Pinoresinol Diglucoside

Pinoresinol Diglucoside is an orally active lignan with multifunctional bioactivity. Pinoresinol Diglucoside interacts with targets including ALB, HIF1A, GSK3B, BCL2, MARK3, IL6, NF-κB p65, Nrf2, HO-1, and TLR4, and modulates pathways including PI3K-Akt, estrogen, MAPK, Rap1, AKT/mTOR/NF-κB, and TGF-β1/Smads. Pinoresinol Diglucoside regulates osteogenesis, bone resorption, oxidative stress, inflammation, apoptosis, ferroptosis, ferritinophagy, cardiac fibrosis, and vasorelaxation. Pinoresinol Diglucoside can be used for the research of osteoporosis, ischemia/reperfusion-induced brain injury, Alzheimer’s disease, myocardial ischemia-reperfusion injury, chondrodysplasia, diabetic cardiomyopathy, cardiac hypertrophy, hypertension, cisplatin-induced hearing loss, atherosclerotic cardiovascular diseases, and disuse osteoporosis^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]}. In Vitro:Pinoresinol diglucoside (20-80 μM) inhibits RANKL-induced differentiation of RAW264.7 cells into osteoclasts^[3].
Pinoresinol diglucoside (20-80 μM; 3 days) disrupts F-actin ring formation in RANKL-differentiated RAW264.7 osteoclasts, with complete disruption at 80 μM^[3].
Pinoresinol diglucoside (20-80 μM; 3 days) inhibits the expression of osteoclast differentiation-related proteins NFATc1, c-Fos, CTSK, and TRAP in RANKL-differentiated RAW264.7 cells^[3].
Pinoresinol diglucoside (20-80 μM; 3 days) inhibits activation of the NF-κB and AKT-GSK-3β signaling pathways in RANKL-treated RAW264.7 cells^[3].
Pinoresinol diglucoside (80 μM) inhibits RANKL-induced nuclear translocation of p65 in RAW264.7 cells^[3].
Pinoresinol Diglucoside alleviates oxLDL-induced dysfunction in human umbilical vein endothelial cells by restoring SOD activity, eNOS expression, and NO production^[4].
Pinoresinol diglucoside (1 μM) attenuates hypoxia/reperfusion-induced injury in H9c2 cardiomyocytes by reducing oxidative stress, cell damage markers, and apoptosis, promoting cell viability, upregulating miR-142-3p, and downregulating HIF1AN^[5].
Pinoresinol diglucoside (1 μM) has its protective effects against hypoxia/reperfusion-induced injury in H9c2 cardiomyocytes reversed by miR-142-3p overexpression, resulting in elevated oxidative stress, cell damage markers, and apoptosis, and reduced cell viability^[5].
Pinoresinol diglucoside interacts strongly with zebrafish FZD2 and FZD5 in silico, with binding energies of -8.27 kcal/mol and -8.63 kcal/mol, respectively, indicating potential activation of Wnt signaling^[6].
Pinoresinol Diglucoside (2.5-7.5 μg/mL; 24 h) inhibits high glucose-induced cardiac fibrotic responses in H9c2 cells by downregulating the TGF-β1/Smads signaling pathway^[7].
Pinoresinol Diglucoside (2.5-7.5 μg/mL; 48 h) inhibits high glucose-induced EndMT in HUVECs^[7].
Pinoresinol Diglucoside (2.5-7.5 μg/mL; 48 h) inhibits exogenous TGF-β1-induced EndMT in HUVECs^[7].
The inhibitory effect of Pinoresinol Diglucoside (2.5-7.5 μg/mL; 48 h) on high glucose-induced EndMT in HUVECs is abolished by TGF-β1 knockdown, indicating PDG acts via the TGF-β1 pathway^[7].
Pinoresinol diglucoside (25 μM; 24 h) preserves cell viability in HEI-OC1 cells, does not induce oxidative stress alone, and attenuates Cisplatin-induced oxidative stress and cell death in HEI-OC1 cells^[9].
Pinoresinol diglucoside (25 μM; 24 h) downregulates SOCS1 protein expression in ex vivo neonatal mouse basilar membranes, and attenuates cCisplatin-induced SOCS1 upregulation in these membranes^[9].
