Isorhamnetin

The broadest and most in-vivo signal. Isolated isorhamnetin given to mice for eight weeks after aortic banding blunted pressure-overload cardiac hypertrophy and fibrosis, an effect traced to blocking PI3K–AKT signaling ^{9Reference 9Gao L et al. · 2017AnimalIsorhamnetin protects against cardiac hypertrophy through blocking PI3K–AKT pathway — mouse aortic-banding modelView study →}.

In isolated rat hearts it reduced ischemia-reperfusion infarct size and marker-enzyme release (LDH, CK) dose-dependently, limiting cardiomyocyte apoptosis and oxidative stress (↑Bcl-2, ↓Bax/caspase-3, ↓MDA) ^{10Reference 10Xu Y et al. · 2020AnimalCardioprotective effect of isorhamnetin against myocardial ischemia reperfusion (I/R) injury in isolated rat heart through attenuation of apoptosis — rat modelView study →}.

At the vessel wall it protected TNF-α-injured endothelial cells (HUVECs), cutting apoptosis and the adhesion molecules ICAM-1, VCAM-1 and E-selectin via NF-κB suppression while restoring eNOS ^{8Reference 8Chen TL et al. · 2015In vitroProtective effects of isorhamnetin on apoptosis and inflammation in TNF-α-induced HUVECs injury — in vitroView study →}.

The pharmacological review catalogues further anti-atherosclerotic and anti-thrombotic actions ^{1Reference 1Gong G et al. · 2020ReviewIsorhamnetin: A review of pharmacological effects — reviewView study →}.

Gap: every result is cell or rodent; there is no human cardiovascular trial, and the doses were not bioavailability-matched to what oral intake achieves.

A consistent mechanistic through-line: isolated isorhamnetin dampens NF-κB-driven inflammation. In LPS-challenged mice it lowered TNF-α, IL-1β and IL-6 and reduced tissue injury by downregulating NF-κB signaling ^{12Reference 12Li Y et al. · 2016In vitroIsorhamnetin ameliorates LPS-induced inflammatory response through downregulation of NF-κB signaling — in vitro and mouse modelView study →}, and in an LPS acute-lung-injury model it attenuated lung edema, MPO activity and cytokine release (also implicating mTOR) ^{14Reference 14Yang B et al. · 2022AnimalIsorhamnetin alleviates lipopolysaccharide-induced acute lung injury by inhibiting mTOR signaling pathway — mouse modelView study →}. The same NF-κB suppression underlies its endothelial protection ^{8Reference 8Chen TL et al. · 2015In vitroProtective effects of isorhamnetin on apoptosis and inflammation in TNF-α-induced HUVECs injury — in vitroView study →}.

Gap: rodent and cell models only; the anti-inflammatory doses have no human counterpart, and NF-κB inhibition is a shared flavonol mechanism rather than something specific to isorhamnetin.

Isolated isorhamnetin promotes glucose disposal and opposes adiposity in mechanistic models. In cultured myotubes it increased glucose uptake by translocating GLUT4 — notably through the JAK2/STAT pathway, a different route from quercetin’s CaMKKβ/AMPK, and active at low-nanomolar concentrations ^{7Reference 7Jiang H et al. · 2019In vitroQuercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes — in vitroView study →}. Dedicated reviews summarize anti-diabetic actions (aldose-reductase inhibition, improved insulin signaling, protection against diabetic complications) ^{2Reference 2Kalai FZ et al. · 2022In vitroEffects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis — reviewView study →} and anti-obesity effects (suppressed adipogenesis, PPARγ modulation) ^{3Reference 3González-Arceo M et al. · 2022ReviewAnti-Obesity Effects of Isorhamnetin and Isorhamnetin Conjugates — reviewView study →}.

Gap: the evidence is cell-based or review-level; there are no clinical glucose or weight outcomes for the isolated molecule.

Isolated isorhamnetin protects the liver across injury models. In a diet-induced NASH mouse it reduced steatosis and fibrosis at 50 mg/kg — cutting hepatic triglyceride and collagen by downregulating lipogenic (SREBP1c/FAS/ACC1) and fibrogenic (TGF-β/collagen-I) programs ^{11Reference 11Ganbold M et al. · 2019AnimalIsorhamnetin Alleviates Steatosis and Fibrosis in Mice with Nonalcoholic Steatohepatitis — mouse modelView study →}. In a separate mouse model of chemical liver injury it lowered transaminases and inflammatory cytokines and regulated apoptosis/autophagy via the P38/PPAR-α pathway ^{5Reference 5Lu X et al. · 2018AnimalIsorhamnetin: A hepatoprotective flavonoid inhibits apoptosis and autophagy via P38/PPAR-α pathway in mice — mouse modelView study →}.

Gap: in-vivo but single-laboratory rodent work with no human data; the NASH finding awaits independent replication.

The broadest but thinnest signal. Isolated isorhamnetin induces apoptosis and cell-cycle arrest across cultured tumor lines: in human bladder-cancer cells it triggered ROS-dependent G2/M arrest and both intrinsic and extrinsic apoptosis through AMPK activation ^{13Reference 13Park C et al. · 2019In vitroIsorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells — in vitroView study →}, and a 2024 review catalogues similar in-vitro activity (AMPK/mTOR, PI3K-Akt and EMT effects) in breast, gastric, colon and lung lines ^{4Reference 4Lei J et al. · 2024In vitroIsorhamnetin: what is the in vitro evidence for its antitumor potential and beyond? — reviewView study →}.

Gap: almost entirely in-vitro at concentrations the poor oral bioavailability makes hard to reach systemically; in-vivo tumor data are sparse and there are no human oncology data ^{4Reference 4Lei J et al. · 2024In vitroIsorhamnetin: what is the in vitro evidence for its antitumor potential and beyond? — reviewView study →}.