Background The vast majority of systemic lupus erythematosus patients develop lupus nephritis (LN) with severe renal manifestations, such as inflammatory responses, oxidative stress, and fibrosis. The purpose of this research was to investigate Cordyceps cicadae as a potential therapeutic target for treating inflammatory responses, oxidative stress, and fibrosis in LN. Methods The effects of C. cicadae on lupus symptoms in mice with LN were determined. MRL/lpr mice were treated with C. cicadae (4 g/kg/day, i.e., CC group, n = 8) or an equal volume of saline (model group, n = 8), and MRL/MP mice were treated with an equal volume of saline (control group, n = 8). Renal function indices, renal pathology, inflammatory markers, oxidative stress markers, and renal interstitial fibrosis levels were evaluated after C. cicadae treatment. Western blot analysis was performed to investigate the effect of C. cicadae on the expression of fibrosis biomarkers and the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-mediated autophagy pathway in the renal tissues of mice. Results C. cicadae ameliorated renal lesions, the inflammatory response, and oxidative stress damage in MRL/lpr mice. C. cicadae treatment inhibited renal fibrosis (16.31 ± 4.16 vs. 31.25 ± 5.61) and downregulated the expression of the fibrosis biomarkers alpha-smooth muscle actin, fibronectin, and collagen I (COL I) in the kidneys of MRL/lpr mice. In addition, further research showed that the PI3K/mTOR-mediated autophagy pathway was involved in C. cicadae -mediated effects on renal fibrosis in MRL/lpr mice. Furthermore, the therapeutic effect of C. cicadae on repairing renal fibrosis and damage in MRL/lpr mice was abolished by the PI3K agonist 740 Y-P. Conclusions The findings of the present research showed that C. cicadae could alleviate inflammatory responses, oxidative stress, and fibrosis in the renal tissues of mice with LN by targeting the PI3K/mTOR-mediated autophagy pathway.
Introduction: Triple-negative breast cancer (TNBC), an aggressive type of
breast cancer, remains difficult to treat. Isoliquiritigenin (ISL) is a bioactive compound
that is insoluble in water and exhibits significant anti-TNBC activity. Method: We previously
prepared oral aqueous ISL@ZLH NPs; however, they were less stable in a freezing
environment. Hence, the present study aimed to improve the stability of ISL@ZLH
NPs using cryoprotectants that can withstand long storage times and are effective in TNBC
treatment by creating an efficient oral drug delivery system. Freeze-dried ISL@ZLH
NP powder was prepared by solvent evaporation, followed by the addition of trehalose
and sucrose. The freeze-dried ISL@ZLH NP pow was optimized and characterized. The
anti-TNBC efficacy and pharmacokinetics of the ISL@ZLH NP-pow were examined in
plasma and organs, compared with those of aqueous ISL@ZLH NPs. Result: The ideal
particle size of the ISL@ZLH NP pow was 118 nm, which was not filtered out by the
glomerulus and allowed the drug to be delivered to the lesions more effectively. Cellular
uptake and biodistribution of the ISL@ZLH NP-pow in vivo and in vitro showed prolonged
storage in the organs. In addition, cryopreserved ISL@ZLH NP-treated tumors
showed significant anti-proliferative and anti-migratory effects through the downregulation
of the PI3K-Akt-mToR and MMP2/9 signaling pathways. Conclusion: These results
suggest that oral ingestion of cryopreserved ISL@ZLH NP has the potential for longterm
storage and can be employed as a clinical therapeutic approach to treat TNBC.