Pinoresinol Diglucoside (PDG) (2.5-7.5 μg/mL; 2 h pre-incubation, 24 h with ISO stimulation) inhibits isoproterenol-induced cardiac hypertrophy and inflammation in neonatal rat ventricular cardiomyocytes by reducing hypertrophic biomarker and pro-inflammatory cytokine mRNA expression^[10].
Pinoresinol Diglucoside (PDG) (2.5-7.5 μg/mL; 24 h with PE stimulation) inhibits phenylephrine-induced activation of the AKT/mTOR/NF-κB signaling pathway in neonatal rat ventricular cardiomyocytes, reducing cardiac hypertrophy-associated protein expression^[10].
Pinoresinol Diglucoside (2.5-7.5 μg/mL; 24 h) inhibits HG-induced fibrotic responses and downregulates the TGF-β1/Smads signaling pathway in H9c2 cells^[12].
Pinoresinol Diglucoside (2.5-7.5 μg/mL; 48 h) inhibits HG-induced EndMT in HUVECs^[12].
Pinoresinol diglucoside (0.1-1 μM; 60 min pre-incubation + 24 h co-treatment with oxLDL, or 24 h alone) inhibits oxLDL-induced apoptosis in HUVECs, with 1 μM completely abrogating the apoptotic effect and 0.1 μM reducing apoptotic cells to 17.2%^[13].
Pinoresinol diglucoside (1 μM; 60 min pre-incubation + 24 h co-treatment with oxLDL, or 24 h alone) alleviates oxLDL-induced ROS and MDA production in HUVECs, reducing ROS levels by more than 20% compared to oxLDL-only treated cells^[13].
Pinoresinol diglucoside (1 μM; 60 min pre-incubation + 24 h co-treatment with oxLDL, or 24 h alone) reverses oxLDL-induced inhibition of total SOD activity in HUVECs, restoring activity to near control levels^[13].
Pinoresinol diglucoside (1 μM; 60 min pre-incubation + 24 h co-treatment with oxLDL, or 24 h alone) alleviates oxLDL-induced inhibition of NO production and eNOS mRNA expression in HUVECs, fully restoring both parameters to control levels^[13].
Pinoresinol diglucoside (1 μM; 60 min pre-incubation + 24 h co-treatment with oxLDL, or 24 h alone) inhibits oxLDL-induced upregulation of LOX-1, ICAM-1, and NF-κB mRNA and protein expression in HUVECs, essentially abrogating the 1.7- to 3.5-fold upregulation caused by oxLDL^[13].
Pinoresinol diglucoside (1 μM; 60 min pre-incubation + 45 min co-treatment with oxLDL, or 45 min alone) inhibits oxLDL-induced activation of the p38MAPK/NF-κB signaling pathway in HUVECs by reducing phosphorylation of p38MAPK and NF-κB p65^[13].
Pinoresinol diglucoside (PG2) (1 μg/mL; 30 min at 38°C) inhibits β-glucuronidase activity by 80.0% in a cell-free anti-inflammatory assay^[14].
Pinoresinol diglucoside (PG2) (1-1000 μM; 10 min) has an IC₅₀ of 600 μM for DPPH radical scavenging activity in a cell-free assay, with activity increasing at higher concentrations^[14].
Pinoresinol diglucoside (10 nM-10 μM; 3 days) at 1 μM maximally enhances osteogenic differentiation of neonatal mouse calvarial osteoblasts, as measured by ALP activity after 3 days of treatment^[15].
Pinoresinol diglucoside (1 μM; 12-hour SMG exposure for proliferation, apoptosis, oxidative stress, cell cycle assays; 6 days of daily 12-hour SMG exposure for osteogenic differentiation assays) preserves osteogenic differentiation, reduces oxidative stress, enhances proliferation, inhibits apoptosis, and reverses G0/G1 cell cycle arrest in simulated microgravity-exposed neonatal mouse calvarial osteoblasts^[15].
Pinoresinol diglucoside (1 μM; 3 days) maximally enhances alkaline phosphatase activity, a marker of osteogenic differentiation, in neonatal mouse calvarial osteoblasts^[16]. In Vivo:Pinoresinol diglucoside (10 mg/kg/day; p.o.; daily; 3 days) first undergoes deglycosylation to form metabolite M49, followed by in vivo metabolic reactions including furan-ring opening, demethoxylation, glucuronidation, and sulfation, and acts via 146 overlapping osteoporosis-related targets including BCL2, MARK3, GSK3B, HIF1A, ALB, and IL6 to modulate pathways including PI3K-Akt and estrogen signaling for potential anti-osteoporosis effects^[1].
