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Safety is an important aspect of dietary components. In general, dietary plants containing flavonoids have not been associated with negative health impact, but they are rather considered to be beneficial. Apigenin is known for its low toxicity [ 9, 11, 43, 44]. Evidence has also shown that a flavonoid-rich diet is inversely associated with cancer risk [ 45– 50]. Therefore, the consumption of flavonoids has been assumed to be safe. Doses as low as 2.5mg have been used to improve sleep. Upper doses are shown to be safe. When to take Apigenin? Efficacy and safety of topical Matricaria chamomilla L. (chamomile) oil for knee osteoarthritis: A randomized controlled clinical trial.
Apigenin can improve your cardiovascular health by reducing inflammation and blood pressure, which are two of the most significant risk factors regarding heart health. This benefit was shown in a study conducted on rats. This study has shown Apigenin to have cardioprotective effects in heart damaged rats. The researchers suggest that this is due to Apigenin's ability to suppress myocardial apoptosis (heart cell death) and inflammation by decreasing the activity of a major inflammatory pathway ( 15). What is the recommended Apigenin dosage? Apigenin may have multiple productive interactions with chemotherapeutic agents through its effects on cellular signaling pathways, and this might be of particular importance in cancer cells that have developed further resistance mechanisms ( Lefort and Blay, 2011). Apigenin has a synergistic effect with the chemotherapeutic agent 5-FU in inducing apoptosis in p53-mutant human colon adenocarcinoma cells ( Zhang et al., 2009). It induces the autophagy mediators LC3-II and Beclin-1 in colorectal carcinoma cells resistant to cisplatin ( Chen et al., 2019). Apigenin also enhances the effect of doxorubicin in chemotherapy-resistant hepatocarcinoma cells, likely by down-regulating the PI3K/Akt pathway ( Ga et al., 2013). Finally, apigenin is thought to down-regulate the PI3K/Akt pathway and in reduce expression of nuclear factor erythroid 2-related factor (a key player in chemoresistance) at the RNA and protein level ( Ga et al., 2013). Combining apigenin with chemotherapeutic drugs may be a worthwhile clinical strategy for the support of cytotoxic action as a chemosensitizer. Author Contributions Taking the higher 4.2g dose and with the density of apigenin being ∼1.5g/ml ( National Center for Biotechnology Information, 2021), this would correlate to a product volume of 2.8ml. The largest commonly used capsules hold 1.37ml of material( Medisca, 2021). Therefore, 2.8ml of apigenin powder (which represents the dose we predict should yield a 5μmol/L plasma concentration of apigenin) would require two large capsules of purified flavone to provide this oral dosage in humans. This is feasible. Apigenin is a naturally occurring flavonoid, most notably found in chamomile and many vegetables, fruits, and medicinal plants. It is known for its numerous health benefits, including anti-inflammatory, antioxidant, and anticancer properties.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. Apigenin is one of the most renowned phenolic compounds with many beneficial properties, and it is available in nutraceutical formulations and dietary supplements. It is worth mentioning again that apigenin exists in plants as glycosides naturally; therefore, the absorption of the apigenin glycosides and the bioavailability after consumption of glycosides are useful information. Nevertheless, such information on apigenin glycosides is rare, and most research done looked into other flavonoids, in particular quercetin [ 66, 67]. In fact, in comparison to the other classes of flavonoids, little is known about the bioavailability of flavones [ 68].
