The most prevalent cancer that kills women globally is breast cancer. Therefore, scientists need to look into ways to lower or perhaps reverse the incidence. Thus far, many therapy regimens involving the use of plant-based drugs have been reported (Arumuggam et al., 2015). More study on the treatment of breast cancer is urgently needed. Currently, breast cancer tumor immunology are the main topics of tumor research. Across the world, oncologists are quite interested in tumor immunology. Targeted suppression of key pathways involved in cancer metabolism is therefore gaining popularity as a tumor therapeutic approach (Dvir et al., 2024).

Modern science and continuing research studies have produced impressive advancements in the prevention and treatment of breast cancer, despite the enormous rise in cancer diagnoses and death rates. Immunotherapy, hormone therapy, targeted therapy, and chemotherapy have all been used extensively to treat cancer throughout the years (Siegel et al., 2012). Chemotherapy is still the major treatment for cancer cells, according to earlier research, but the negative effects it has on other healthy cell types in the body have raised serious concerns (Ahles and Saykin, 2007). The utilization of naturally occurring plant-based compounds that have anti-cancer qualities and have negligible or no negative effects on healthy cells is therefore urgently needed.

African mistletoe (L. micranthus), a member of the Loranthaceae family, is used extensively in traditional medicine and folklore due to its antioxidant and immune-boosting properties, particularly for immune-related illnesses including cancer and diabetes (Park et al., 1998, Omeje et al., 2011, Ebokaiwe et al., 2018). Over time, dry leaves of L. micranthus have become more widely accepted as a tea in Africa, Asia, America, and Europe. There are commercial mistletoe preparations on the market that are used to treat cardiovascular disorders and cancer, mainly in Europe (Park et al., 1998) and Africa, especially in Nigeria. Alcoholic-aqueous extraction and aqueous extract fermentation are the methods used to prepare mistletoe. Recommendations are numerous in the far east, where dried mistletoe leaves and twigs/stems are taken as tea over an extended period of time as a traditional therapy for lumbago, hypertension, tumors, etc. (Huang, 1993). Formulated preparations can be administered subcutaneously or intravenously, and mixtures with other extracts can be given as functional (medicinal) foods in the form of capsules or tea (Park et al., 1998). Infusing sun-dried mistletoe leaves and twigs/stems in hot water is the most common method of preparing the tea.

In keeping with L. micrranthus's traditional medicinal claims, its phytoconstituents have been structurally elucidated (Omeje et al., 2011, Moghadamtousi et al., 2013). These compounds, which include triterpinoids, alkaloids, steroids, and flavonoids, are known to have anti-inflammatory, antioxidant, antitumor, and immunomodulatory properties (Omeje et al., 2011, Moghadamtousi et al., 2013).

Earlier research showed that indoleamine 2,3-dioxygenase (IDO) and TRP-2,3-dioxygenase (TDO) act in tumor, stromal, and immune cells to induce pathogenic inflammatory processes that stimulate immune tolerance to tumor antigens (Levina et al., 2012), which aim to instigate cancer-induced immuno-suppression (Peng et al., 2022). Genetic and pharmacological evaluation of these enzymes has confirmed that they are key mediators of malignant growth and progression. Furthermore, the significance of tryptophan breakdown enzymes as essential mediators of immunologic responses, including autoimmunity and the growth and multiplication of cancer cells, is highlighted by the pharmacological and genetic assessment of TDO/IDO activities (Zhang et al., 2013, Prendergast et al., 2014, Du et al., 2020). Tryptophan is converted by the enzyme IDO to kynurenine, an essential byproduct that has been connected to inflammatory and immunological reactions, the onset of cancer, and different types of organ damage (Levina et al., 2012, Prendergast et al., 2014).

We hypothesize that L. micranthus may have a protective effect against breast cancer by preventing the breakdown of the essential amino acid (tryptophan) in the cancer microenvironment, which would strengthen the immune system. The current work attempts to identify the basic processes by which the extracts of L. micranthus reduce IDO activity and protein expression, with an emphasis on network pharmacology, in silico, in vitro, and in vivo evaluations.