<i>Commelina benghalensis</i> attenuates cyclophosphamide‐induced hepatotoxicity by preserving hepatic mitochondrial activity through upregulating pro‐mitochondrial proteins

Abstract Aim Cyclophosphamide (CP) is used as antineoplastic agent. However, anticancer therapy is largely impeded by its toxicity arising from oxidative stress. Strategies that can attenuate this off‐target effect of CP could be helpful. Commelina benghalensis L. is widely used in oriental traditional medicine for management of jaundice, fever, inflammation, leprosy and snake bites; its potential against chemotherapy‐induced hepatotoxicity is unknown. The present study evaluates the hepatoprotective effect of hydro‐ethanolic extract of C. benghalensis (HECB) in a rat model of CP‐induced hepatotoxicity. Methods Chemical characterization of HECB was carried out followed by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay. Hepatic functional tests including phenobarbitone‐induced sleeping time were done and anti‐oxidant reserves were estimated after oral treatments at 50 and 100 mg/kg for eight weeks. Inflammatory markers and mitochondrial integrity (complex I activity, nuclear factor erythroid 2–related factor 2 [Nrf2] and mitochondrial transcriptional factor A [TFAM] levels) were analyzed in the tissue lysates. Results Flavonoids and phenolic compounds were found at higher concentrations of 50 and 100 μg/mL with a significant free radical scavenging activity as displayed by DPPH assay. Administration of CP has resulted in increased liver weight, elevated serum hepatic enzyme activity along with inflammatory markers, decreased hepatic anti‐oxidant reserves, and impaired mitochondrial activity. Correspondingly, daily oral administration of HECB ameliorated these parameters and restored anti‐oxidant reserves. Further, hepatic mitochondrial activity, Nrf2 and TFAM levels were also improved. The hepatoprotective effect of HECB was further confirmed by histopathological analysis and phenobarbitone‐induced sleeping time. Conclusion Conclusively, the study provides preliminary evidence regarding the hepatoprotective activity of HECB and the contribution of its anti‐oxidant potential towards this pharmacological effect.