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| Isoquercitrin - Quercetin-3-O-Glucoside Alternative Names: Isoquercetin, quercetin-3-O-glucoside, quercetin-3-O-β-D-glucopyranoside, Q3G, IQ Type: Flavonol glycoside / quercetin glycoside / natural phytochemical Sources: Naturally present in numerous medicinal plants, fruits, vegetables, and plant-derived foods. Isoquercitrin can also be produced from rutin by enzymatic removal of the rhamnose residue. Function: Isoquercitrin is a bioactive quercetin glycoside with antioxidant, anti-inflammatory, anticancer, metabolic, and neuroprotective effects. Reported mechanisms include modulation of Nrf2/ARE, NF-κB, JAK/STAT3, PI3K/AKT, MAPK, AMPK, Wnt signaling, oxidative stress, and programmed cell death. Cancer: Preclinical studies demonstrate inhibition of cancer-cell proliferation, survival, migration, and tumor-associated signaling together with induction of apoptosis and modulation of oxidative stress. Anticancer mechanisms include regulation of Wnt, MAPK, JAK/STAT3, PI3K/AKT, NF-κB, and related signaling pathways. Alzheimer's Disease: Preclinical studies indicate neuroprotective activity, including improved learning and memory in amyloid-β-induced models and reduction of oxidative and inflammatory neuronal injury. Isoquercitrin — also called isoquercetin, quercetin-3-O-glucoside, quercetin-3-O-β-D-glucopyranoside, Q3G, IQ, or ISQ, is a naturally occurring flavonol glycoside consisting of quercetin conjugated to glucose at the 3-O position. It is a dietary phytochemical and quercetin derivative found in many fruits, vegetables, medicinal plants, and plant-derived foods; it can also be produced from rutin by enzymatic removal of rhamnose. Isoquercitrin is generally absorbed more efficiently than quercetin aglycone or rutin, but circulating intact isoquercitrin is limited because intestinal and hepatic metabolism rapidly produces quercetin glucuronide, sulfate, methylated, and other metabolites. Enzymatically modified isoquercitrin and α-glycosyl isoquercitrin are related higher-solubility preparations but should not be treated as pharmacokinetically identical to native isoquercitrin. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral isoquercitrin is absorbed substantially better than rutin and is rapidly processed in the intestine and liver. Human administration of quercetin-3-glucoside produces plasma quercetin-derived conjugates with peak total quercetin concentrations in the low-micromolar range; intact glucoside is essentially absent or present only in very small quantities in plasma. Therefore, systemic biological activity after oral administration is likely mediated substantially by quercetin conjugates and downstream metabolites rather than prolonged exposure to intact isoquercitrin. Enzymatic glycosylation can further improve solubility and systemic exposure, but EMIQ/AGIQ should be distinguished from native isoquercitrin. In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 20–200 µM isoquercitrin, whereas human oral exposure produces predominantly quercetin metabolites at substantially lower free/intact isoquercitrin concentrations. Consequently, direct tumor-cell effects demonstrated at tens to hundreds of micromolar intact isoquercitrin may exceed realistically achievable systemic exposure after conventional oral dosing. Lower-micromolar or metabolite-mediated effects have greater translational plausibility. The bladder is a potential special context because urinary exposure to flavonoid metabolites may differ from plasma exposure, but this has not established clinical anticancer efficacy. Clinical evidence status: Cancer: preclinical only; cell-culture and xenograft evidence exists for hepatocellular, bladder, pancreatic, colorectal, melanoma, osteosarcoma, esophageal and other tumor models, but there is no established anticancer indication or convincing human oncology trial evidence. Human studies of isoquercitrin-related preparations have primarily evaluated cardiovascular, antioxidant, exercise/nutrition, or allergic outcomes rather than cancer. Alzheimer’s disease: preclinical only, with cell and rodent evidence for anti-amyloidogenic, antioxidant, mitochondrial-protective, and cognitive effects; no established human AD efficacy. Regulatory use should not be confused with therapeutic validation: Health Canada lists isoquercitrin as an approved NHP ingredient, while α-glycosyl isoquercitrin has FDA GRAS-notice status for specified food uses; neither status represents approval as a cancer or Alzheimer treatment. Isoquercitrin Cancer-Relevant Mechanisms
TSF: P: 0–30 min R: 30 min–3 hr G: >3 hr Alzheimer’s disease relevance: Isoquercitrin has meaningful but entirely preclinical AD-related evidence. Reported effects include direct inhibition of β- and γ-secretase activity, ↓ Aβ aggregation with enhanced disaggregation in cell-free systems, ↓ amyloidogenic proteins including β-secretase and presenilins in animal models, ↓ neuronal oxidative stress, preservation of mitochondrial function, ↓ apoptosis, and improved learning and memory in Aβ- and streptozotocin-based rodent models. These findings support an anti-amyloidogenic and neuroprotective research classification, but there is currently no convincing human clinical evidence demonstrating prevention or treatment of Alzheimer’s disease. Translation constraint: Most AD evidence uses experimental Aβ25-35 injection, streptozotocin, cell-based amyloid systems, or other simplified models that do not reproduce the full biology of sporadic human AD. Oral metabolism also means that brain exposure to intact isoquercitrin is uncertain and circulating quercetin metabolites may contribute substantially to any systemic effect. Isoquercitrin Alzheimer-Relevant Mechanisms
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| In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+. Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors. In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2). Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways. Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer. Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation. High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses. Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes. |
| - | in-vitro, | AD, | HT22 |
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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