Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1β/IL-6/TNF-α Mediated Signaling Mechanisms in Type-2 Diabetic Rats

Abstract

The prevalence of obesity in contemporary society has brought attention to how serious it is all around the world. Obesity, a proinflammatory condition defined by hypertrophied adipocytes and immune cells that reside in adipose tissue, is characterized by elevated circulating levels of proinflammatory cytokines. The pro-inflammatory mediators trigger a number of inflammatory pathways and affect the phosphorylation of a number of insulin-signaling pathways in peripheral tissues. In this work, we pointed the outcome of the leaves of Carica papaya (C. papaya) on the inflammatory molecules by in vivo and in silico analysis in order to prove its mechanisms of action. Adipocytokines, antioxidant enzymes, gene and protein expression of pro-inflammatory signaling molecules (mTOR, TNF-α, IL-1β, IL-6 and IKKβ) by q-RT-PCR and immunohistochemistry, as well as histopathological analysis, in adipose tissues were carried out. C. papaya reinstated the levels of adipocytokines, antioxidant enzymes and mRNA levels of mTOR, TNF-α, IL-1β, IL-6 and IKKβ in the adipose tissues of type 2 diabetic rats. Molecular docking and dynamics simulation studies revealed that caffeic acid, transferulic acid and quercetin had the top hit rates against IKKβ, TNF-α, IL-6, IL-1β, and mTOR. This study concludes that C. papaya put back the altered effects in fatty tissue of type 2 diabetic rats by restoring the adipocytokines and the gene expression.

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

“…In comparison to the insulin-treated group, kiwi extract treatment ameliorated the levels of these adipocytokines to levels that were nearly normal. In a similar line, Rebecca et al [ 18 ] documented that an ethanolic extract of Carica papaya enhanced insulin resistance in high HFD/STZ-induced T2DM with an increase in adiponectin and a drop in leptin synthesis in fat cells. Likewise, this also occurs in rat models with high-fat diets and streptozotocin induction.…”

“…Adipocytokine fluctuations are thought to be a symptom of adipose tissue dysfunction. Adipocytokines could also provide pertinent details on the pathophysiological origins of T2DM [ 18 ]. Leptin and adiponectin hormones generated from adipocytes play an indispensable role in the etiology of T2DM through heightened insulin sensitivity [ 17 ].…”

“…Likewise, obesity typically throws off the inflammation balance, which raises the concentration of proinflammatory cytokines. Peripheral insulin resistance and hyperglycemia can be ignited by inflammation [ 18 ]. We focused on the protein levels of proinflammatory cytokines such as NF-κB, TNF-α, INF-γ, and IL-6 in both control and experimental rats to ascertain whether kiwi extract can lessen inflammation and insulin resistance brought on by HFD and STZ.…”

Bioactives and Inflammation

“…Carica papaya leaf extraction exhibits anti-inflammatory and anti-hyperglycemic activities by modulating inflammatory molecules, such IL-1β, IL-6, TNF-α, and inhibiting nuclear factor kappa-B kinase subunit beta (IKKβ) and the mammalian target of rapamycin (mTOR); meanwhile, it restores normal levels of antioxidant enzymes, oxidative stress markers, and gene expression analysis in type-2 diabetes experimental rats fed with a high-fat diet [7].…”