Insights & Discussion
The research unveils luteolin, quercetin, and kaempferol in RALRG as promising complementary components for RP treatment, with a key role in managing oxidative stress and PI3K/AKT signaling pathways.
The research used various databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCards, and the Online Mendelian Inheritance in Man database to gather the ingredients of RALRG and potential targets of RP and RALRG. A protein-protein interaction network was constructed to visualize these interactions. The R program was utilized to perform functional enrichment. The researchers constructed a visual RALRG-RP-pathway pharmacology network using Cytoscape 3.9.1 and applied molecular docking to compute binding affinity.
The research revealed a total of 132 effective active elements in RALRG correlating to 248 target genes. Ninety-two intersection target genes were discovered from the overlap of RP- and RALRG-related genes. These intersection targets were discovered to be primarily involved in oxidative stress, responding to metal ions, and handling chemical stress. Several molecular pathways such as PI3K-AKT and MAPK were identified as closely connected to RP therapy. A potential pharmacology network was designed for the RALRG-RP-pathway with AKT1 and JUN being considered the main targets. The active ingredients luteolin, quercetin, and kaempferol were highlighted as crucial for this mechanism. RALRG overall was established as a main regulator for oxidative stress and PI3K/AKT signaling pathways in the treatment of RP.
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Lycium barbarum polysaccharide may decrease apoptosis in retinal photoreceptor cells of retinitis pigmentosa mice by suppressing nuclear factor-kappa B/NOD-like receptor thermal protein domain-associated protein 3 pathway.
2023 Digital Chinese Medicine Inhibition of photoreceptor apoptosis in mice with retinitis pigmentosa through NF-κB/NLRP3 pathway suppression with Lycium barbarum polysaccharide Wang Y, Deng Y, Lu J, Peng J, Zhou Y, Yang Y, et al.
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The team carried out both in vivo and in vitro studies. Initially, mouse retinal ganglion cells were categorized into groups based on the doses of Lycium barbarum polysaccharide they were given and a positive drug control group. These cells were then subject to different H2O2 concentrations to induce apoptosis. Techniques such as flow cytometry, immunofluorescence, and western blot were used to evaluate cell viability, apoptosis rate, and expression of various markers. For in vivo research, the team used C57/BL6 and Rd10 mice divided into similar groups as the in vitro experiment. The mice underwent drug treatment for four weeks, after which their retina's response to light and general health were evaluated using an electroretinogram and histopathological examination.
The in vitro experiments showed that the apoptosis rate of ganglion cells significantly increased in the model group, along with up-regulation of certain proteins. However, a high dose of Lycium barbarum polysaccharide decreased the cell apoptosis rate and the levels of certain proteins. Similarly, in vivo testing showed that a high dose of the substance significantly aided in morphological alterations in a retina layer of Rd10 mice, and down-regulated the expression levels of a number of apoptosis-related proteins.
Zhangyanming Tablets show potential as a protective agent for retinal function in early-stage, genetically-caused blindness in mice, possibly due to their antioxidant and anti-/pro-apoptotic properties.
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Eighty mice with Retinitis Pigmentosa (RP) were divided into two groups, with one group receiving Zhangyanming Tablets (ZYMT) and a control group getting distilled water. After a period of 7 and 14 days, the researchers conducted tests through electroretinogram, fundus photography, and histological examination to assess the retinal function and structure of the subjects. They furthered the study using TUNEL, immunofluorescence and qPCR to evaluate cell apoptosis and the expressions of particular genes.
The ZYMT-treated mice displayed a notable enhancement in retinal reactions and overall preservation of retinal structure when compared to the control group. Particularly noticeable were increases in retinal thickness and cell count, alongside a significantly lowered rate of cell death. A comprehensive follow-up shows the altered expressions of several genes in the retina following the application of ZYMT. These results, combined, suggest a key role of ZYMT in mitigating the effects of RP especially in early stages.
Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) shows potential as a clinical treatment for retinitis pigmentosa by inhibiting photoreceptor cell death following oxidative stress.
