Calycosin-loaded nanoliposomes as potential nanoplatforms for treatment of diabetic nephropathy through regulation of mitochondrial respiratory function

Abstract

Backgrounds One of the most common complications in diabetic nephropathy is generation of high levels of ROS which can be regulated by herbal antioxidants. However, polyphenols like calycosin, the bioactive compound of Radix astragali suffer from low solubility and poor bioavailability. Methods Therefore, in the present study, calycosin-loaded nanoliposomes were fabricated and characterized by TEM, DLS and FTIR techniques. Afterwards, the drug loading (DL) and entrapment efficiency (EE), drug release, solubility, stability, and pharmacodynamic assays were performed. Finally, the antinephropathic effects of calycosin-loaded-nanoliposomes on mitochondria of kidney cells were explored by MTT, ROS, MDA, mitochondrial respiratory function assays. Results The result showed that the size, hydrodynamic radius, zeta potential, EE, and DL were, 80 nm, 133.99 ± 21.44 nm, − 20.53 ± 3.57, 88.37 ± 2.28%, and 7.48 ± 1.19%, respectively. The outcomes of in vitro release assay showed that calycosin-loaded nanoliposomes were significantly slow-release in dialysis media with pH 1.2, pH 6.9 and pH 7.4, at about 30 min, the dissolution of calycosin from nanoliposome became almost complete, and after 2 months, the calycosin-loaded nanoliposomes were still stable. Pharmacokinetic assay revealed that the AUC0−t of calycosin in calycosin-loaded nanoliposome group was 927.39 ± 124.91 μg/L*h, which was 2.26 times than that of the free calycosin group (**P < 0.01). Additionally, the MRT0−t and t1/2 of calycosin in the calycosin-loaded nanoliposome group were prolonged by 1.54 times and 1.33 times than that of free calycosin group, respectively (*P < 0.05). Finally, it was shown that calycosin-loaded nanoliposomes regulated the viability, ROS production, lipid peroxidation and function of mitochondria in kidney cells of diabetic rats as a model of diabetic nephropathy. Conclusion In conclusion it may be suggested that new therapies based on nano-formulated calycosin can restore mitochondrial function which can improve diabetic nephropathy. Graphic abstract

The Active Compounds and Therapeutic Target of Tripterygium wilfordii Hook. f. in Attenuating Proteinuria in Diabetic Nephropathy: A Review

“…Oxidative stress caused by the overaccumulation of reactive oxygen species (ROS) induces protein and nucleic acid damage, thereby leading to impaired cellular damage and tissue pathology (74). The mitochondria are the major sources of ROS as well as the main targets of ROS (75). The damaged mitochondria with impaired respiration block the transfer of electrons along the respiratory chain, which then react with O 2 in upstream respiratory chain components to form superoxide free radicals and ROS (76).…”

Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease

“…Formononetin treatment could reduce serum glucose level, improve glucose tolerance, insulin sensitivity and lipid profile, and also reduce Scr and BUN in diabetic rats ( Oza & Kulkarni, 2018 , 2019 ). In addition, calycosin have also been reported to treat mitochondrial dysfunction and DKD ( Huang, et al, 2021b ; Xia et al, 2021 ). Calycosin could suppress oxidative stress by increasing superoxide dismutase and glutathione, reducing malondialdehyde and mitochondrial ROS levels ( Xia et al, 2021 ).…”

“…Calycosin could suppress oxidative stress by increasing superoxide dismutase and glutathione, reducing malondialdehyde and mitochondrial ROS levels ( Xia et al, 2021 ). Calycosin-loaded nanoliposomes could regulate ROS production, lipid peroxidation and mitochondrial function in DKD ( Huang, et al, 2021b ). However, these documents could only provide evidence that the above constituents regulate mitochondrial function or diabetic complications to some extent.…”

Unveiling the potential anti‐cancer activity of calycosin against multivarious cancers with molecular insights: A promising frontier in cancer research

“…115 Nanocarriers that have received clinical approval are used to treat and diagnose numerous diseases, including cancer. 116 diabetic nephrology, 114 and ischemic heart disease. 117 Calycosin performed in vitro and in vivo studies with nanostructured lipid carriers against cancer.…”