL is significantly excelling over Orly in decreasing leptin, insulin, glucose, and α-amylase levels (*p* < 0.05).

#### 2.1.4. Effect of CLL on Oxidative Stress and Lipid Peroxidation

In the current study, elevated plasma levels of butyrylcholinesterase (BChE) were observed in the obese control (415.7 U/L) in agreement with [22], compared to different experimental groups (250.7, 274.8, and 285.2 U/L in normal, CLL and Orly treated groups, respectively). High plasma BChE activity is associated with aberrant lipid profiles, insulin resistance, and hypertension [23], suggestive for BChE role in many metabolic functions [24]. Oral administration of Orly as well as CLL reduced BchE plasma elevation significantly at different levels (285.2 and 274.8 U/L, respectively). Malondialdehyde (MDA), a biomarker used for assessing oxidative stress, was significantly enhanced in obese rats (15.1 nmol/mL) compared to those of normal ones (5.6 nmol/mL), as an indicator of lipid peroxidation, while catalase enzyme activity, an indicator of antioxidant status, showed reduction by 1.9 fold. Rats treated with Orly and CLL exhibited improved oxidative stress markers at different levels (Figure 1D,E, Table 1). CLL revealed significant improvement in oxidative stress markers and lipid peroxidation profiles, better than Orly (*p* < 0.05).
