Antitumor activity of methoxylated flavonoids separated from Achillea fragrantissima extract in Ehrlich’s ascites carcinoma model in mice

Abstract

Introduction: Achillea fragrantissima extract has been used in folk medicine as an anticancer. The present study describes the antitumor activities of the extract and the flavonoid compounds and attempts to explain the mechanisms underlying these activities. Methods: The whole plant of A. fragrantissima was collected and ground to produce a fine powder which subjected to the maceration process. Step gradient elution was used using silica gel vacuum liquid chromatography (VLC). The fractions were compared by thin layer chromatography (TLC) and concentrated. Final purification was performed using Sephadex LH-20 to give three compounds cirsiliol, chrysosplenol D and cirsimaritin from F4 and one compound, eupatilin-7-methyl ether from F6. In this study, Ehrlich’s ascites carcinoma (EAC) model was used as the model of cancer. Results: Achillea fragrantissima extract and its isolated methoxylated flavonoids significantly reduced the weight of tumor discs compared to EAC-control group. In addition, cirsimaritin and eupatilin 7-methyl ether treatments produced a dose-dependent reduction in tumor weight. Serum tumor necrosis factor-alpha (TNF-ɑ) level showed that A. fragrantissima extract and its isolated methoxylated flavonoid compounds significantly reduced its serum level compared to the EAC-control group. Furthermore, A. fragrantissima extract and the flavonoids significantly increased the Total antioxidant capacity (TAC) compared to EAC-control. A. fragrantissima extract and its isolated methoxylated flavonoids produced a better differentiation of tumor cells, with reduced nuclear pleomorphism and better formed tubular structures especially with high dose indicating the induction of apoptotic mechanism. Conclusion: Achillea fragrantissima extract and its isolated methoxylated flavonoids exhibit antitumor activities that may be attributed to the antioxidant properties and the induction of the apoptotic process.

Comparative Assessment of the Antioxidant and Anticancer Activities of Plicosepalus acacia and Plicosepalus curviflorus: Metabolomic Profiling and In Silico Studies

“…Additionally, they formed promising interactions with the key amino acids Leu 83 and Lys 89 inside the CDK-2 protein, and Met 769 inside the EGFR active sites. It deserves mention that the docking results in the current study are in line with the reported antitumor activities of these phytoconstituents, especially for prostate cancer, and their cycle arrest and apoptotic effects are mediated through the deactivation of cyclins/CDKs and the activation of apoptotic proteins such as caspases, p53 and p21, the CDK inhibitor [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ].…”

“…Data has shown that P. curviflorus (41.89 ± 3.15 mg GAE/g) exhibited a higher TAC than P. acacia (32.67 ± 2.81 mg GAE/g), while the TAC of ascorbic acid (the positive control) was 69.23 ± 4.51 mg GAE/g. Evidence of the antioxidant and antitumor effects of polyphenolics has been acquired in several studies, and is well accepted [ 5 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Thus, the exhibited variation in the total antioxidant capacity between P. curviflorus and P. acacia may be attributed to the differences in their total phenolic contents.…”

Jaceidin Flavonoid Isolated from Chiliadenus montanus Attenuates Tumor Progression in Mice via VEGF Inhibition: In Vivo and In Silico Studies

“…These findings are in line with those of in vitro cytotoxicity assay. In addition, they are in agreement with the in vivo antitumor activity of methoxylated flavonoids of Achillea fragrantissima [ 34 ] and Gomphrena martiana [ 35 ]. The in vivo efficacy of the methoxylated flavonoid may be attributed to their improved hepatic metabolic stability as they are less susceptible to glucuronic acid or sulfate conjugation.…”

The Current State of Knowledge in Biological Properties of Cirsimaritin

“…Several studies have been carried out on cell cultures showed that cirsimaritin exerts antiproliferative activities [ 97 , 98 , 99 , 100 , 101 , 102 , 103 ] on numerous cancer cell lines ( Table 4 ). In this regard, Moghaddam et al [ 97 ] studied, in vitro, the antiproliferative activity of cirsimaritin isolated from Dracocephalum kotschyi against normal and malignant cell lines using the MTT test.…”

“…Using an in vivo cancer model, Awad et al [ 101 ] recorded an antitumor activity of this molecule (separated from Achillea fragrantissima extract), characterized by the decrease in tumor size which can be explained by its antioxidant activities, confirmed by the increase in serum rate of TAC and reduction in serum TNF-α ( Figure 5 ). Furthermore, the results of the histopathological examination demonstrated the induction of apoptosis.…”