Therapeutic potential of senolytic agent quercetin in osteoarthritis: A systematic review and meta-analysis of preclinical studies

Yamaura, Kohei; Nelson, Anna Laura; Nishimura, Haruki; Rutledge, Joan C.; Ravuri, Sudheer; Bahney, Chelsea S.; Philippon, Marc J.; Huard, Johnny

doi:10.1016/j.arr.2023.101989

Cited by 10 publications

(5 citation statements)

References 53 publications

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“…This prompts the intriguing question of whether the previously observed protective effects of quercetin in pancreatitis are predominantly mediated by its metabolite, ISO. Unfortunately, unlike quercetin, which has undergone extensive clinical trials confirming its safety and potential efficacy in treating inflammatory diseases [25][26][27], ISO has not yet been tested in clinical trials in human. Nevertheless, considering ISO's status as the primary metabolite of quercetin, concerns about its safety may be minimal.…”

Section: Discussionmentioning

confidence: 99%

Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway

Li,

Wang,

Zhou

et al. 2024

IJMS

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Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.

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Section: Discussionmentioning

confidence: 99%

Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway

Li,

Wang,

Zhou

et al. 2024

IJMS

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“…Quercetin is modified by optimizing the structure and formulation to form its derivatives and related formulations in order to improve its bioavailability in the human body. In recent years, quercetin has also been shown to have good efficacy in the treatment of rheumatoid arthritis and interstitial lung fibrosis [ 34 , 35 ]. Therefore, there is an urgent need to develop its suitable dosage form [ 19 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Activity of Quercetin-Containing Liposomes-in-Gel and Its Effect on Prevention and Treatment of Cutaneous Eczema

Liu,

Cheng,

et al. 2023

Pharmaceuticals

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Cutaneous eczema is a kind of skin disease is characterized by inflammation. The main manifestations are various types of dermatitis, eczema, and urticaria. There are usually complications such as erythema, blisters, and epidermal peeling. The quercetin might have a therapeutic effect on cutaneous eczema due to its favorable antioxidant activity and anti-inflammatory effects. Currently, there are few studies on transdermal administration of antioxidant drugs for the treatment of cutaneous eczema. The aim of this study was to prepare quercetin-containing liposomes-in-gel (QU-LG), its antioxidant properties were evaluated, and it was used in the skin of mice suffering from dermal eczema to see if it had preventive and therapeutic effects in an attempt to make it a new option for the treatment of cutaneous eczema. QU-LG was prepared by the injection method to form the quercetin-containing liposomes (QU-L) and evenly dispersed in the natural dissolution of carboxymethylcellulose sodium (1%, CMC-Na). The release of QU-LG across the dialysis membranes was up to 30% and clearance of 1,1-diphenyl-2-picrylhydrazyl (DPPH) was 65.16 ± 3.513%. In anti-oxidation assay QU-LG inhibited malondialdehyde (MDA) production in liver better than the commercially available drug dexamethasone acetate cream. Compared with untreated mice, mice treated with QU-LG showed a statistically significant reduction in dermatopathologic symptoms. The results suggested that QU-LG had good antioxidant activity in vivo and in vitro and could be used for the prevention and treatment of cutaneous eczema.

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“…Animal models are necessary to validate the effects of treatments before they enter clinical trials, because in vivo studies can focus on specific conditions without confounding effects or factors. 22 To the best of our knowledge, no review has systematically summarized the effects of Sal on AD in vivo. Hence, we performed a quality assessment and meta-analysis of preclinical studies conducted on animal models of AD using Sal, aiming to form a preclinical evidence chain to provide rigorous and systematic scientific support for further clinical studies.…”

Section: Introductionmentioning

confidence: 99%

“…To determine the clinical indication of Sal for anti-AD use, it is critical to fully evaluate and critique preclinical in vivo animal studies. Animal models are necessary to validate the effects of treatments before they enter clinical trials, because in vivo studies can focus on specific conditions without confounding effects or factors . To the best of our knowledge, no review has systematically summarized the effects of Sal on AD in vivo .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Mechanisms of Salidroside in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Preclinical Studies

Zhang,

Nao,

Dong

2023

J. Agric. Food Chem.

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Alzheimer’s disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction and behavioral impairment. Salidroside (Sal) is a phenylpropanoid mainly isolated from Rhodiola species with various pharmacological effects. However, the exact anti-AD mechanism of Sal has not been clearly elucidated. This meta-analysis aims to investigate the possible mechanisms by which Sal exerts its anti-AD effects by evaluating behavioral indicators and biochemical characteristics. A total of 20 studies were included, and the results showed that the Sal treatment significantly improved behavior abnormalities in AD animal models. With regard to neurobiochemical indicators, Sal treatment could effectively increase the antioxidant enzyme superoxide dismutase, decrease the oxidative stress indicator malondialdehyde, and decrease the inflammatory indicators interleukin 1β, interleukin 6, and tumor necrosis factor α. Sal treatment was effective in reducing neuropathological indicators, such as amyloid-β levels and the number of apoptotic cells. When the relevant literature on the treatment of rodent AD models is combined with Sal, the therapeutic potential of Sal through multiple mechanisms was confirmed. However, further confirmation by higher quality studies, larger sample sizes, and more comprehensive outcome evaluations in clinical trials is needed in the future.

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Therapeutic potential of senolytic agent quercetin in osteoarthritis: A systematic review and meta-analysis of preclinical studies

Cited by 10 publications

References 53 publications

Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway

Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway

Antioxidant Activity of Quercetin-Containing Liposomes-in-Gel and Its Effect on Prevention and Treatment of Cutaneous Eczema

Neuroprotective Mechanisms of Salidroside in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Preclinical Studies

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