Pinoresinol diglucoside (5-10 mg/kg; i.v., caudal vein; single dose; 1 hour before MCAO induction) exerts dose-dependent neuroprotective effects against mouse MCAO/R-induced brain injury, and modulating anti-inflammatory and antioxidant pathways^[2].
Pinoresinol Diglucoside (5-10 mg/kg; i.v. via caudal vein; single dose 1 h before MCAO) dose-dependently alleviates MCAO/R-induced brain injury in male C57BL/6 mice via inhibiting neuroinflammation through the NF-κB pathway and enhancing antioxidant activity through the Nrf2/HO-1 pathway, with the 10 mg/kg dose producing greater protective effects than the 5 mg/kg dose^[4].
Pinoresinol Diglucoside (5-10 mg/kg; i.g.; daily; 3 weeks) significantly attenuates Aβ₁-42-induced cognitive impairment, neuroinflammation, oxidative stress, and neuronal apoptosis in male BALB/c mice via modulation of the TLR4/NF-κB and Nrf2/HO-1 pathways^[5].
Pinoresinol diglucoside (0.75-3 μM; exposure in culture medium; daily; 7 dpf to 9 dpf) mitigates dexamethasone-induced osteoporosis and chondrodysplasia in larval Danio rerio (zebrafish) by enhancing bone mineralization, correcting skeletal and cartilage malformations, improving motor function, upregulating osteogenesis-related genes, and activating Wnt signaling via interactions with FZD2 and FZD5 receptors^[7].
Pinoresinol diglucoside (1-5 mg/kg/day; i.p.; daily; 8 weeks) dose-dependently alleviates DCM-induced cardiac fibrosis and endothelial-to-mesenchymal transition in db/db mice by downregulating the TGF-β1/Smads signaling pathway, with the 5 mg/kg/day high dose producing the most significant effects^[8].
Pinoresinol diglucoside (25 mg/kg; i.p.; once daily; concurrent with Cisplatin dosing cycles) significantly attenuates Cisplatin-induced ototoxicity in male C57BL/6 mice by preserving cochlear hair cell survival, auditory function, and endocochlear potential, while inhibiting ferroptosis and NCOA4-mediated ferritinophagy via downregulation of SOCS1^[10].
Pinoresinol Diglucoside (2.5-7.5 mg/kg per day; i.p.; daily; 3 weeks) dose-dependently attenuates AAC-induced cardiac hypertrophy in male Sprague Dawley rats, with the 7.5 mg/kg per day dose producing the most significant reduction in cardiac mass indices, hypertrophic biomarkers, fibrosis, inflammation, and activation of the AKT/mTOR/NF-κB signaling pathway^[11].
Pinoresinol Diglucoside (7.5 mg/kg per day; i.p.; daily; 3 weeks) does not produce significant effects on cardiac structure, hypertrophic biomarkers, inflammation, or AKT/mTOR/NF-κB signaling in healthy male Sprague Dawley rats^[11].
Pinoresinol diglucoside (1-5 mg/kg; i.p.; daily; 8 weeks) dose-dependently alleviates diabetic cardiomyopathy-induced cardiac fibrosis in db/db mice by inhibiting endothelial-mesenchymal transition via downregulation of the TGF-β1/Smads signaling pathway^[12].
Pinoresinol Diglucoside (18-72 mg/kg; p.o.; daily; 21 days) effectively counteracts hindlimb unloading-induced bone loss in male C57BL/6J mice, with the 18 mg/kg oral daily dose for 21 days producing the greatest improvements in bone mechanical strength, mineral apposition rate, and markers of bone formation, resorption, oxidative stress, and inflammation^[15].
Pinoresinol Diglucoside (18-72 mg/kg; p.o.; daily; 21 days) effectively counteracts hindlimb unloading-induced bone loss in male C57BL/6J mice, with the 18 mg/kg dose exhibiting optimal efficacy in restoring bone density, microstructure, mechanical strength, and bone metabolism balance^[16].
Pinoresinol Diglucoside (30-100 mg/kg; i.v.; single dose) produces dose-dependent diastolic blood pressure reduction in anesthetized spontaneously hypertensive rats, with decreases ranging from 25 mmHg at 30 mg/kg to 120 mmHg at 100 mg/kg^[17].