Diabetic kidney disease (DKD) is a common diabetes complication mainly caused by lipid toxicity characterized by oxidative stress. Studies have shown that adropin (Ad) regulates energy metabolism and may be an effective target to improve DKD. This study investigated the effect of exogenous Ad encapsulated in reactive oxygen species (ROS)-responsive nanocapsules (Ad@Gel) on DKD. HK2 cells were induced with high glucose (HG) and intervened with Ad@Gel. A diabetes mouse model was established using HG and high-fat diet combined with streptozotocin and treated with Ad@Gel to observe its effects on renal function, pathological damage, lipid metabolism, and oxidative stress. Results showed that Ad@Gel could protect HK2 from HG stimulation in vitro. It also effectively controls blood glucose and lipid levels, improves renal function, inhibits excessive production of ROS, protects mitochondria from damage, improves lipid deposition in renal tissues, and downregulates the expression of lipogenic proteins SEBP-1 and ADRP in DKD mice. In HG-induced HK2 cells or the kidney of DKD patients, the low expression of neuronatin (Nnat) and high expression of translocator protein (TSPO) were observed. Knockdown Nnat or overexpression of TSPO significantly reversed the effect of Ad@Gel on improving mitochondrial damage. In addition, knockdown Nnat also significantly reversed the effect of Ad@Gel on lipid metabolism. The results suggest that the effect of Ad on DKD may be achieved by activating Nnat to improve lipid metabolism and inhibit TSPO activity, thereby enhancing mitochondrial function.

Background: Osteoarthritis (OA) is a disorder of joints involving degeneration and destruction of cartilages. Inflammation has been found to play an important role in the development of OA. Hidrosmin (HDS) is a flavone useful in venous insufficiency disorders and cancer. However, its role in OA remains unexplored. Here we reported the anti-inflammatory effect of Hidrosmin in OA utilizing both in vivo and in vitro studies. Methods: The primary chondrocytes were used for in vitro studies. Chondrocytes were submitted to immunofluorescence and toluidine blue staining. C57BL/6 male mice were used for In vivo experiment for creating an osteoarthritis model by surgical destabilization of the medial meniscus. CCK-8 assay was done for cell viability studies, Levels of nitric oxide were studied by Griess reaction, western blot analysis and qRT-PCR analysis was done for analyzing the levels of PGE-2, TNF-α, IL-6, collagen II, COX-2, iNOS, MMP-13, ADAMTS, Nrf2, HO-1, p65 and IκBα. Immunohistochemical assay and histopathological analysis were done for tissue studies. In silico analysis was done by performing molecular docking studies with MGL tools. Results: The in vitro results suggested HDS inhibited the levels of cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO) and IL-1β mediated levels of iNOS. Hidrosmin also suppressed the levels of ADAMTS-5 and IL-1β-induced MMP-13, whereas the levels of aggrecan and collagen II were up-regulated. Mechanistic study suggested HDS suppressed the nuclear factor kappa B (NF-κB) via targeting the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in chondrocytes. The outcomes of molecular docking studies confirmed that Nrf2 had a potential binding affinity with Hidrosmin as seen by lower binding energies. Conclusion: The findings of the study suggested HDS could be a potential molecule for halting the progression and development of osteoarthritis. conclusion: The findings of the study suggested HDS could be a potential molecule for halting the progression and development of osteoarthritis.