Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies)

Abstract: Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative
stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of
diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal
damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in
silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats
accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there
were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with
diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin
(mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However,
the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory
processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway.
Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic
acid, and melezitose as components of kiwi extract that docked well with potential as effective natural
products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic
acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have
the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can
be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the
treatment of diabetic hepatorenal complications.