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Background: Photoreceptor degeneration underpinned by oxidative stress-mediated mitochondrial dysfunction and cell death leads to progressive and irreversible vision impairment. Drug treatments that protect against photoreceptor degeneration are currently available in the clinical settings. It has been shown that hyperoside, a flavonol glycoside, protects against neuronal loss in part by suppressing oxidative stress and maintaining the functional integrity of mitochondria. However, whether hyperoside protects against photoreceptor degeneration remains unknown., Methods: To address the pharmacological potentials of hyperoside against oxidative stress-mediated photoreceptor degeneration on molecular, cellular, structural and functional levels, multiple in vitro and in vivo methodologies were employed in the current study, including live-cell imaging, optical coherence tomography, electroretinography, histological/immunohistochemical examinations, transmission electron microscopy, RNA-sequencing and real-time qPCR., Results: The in vitro results demonstrate that hyperoside suppresses oxidative stress-mediated photoreceptor cell death in part by mitigating mitochondrial dysfunction. The in vivo results reveal that hyperoside protects against photooxidative stress-induced photoreceptor morphological, functional and ultrastructural degeneration. Meanwhile, hyperoside treatment offsets the deleterious impact of photooxidative stress on multiple molecular pathways implicated in the pathogenesis of photoreceptor degeneration. Lastly, hyperoside attenuates photoreceptor degeneration-associated microglial inflammatory activation and reactive Müller cell gliosis., Conclusions: All things considered, the present study demonstrates for the first time that hyperoside attenuates oxidative stress-induced photoreceptor mitochondrial dysfunction and cell death. The photoreceptor-intrinsic protective effects of hyperoside are corroborated by hyperoside-conferred protection against photooxidative stress-mediated photoreceptor degeneration and perturbation in retinal homeostasis, warranting further evaluation of hyperoside as a photoreceptor protective agent for the treatment of related photoreceptor degenerative diseases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Photoreceptor death leads to vision impairment in several retinal degenerative disorders. Therapies protecting photoreceptor from degeneration remain to be developed. Anti-inflammation, anti-oxidative stress, and neuroprotective effects of celastrol have been demonstrated in a variety of disease models. The current study aimed to investigate the photoreceptor protective effect of celastrol., Methods: Bright light-induced retinal degeneration in BALB/c mice was used, and morphological, functional, and molecular changes of retina were evaluated in the absence and presence of celastrol treatment., Results: Significant morphological and functional protection was observed as a result of celastrol treatment in bright light-exposed BALB/c mice. Celastrol treatment resulted in suppression of cell death in photoreceptor cells, alleviation of oxidative stress in the retinal pigment epithelium and photoreceptors, downregulation of retinal expression of proinflammatory genes, and suppression of microglia activation and gliosis in the retina. Additionally, leukostasis was found to be induced in the retinal vasculature in light-exposed BALB/c mice, which was significantly attenuated by celastrol treatment. In vitro, celastrol attenuated all-trans-retinal-induced oxidative stress in cultured APRE19 cells. Moreover, celastrol treatment significantly suppressed lipopolysaccharides-stimulated expression of proinflammatory genes in both APRE19 and RAW264.7 cells., Conclusions: The results demonstrated for the first time that celastrol prevents against light-induced retinal degeneration through inhibition of retinal oxidative stress and inflammation.

Myocardial fibrosis is the endpoint pathology common to many cardiovascular disorders. We have previously shown that apocynin (APO), a naturally occurring NADPH oxidase inhibitor, significantly prevents the development of isoproterenol (ISO)-induced myocardial injury and fibrogenesis. The current study investigated the changes in microRNAs (miRNAs) and their potential implication in the cardioprotective effects of APO. Integrative analyses of whole-genome miRNA and gene expression profiles were first performed, revealing that altered expression of miRNAs likely contributed to dysregulated expression of genes associated with multiple interconnected fibrogenic signaling pathways. Importantly, APO treatment exhibited a broad impact on these signaling pathways, which could in part be mediated through miRNA-mediated gene expression regulation. The expression of differentially expressed miRNAs was further validated by real-time PCR analyses. Consistent with the data from miRNA array, compared to that from vehicle-treated normal controls, significantly decreased expression of miR-10b, miR-29c*, miR-30c-1*, miR-30e*, miR-148b, miR-181d, miR-218 and miR-3107* was observed in ISO-challenged vehicle-treated mouse hearts. In contrast, significantly increased expression of these miRNAs was observed in ISO-challenged APO-treated hearts compared to that from ISO-challenged vehicle-treated mice. Moreover, increased expression of miR-21 was observed as a result of ISO administration, which was significantly reduced by APO treatment. Altered protein levels of Col1, TIMP1, Rac2 and gp91 phox were also validated. Lastly, APO treatment was shown to attenuate pre-established myocardial fibrosis induced by ISO. The results therefore demonstrated for the first time that complex changes in miRNA-mRNA interactome network are associated with the protective effects of APO against ISO-induced myocardial injury and fibrogenesis. [ABSTRACT FROM AUTHOR]

