Hesperidin reduces adverse symptomatic intracerebral hemorrhage by promoting TGF-β1 for treating ischemic stroke using tissue plasminogen activator

Qin, Zhanzhong; Chen, Linlin; Liu, Min; Tan, Haihua; Zheng, Lei

doi:10.1007/s10072-019-04054-4

Cited by 17 publications

(10 citation statements)

References 35 publications

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“…The identified RBD-binders hesperidin and diosmin, alone or in combination, are indicated mainly for the treatment of venous disease symptoms ( Steinbruch et al, 2020 ). However, other interesting effects on stroke-related disorders in preclinical studies have been reported for both hesperidin ( Gaur et al, 2011 ; Ikemura et al, 2012 ; Qin et al, 2020 ) and diosmin ( Delbarre et al, 1995 ; Liu et al, 2014 ). Likewise, sitogluside also exhibited some effects on neurological disorders ( Chung et al, 2016 ; Ji et al, 2017 ; Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 98%

In silico identification of strong binders of the SARS-CoV-2 receptor-binding domain

Behloul

Baha

Guo

et al. 2021

European Journal of Pharmacology

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The world is currently witnessing the spread of the deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19). In less than three months since the first cases were reported, the World Health Organization declared it a pandemic disease. Although several treatment and prevention strategies are currently under investigation, a continuous effort to investigate and develop effective cures is urgently needed. Thus, we performed molecular docking and structure-based virtual screening of libraries of approved drugs, antivirals, inhibitors of protein-protein interactions, and one million other small molecules to identify strong binders of the SARS-CoV-2 receptor-binding domain (RBD) that might interfere with the receptor recognition process, so as to inhibit the viral cellular entry. According to our screening and selection criteria, three approved antivirals (elbasvir, grazoprevir, and sovaprevir) and 4 other drugs (hesperidin, pamaqueside, diosmin, and sitogluside) were identified as potent binders of the RBD. The binding of these molecules involved several RBD residues required for the interaction of the virus with its cellular receptor. Furthermore, this study also discussed the pharmacological action of the 4 non-antiviral drugs on hematological and neurological disorders that, in addition to inhibiting the viral entry, could be beneficial against the neurological disorders identified in COVID-19 patients. Besides, six other small-molecules were identified, with no pharmacological description so far, exhibiting strong binding affinities to the RBD that we believe worth being investigated as inhibitors of the SARS-CoV-2-receptor interaction.

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Section: Discussionmentioning

confidence: 98%

In silico identification of strong binders of the SARS-CoV-2 receptor-binding domain

Behloul

Baha

Guo

et al. 2021

European Journal of Pharmacology

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“…Additionally, it has been reported that HDN has numerous beneficial effects, such as anti-inflammatory, antibacterial, anticancer and anti-edema properties (13)(14)(15)(16). Thus, HDN has a protective effect on sterile organ injuries, including ischemic stroke and arthritis, and infectious diseases such as lipopolysaccharide-induced inflammation (17)(18)(19)(20). A number of studies reveal that the activation of PI3K/Akt pathway is one of the most important mechanisms for the biological effects of HDN (16,18,21,22).…”

Section: Introductionmentioning

confidence: 99%

Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway

Qin

Luo

et al. 2020

Mol Med Rep

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“…There were no significant differences in sex, age, or course of disease between the study groups, with comparable baselines. Most RCTs focused on GEDM (7 RCTs, 46.6%) ( Su et al, 2018 ; Feng et al, 2020 ; Sun et al, 2019 ; Zheng and Jiang, 2018 ; Huang et al, 2021 ; Bao and Peng, 2019 ; Wang et al, 2017 ), followed by GDI (4 RCTs, 26.6%) ( Dong et al, 2021 ; Zhang et al, 2021 ; Zhou, 2021 ; Liu, 2018 ), GBDP (1 RCT, 6.7%) ( Sun et al, 2018 ), HES (1 RCT, 6.7%) ( Qin et al, 2020 ), GSRI (1RCT, 6.7%) ( Liu et al, 2020 ), and HSYA (1 RCT, 6.7%) ( Hu et al, 2020 ). The course of treatment ranged from 7 days to 90 days.…”

Section: Resultsmentioning

confidence: 99%

“…Hesperidin is the major flavanone glycoside in citrus fruits, and a flavonoid representative of PAFRAs. In one trial ( Qin et al, 2020 ), patients with AIS were randomly assigned to two groups to receive either rt-PA plus hesperidin or rt-PA plus placebo (PLC). Follow-up hesperidin treatment for seven consecutive days was found to improve the long-term favorable recovery of neurological function, as indicated by the proportion of scores in the range of 0–1 for mRS and NIHSS after 2 months.…”

Section: Resultsmentioning

confidence: 99%

“…However, after IVT for 7 consecutive days, HES treatment did not lead to significant improvements in the long-term favorable recovery of neurological function, as indicated by the proportion of scores of 0–1 on the mRS and NIHSS after 2 months. Interestingly, the study of Qin et al (2020 ) suggested the potential clinical application of HES with rt-PA therapies to reduce SIH. It is worth noting that GSRI and HES had only one study each; therefore, we suggest being cautious in understanding and interpreting the results, until further confirmation is done to elucidate these findings.…”

Section: Discussionmentioning

confidence: 99%

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Platelet-activating factor receptor antagonists of natural origin for acute ischemic stroke: a systematic review of current evidence

Zhang

Jiang

et al. 2022

Front. Pharmacol.

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Background: Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS.Methods: A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075).Results: Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), ginkgo biloba dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for (1) GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MDmRS = −0.42, 95% CI (−0.47, −0.37), five trials, p < 0.00001; GEDM + CM for AIS on NIHSS: MDNIHSS = −1.02, 95% CI (−1.51, −0.52), four trials, p < 0.0001]; (2) GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MDmRS = −0.40, 95% CI (−0.54, −0.26), p < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MDNIHSS = −3.93, 95%CI (−7.72, −0.14), p = 0.04]; (3) GBDP in patients treated with CM; (4) GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and (5) HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs.Conclusions: This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.

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Hesperidin reduces adverse symptomatic intracerebral hemorrhage by promoting TGF-β1 for treating ischemic stroke using tissue plasminogen activator

Cited by 17 publications

References 35 publications

In silico identification of strong binders of the SARS-CoV-2 receptor-binding domain

In silico identification of strong binders of the SARS-CoV-2 receptor-binding domain

Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway

Platelet-activating factor receptor antagonists of natural origin for acute ischemic stroke: a systematic review of current evidence

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