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| Flavonoids — a large class of plant polyphenols (natural products) including flavonols (quercetin, kaempferol), flavones (apigenin, luteolin), flavanones (naringenin), isoflavones (genistein), flavan-3-ols (EGCG/catechins), and anthocyanins. Sources: fruits/berries, tea/cocoa, legumes, herbs, and standardized extracts. Primary mechanisms (conceptual rank): Bioavailability / PK relevance: Many flavonoids have low oral bioavailability (rapid phase II conjugation: glucuronidation/sulfation; microbiome-derived metabolites). Plasma free aglycone levels are typically low; tissue effects often reflect metabolites and chronic exposure. In-vitro vs oral exposure: Many “anti-cancer” cytotoxic effects occur at micromolar aglycone concentrations exceeding typical systemic exposure from diet/supplements (high concentration only), unless specialized formulations or local GI exposure is the intent. Clinical evidence status: Broad epidemiology + small human trials for cardiometabolic/inflammatory endpoints; oncology evidence mostly preclinical/adjunct-hypothesis; no class-wide RCT oncology approval. Flavonoids are classified into seven structural classes: 1.flavanones -Nargenin, Naringin, Hesperetin, Isosakuranetin, Eriodictyol, Taxifolin 2.flavonols -Quercetin, Myrcetin, Fisetin, Rutin Morin, Kaempferol 3.chalcones -Butein, Xanthohumol, Isoliquintigenin, Cardamonin, Bavachalone, Xanthohumol, Phloretin 4.flavanols -Catechin, Gallocatechin, Epicatechin, Epigallocatechin-3-galate 5.anthocyanidins -Cyanidin 6.flavones -Chrysin, Apigenin, Luteolin, Vitexin, Orientin, Bacalein, Wogonin, Oroxylin A, Saponarin 7.isoflavonoids -Daidzein, Genistein, Glycitein Flavonoids — a structurally diverse superfamily of plant-derived polyphenolic secondary metabolites characterized broadly by a C6–C3–C6 carbon framework. They are a phytochemical class rather than a single drug or uniform therapeutic modality. Standard abbreviations include flavonoids and Flav; individual subclasses require separate names. Major dietary subclasses are flavonols, flavones, flavanones, flavan-3-ols, anthocyanins and isoflavones; chalcones are also commonly included in the broader flavonoid family. Representative compounds include quercetin, kaempferol, fisetin, apigenin, luteolin, naringenin, hesperetin, catechin, epicatechin, EGCG, cyanidin, genistein and daidzein. Principal sources include fruits, berries, tea, cocoa, citrus, legumes, herbs and vegetables. Because flavonoids differ markedly in structure, metabolism and target selectivity, class-level statements describe recurring patterns rather than effects shared uniformly by every compound. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral pharmacokinetics vary substantially by subclass, glycosylation pattern, food matrix and intestinal microbiota. Most absorbed flavonoids undergo extensive intestinal and hepatic glucuronidation, sulfation and methylation, while unabsorbed material is converted by the microbiome into smaller phenolic metabolites. Circulating exposure therefore consists predominantly of conjugated and microbial metabolites rather than the free aglycones commonly used in laboratory experiments. Certain flavonoids can also affect drug transporters or CYP-mediated metabolism, but the clinical significance is compound-, dose- and medication-dependent. In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM free aglycone, whereas normal dietary intake commonly produces much lower concentrations of unconjugated parent compound in plasma. Consequently, direct kinase inhibition, mitochondrial toxicity, apoptosis and ferroptosis observed at high micromolar concentrations may not be systemically achievable through ordinary foods or conventional supplements. Gastrointestinal tissues, concentrated formulations and pharmacologically developed derivatives may experience different exposure conditions. Clinical evidence status: Human evidence is strongest for dietary patterns or standardized flavonoid-rich foods affecting vascular, cardiometabolic and selected cognitive endpoints. Cancer-prevention evidence is primarily observational and subclass-specific, while cancer-treatment evidence remains predominantly preclinical with limited early-phase or adjunct studies involving individual flavonoids. Flavonoids are not approved as a class for treating cancer or Alzheimer’s disease, and class-wide efficacy cannot be inferred from results obtained with one constituent. Flavonoid Mechanistic Profile
