Gerritsen ME, Carley WW, Ranges GE, Shen CP, Phan SA, Ligon GF, Perry CA Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. Am J Pathol. (1995-Aug)

In mice, topical apigenin improved skin permeability barrier function by promoting skin cell growth and the production of fatty molecules and antimicrobial proteins. This suggests it may help with conditions characterized by permeability barrier dysfunction such as atopic dermatitis [ 7].

Yiqing Song, JoAnn E Manson, Julie E Buring, Howard D Sesso, Simin Liu Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis J Am Coll Nutr. (2005 Oct)

Li W, Dai RJ, Yu YH, Li L, Wu CM, Luan WW, Meng WW, Zhang XS, Deng YL Antihyperglycemic effect of Cephalotaxus sinensis leaves and GLUT-4 translocation facilitating activity of its flavonoid constituents. Biol Pharm Bull. (2007-Jun) Kawai M, Hirano T, Higa S, Arimitsu J, Maruta M, Kuwahara Y, Ohkawara T, Hagihara K, Yamadori T, Shima Y, Ogata A, Kawase I, Tanaka T Flavonoids and related compounds as anti-allergic substances. Allergol Int. (2007-Jun) Apigenin is a natural compound found in many fruits and vegetables. While its full effects in humans have been barely figured out, there is some preliminary evidence that apigenin can help calm nerves, provide antioxidant effects, and even help fight cancer. What Is Apigenin? Testosterone is respected as one of the most important hormones in the human body, especially in regard to muscle growth, fat loss, energy levels and libido. Unfortunately, as we age and due to lifestyle factors, our production of this male sex hormone begins to decline.Kuo ML, Lee KC, Lin JK Genotoxicities of nitropyrenes and their modulation by apigenin, tannic acid, ellagic acid and indole-3-carbinol in the Salmonella and CHO systems. Mutat Res. (1992-Nov-16) In a clinical trial on 40 women, apigenin cream increased skin density and elasticity while reducing wrinkle length. In cells, it reduced the damage caused by UV radiation [ 6].

Flavonoids that cannot be absorbed from the small intestine, as well as the absorbed flavonoids secreted with bile, will be degraded in the colon by the microbiota [ 66]. Abugri DA, Witola WH Interaction of apigenin-7-O-glucoside with pyrimethamine against growth. J Parasit Dis. (2020-Mar) The anti-mutagenic effect has been reported in in vitro cell models, in vivo experiments, and AMES test using bacterial models showing that apigenin could prevent, inhibit, or reverse chemically induced genotoxicity [ 9, 94– 96]. The anti-carcinogenic effect of apigenin has been widely reported. Apigenin has been found to be protective against multiple types of cancer including breast cancer [ 18], cervical cancer, colon cancer, leukemia (concentrations 0-200 μM or 0.0-54.048 μg/mL) [ 97], lung cancer, prostate cancer (concentrations 0.0-80 μM or 0.0-21.619 μg/mL) [ 98], skin cancer, thyroid cancer, endometrial cancer, neuroblastoma, and adrenocortical cancer [ 9, 10]. Derivatized compounds based on apigenin displayed higher antiproliferative activity in human lung, cervical, hepatocellular liver and breast cancer cell lines than apigenin itself (concentrations 62.5-2000 μg/mL) [ 99].Reverse antibiotics (RA) are chemicals that are ineffective against antibiotic-susceptible bacteria but active against the relevant antibiotic-resistant bacteria [ 112]. RAs can help put a stop to the accumulation of antibiotic resistance by bacteria, because treatment with RA kills the bacteria that have acquired the antibiotic resistance and leaves only the bacteria that possess the original phenotype resistant to RA and susceptible to that antibiotic [ 112]. Apigenin has RA activities against quinolone-resistant S. aureus [ 107]. The minimum inhibitory concentrations (MICs) of apigenin against quinolone-resistant S. aureus strain Mu50 and quinolone-susceptible S. aureus FDA 209P are 4 mg/L and more than 128 mg/L [ 107]. Apigenin was also found to reverse bacterial resistance to cephalosporin ceftazidime in Enterobacter cloacae [ 102]. The MIC of apigenin in ceftazidime-resistant E. cloacae (CREC) was higher than 512 μg/mL, which indicated no inhibitive effects [ 102]. Ceftazidime applied in combination with apigenin showed a synergistic effect with a fractional inhibitory concentration index smaller than 0.01 [ 102]. The 5,7- OH group of A ring and one 4′- OH group of the B ring in apigenin were found important in reversing antimicrobial resistance [ 102]. The significantly enhanced activities of ceftazidime by apigenin may have been the result of peptidoglycan synthesis inhibition, certain β-lactamase enzymes inhibition, and alteration of outer membrane and cytoplasmic membrane permeabilization [ 102].

