## 4 Discussion  
Although _L. regularis_ has been used in the management of many diseases such as diabetes, nephrolithiasis and inflammatory diseases [24, 26], little is known about its impact in DN. Therefore, we evaluated the effects of _L. regularis_ extract in STZ-induced DN. Following the treatment by _L. regularis_ extract, a dramatic reduction in blood glucose levels, toxic renal markers, proinflammatory cytokines and oxidative stress markers as well as improvement in renal histopathology were observed. This study found that DN development may be inhibited by _L. regularis_ extract administration. We found that _L. regularis_ extract could increase the antioxidant ability of diabetic rats which displayed high glucose levels. Treatment with _L. regularis_ extract improved the antioxidant potential by increasing SOD and CAT activities, and GSH levels, in diabetic rats. The progression of DN is mainly attributed to oxidative stress generated by hyperglycemia [27, 28]. In this context, the generation of ROS results in loss of renal function and elevation of lipid profiles [29, 30]. Most medicinal plant-isolated compounds are relatively safe and readily available. The presence of active phenols, flavonoids, and tannins in _L. regularis_ extract may explain its hypoglycemic effect as evidenced by our data. [PERSON] et al. (2003) have shown that supplementation with flavonoids, specifically quercetin, which is one of the main constituents of _L. regularis_, had the ability to regenerate pancreatic islets and increase insulin release in STZ-induced diabetic rats [31]. Quercetin 3-O-b-L-galactopyranoside, quercetin 3-O-L-arabinopyranoside and quercetin 3-O-a-L-rhamnopyranoside are three flavonoid glycosides present in _L. regularis_, according to phytochemical analysis performed by [PERSON] et al. (2013). Such ingredients in the extract may explain the strong hypoglycemic effect in diabetic rats [32]. In addition, [PERSON] and [PERSON] (2017) attributed the antidiabetic properties of quercetin to various mechanisms including the inhibition of intestinal glucose absorption, insulin secretory and insulin sensitizing activities as well as increased glucose usage in peripheral tissues [33]. The significant increase in serum insulin level after _L. regularis_ treatment could be related to the plant extract ability to protect and regenerate damaged pancreatic \(\beta\) cells resulting in enhancing insulin secretion. Different diabetes-related complications occur with the progression of disease, including DN, which can further aggravate the patient's health condition [34, 35]. In this study, elevation in creatinine and urea levels concomitant with structural and histopathological alterations have confirmed the presence of DN. However, serum creatinine and urea levels were decreased and renal histopathology was alleviated following the treatment of diabetic animals with _L. regularis_ extract, which can be linked to its active phenolic constituents [24]. Hypercholesterolemia and hypertriglyceridemia are also among the complications caused by diabetes, which are well-recognized causative agents of chronic vascular disease [36]. Consistent with many previous reports, STZ-induced diabetes-induced dyslipidemia, as evidenced by increased serum cholesterol, TG and LDL [37, 38]. Interestingly, the extract from _L. regularis_ not only lowered TC but also increased HDL. In addition, it reduced TG and LDL in diabetic rats, perhaps due to the presence of quercetin [39, 40]. In this study, the most significant finding is that _L. regularis_ extract administration could restrict oxidative damage, lipid peroxidation and inflammation in STZ-induced diabetic rats, which together may account for its renorprotective impact. Chronic hyperglycemia mediated DN induces oxidative damage and inflammation [41]. As a consequence, release of ROS can damage lipids, DNA and other cellular components, leading to cell death. Inaddition, the generation of ROS results in the elevation of TNF-\(\alpha\), IL-18, IL-6 and other inflammatory mediators [42].