ts [89] and immunomodulatory activities [90]. A variety of preparations are made by honeybees, which include royal jelly, propolis, bee wax, pollen grain, and bee venom [91]. A multitude quantity of bioactive compounds derived from honeybee products could be of worth within the therapy of CKD and management of CKD complications [92,93]. Honeybee propolis is one of the considerable useful elements derived from honeybee merchandise. Propolis includes bioactive compounds, like flavonoids which include chrysin and rutin, and phenolic compounds, such as caffeic acid as well as a stilbene derivative resveratrol [94]. The antioxidants traits of propolis are determined by its content material of flavonoids and phenolic compounds [957]. In a current study, propolis was able to attenuate tubulointerstitial fibrosis by modulating canonical SMAD signaling pathway and JNK/ERK activation inside the TGF- cascade in a murine model of aristolochic acids-induced nephropathy [93]. Teles et al. demonstrated that Brazilian red propolis decreased hypertension and renal morphological alterations manifested by decreased serum creatinine, proteinuria, and infiltration of macrophages in 5/6 nephrectomized rats [98]. The authors recommended that the beneficial effects of Brazilian red propolis are because of its anti-inflammatory and antioxidantAntioxidants 2022, 11,6 ofactivity. Also, by means of lowering oxidative anxiety and blood stress, Indonesian propolis extract has been shown to attenuate UUO-induced renal damage [99], and Iranian propolis extract could improve the antioxidant levels and amend histopathological alterations within the DN rats model [100]. Within a randomized, double-blinded, and placebo-controlled clinical trial in humans, Brazilian green propolis substantially attenuated proteinuria in diabetic and non-diabetic CKD patients [92] and decreased inflammation in individuals on hemodialysis [101]. Chrysin derived from bee propolis decreased kidney fibrosis induced by the accumulation of AGEs in in vitro and in vivo research. Inside the in vitro study, chrysin therapy reduced AGEs-induced deposition of collagen, induction of -SMA, and matrix metalloproteinases in human mesangial cells by way of downregulation of TGF1 and SMAD 2/3. In addition, these findings had been confirmed in an animal model of diabetic kidney illness [102]. In addition, chrysin attenuated adenine-induced CKD in rats by means of the reduction in inflammatory cytokines, boosting antioxidant status, and enhancing renal histopathological alterations [103]. Caffeic acid phenethyl ester (CAPE) is one of the constituents of honeybee propolis which has been shown to defend against lithium-induced renal COX Activator Purity & Documentation tubular damage and oxidative stress within a rat model by boosting the antioxidant enzymes activities (SOD, CAT, GSH-Px) in renal tissue [104]. Caffeic acid also had anti-inflammatory effects in the model of diabetic nephropathy (DN) mice by decreasing renal IL-6, IL-1, TNF-, and MCP-1 levels [105]. Pinocembrin, isolated from Mexican brown propolis, has been shown within the DN rat model to be in a position to improve lipid profile, glomerular filtration rate, urinary protein, protect against urinary biomarker increases, oxidative pressure, and glomerular basement membrane thickness [106]. Bee venom can be a all-natural toxin developed by honeybees and possesses a multitude of CCR3 Antagonist custom synthesis valuable well being activities [107]. Bee venom remedy attenuated renal fibrosis in unilateral ureteral obstruction (UUO)-induced CKD through a reduction in the expression of inflammatory markers (TNF-
