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| Vitamin like substance. Found in cereals, nuts and legumes. Inositol hexaphosphate (IP6) is a dietary component that constitutes approximately 1 to 5% of the weight of most cereals, nuts, oil seeds, legumes, and grains [1, 2]. In particular, approximately 9.5 to 14.5% of the weight of rice bran is composed of IP6. IP6 (inositol hexaphosphate) — also called myo-inositol hexakisphosphate, InsP6, phytic acid, or phytate, is a naturally occurring highly phosphorylated inositol carbohydrate abundant in cereal grains, legumes, nuts, seeds, and rice bran and also present at lower concentrations in mammalian cells. It is formally classified as a dietary phytochemical / polyphosphorylated inositol and is marketed as a dietary supplement rather than an approved anticancer drug. Standard abbreviations include IP6 and InsP6. Its unusually high negative charge gives it strong multivalent-cation binding properties, particularly toward iron, zinc, calcium, and magnesium. Experimental anticancer effects are broad but predominantly preclinical, and the extracellular millimolar concentrations commonly used in cancer-cell experiments are far above measured circulating human concentrations. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral IP6 is measurably absorbed in humans but systemic exposure is very low. Human studies report basal plasma concentrations around 0.07 mg/L during an IP6-poor diet and approximately 0.26 mg/L during a normal IP6-containing diet, with a plasma maximum occurring roughly 4 hours after an oral dose. IP6 is highly charged, undergoes gastrointestinal interactions with minerals, and can be dephosphorylated to lower inositol phosphates after uptake. Oral exposure therefore does not reproduce the extracellular millimolar concentrations commonly used in cell culture. In-vitro vs systemic exposure relevance: This is a major translational limitation. Many anticancer experiments use approximately 0.5–5 mM IP6, equivalent to roughly 330–3300 mg/L, whereas measured human plasma IP6 is typically well below 1 mg/L. Thus common in-vitro concentrations exceed measured circulating exposure by roughly three to four orders of magnitude. At millimolar concentrations IP6 also strongly chelates cations and can alter culture-medium chemistry, so some reported effects require cautious interpretation. Tissue uptake, local gastrointestinal exposure, and formation of lower inositol phosphates may nevertheless produce biological effects not predicted solely from plasma IP6 concentration. Clinical evidence status: Small human / adjunct use; not established anticancer therapy. The strongest cancer evidence remains cell-culture and animal work. Small randomized or prospective breast-cancer studies of IP6 with myo-inositol and/or topical IP6 during chemotherapy have reported better quality-of-life measures and attenuation of some treatment-associated hematologic or local symptoms, but these trials were small and were not adequate demonstrations of improved tumor response, progression-free survival, or overall survival. IP6 has no established regulatory approval for cancer treatment. A separate long-term oral IP6 study in superficial siderosis is registered but remains listed as not yet recruiting and does not establish efficacy. The principal practical safety constraint is mineral chelation: high phytate exposure can reduce iron and zinc absorption, particularly when nutritional status is marginal. Caution is also appropriate with significant iron deficiency and with anticoagulant therapy because antiplatelet effects have been reported. IP6 Cancer-Relevant Mechanisms
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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] |
| 7714- | IP6, | ACNs, | Enhanced absorption of anthocyanins after oral administration of phytic acid in rats and humans |
| - | 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
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