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The study utilized hydrogen peroxide to induce oxidative stress in 661 W cells, which were examined with flow cytometry and an enzyme-linked immunosorbent assay. The impact of this oxidative stress on the cells’ mitochondria was observed using an electron microscope to understand the nature of cell death. The study also analyzed the compensatory effect of the Fructus Lycii and Salvia miltiorrhiza Bunge extract on the retinal structure and function of rd10 mice using histopathological examination, fundus photographs, and electroretinography. Protein levels were evaluated using Western blot assays, specifically targeting proteins including Tumor Protein p53, Solute Carrier Family 7 Member 11, Glutathione peroxidase 4, Arachidonate-12-Lipoxygenase, and Dipeptidyl peptidase 4.
The results showed that hydrogen peroxide-induced oxidative stress in 661 W cells increased oxidative stress products and certain protein expressions, while decreasing others. Notably, the activation of Glutathione peroxidase 4 did not lessen reactive oxygen species generation and had little impact on cell death. The research discovered that both Ferrostatin-1 and the extract could lessen reactive oxygen species generation and inhibit cell death of photoreceptors in retinitis pigmentosa, achieving this by inhibiting the expression of one protein and increasing the expression of two others.
Fructus Lycii and Salvia miltiorrhiza Bunge extract improve retinal morphology and function by regulating the Nrf2/HO-1 pathway to curb oxidative reactions.
2021 Journal of Ethnopharmacology Fructus Lycii and Salvia miltiorrhiza Bunge extract alleviate retinitis pigmentosa through Nrf2/HO-1 signaling pathway Ou C, Jiang P, Tian Y, Yao Z, Yang Y, Peng J, et al.
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In terms of methodology, Fructus Lycii and Salvia miltiorrhiza Bunge (FS) extracts were identified through Ultra Performance Liquid Chromatography analysis and administered intragastrically over four weeks to Rd10 mice, known to model retinitis pigmentosa. Following the animals' sacrifice, histopathological examination and Scotopic electroretinography analysis were performed. Oxidative stress markers were determined and the expression levels of Nrf2 and HO-1 mRNA were evaluated via quantitative real-time PCR. Western blot and immunohistochemistry were employed to identify the expression and distribution of Nrf2 and HO-1 protein.
In the discussion of the results, substantial morphological improvements were observed regarding the thickness and number of the Outer Nuclear Layer, along with significant functional enhancements in a-amplitude and b-wave amplitude measurements, following FS extract treatment. In addition, the treatment led to a considerable escalation in superoxide dismutase and glutathione peroxidase levels and a reduction in malondialdehyde levels. Furthermore, FS extract was found to stimulate the up-regulation of Nrf2 and HO-1 mRNA and protein expression, possibly underlying the observed retinal enhancements.
Zeaxanthin dipalmitate, a wolfberry-derived carotenoid, can delay retinal degeneration in mice modelling Retinitis Pigmentosa mainly through its anti-inflammatory and oxidative stress effects.
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In the study's methodology, Zeaxanthin dipalmitate (ZD) was intravitreally injected into mice on postnatal day 16. Subsequent assessment of retinal function and structure were made at P25 using visual behavior tests, multi-electrode-array recordings, and immunostaining. The involved gene expressions and their regulation by ZD were delved into through transcriptome sequencing and western blotting.
In the discussion of results, it was discovered that ZD treatment significantly improved the visual behavior of the mice and delayed degeneration of the retinal photoreceptors, enhancing the light responses of photoreceptors, bipolar cells, and retinal ganglion cells. The ZD treatment led to a decline of up-regulated genes connected to inflammation, apoptosis, and oxidative stress. The study found that ZD reduces the activation of signal transducer and activator of transcription 3 and chemokine ligand 2, down-regulates the expression of the inflammatory factor GFAP, and withholds extracellular signal regulated protein kinases and P38, but not JNK pathways. All these findings indicate the potential of ZD as treatment for Retinitis Pigmentosa.
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