Chemopreventive potential of Saurauia vulcani korth in improving Rhodamine B induced hepato-renal carcinoma in Rats

Abstract

ObjectiveRhodamine B (RhB) is a xenobiotic leading to induce severe oxidative stress associated with hepato-renal carcinoma. Traditional herbal medicine, for instance Chinese herbal medicine, has been used to suppress metastasis development in hepatocellular and renal carcinoma. Saurauia vulcani Korth., is known “Bitiguo” in traditional chinese medicine, reported to be effective treatment for anti-diabetic, diarrhea, wound healing, hepatoprotectant agent, and immunostimulatory properties. The current study focused on evaluating the chemopreventive of extract ethanol S.vulcani (EEP) against hepato-renal carcinoma induced Rhodamine B through in vivo and in silico approach. MethodsTwenty-four rats were divided into four groups; P1 as control group, P2 received orally rhodamine B 980 mg/kg; P3 was administered EEP at dose 500 mg/kg for 22 days; P4 was given orally rhodamine B 980 mg/kg and EEP 500 mg/kg. Hematoxylin and eosin (HE) staining was used to analysis the pathological alteration in rats induced Rhodamine B. Then, the network pharmacology was constructed to demonstrate the mechanism involved in the anti-hepato- renal carcinoma effect of EEP. Furthermore, the docking study was applied to predict the molecular interaction between the evaluated compound of S. vulcani and target proteins. Lastly, the molecular dynamic (MD) simulation displayed the bioactive compound of S. vulcani – protein complex fluctuation by using CABSflex 2.0 server. ResultsHistopathological measurement exhibited the severe abnormalities architecture with the damaged liver level at 1.8950 ± 0.06863 in the RhB treated group, while EEP significantly altered the level of damage at 1.4417 ± 0.02639. In addition, EEP at a dose of 500 mg/kg improved tubulus injury scores at 52.83 ± 4.44 % compared to RhB treated groups at 65.66 ± 10.17 %. Six active compounds and fifteen protein targets were constructed against hepato-renal carcinoma by network pharmacology. Furthermore, the docking study predicted that the bioactive compounds of S.vulcani have the best binding affinity toward AKT1, GLUT1, and HIF-1α compared to the control compound, doxorubicin. Moreover, the MD study indicated the most active compound of S.vulcani, such as corosolic acid, maslinic acid, and ursolic acid bound dynamically to the protein. ConclusionThis study confirmed that S. vulcani extract could be used as an underlying drug treatment for hepato-renal carcinoma for further validations.