TSF: P: 0–30 min R: 30 min–3 hr G: >3 hr Flavonoids and Alzheimer’s disease — dietary flavonoids and flavonoid-rich foods are investigated as supportive neurovascular and neuroprotective exposures rather than established Alzheimer’s disease therapies. The most defensible class-level mechanisms are attenuation of oxidative and inflammatory stress, enhancement of endothelial function and cerebral perfusion, and chronic modulation of synaptic-plasticity signaling. Effects on amyloid-β aggregation, amyloid processing, tau phosphorylation and clearance are primarily preclinical and vary markedly among compounds. Primary mechanisms (ranked):
Bioavailability / PK relevance: Brain exposure is likely mediated largely by circulating conjugates, microbiome-derived phenolic metabolites and indirect vascular or peripheral signaling rather than sustained high concentrations of free parent flavonoids. Blood–brain barrier penetration differs considerably among compounds and metabolites. Clinical evidence status: Observational cohorts associate higher flavonoid intake with slower cognitive decline or reduced dementia risk, and some randomized trials of cocoa flavanols, berries or anthocyanin-rich interventions report modest cognitive or vascular benefits. Results are heterogeneous, and biomarker-confirmed Alzheimer’s disease modification has not been established. Alzheimer’s Disease Mechanistic Profile
TSF: P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| A bioenhancer is an agent capable of enhancing bioavailability and efficacy of a drug with which it is co-administered Query Database for BioEnhancers but the bioenhancers mainly show up under the target notes Bioenhancers - piperine and quercetin are considered bio-enhancers - genistein Piperine act by suppressing P-gp and cytochrome P450 enzymes, which counteract the metabolism of rifampicin via these proteins, thus enhancing the oral bioavailability of rifampicin. It also decreases the intestinal production of glucuronic acid, thus allowing more substances to enter the body in active form. It was found to increase the bioavailability of various drugs from 30% to 200%.[25] Table 1: Published research on bioenhancer effect of piperine with various medicines Drug Studied in Reference Antimicrobial agents Rifampicin In vitro Balakrishnan et al, 2001[11] Isoniazid Rabbits Karan et al, 1998 [12] Pefl oxacin Mountain Gaddi goats Madhukar et al, 2008[13] Tetracycline Rats Atal et al, 1980[14] Sulfadiazine Rats and dogs Atal et al, 1980[14] Oxytetracycline Poultry birds Singh et al, 2005[15] Ampicillin Rabbits Janakiraman and Manavalan, 2008[16] Norfl oxacin Rabbits Janakiraman and Manavalan, 2008 [16] Nevirapine Adult males Kasibhatta et al, 2007 [17] Metronidazole In vitro Singh et al, 2010[18] Analgesics Diclofenac sodium Albino mice Pooja et al, 2007[19] Pentazocine Albino mice Pooja et al, 2007[19] Nimesulide Mice Gupta et al, 1998[20] Antiepileptics Carbamazepine In vitro Pattanaik et al, 2009 [21] Phenytoin Human volunteers Bano et al, 1987[22] Pentobarbitone Rats Majumdar et al, 1990[23] Other drugs Propranolol In vitro Bano et al, 1991 [24] Theophylline In vitro Bano et al, 1991 [24] Nutrients In vitro Pooja et al, 2007 [19 ***Borneol -Borneol is thought to temporarily open tight junctions between endothelial cells, enhancing drug penetration. It may also downregulate efflux transporters such as P-glycoprotein (P-gp), allowing higher intracellular concentrations of co-administered drugs. -presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin Quercetin is found in citrus fruits and is a dual inhibitor of cytochrome P 3A4 (CYP3A4) and P-gp. Table 2: Effect of quercetin pretreatment/co-treatment on pharmacokinetic parameters of different drugs Drugs