Umbelliferone β-d-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB

Abstract

Umbelliferone (7hydroxycoumarin) compound possesses strong anti-inflammatory and free radical scavenging activity. The intend of the current study was to conclude the renalprotective efficacy of Umbelliferone β-D-galactopyranoside (UFG) over diethylinitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted the oxidative stress, inflammation and renal injury in Wistar rats. The capacity of UFG to scavenge the reactive nitrogen species (RNS) and reactive oxygen species (ROS) was evaluated and its also scrutinized scavenging against the hydroxyl (OH), superoxide (O 2 ), nitric acid (NO) and hydrogen peroxide (H 2 O 2 ) radicals. Renal carcinoma was induced by single intraperitoneal injection of DEN (200 mg/kg, b.w.) and promoted by twice weekly treatment of Fe-NTA (9 mg/kg, b.w.) for 22 weeks. To estimated the molecular mechanism implicated in the antitumor potential of UFG, its consequence was appraised on renal tumor inflammation; proinflammatory cytokines including interleukin-1β (IL-1β), interlukin-6 (IL-6) and tumor necrosis factor (TNF-α); inflammatory mediator including prostaglandin E 2 (PGE 2 ), ornithine decarboxylase (ODC) and nuclear factor kappa B cell (NFκB). It's also induced the serum abnormability including creatinine, lactate dehydrogensae (LDH) blood urea nitrogen (BUN) and [ 3 H] thymidine incorporation. Further, augments the renal lipid peroxidation (LPO), endogenous antioxidant enzymes, phase II metabolizing enzymes and concomitant reduction in glutathione (GSH). UFG showed the 95% and 99% antioxidant activity in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) model. UFG significantly inhibited the RNS and ROS radical and 2 indicated the antioxidant activity (in vitro). The results showed momentous renal markers and oxidative stress protection impaired by UFG. UFG also restored the altered inflammatory and proinflammatory cytokines, which further strengthens the renal protection of UFG in DEN+Fe-NTA induced renal carcinogenesis. These results recommend that UFG as an efficient chemoprotective agent having the ability to thwart the DEN induced and Fe-NTA promoted renal carcinoma in experimental rats.

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…The Umbelliferae family is inclusive of economically important herbs, such as celery, cumin, fennel, parsley alexanders, angelica, asafoetida, and giant hogweed [9,170]. UMB possesses a variety of bioactivities, and several investigators have previously reported its in vivo antioxidant and anti-inflammatory effects and studied the underlying mechanisms of action in several animal models [30,[171][172][173][174][175]. The anticancer activity of UMB in hepatocellular [176], colon [177], and oral [178] carcinomas has been well-acknowledged.…”

Deconvoluting the dual hypoglycemic effect of wedelolactone isolated fromWedelia calendulacea: investigationviaexperimental validation and molecular docking

“…The hepatic parameters, namely alkaline phosphatase (AST), aspartate aminotransferase (AST), alanine transaminase (ALT); serum renal parameters, including blood urea nitrogen (BUN), total protein, creatinine, albumin; lipid parameters, such as total cholesterol (TC), high density lipoprotein (HDL), triglyceride (TG), very low density lipoprotein (VLDL) and, low density lipoprotein (LDL), were scrutinized using commercially available diagnostic kits. The atherogenic index and coronary risk index were scrutinized as per the given formula: [24][25][26][27][28][29][30][31] Inammatory and pro-inammatory mediators Pro-inammatory cytokines, namely interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), and inammatory mediators, such as C-reactive protein (CRP), were also estimated as per the instructions in the available commercial kits.…”

Dietary Coumarins

“…The in vivo anti-inflammatory activity of umbelliferone (2), the most common natural coumarin, has recently been reported by Wang et al (2019b), showing the protective effect and underlying mechanism of action of 2 against lipopolysaccharide (LPS)-induced acute lung injury, following the similar mechanism as stated earlier. However, in fact, several researchers previously demonstrated the in vivo anti-inflammatory and antioxidant effects of 2, and associated mechanisms of actions were also studied quite extensively in various animal models (Rauf et al 2014;Anwar et al 2015;Sim et al 2015;Germoush et al 2018). The role of esculin (18) against macrophages and endotoxin shock induced by LPS in mice was analyzed by Li et al (2016a), where they showed that this glycoside could suppress inflammatory reactions in macrophages and protected mice from LPS-induced endotoxin shock.…”