Background: Photoreceptor death leads to vision impairment in several retinal degenerative disorders. Therapies protecting photoreceptor from degeneration remain to be developed. Anti-inflammation, anti-oxidative stress, and neuroprotective effects of celastrol have been demonstrated in a variety of disease models. The current study aimed to investigate the photoreceptor protective effect of celastrol.Methods: Bright light-induced retinal degeneration in BALB/c mice was used, and morphological, functional, and molecular changes of retina were evaluated in the absence and presence of celastrol treatment.Results: Significant morphological and functional protection was observed as a result of celastrol treatment in bright light-exposed BALB/c mice. Celastrol treatment resulted in suppression of cell death in photoreceptor cells, alleviation of oxidative stress in the retinal pigment epithelium and photoreceptors, downregulation of retinal expression of proinflammatory genes, and suppression of microglia activation and gliosis in the retina. Additionally, leukostasis was found to be induced in the retinal vasculature in light-exposed BALB/c mice, which was significantly attenuated by celastrol treatment. In vitro, celastrol attenuated all-trans-retinal-induced oxidative stress in cultured APRE19 cells. Moreover, celastrol treatment significantly suppressed lipopolysaccharides-stimulated expression of proinflammatory genes in both APRE19 and RAW264.7 cells.Conclusions: The results demonstrated for the first time that celastrol prevents against light-induced retinal degeneration through inhibition of retinal oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Shexiang Tongxin dropping pill (STDP) is a formulation of Traditional Chinese Medicine mainly used for clinical treatment of stable angina pectoris in China. Aim of the study To investigate the effects and mechanisms of STDP treatment on atherosclerosis. Materials and methods ApoE deficient (ApoE −/− ) mice were utilized to evaluate the effect of STDP treatment (30 mg/kg/day) on atherosclerotic lesions. Histopathological features of atherosclerotic lesions, serum levels of lipid proteins, parameters of oxidative stress and pro-inflammatory cytokines were measured by H&E staining, Masson’s trichrome staining and ELISA, respectively. Real-time PCR analyses were performed to examine the aortic expression of atherosclerosis-associated microRNAs. Results The STDP treatment resulted in attenuated atherosclerotic lesion manifested by reduced lipid deposition, fibrosis and oxidative stress. It also led to increase in serum levels of GSH and SOD, decrease in MDA, decrease in CHO, TG, LDL, ox-LDL and increase in HDL, respectively. Additionally, the levels of pro-inflammatory cytokines including IL-2, IL-6, TNF-α and γ-IFN were markedly reduced by STDP treatment. Furthermore, STDP treatment was associated with a significant reduction in the aortic expression of miR-21a, miR-132, miR-126a, miR-155 and increased expression of miR-20a. Conclusion Our results demonstrated for the first time that STDP attenuated atherosclerotic lesions in ApoE −/− mouse model. Moreover, STDP treatment exhibited multi-targeting effects on pathological, biochemical and molecular aspects of atherosclerosis implicating lipid regulation, fibrosis, inflammation and oxidative stress. Findings from the current study warrant further evaluation of the clinical application of STDP in atherosclerosis treatment. [ABSTRACT FROM AUTHOR]

Vision impairment in retinal degenerative diseases such as age-related macular degeneration is primarily associated with photoreceptor degeneration, in which oxidative stress and inflammatory responses are mechanistically involved as central players. Therapies with photoreceptor protective properties remain to be developed. Apigenin-7-diglucuronide (A7DG), a flavonoid glycoside, is present in an assortment of medicinal plants with anti-inflammatory or ant-oxidant activities. However, the pharmacological significance of A7DG remains unknown in vivo . The current study isolated A7DG from Glechoma longituba (Nakai) Kuprian and investigated the retinal protective effect A7DG in mice characterized by bright light-induced photoreceptor degeneration. The results showed that A7DG treatment led to remarkable photoreceptor protection in bright light-exposed BALB/c mice. Moreover, A7DG treatment alleviated photoreceptor apoptosis, mitigated oxidative stress, suppressed reactive gliosis and microglial activation and attenuated the expression of proinflammatory genes in bright light-exposed retinas. The results demonstrated for the first time remarkable photoreceptor protective activities of A7DG in vivo . Inhibition of bright light-induced retinal oxidative stress and retinal inflammatory responses was associated with the retinal protection conferred by A7DG. The work here warrants further evaluation of A7DG as a pharmacological candidate for the treatment of vision-threatening retinal degenerative disorders. Moreover, given the general implication of oxidative stress and inflammation in the pathogenesis of neurodegeneration, A7DG could be further tested for the treatment of other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]