Robinin Attenuates Xenobiotic Enzymes, Inflammation, and Apoptosis on DMH‐Induced Colon Cancer via Modulating Ras/PI3K/Akt/mTOR and NF‐κB/Bax/Caspase‐3 Signalling Pathways in Wistar Rats

ABSTRACT

With a high death rate, colorectal cancer (CRC) is the third most frequent cancer worldwide. Despite advances in medical therapeutics, effective treatments for CRC remain a significant challenge. Understanding the fundamental molecular mechanisms underlying the onset of CRC is crucial for developing innovative and effective therapeutic targets. Robinin (RB), a kaempferol derivative flavonoid glycoside isolated from Astragalus species, exhibits remarkable pharmacological properties, including antioxidative, anti‐inflammatory, apoptotic, and antitumor effects. Thus, the purpose of this work is to examine the anticancer effects of RB on 1, 2‐dimethylhydrazine (DMH)‐alone CRC in a rat model. Rats were assigned to six groups: Normal control (NC); CRC control (DMH, 20 mg/kg/week, i.p.); RB treatment (DMH + RB at 5, 10, and 20 mg/kg bw), and RB‐alone (20 mg/kg bw) for 15 weeks. Our results revealed that reduced the volume and number of tumours, incidence of aberrant crypt foci (ACF), the number of crypts, and crypt multiplicity were elevated ( p  < 0.01) in the DMH‐alone rats (100%). However, treatment with RB (5, 10, and 20 mg/kg bw) reduced ( p  < 0.05) these pre‐cancerous lesions in a dose‐dependent manner. RB also diminished DMH‐alone weight loss, inflammatory cytokine levels, histopathological alterations and IHC (Bax, Caspase‐3 and NF‐κB), while restoring cAMP and normalising enzyme activities through the regulation of hepatic xenobiotic enzymes, inflammation, and apoptosis. Targeting important signalling pathways, such as NF‐κB and PI3K/Akt/mTOR/Ras, facilitated these results.