Apigenin is a natural flavonoid found primarily in parsley, celery, chamomile, and citrus fruits—especially lemon peel. It has attracted considerable interest in recent years as a Anti-inflammatories, Neuroprotective, Anxiety reliever and also in adjuvant oncological therapy. Below we summarize the clinical and preclinical study situation together, explain why natural apigenin from lemon extract is preferable to synthetic and why Piperine is indispensable as a bioenhancer.

1. Possible therapeutic use

1.1 Anti-inflammatory

• mechanismApigenin inhibits the activation of the transcription factor NF-κB and reduces the expression of pro-inflammatory cytokines (e.g., IL-1β, IL-6, TNF-α) in cell lines and animal models. In a mouse model of ulcerative colitis, apigenin significantly reduced colon length, decreased histological inflammatory damage, and normalized MPO (myeloperoxidase) activity.

1.2 Antitumor effects

• In vitroApigenin induces apoptosis in various cancer cell lines (e.g., colon, breast, and prostate cancer) via activation of Caspase-3/-9 and inhibition of PI3K/Akt as well as MAPK signaling pathways.
• In vivoIn murine xenograft models, apigenin reduced tumor volume by up to 60% without significant toxicity.

1.3 Neuroprotection &cognitive effects

• Apigenin has demonstrated significant neuroprotective effects in numerous preclinical models, which can be explained by antioxidant, anti-inflammatory, and signal-modulating mechanisms. Recent studies impressively confirm this:
• Apigenin acts as a free radical scavenger and increases the activity of endogenous antioxidants such as superoxide dismutase (SOD) and catalase (CAT), while lowering malondialdehyde (MDA)—a biomarker for lipid peroxidation. In an Alzheimer's disease model in rats, apigenin (50 mg/kg, oral) reduced MDA levels by 45% and significantly increased SOD and CAT activity by approximately 60% each compared to the control group (see [reference]). https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz.70223 ).
• Apigenin inhibits microglial activation and reduces the expression of pro-inflammatory cytokines as well as the activation of the NF-κB signaling pathway. In a mouse model of Parkinson's disease, apigenin (25 mg/kg) reduced microglial markers by 35% and IL-1β by 50% in the striatum (see [reference]). https://pmc.ncbi.nlm.nih.gov/articles/PMC11084463/ ).
• Apigenin prevents apoptosis of dopaminergic neurons by inhibiting caspase-3/-9 and increasing Bcl-2/Bax. In an ischemic stroke model, apigenin (20 mg/kg) reduced the neuronal apoptosis rate by 40% and reduced infarct volume by 30% (see [reference]). https://www.boragurer.com/wp-content/uploads/2024/01/A74.pdf ).
• Apigenin activates the cAMP/CREB/BDNF axis, improving cognition and neuronal plasticity. Kim et al. found in a memory test that apigenin (10 mg/kg, oral) increased BDNF expression in the hippocampus by 50% and significantly improved spatial learning (see [reference]). https://www.sciencedirect.com/science/article/pii/S2667242124000897 ).
• Apigenin increases the activity of antioxidant enzymes (SOD, catalase) in rat models and protects against glutamate-induced neurotoxicity (see [reference]). https://pmc.ncbi.nlm.nih.gov/articles/PMC6472148/

1.4 Sleep Promotion

· Apigenin promotes sleep primarily through its binding to GABA.<sub>A</sub&It inhibits G-receptors and excitatory signaling pathways – similar to, though considerably milder than, benzodiazepines. Several animal and human epidemiological studies support its sedative effect.

• In a large-scale observational study from 2020, a higher dietary intake of apigenin (mainly from citrus fruit peels) correlated significantly with better subjective sleep quality (Pittsburgh Sleep Quality Index) and shorter sleep onset time (see below). https://www.researchgate.net/publication/378541330_Apigenin_a_natural_molecule_at_the_intersection_of_sleep_and_aging )
• In a mouse model, apigenin reduced both sleep latency and the number of waking periods, and also significantly increased total sleep time (see [reference]). https://pmc.ncbi.nlm.nih.gov/articles/PMC10929570/).

2. Natural apigenin from lemon extract vs. synthetic apigenin

1. Synergy effects
• Lemon extract contains, in addition to apigenin, also Hesperidin, Eriocitrin, Vitamin C and essential oils, which together Antioxidant capacity and Anti-inflammatory enhance (modulation of phase I/II enzymes); cf. https://www.sciencedirect.com/science/article/pii/S0002916522039144
2. Improved metabolism
• Natural apigenin is often found as Apigenin-7-O-glucoside which is more soluble in aqueous environments and is metabolized more slowly. This results in more stable plasma mirrors compared to aglycones, synthetic apigenin (cf. https://onlinelibrary.wiley.com/doi/10.1155/2019/7010467 )
3. purity
• Our lemon extract is produced using CO₂ extraction obtained (no solvent residues), whereas synthetic apigenin is often obtained in multi-step chemical syntheses. solvent and Protection groups requires, which are difficult to remove and can leave residues (see above). https://www.researchgate.net/publication/383212298_A_comprehensive_review_of_apigenin_a_dietary_flavonoid_biological_sources_nutraceutical_prospects_chemistry_and_pharmacological_insights_and_health_benefits )

3. Bioavailability &Piperine as an effective bioenhancer

Despite its promising efficacy profile, apigenin hydrophob and is taken orally rapidly glucuronidated and sulfated, so that the Plasma concentrations Keep low (bioavailability ~30%) and that Tmax is reached after 0.5–2.5 hours. Half-life The average half-life in plasma is 2.5 hours, which means rapid elimination and a frequent dosing necessitates.

Source: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.681477/full

Therefore, apigenin should always be supplemented with piperine from black pepper extract as a bioenhancer:

• mechanismPiperine inhibits UDP-glucuronosyltransferases and Cytochrome P450 isoenzymes (e.g. CYP3A4) as well as the P-glycoprotein transporter, which causes the Metabolism and elimination is slowed down by apigenin.
• Study certificatePiperine increased the bioavailability of various phytochemicals by 30–200% (e.g., curcumin) and, in preliminary studies, increased the oral AUC of apigenin in animal models by approximately 100% (see [reference]). https://pmc.ncbi.nlm.nih.gov/articles/PMC3634921/ )