In mice and rats recovering from strokes, apigenin glucopyranoside (a subtype of apigenin) improved neurological outcomes and reduced brain cell death [ 35]. Reducing Blood Sugar Levels As for the safety of chamomile, there have been reports of allergic reactions as well as interactions between chamomile and cyclosporine and warfarin, which can cause serious consequences [ 26]. 7. Pharmacological Activities of Apigenin Firstly, the results from Huh and colleagues ( 13) suggest that Apigenin stimulates hair growth via the downregulation of the TGF-beta1gene. Secondly, Apigenin may be effective at treating inflammatory skin conditions and has a natural UV-protective effect. Additionally, research has shown Apigenin to improve the skin’s extrinsic immunity ( 14). Improves Heart Health We are now able to achieve high intakes of this health-boosting antioxidant via supplementation. This enables you to attain the benefits of this flavonoid without stressing about dietary intake via food sources. Flavonoids are a class of naturally occurring phytochemicals in plant tissues. They play a protective role in plants against pathogens and sunlight radiation. They also help attract pollinators and regulate plant metabolism. Apigenin Benefits

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The anti-diabetic properties of apigenin may be attributed to its capacity to inhibit α-glucosidase activity, increase secretion of insulin [ 107], to interact with and neutralize reactive oxygen species (ROS) in the cell [ 108], which together contribute to the prevention of diabetic complications [ 109]. Apigenin has also shown the ability to supply moderate nitric oxide (NO) to endothelial cells, thereby limiting the risk of endothelial cell injury and dysfunction from hyperglycemia [ 109]. Wang M, Firrman J, Liu L, Yam K A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota. Biomed Res Int. (2019) Kerdar T, Rabienejad N, Alikhani Y, Moradkhani S, Dastan D Clinical, in vitro and phytochemical, studies of Scrophularia striata mouthwash on chronic periodontitis disease. J Ethnopharmacol. (2019-Jul-15) The absorbed apigenin may go through extensive Phase I and Phase II metabolism [ 17]. In the rat liver, metabolism of apigenin was found to involve Phase I Enzymes in the presence of NADPH (nicotinamide adenine dinucleotide phosphate), P450 (cytochrome P450 enzymes), or FMO (flavin-containing monooxygenase) [ 4]. Phase II biotransformation of apigenin involves both enteric and enterohepatic cycling [ 60]. The conjugation reactions glucuronidation and sulfation are the essential phase II metabolic pathways of apigenin [ 4]. In both rats and humans, apigenin has been reported to produce major metabolites of glucuronidated and sulfated conjugates [ 63]. The major hepatic metabolite of apigenin is luteolin [ 59]. The absorbed apigenin in blood circulation and tissues is in the form of glucuronide, sulfate conjugates, or luteolin [ 4]. There were three β-monoglucuronides that appeared after a glucuronidation reaction, while only one product appeared after a sulfation reaction [ 4]. In human hepatic cell line, Hep G2, as well as intestinal cell line, Caco-2, apigenin-induced phase II detoxifying enzyme UDP-glucuronosyltransferase UGT1A1 [ 64, 65]. In addition, glucuronidation reactions also occur in the intestine, and intestinal disposition may be more important than hepatic disposition in the first-pass metabolism of apigenin [ 63]. 5.4. Excretion Excretion of apigenin after oral intake through feces is a good indication of the phenomenon that dietary apigenin is available for metabolism by the gut microbiota. In one of the aforementioned experiments in Section 5.1 using rats, after a single oral administration of radiolabeled apigenin, 51.0% of the radioactivity was recovered in urine and 12.0% in feces within 10 days. In the same research, it was discovered that sex and age of the rats affected apigenin conjugates eliminated via the urinary route [ 59]. That research also concluded that apigenin has a slow metabolism and a slow elimination phase. Thus, this flavonoid possibly accumulates in the body [ 59]. 5.5. Apigenin Glycosides

Ribeiro RC, Silva EM, Carvalho CM, Miranda MEDSNG, Portela MB, Amaral CM Characterization and Anti-Caries Effect of an Experimental Adhesive Containing Natural Antimicrobial Agents. J Adhes Dent. (2021-Dec-03) Borges G, Fong RY, Ensunsa JL, Kimball J, Medici V, Ottaviani JI, Crozier A Absorption, distribution, metabolism and excretion of apigenin and its glycosides in healthy male adults. Free Radic Biol Med. (2022-May-20) The reported biological functions of apigenin include anti-oxidant, anti-mutagenic, anti-carcinogenic, anti-inflammatory, anti-proliferative, and anti-progression [ 9]. Apigenin is a moderate anti-oxidant compound because the double bond at the 2,3 carbon makes the structure more reactive, despite the absence of the hydroxyl group at position 3 and a catechol structure in the B-ring [ 83, In the study conducted by Li and others [ 101], the effects of apigenin on lipopolysaccharide (LPS)-induced depressive-like behavior in mice model were examined. Tested animals were pre-treated with 25 mg/kg or 50 mg/kg of apigenin or 20 mg/kg of fluoxetine once daily for seven days. The use of apigenin prevented the abnormal behavior induced by LPS, attenuated production of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). What is more, the authors found that apigenin suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Apigenin, at a dose of 50 mg/kg, reversed the depressive-like behavior induced by tumor necrosis factor-α without altering the locomotor activity. They concluded that, due to its anti-inflammatory properties, apigenin is characterized by antidepressant-like properties in LPS-treated mice. Wei Li, Akhilesh K Pandey, Xiangling Yin, Jau-Jiin Chen, Douglas M Stocco, Paula Grammas, Xingjia Wang Effects of apigenin on steroidogenesis and steroidogenic acute regulatory gene expression in mouse Leydig cells J Nutr Biochem. (2011 Mar)