combined Increase in pharmacokinetic parametera Cmax AUC ABA Verapamil Two fold Two fold SH Diltiazem SH SH Not known Paclitaxel SH SH T wo fold Digoxin 413% 170% Not known Tamoxifen SH SH 59% Compared to drug in question alone. Cmax, peak plasma concentration; AUC, area under the curve; ABA, absolute bioavailability; SH, significantly higher. Another flavonoid, genistein belongs to the isoflavone class of flavonoids. It is a well-known phytoestrogen. The presence of genistein (10 mg/kg) caused an increase in AUC (54.7%) and a decrease in the total plasma clearance (35.2%) after oral administration of paclitaxel at a dose of 30 mg/kg in rats.[37] Naringin is the major flavonoid glycoside found in grapefruit and makes grapefruit juice taste bitter. Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before and after intravenous administration of paclitaxel (3 mg/kg), the AUC was significantly improved (40.8% and 49.1% for naringin doses of 3.3 and 10 mg/kg, respectively).[38 Carum carvi/Cuminum cyminum ( Jeera) Carum carvi seeds are a prized culinary herb. Extracts of its parts increased significantly (25%–300%), the bioavailability of a number of classes of drugs, such as antibiotics, antifungals, antivirals, anticancer, cardiovascular, anti-inflammatory/ antiarthritic, anti-TB, antileprosy, antihistaminic/respiratory disorders, corticosteroids, immunosuppressants, and antiulcers. Such extracts either in the presence or absence of piperine have been found to be highly selective in their bioavailability/bioefficacy-enhancing action.[40] Capmul One of the widely used bioenhancers is Capmul MCM C10, a glyceryl monocaprate, produced from edible fats and oils and is commonly used in lip products. In a study in rats, antibiotic ceftriaxone when given concomitantly with capmul, increased the bioavailability of ceftriaxone by 80%.[41] Nitrile glycoside Nitrite glycoside is a bioenhancer for drugs and nutrients. Novel bioactive nitrile glycosides, niaziridin and niazirin is obtained from the leaves, pods, and bark of Moringa oleifera. [42] An immunoenhancing polysaccharide and niaziminin, having structural requirement to inhibit tumor promoter-induced Epstein–Barr virus activation have been reported from the leaves of Moringa.[43,44] It enhances the bioactivity of commonly used antibiotics, such as rifampicin, tetracycline, and ampicillin, and also facilitate the absorption of drugs, vitamins, and nutrients through the gastrointestinal membrane, thus increasing their bioavailability. [41] Niazirin is another bioactive nitrile glycoside belonging to M. oleifera. [45,46] Process of isolation of nitrite glycoside from M. oleifera has been patented (US 6858588) by Khanuja et al in 2004–2005. [42 Mechanism of Action Of Bioenhancers Bioavailability-enhancing activity of natural compounds from the medicinal plants may be attributed to various mechanisms, such as P-gp inhibition activity by flavone, quercetin, and genistein; [51] inhibition of efflux transporters, such as P-gp and breast cancer resistance protein (BCRP),[52,53] by naringin and sinomenine thus preventing drug resistance; DNA receptor binding, modulation of cell signaling transduction, and inhibition of drug efflux pumps[54-56] ; by stimulating leucine amino peptidase and glycyl–glycine dipeptidase activity, thus modulating the cell membrane dynamics related to passive transport mechanism as seen with piperine [57] ; nonspecific mechanisms, such as increased blood supply to the gastrointestinal tract, decreased hydrochloric acid secretion, preventing breakdown of some drugs[6] ; and inhibition of metabolic enzymes participating in the biotransformation of drugs, thus preventing inactivation and elimination of drugs and thereby, increasing their bioavailability. [57-5] |
| 2642- | Flav, | QC, | Api, | KaempF, | MCT | In Vitro–In Vivo Study of the Impact of Excipient Emulsions on the Bioavailability and Antioxidant Activity of Flavonoids: Influence of the Carrier Oil Type |
| - | in-vitro, | Nor, | NA | - | in-vivo, | Nor, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:227 Target#:1310 State#:% Dir#:%
wNotes=0 sortOrder:rid,rpid