By Musa Adekunle
Scientists have confirmed the chemo-preventive potential of the active ingredient, Mangiferin (MF), in mangoes on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) otherwise known as colon cancer in rats. Researchers in the recent study published in the journal Scientific Reports concluded: “Based on the experimental findings, MF treatment had no toxic effects or behavioral changes in treated rats throughout the study period. The current study presented the chemo-protective effects of MF using AOM-induced colon cancer in rats. Taken together, MF could be used as an alternative intervention to treat colorectal cancers.”
Colorectal cancer (CRC) has been recognised as the third most dominant cancer type that enhances mortality rates in both sexes. However, compared to males, females are marginally at a higher risk of acquiring colorectal cancer. Some of the factors that increase the risk of this type of cancer are malnutrition, stress, obesity, alcohol, and smoking.
The AOM-based colon carcinogenesis model is the most popular method to evaluate the chemo-protective efficacy of a particular compound. Although many anti-cancer drugs against colorectal cancer have been developed, these synthetic chemicals are associated with many side effects that include hair loss, digestive problems, sexual disability, neuropathy, and nephropathy.
Therefore, there is a need for an alternative natural medicine or chemo-protective agent that has minimal side effects. These natural compounds could lower morbidity and mortality rates linked to colorectal cancer. Secondary metabolites, such as alkaloids and flavonoids, extracted from plants have exhibited excellent chemotherapeutic properties without significant side effects. For instance, MF, a natural C-glucosylxantone compound, showed an inhibitory effect against several cancer cells, such as acute leukemia cells, HeLa S3 and KBvin cells, and colon cancer.
Although MF is predominantly present in Salicia chinesis (saptarangi) and Mangifera Indica (Mango), this compound has also been extracted from the Anacardiaceae and Gentianaceae families.
Several studies have documented the antioxidant, antifungal, analgesic, antimicrobial, anti-diabetic, anti-inflammatory, cardio-protective, and anti-apoptotic properties of MF.
Interestingly, several drug-like properties have been identified in MF, including catechol moiety, weight of particles, and estimated partition coefficient (C Log P) number.
Despite identifying the therapeutic potential of MF in vivo and in vitro experiments, the underlying mechanism of action for the same remains elusive. The current study rationally designed an experiment to assess the chemo-protective potentials of MF in AOM-induced oxidative stress-mediated colorectal cancer in rats.
The in vivo gross morphology, immunohistochemistry, and the levels of inflammatory cytokines, antioxidants (enzymatic and non-enzymatic), and blood biochemical parameters were measured at varied MF dosages. A total of fifteen rats were randomly segregated into three cages, that is, group 1, group 2, and group 3. Group 1 rats received 10% Tween 20 and were referred to as the control group. Group 2 rats received a low dosage (250 mg/kg), and group 3 received a high dose (500 mg/kg) of MF by oral gavage.
The current study observed that rats that only ingested AOM developed numerous colonic adenomas and adenocarcinomas with significant organ metastasis, particularly in ileocecal lymph nodes and cecum.
MF treatment resulted in a decrease in the volume and extent of colon adenomas and adenocarcinomas. Furthermore, the MF-treated rats exhibited a lower total ACF than the control group.
Previous studies showed that different routes of administration of chemo-protective agents, such as oral, intramuscular, and subcutaneous administrations, have different incidence rates of colorectal cancer.
In this study, 15 mg/kg AOM was subcutaneously introduced to rats to evaluate its chemo-protective effect on MF. The current study revealed that both MF supplementation doses were safe for two weeks, as no side effects occurred. However, a higher dose beyond 500 mg/kg could generate toxic effects. The study rats were assessed every eight hours, and no abnormal physiological features were observed. The physical activity level and feed intake of the control group and MF-ingested rats were comparable.
Similarly, histological studies also exhibited similar liver and kidney tissue structures between the control and treated groups of rats. Compared with the MF-treated rats, an elevated mucin content and higher ACF values were found in the colon of the control rats.
Furthermore, compared to the treated group, the control group exhibited reduced Bax protein expression and increased β-catenin protein expression.
These results indicate a significant imbalance between these two proteins, which may cause cellular dysfunctions and alter the mitochondrial route of apoptosis. Significant antioxidant potential of MF was observed through up-regulation of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and antioxidant enzymes; and down-regulation of malondialdehyde (MDA) level in colon tissue homogenates.
A significant increase in IL-6 and TNF-α cytokines levels and a reduction in anti-inflammatory cytokine (IL-10) were found in the blood of rats that only received AOM. MF reduced immune and inflammatory responses via up-regulation of IL-6, TNF-α, and down-augmented IL-10 cytokines in rats
– Courtesy Guardian Newspaper, Nigeria