## 4 Discussion  
The liver is primarily susceptible to the effects of hyperglycemia-induced oxidative stress [27]. Different mechanisms endorse the hepatocyte injury through inflammation and oxidative stress [28]. STZ is a diabetogenic and hepatotoxic material which damages the pancreatic beta-cell membrane, fragments DNA, and reacts with several enzymes including glucokinase, and significantly decreases the insulin levels [29]. In STZ-induced hyperglycemia in experimental models, it is important to study the role of anti-diabetic agents. In this study, TQ (50 mg/kg b.w.) was given to the animals to evaluate its antidiabetic potential. STZ-induced diabetes leads to loss of body weight, which may be due to muscle wasting [30]. In the current study, STZ caused a major weight loss of rats in the diabetic control group (19.93%) in comparison to the normal control animals. Supplementation with TQ to the diabetic rats presented a remarkable diminishing effect on the percentage changes of body weight (11.04%) as compared to the diabetic rats fed with just normal diet. Some previous studies are in accordance with the current finding, which also report that the body weights of the STZ-injected diabetic animals are reduced significantly. However, _Nigella sativa_ oil treatment to such animals increased their body weights in comparison to diabetic non-treated rats [31]. The possible mechanism of TQ may play an important role in the maintenance of body weight or its increment through the prevention of loss of muscle mass in STZ-induced rats. A high fasting glucose level is a key indicator in diabetic animals. The STZ-treated group presented increased blood glucose levels (225 \(\pm\) 7 mg/dL) as compared to the animals in the control group (94 \(\pm\) 5 mg/dL). STZ-induced diabetic animals treated with TQ showed decreased blood glucose levels (146 \(\pm\) 7 mg/dL). Some previous reports show that there was a gradual enhancement in blood glucose level due to the administration of STZ and blood glucose concentration is lowered by TQ treatment [32]. Hyperglycemia in STZ diabetic rats results from STZ-induced damage of the pancreatic \(\beta\)-cells, decreased secretion of insulin and its sensitivity, decreased overall glucose uptake, and also increased glucose production in the liver [33; 34]. A study reported that thymoquinone ameliorates chemical induced oxidative stress and \(\beta\)-cell damage in experimental hyperglycnic rats [35]. The meta-analysis examined by some previous studies evaluated the serum glucose (SG) level or serum insulin level or body weight (BW). In those studies, it has been observed an overall pooled standardized mean difference (SMD) of \(-\)9.176 mg/dL. Figure 12: The Cox-2 protein expression was analyzed in different experimental groups. (**a**) The control animals did not show any expression; (**b**) The significantly high expression of Cox-2 protein was noticed in STZ-induced diabetic rats; (**c**) Cox-2 protein expression was diminished in STZ-induced plus TQ administered rats; (**d**) PC group did not show any expression (Scale bar = 100 \(\upmu\)m). The TQ decreased the SG level (\(-\)9.176 mg/dL) significantly in the STZ-induced diabetic models. Moreover, a meta-analysis of the effect of TQ on body weight revealed that TQ has a significant effect on the body weight of diabetic animals. In addition, the overall pooled estimate of the level of serum insulin was significant with SMD of 1.681 [36]. _Nigella sativa_ has been shown to significantly improve clinical parameters like hyperglycemia, with a significant fall in fasting blood glucose, blood glucose level 2 h postprandial, glycated hemoglobin, and insulin resistance, and a rise in serum insulin [37]. The treatment of the STZ diabetic animals with TQ caused improved blood glucose and insulin secretion indicating that TQ is an effective anti-hyperglycemic agent.