Finally, through its intracellular actions apigenin has effects on cellular survival by altering apoptosis and autophagy pathways. Apigenin-mediated apoptosis involves diverse regulators of cell death. Apigenin suppresses cell proliferation and induces apoptosis in a caspase- and concentration-dependent manner in colorectal HT29, COLO320, DLD-1, and HCT116 cells ( Maeda et al., 2018). Notable effects include the following: i) marked increases in the cleavage of PARP, ii) downregulation of anti-apoptotic Bcl2 proteins (Bcl-xL and Mcl-l) via apigenin-directed inhibition of STAT3 (a Bcl2-activating kinase), iii) increased expression of pro-apoptosis regulators of both the intrinsic (Bax proteins, Cytochrome C, caspases -3,-8, -9) and extrinsic (CHOP, DR5, caspase-8) pathways, iv) increased expression of pro-apoptotic proteins NAG1 and p53, and v) increased expression of the cell cycle inhibitor p21 ( Horinaka et al., 2006; Zhang et al., 2009; Zhong et al., 2010; Ai et al., 2017; Wang and Zhao, 2017; Maeda et al., 2018). As Apigenin is a naturally occurring flavonoid found in common foods, Apigenin is generally safe for both men and women. However, research now suggests that women on hormone replacement therapy shouldn't supplement pure Apigenin as issues are being raised. How much Apigenin for sleep? 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
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From reducing anxiety to improving sleep, enhancing testosterone synthesis to preventing chronic diseases, apigenin has much to offer. In this article, we'll review the top eight benefits of apigenin based on scientific evidence. What is apigenin? SelfDecode has an AI-powered app that allows you to see how Apigenin benefits your personal genetic predispositions. These are all based on clinical trials. The red sad faces indicate an increased likelihood to develop conditions that Apigenin may improve. Several natural bioactive compounds have been implicated in improving learning and memory . Various clinical trials have shown the therapeutic potential of apigenin as a neuroprotective agent. German Pharma have recently released their own Apigenin supplement, that delivers 150mg per serving. What are the Apigenin side effects?
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 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]. Before the discussion of the effects of dietary apigenin on gut bacteria, it is necessary to look at the dietary intake level of apigenin. The distribution of apigenin in the plant kingdom is wide, as it has been found in many vegetables, herbs, and fruits [ 5]. Fresh parsley, vine spinach, celery seed, green celery heart, Chinese celery, and dried oregano are dietary sources with high apigenin content [ 5]. Other plants in which apigenin has been identified include red and white sorghum, rutabagas, oranges, kumquats, onions, wheat sprouts, tea, and cilantro [ 5, 9, 18]. Dried parsley has a particularly high level of apigenin that far exceeds any other vegetables or herbs [ 5]. Chamomile tea, high in apigenin content, is one of the most common sources of apigenin intake from a single ingredient [ 19]. In nature, apigenin is typically found in a glycosylated form, with the tricyclic core structure linked to a sugar moiety through hydroxyl groups ( O-glycosides) or directly to carbon ( C-glycosides). The common apigenin glycosides are apiin, apigenin-7- O-glucoside, apigenin-8- C-glucoside (vitexin), apigenin-6- C-glucoside (isovitexin), apigenin-7- O-neohesperidoside (rhoifolin), and apigenin-6- C-glucoside 8- C-arabinoside (schaftoside) [ 4, 13, 20]. The decomposition for flavonoids depends on the number of substituents in the flavonoid molecule. Hydroxyl groups promote degradation of flavonoids, whereas sugar moiety and methoxyl groups protect flavonoids from degradation during microwave and ultrasonic-assisted extraction [ 33]. Therefore, the glucosides, other than having a higher solubility than the aglycone, are also chemically more stable, which may be one of the reasons why they have enhanced biological activities [ 42]. 4. Safety: Mutagenicity and Hemolysis Tests Apigenin sleep and relaxation benefits are largely accredited to its ability to reduce feelings of anxiety and increase feelings of sedation. This could largely be due to its ability to reduce cortisol levels ( 7).
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This article will now discuss Apigenin's health benefits and provide the evidence that has been put forward by the scientific literature to support these claims. Increase Testosterone Due to its anti-inflammatory properties, Apigenin can reduce discomfort and pain caused by inflammatory issues, such as delayed onset muscle soreness, digestive issues and migraines. Research has shown this compound to reduce the release of cytokines, and it is these molecules that are associated with feelings of pain ( 11). Fights Against Cancer
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