Polyphenols and Cancer Immunology
Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri in Plants That Fight Cancer, 2019
Apigenin (4¢,5,7-tyrihydroxyflavone) is a cell-permeable polyphenol present in dietary plants, such as parsley, fruits, and herbs (Kang et al. 2009, Erdogan et al. 2016). This flavonoid has been shown to inhibit cancer cell growth by inducing apoptosis via both intrinsic and extrinsic pathways and arresting cell cycle mainly in the G0/G1 phase via regulation/induction of p21 and p27 inhibitors of cyclin-dependent kinases. Apigenin has been observed to upregulate the levels of caspase-8 and -3, Apaf-1, Bcl-2, and TNF-α, leading to apoptotic death of tumor cells. Moreover, by decreasing MMP-2 and MMP-9 levels, apigenin strongly influences the migratory capacity of tumor cells (Erdogan et al. 2016). A relationship has also been suggested between apigenin and macrophage M1/M2 polarization balance, which is achieved through modulating the activation of peroxisome proliferator-activated receptor γ (PPARγ) (Feng et al. 2016). In addition, apigenin can block COX-2 expression without influencing its activity in tumor cells, which is important in inflammation, autoimmunity, and the functioning of immune cells. Decreased autoimmune activity of Th1, Th17, and IL-6 has been observed after treatment with apigenin.
Heterocyclic Drugs from Plants
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
Flavones and related derivatives are very important to develop new and novel phytoceuticals. An important flavone is an apigenin, which has been tested and showed therapeutic promise of becoming a chemo-preventive agent (Shankar et al., 2017). Apigenin is known to have several medicinal properties that affect different molecular and cellular pathways on various diseases. This flavone also demonstrated anti-cancer, anti-inflammatory, and anti-oxidant properties. Apigenin lowered down the risk of several cancers and has synergized the chemotherapeutic outcome of some anticancer drugs (Shankar et al., 2017). Furthermore, apigenin has not only been used to prevent the risk of cancer but has also been studied for its activity to reduce neuroinflammation. Apigenin is capable of restoring cAMP which is the response element-binding protein, and this protein is essential for the up-regulation of brain-derived neurotrophic transcription factors (Bonetti et al., 2017). In vivo animal studies of this flavone showed an effect on inflammatory cytokines which are originated in certain immune cells and influence other cells.
Potential of Fenugreek in Management of Fibrotic Disorders
Dilip Ghosh, Prasad Thakurdesai in Fenugreek, 2022
Furthermore, experimental studies suggested that daily intake of anti-fibrotic fenugreek seed phytoconstituents (trigonelline, glycosides, apigenin) did not show any toxic effect during long-term administration (Kandhare, Bodhankar et al. 2016; Kandhare et al. 2019; Salehi et al. 2019; Zeiger and Tice 1997). Trigonelline demonstrated excellent safety (LD50 > 5000 mg/kg) with no adverse effects at doses 50 mg/kg for 21 days or 3500 mg for 70 days, no carcinogenicity or mutagenicity (Zeiger and Tice 1997). Acute oral toxicity study suggested flavonoid glycosides (Vicenin-1) exhibited median lethal dose (LD50) of 4837.5 mg/kg and NOAEL of 75 mg/kg during a subacute toxicity study (Kandhare, Bodhankar et al. 2016). Apigenin is considered safe, and evidence from experimental studies has shown that apigenin is non-mutagenic and non-genotoxic (Salehi et al. 2019). Moreover, fenugreek seed is a certified GRAS (Generally Recognized as Safe) ingredient (21 CFR § 182.20 2010). Thus, fenugreek seed and its phytoconstituents have a broad margin of safety and can be evaluated for further clinical development to manage fibrotic disorders.
Apigenin Enhanced Antitumor Effect of Cisplatin in Lung Cancer via Inhibition of Cancer Stem Cells
Published in Nutrition and Cancer, 2021
Yunxia Li, Xin Chen, Wei He, Shuyue Xia, Xiaochuan Jiang, Xiaoyang Li, Jiayu Bai, Nan Li, Lei Chen, Biao Yang
Apigenin (4, 5, 7-trihydroxy flavone; API) is a natural flavone present in common fruits and vegetables including parsley, celery, celeriac, and chamomile tea. It exerts strong anti-inflammatory and protective effects in collagen-induced arthritis (11). Moreover, antimetastatic effects have been reported in multiple cancers including breast, prostate, skin, lung and ovarian cancers (12–14). Additionally, API suppresses CSC-like properties in triple-negative breast cancer cells (15), and it represses hypoxia-induced CSC marker gene expression in a head and neck squamous cell carcinoma cell line (16). In NSCLC, API induces human lung cancer H460 cell death (17), and enhances the cytotoxic effects of CDDP (18). Thus, we are interested in whether API plays an anti-tumor role in the CDDP-induced increase in CSCs and acquired resistance in NSCLC.
Therapeutic potentials of the natural plant flavonoid apigenin in polycystic ovary syndrome in rat model: via modulation of pro-inflammatory cytokines and antioxidant activity
Published in Gynecological Endocrinology, 2020
Parisa Darabi, Homayoun Khazali, Mahbobeh Mehrabani Natanzi
Apigenin, chemically known as 4′, 5, 7,-trihydroxyflavone, with molecular formula C15H10O5, is a nontoxic active biological flavonoid compound [11]. Apigenin is abundantly present in common fruits such as grapefruit, plant-derived beverages and vegetables such as parsley, onions, oranges, tea, chamomile, wheat sprouts, and in some seasonings [11]. The anti-cancer, anti-inflammatory, anti-mutagenic, antiviral, purgative effects, and antioxidant apigenin and its role in scavenging free radicals have been shown in several studies [12]. In the present study, regarding the role of OS and inflammation in the pathogenesis of PCOS and vice versa, a positive relationship between decreased OS and increased oocyte maturation in infertile women with PCOS is aimed to determine the effect of apigenin on serum levels of sex hormones and gonadotropins, inflammatory factors and OS indexes in ovarian tissue of PCOS control group.
Effects of the total flavonoid extracts and the monomers of Daphne genkwa on CYP2C8 activity
Published in Xenobiotica, 2022
Qiaoyu Hou, Yanzhi Liu, Xueting Xing, Shuo Li, Jiaqi Li, Wen Qian, Changqing Yang, Hanhan Li
Moreover, VDI values of each monomer were calculated to predict the potential inhibition in vivo. Generally, the VDI cut-off value will be different for different sites of interaction. The VDI cut-off value for enzymes present in the intestine, such as CYP3A, was 2 L; and for enzymes present mainly in the liver, such as CYP2C8, the VDI cut-off value was 5 L (Aaaa and Rff 2019). Moreover, the European average apigenin intake is 3 ± 1mg/day, using the food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database; while in China, the daily intake level of apigenin is 4.23 mg/day (Wang et al. 2019). If according to the Chinese recommended daily dose and the IC50 value of apigenin (7.27 μM) in our results, the VDI value of apigenin for CYP2C8 was 2.15 L (< 5 L) calculated by Eq. (1), which indicated that apigenin generally would not affect the metabolic activity of CYP2C8. However, apigenin was commonly found in many foods and herbs. When taking foods or herbs containing high apigenin until the amount of apigenin consumed by the human body is greater than 9.28 mg/d, it will inhibit the enzyme activity of CYP2C8. Therefore, when taking drugs mainly metabolised by CYP2C8, we should control the intake of foods or herbs with high apigenin content. At present, there is no report about the acceptable daily intake of luteolin, hydroxy-genkwanin, and genkwanin, so the VDI value for these three monomers cannot be inferred by IC50.