Evaluation of Cytotoxic and Antitumour Properties of Apodytes dimidiata and Characterisation of the Bioactive Component

Abstract

Apodytes dimidiata, belonging to the family Icacinaceae, is used for treating inflammation and various gastrointestinal ailments in Zulu traditional medicine. In the present study, significant cytotoxicity was exhibited by the methanolic extract of the A. dimidiata leaf against various cancer cell lines. The extract was purified partially through silica gel column by successive elution using various solvents of increasing polarity. Among these, the active methanolic fraction was found to be the most cytotoxic with IC50 values ranging from 0.92 to 3.95 µg/mL for Ehrlich's ascites carcinoma (a carcinoma cell line), Jurkat (human T lymphocyte cell line), and SK-BR-3 (mammary tumour cell line). The treated cells showed morphological alterations characteristic of apoptosis. Upon oral administration of active methanolic fraction at a dose of 250 mg/kg body weight, the solid tumour volume in mice was significantly reduced to 55.14% and the life span of the ascites tumour-bearing mice increased to 44.65% compared to untreated control. The active fraction with Rf value 0.56 was purified from the methanolic fraction by preparative thin-layer chromatography and was subjected to high-performance thin-layer chromatography, high-performance liquid chromatography, liquid chromatography-mass spectrometry, and nuclear magnetic resonance analysis. The iridoid glycoside genipin was identified as the active component.

Regeneration of skeletal system with genipin crosslinked biomaterials

“…However, the current in vivo anti-tumor function of genipin was assessed through oral administration or intraperitoneal injection, making it difficult to predict the actual local drug concentration in target tissue, especially after first pass elimination by liver. 159,160 So far, there is no relative study to investigate the antitumor function of genipin crosslinked biomaterials. The effective concentration of genipin in local anti-tumor administration and whether the degradation products of genipin crosslinked biomaterials can influence on the outcomes of anti-tumor still remain unclear.…”

“…However, the current in vivo anti-tumor function of genipin was assessed through oral administration or intraperitoneal injection, making it difficult to predict the actual local drug concentration in target tissue, especially after first pass elimination by liver. 159,160…”

Ameliorative effect ofApodytes dimidiataon cisplatin-induced nephrotoxicity in Wistar rats

“…The phytochemical screening of leaf acetone extract showed the presence of saponins, tannins, terpenes, steroids and flavonoids (Masoko & Nxumalo 2013). Moreover, in our previous studies, the antitumour (Divya et al 2015) and chemopreventive (Divya et al 2016) effects of A. dimidiata were revealed.…”

“…It is thus suggested that nephroprotective effect of A. dimidiata may be due to its polyphenol and flavonoid contents. Moreover, in our previous studies, the presence of an iridioid glycoside, genipin in the AMF fraction was detected while ascertaining the cytotoxic and antitumour properties of AMF (Divya et al 2015). Drewes et al (1996) had isolated genipin from the bark of A. dimidiata.…”

Attenuation of DMBA/croton oil induced mouse skin papilloma byApodytes dimidiatamediated by its antioxidant and antimutagenic potential

“…Apart from these, a well-known anticancer alkaloid, camptothecin, was isolated from the bark of this plant (Ramesha et al 2013). In our previous studies regarding the anticancer activities of AMF, we have isolated the compound, genipin, as the most cytotoxic component (Divya et al 2015). Genipin is reported to possess antioxidant (Lee et al 2009) and anticancer properties (Cao et al 2010).…”