ReferenceID 4633
Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure
Int J Mol Sci
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive ex
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- Reference Id
- 4633
- Evidence Id
- 21223
- Core Evidence Id
- 21223
- Source Reference Id
- 2532
- Herb2 Reference Id
- HBREF003329
- Subject Paper Key
- HBIN017508_35806375
- Pubmed Id
- 35806375
- Doi
- 10.3390/ijms23137372
- Paper Title
- Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure
- Paper Abstract
- Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1-100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP.
- Journal
- Int J Mol Sci
- Publish Year
- 2022
- Experiment Subject
- mouse; human; ba relaxed htm cells; htm cells; primary human tm (htm) cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Htm; Glaucoma
- Paper Title Cn
- Paper Title En
- Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure
- Bilingual Status
- semi_complete