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

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.