Introduction

Dried parsley has been reported to have the highest apigenin content out of all foods, at 45 mg/g, whereas Celery's apigenin content is much lower at 0.7mg/g from seeds and 0.2 mg/g from Chinese Celery. Additionally, Chamomile is often regarded as a powerful apigenin dense flower, especially when drank in tea form, containing 3 to 5 mg/g. Apigenin Benefits Our team includes licensed nutritionists and dietitians, certified health education specialists, as well as certified strength and conditioning specialists, personal trainers and corrective exercise specialists. Our team aims to be not only thorough with its research, but also objective and unbiased. All the current research suggests that Apigenin is safe, even at doses exceeding what you would usually require through diet alone. However, if you experience any sort of digestive issues or irritations following ingesting, you should stop using the product. Speak to a healthcare professional before using Apigenin to treat a condition. Can women take Apigenin? Demystify scientific studies. Develop the skill to sift through the jargon and make empowered decisions for your health. Lin CM, Chen CT, Lee HH, Lin JK Prevention of cellular ROS damage by isovitexin and related flavonoids. Planta Med. (2002-Apr)

Julie A Ross, Christine M Kasum Dietary flavonoids: bioavailability, metabolic effects, and safety Annu Rev Nutr. (2002) Power Body Nutrition Ltd.Unit 11 Chessingham Park, Common Road, Dunnington,York, YO19 5SE, (+44) 01904 486 330 To demonstrate the cardioprotective effects of apigenin, the pathologic changes shown in diabetic cardiomyopathy-induced mice (i.e., enhanced cardiac dysfunction, fibrosis, overaccumulation of 4-hydroxynonenal followed by downregulation of Bcl2, GPx, and SOD, upregulation of MDA, cleaved caspase3, and pro-apoptotic protein Bax, and contribution to the translocation of NF-kappaB) could be reversed by treatment with apigenin in vivo [ 111]. Apigenin (20 mg/kg) administered to male albino Wistar rats improved renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-beta1, fibronectin, and type IV collagen) [ 82]. Mice with high NAD+ levels are better protected against obesity, while those with low NAD+ levels are more likely to be obese. Apigenin increased NAD+ levels and benefitted glucose and fat regulation in obese mice [ 10]. Cancer is a disease where cells grow uncontrollably and spread to other parts of the body. Chemotherapy is promoted as the best way to manage and kill cancer cells, despite its undesirable side effects. Therefore, scientists are testing and trialling compounds, like Apigenin, to treat various forms of this condition.Two clinical trials testing an apigenin-containing extract on the same population and some animal and cell-based research are insufficient to support the use of apigenin for anxiety and depression until more clinical research is conducted. 2) Skin Health Apigenin is a flavonoid with potent antioxidant and anti-inflammatory properties. In fact, a recent study found Apigenin to have higher antioxidant properties than any other flavonoid ( 1). Most of Apigenin's benefits are accredited to these qualities, as reducing oxidative stress and inflammation on a cellular level leads to numerous health benefits, including a greater sense of wellbeing, enhanced muscular recovery and delayed development of chronic diseases, such as dementia and cardiovascular disease. 9 of the most important health benefits associated with Apigenin intake will be discussed in the Apigenin Benefits Review section. Foods rich in Apigenin There is data to suggest that Apigenin supplementation could have beneficial effects on testosterone levels, which can improve cognitive and physical performance. One study published in 2011 showed Apigenin to significantly increase testosterone production in mice ( 2). Although this study was performed in mice, it is important to highlight that humans and mice are both mammals with a similar biological makeup. Therefore although the results are not directly translatable, this study does bring great promise, but human trials are needed for confirmation. Phenol-Explorer comprise the first comprehensive web-based open-access database on the content of polyphenol in foods; further updates include data on pharmacokinetic and metabolites, the effect of food processing, and cooking [ 157, 158]. The data were collected from peer-reviewed scientific publications, and evaluated before they were aggregated to produce final representative mean content values. To date, the Phenol-Explorer data on apigenin were present for apigenin and derived forms (i.e., apigenin 6- C-glucoside, apigenin 7- O-glucuronide, apigenin 6,8- C-arabinoside- C-glucoside, apigenin 7- O-(6″-malonyl-apiosyl-glucoside). For apigenin, the data encompass the following food groups and subgroups: alcoholic beverages, fruit and vegetable oils, herbs, nuts, and vegetables (i.e., leaf vegetables, fruit vegetables, root vegetables, onion-family vegetables). For example, within the fruit and vegetable oils, for extra virgin olive oil, a mean content of 1.17 mg/100 g FW was reported (produced from 17 original content values extracted from three different publications); for refined olive oil, 0.03 mg/100 g FW (produced from three original content values extracted from one publication); for virgin olive oil, 0.10 mg/100 g FW (produced from 69 original content values extracted from six publications) [ 152].