Flavonoid quercetin and its glucuronide and sulfate conjugates bind to 67-kDa laminin receptor and prevent neuronal cell death induced by serum starvation

Gopalakrishna, Rayudu; Oh, Andrew; Hou, L. D.; Lee, Emily; Aguilar, Jenny I.; Li, Andrew; Mack, William J.

doi:10.1016/j.bbrc.2023.06.007

Cited by 6 publications

(1 citation statement)

References 44 publications

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“…In the strawberry callus, the synthesis of a flavonoid compound, represented by quercetin-3-glucuronide, was stimulated by all irradiation treatments. Quercetin-3-glucoronide is a conjugated flavonoid that exhibits neuroprotective [ 75 ], antioxidant, anti-inflammatory and antiapoptotic effects against pulmonary injury [ 76 ]. For the pentacyclic triterpenoid and triterpenes determined in this callus, a stimulatory dose was 30 Gy.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in Cotinus coggygria Scop. and Fragaria × ananassa Duch. Red Callus Cultures

et al. 2023

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Cotinus coggygria Scop. (smoketree) and Fragaria × ananassa Duch. (strawberry) are two industrially important species due to their composition in bioactive compounds. In this study, we investigated the effects of acute low-dose gamma irradiation (15, 20, 25, 30, 35 and 40 Gy) on two red callus cultures established in smoketree and strawberry. The biomass production, dry weight, content of phenols, flavonoids, monomeric anthocyanins’, index of anthocyanins polymerization and antioxidant activity were evaluated. For the smoketree callus, a negative correlation between irradiation doses and callus biomass accumulation was observed. For the strawberry callus, irradiation did not significantly affect the accumulation of the biomass. An increased dry weight was observed in irradiated smoketree callus, while for treated strawberry callus, a decrease was recorded. Irradiation with 30 Gy was stimulative for polyphenols’ accumulation in both cultures; however, the increase was significant only in the strawberry callus. The flavonoids increased in the 30 Gy strawberry variants, while it significantly decreased in smoketree callus irradiated with 35 and 40 Gy. In irradiated strawberry callus, except for the 25 Gy variant (1.65 ± 0.4 mg C-3-GE/g DW), all treatments caused an increase in anthocyanins’ accumulation. In smoketree, except for the 15 Gy variant (2.14 ± 0.66 mg C-3-GE/g DW), the irradiation determined an increase in anthocyanins synthesis, with the highest value being seen in the 20 Gy variant (2.8 ± 0.94 mg C-3-GE/g DW). According to UPLC-HRMS investigations, an unidentified compound increased by 99% at the 30 Gy dose in strawberry callus, while in smoketree, maslinic acid increased by 51% after irradiation with 40 Gy. The results of this study showed, for the first time, the differential response of two performant callus cultures to low-dose gamma irradiation, a biotechnological method that can be used to stimulate the synthesis of important flavonoids and triterpenes.

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Section: Discussionmentioning

confidence: 99%

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in Cotinus coggygria Scop. and Fragaria × ananassa Duch. Red Callus Cultures

et al. 2023

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Resveratrol and its metabolites elicit neuroprotection via high‐affinity binding to the laminin receptor at low nanomolar concentrations

Gopalakrishna,

Aguilar,

et al. 2024

FEBS Letters

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Resveratrol prevents various neurodegenerative diseases in animal models despite reaching only low nanomolar concentrations in the brain after oral administration. In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found that trans‐resveratrol, its conjugates (glucuronide and sulfate), and dihydro‐resveratrol (intestinal microbial metabolite) bind with high affinities (Kd, 0.2–2 nm) to the peptide G palindromic sequence (near glycosaminoglycan‐binding motif) of the 67‐kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01–10 nm) of these polyphenols, especially resveratrol‐glucuronide, protected neuronal cells from death induced by serum withdrawal via activation of cAMP‐mediated signaling pathways. This protection was prevented by a 67LR‐blocking antibody, suggesting a role for this cell‐surface receptor in neuroprotection by resveratrol metabolites.

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Nelumbo nucifera leaves extract ameliorated scopolamine‐induced cognition impairment via enhanced adult hippocampus neurogenesis

Lee,

Lin,

Chang

et al. 2024

Environmental Toxicology

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In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine‐induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine‐induced cognition impairment according to Y‐maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine‐treated mice. NLWE and NLPE obviously elevated brain‐derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine‐induced apoptosis by reducing Bax and increased Bcl‐2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH‐SY5Y cells whereas co‐treatment with NLWE or quercetin‐3‐glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl‐2 and reduced Bax expression in the presence of scopolamine in SH‐SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH‐SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine‐induced cognition dysfunction through the regulation of BDNF signaling pathway.

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Flavonoid quercetin and its glucuronide and sulfate conjugates bind to 67-kDa laminin receptor and prevent neuronal cell death induced by serum starvation

Cited by 6 publications

References 44 publications

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in Cotinus coggygria Scop. and Fragaria × ananassa Duch. Red Callus Cultures

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in Cotinus coggygria Scop. and Fragaria × ananassa Duch. Red Callus Cultures

Resveratrol and its metabolites elicit neuroprotection via high‐affinity binding to the laminin receptor at low nanomolar concentrations

Nelumbo nucifera leaves extract ameliorated scopolamine‐induced cognition impairment via enhanced adult hippocampus neurogenesis

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