Elucidation of significant pathways of Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.) flower against cancer through network pharmacology

Dong Ha Cho, Ki Kwang Oh, Md. Adnan
2021 Proceedings of 7th International Electronic Conference on Medicinal Chemistry   unpublished
The definition of cancer is that normal cell damaged via an aberrant endogenous process such as abnormality of DNA replication, instability of DNA sequence transformed to malignancy. The DNA damage responses represent chronic inflammation via the immune signaling pathway, which results in accelerating tumorigenesis. The damaged normal cells undergo cellular senescence, triggering secretion in the inflammatory cytokines leads to cellular mechanical disruption. Because inflammation is a leading
more » ... ctor to cause pathological symptoms such as unknown severe pain, fatigue, and comorbidity in cancer patients, and thus antiinflammation strategy is a key therapeutics. Anti-inflammatory agents for cancer treatment are currently NSAIDs, including Cox-2, due to fewer adverse effects and mortality rate. Most commonly, anti-cancer agents target to inhibit DNA replication and induce cancer cell death; however, cancer chemotherapeutics attack even healthy cells results in serious side effects such as nausea, vomiting, hair loss, and fatigue. On the other hand, traditional herbal plants with innovative bioactives and secondary metabolites play an essential role as an effective anti-inflammatory, anti-oxidant or anticancer agents. For instance, the plant extracts (Urtica membranaceae, Artemesia monosperma, and Origanum dayi Post) with a combination of anti-cancer drugs showed enhanced potency against specific cancer cell lines (lung, breast, colon, and prostate cancer) without exposing cytotoxicity on normal lymphocytes and fibroblasts. Herbal-derived bioactives possess fewer unwanted side effects than chemotherapy, which have led to new clinical drugs such as taxol from Taxus brevifolia L, vincristine from Catharanthus roseus G. Don and Epipodophyllotoxin from Podophyllum peltatum L.. C. maackii is a perennial herbal plant, belong to the family of Compositae, and widely distributed in the mountainous areas of Korea, Japan, and China. Furthermore, Cirsium species have been reported to have diverse pharmacological activities such as anti-oxidant, anti-inflammation, anti-cancer, and hepatoprotection effects. Specifically, C. maackii extract at 200㎍/㎖ concentration showed 36.89% inhibition against breast cancer cell line (MDA-MB-231). Another study demonstrated that HepG2 cells treated with MeOH extract of C. maackii have potent antioxidant efficacy against severe oxidant condition. Anti-inflammatory agents assist protection against cancer development, thereby acting on preventing cytokines storm. It implies that antiinflammatory compounds are important agonists to protect normal cell adjacent to tumor cell because they can block the overflowing of cytokines. Until now, C. maackii flower compounds were identified by HPLC and reported for only anti-Alzheimer efficacy by inhibiting BACE1. Generally, the identification of polar and mid-polar compounds from extracts are based on HPLC due to its good separation capability. In a different perspective, we utilized the GC-MS analysis to discover lipophilic bioactives, which mainly act as drug-like compounds and uptake efficiently into the cells. The lipophilicity is a significant physicochemical parameter that influences membrane permeability and affinity. More importantly, GC-MS along with molecular docking test (MDT) and ADME (Absorption, Distribution, Metabolism, and Excretion) study, are an optimal analytical method to determine drug-likeness compounds [26]. At present, the biactives and mechanisms of C. maackii flower against cancer remain unknown. Hence, we aimed to uncover its potential bioactives with their fundamental mechanisms through network pharmacology.
doi:10.3390/ecmc2021-11354 fatcat:kcglsotuprdehc3yj6v4sfiwqy