S E Nielsen, J F Young, B Daneshvar, S T Lauridsen, P Knuthsen, B Sandström, L O Dragsted Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects Br J Nutr. (1999 Jun) Some insight is available on the mechanism of the antibacterial activity of apigenin. It has been previously indicated that the main targets of apigenin on bacteria may be the nucleic acid processing enzymes and cell wall/membrane [ 34, 106]. In a study where apigenin inhibited S. aureus, mode of action was compared to other antibiotics with known mechanism by clustering the treatments based on intracellular metabolites. Apigenin was clustered with rifampicin and norfloxacin which target RNA polymerase, and gyrase and topoisomerase IV, respectively [ 80], which indicates that the target of apigenin could be nucleic acid processing enzymes [ 75]. The target DNA gyrase was also reported in one other study [ 117]. Apigenin affects the D-Alanine: D-Alanine ligase and the type II fatty acid synthetic pathway, both of which are involved in cell membrane/wall synthesis [ 34]. In apigenin-treated E. caccae, the expression of stress response genes and protein chaperone genes were found to be up-regulated, which indicated the overall adverse effects of apigenin on the bacterium [ 34].Since apigenin is widely distributed in food items, and a diet high in flavonoids has been reported with many beneficial health effects, an estimation of the daily intake of apigenin could be useful in the correct interpretation of the relationship between health outcomes and apigenin. Though dietary intake values have been obtained for some individual flavonoids [ 21], when it comes to the flavone, apigenin, relevant research is very limited [ 22, 23]. Higher estimation of daily dietary intake of flavonoids is 1 g as glycosides or 650 mg as aglycones [ 24], while another study estimated an average of only 23 mg/day in adults in the Netherlands [ 12]. In a study around 1990, the mean flavanol and flavone intake among US health professionals was approximately 20-22 mg per day [ 25]. In the aforementioned study in the Netherlands in 1988, most of the average daily intake was attributed to quercetin, about 16 mg/day, and the actual daily intake of apigenin was only about 0.69 mg/day [ 12]. However, another study on the Dutch diet estimated that the average daily intake of apigenin is about 1 mg [ 22]. A similar number, 1.5 ± 4.9 mg/day (range 0-30.3), was reported in a group of female Flemish dietitians [ 23]. A more recent paper provided information on the mean intake of flavonoid compounds in adults in the European Union by country, region, and overall [ 26]. The European average of apigenin intake is 3 ± 1 mg/day using the food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database. The daily intake level of apigenin is 4.23 mg/day in China [ 27], while among middle-aged and older women in the US, it is 0.13–1.35 mg/d [ 28]. This intake value among US women is similar to the reported 0.2-1.3 mg/day among 66,940 married women in a US nurses’ health study from 1984 through 2002 [ 29]. By measuring the intake of apigenin from major dietary sources of flavones in adult Australians, the mean daily intake value was determined to be 0.45 mg/day [ 30]. Separate from its mental and physical performance-enhancing benefits, Apigenin also possesses beauty advantages.