## 4 Discussion
The level of nitric oxide (NO) also increased in the DM group compared to the control and treated-groups. Nitric oxide has been reported as an oxidative stress indicator [47]. The oral administration of CLE for 6 weeks successfully enhanced enzymatic antioxidant levels, especially for SOD and GPx, while reducing lipid peroxidation products and nitric oxide levels. Increases in pro-inflammatory cytokines such as interleukin (IL)-1\(\beta\), IL-6, and tumor necrosis factor (TNF)-\(\alpha\) have been evaluated in diabetes conditions [48; 49]. The present study also recorded increases in pro-inflammatory cytokines such as IL-1\(\beta\) and TNF-\(\alpha\) in the DM group. A previous study reported that the levels of these cytokines significantly are increased in a hyperglyc condition compared to a healthy condition [48], whereas TNF-\(\alpha\) is also recognized as an inflammatory mediator to promote IR [50]. Kisspeptin (kiss-1 protein) plays important roles in reproductive function. It is also recognized as an upstream regulator of gonadotropin-releasing hormone (GnRH) in the hypothalamic-pituitary-gonadal (HPG) axis [51]. In the present study, the low levels of kisspeptin-1 and reproductive hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were observed in the DM group. A previous study reported that a low level of the kiss-1 protein was evaluated in a diabetes model. Additionally, levels of LH and FSH were also reduced after STZ injections in the diabetic animal model [52]. The disruption of kiss-1 expression was associated with a low level of gonadotropin (hypogonadotropic hypogonadism) [53]. The oral administration of CLE for 6 weeks successfully increased kiss-1 protein, FSH, and testosterone levels. The present study showed low total sperm and sperm motility as well as high sperm abnormality in the DM group compared to the control group. This result proves that disruption of the upstream regulator such as kiss-1 protein and certain male reproductive hormones results in low sperm quality. In men, LH and FSH play an important role in spermatogenesis and maintaining their level of testosterone [54]. A previous study reported that hyperglycemia impairs male reproductive function [55]. In the present study, men in a diabetic condition showed a higher level of sperm DNA fragmentation compared to healthy men, due to the oxidative process, whereas damage to sperm DNA was associated with a reduction in the quality of the sperm [56]. The present study also showed a decrease in semifierous tubule diameter in the DM group. Previous studies have reported that diabetes can result in a decreased diameter of the semififerous tubule [57]. In diabetes, testicular dysfunction is caused by seminiferous tubule atrophy, decreased diameter of the tubule, spermatogenesis cell reduction, and cell apoptosis in germ cells [58]. The oral administration of CLE for 6 weeks successfully ameliorated testicular properties, such as increases in sperm motility and reduced sperm abnormality, while protecting seminiferous tubule morphology. Overall, this study shows that CLE not only possesses an antidiabetic effect, but also improves some proinflammatory cytokines related to male reproductive function. Previous studies have reported that seaweed extracts showed ameliorative effects on reproductive function not only in diabetic models, including dietary supplementation of _U. lactuca_, fucoxanthin-rich extract from _L. japonica_, and _S. angustifolium_[22; 23; 24; 59].