Effects of shikonin and Teucrium polium extract in colorectal cancer: experimental and computational explorations

Abstract

• Colorectal cancer (CRC) was induced using azoxymethane (AOM). • CRC associated several colon histopathological features • CRC associated oxidative injury in both liver and colon tissues. • Teucrium polium extract (TPE) and shikonin (SHK) mitigated most of the AOM-induced CRC associated comorbidities. • The computational study showed that beneficial effects may resulted from the affinity and molecular interactions of TPE and SHK with COX-2, TNF-α and IL-6. Colorectal cancer (CRC) is the third most frequent neoplasms. It is associated with severe burden and reduced patients’ quality of life. The available treatments efficacy is still not satisfactory, which emphasized the need for development of new anticancer drugs. This study assessed the effect of shikonin (SHK) and Teucrium polium L. extract (TPE) against azoxymethane (AOM)-induced CRC in rats. The pro-oxidant/antioxidant status have been explored in colon and liver tissues. Some key receptors (COX-2, TNF-α and IL-6) have been targeted to decipher the molecular interactions with SHK or TPE compounds. Additional histological and biochemical analyses have been carried on the animal colons. CRC group exhibited oxidative injury associated several colon histopathological features; adenoma and inflammatory lesions, increased nuclear polymorphism, increased number of aberrant crypts foci and epithelial desquamation, pre-neoplastic lesions, and malignant neoformations. Both SHK and TPE significantly alleviated the liver injury by counteracting the disrupted alanine aminotransferase, aspartate aminotransferase and lactate deshydrogenase and mitigated most of the AOM-induced CRC associated comorbidities, without turning back to control levels. However, the mitigation effect was more prominent once rats have been treated with TPE. The computational study showed that SHK and TPE beneficial effects may be the result of the affinity and molecular interactions of the compounds with COX-2, TNF-α and IL-6. This study provided valuable mechanistic insights into the promising effects of both SHK and TPE phytochemicals in the future drug design, management and complementary medication of CRC.