Acute toxicity evaluation and immunomodulatory potential of hydrodynamic cavitation extract of citrus peels

Putri, Dyaningtyas Dewi Pamungkas; Maran, Gergorius Gena; Kusumastuti, Yuni; Susidarti, Ratna Asmah; Meiyanto, Edy; Ikawati, Muthi

doi:10.7324/japs.2022.120415

Cited by 8 publications

(5 citation statements)

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“…In summary, although preliminary, our data suggest that the grapefruit IntegroPectin may modulate the inflammatory response and basal microglia activation by inhibiting the cascade of PI3K-NF-kB-iNOS. In support of our conclusions, a recent study concerning the in vivo administration of a similar Citrus pectin derived via hydrodynamic cavitation from the peels of Citrus reticulata (mandarin) has shown immunomodulatory activity and a reduction in LPS-induced lymphocytes in rats, though not linearly associated with dosage [44].…”

Section: Discussionsupporting

confidence: 89%

Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line

Scordino,

Urone,

Frinchi

et al. 2024

Cells

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In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin’s therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation.

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Section: Discussionsupporting

confidence: 89%

Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line

Scordino,

Urone,

Frinchi

et al. 2024

Cells

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“…Coupled to successful in vivo tests proving the powerful cardioprotective activity of this pectin (Flori et al, 2022), these results strongly support further investigations aimed at exploring the therapeutic role of this new pectin in in vivo models of oxidative stress-neuroinflammatory based-diseases, including neurodegenerative disorders. Indeed, a recent study concerning the in vivo administration of a similar Citrus pectin derived via hydrodynamic cavitation from the peels of Citrus reticulata (mandarin) has shown immunomodulatory activity and reduction in LPS-induced lymphocytes in rats, though not linearly associated with dosage (Putri et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Anti-apoptotic and anti-inflammatory properties of grapefruit IntegroPectin on human microglial HMC3 cell line

Scordino

Urone

Frinchi

et al. 2023

Preprint

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Background and aimDespite the intense research, most therapeutic strategies failed in preventing or treating neurodegenerative diseases, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation. The broad protective activity of IntegroPectin derived from industrial waste grapefruit peel via hydrodynamic cavitation has been recently characterized. In this study, we investigated the beneficial effects of grapefruit IntegroPectin treatment in microglia cells exposed to oxidative stress conditions.Experimental procedureHuman microglial HMC3 cells were challenged with tert-butyl hydroperoxide (TBH), a powerful hydroperoxide, in the presence of grapefruit IntegroPectin. The apoptotic process, the oxidative stress and the neuroinflammatory responses with the relative intracellular cascades were evaluated.Key resultsGrapefruit IntegroPectin fully counteracted the apoptotic process induced by cell exposure to TBH. The protective effects of grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the PI3K/Akt cascade. Finally, IntegroPectin treatment inhibited basal microglia activation and the neuroinflammatory response by down-regulating the PI3K-NF-kB-iNOS cascade.Conclusions and implicationsThese findings reveal that the innovative IntegroPectin exerts a potent protective activity on microglia cells and strongly support further investigations aimed at exploring its therapeutic role inin vivomodels of neurodegenerative disorders.

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“…As previously described, orange peel extract was prepared by hydrodynamic cavitation of dried orange peel (HCV) [20]. The HCV extract was freeze-dried to obtain dry extract.…”

Section: Preparation Of Orange Peel Extract Hsd and Hstmentioning

confidence: 99%

The effect ofCitrus reticulatapeel extract containing hesperidin on inhibition of SARS-CoV-2 infection based on pseudovirus entry assays

Septisetyani,

Harsan,

Kumara

et al. 2024

Preprint

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Orange (Citrus reticulata Blanco) peel contains a flavonoid glycoside hesperidin (HSD) as the primary component. HSD, upon enzymatic hydrolysis, forms hesperetin (HST) aglycone derivate. These two flavonoids have been predicted to have in-silico affinities for ACE2 and SARS-CoV-2 spike, crucial proteins in SARS-CoV-2 infection mechanisms. However, in vitro antiviral testing of orange peel extract, HSD, and HST has not been reported. This study presents for the first time a pseudovirus entry assay approach to test the anti-SARS-CoV-2 effect of HSD, HST, and orange peel extract prepared by hydrodynamic cavitation (HCV). We used a non-virulent pseudovirus model as an alternative to the original virus to target the entry point and enable research to be conducted outside the BSL-3 facility. Based on HPLC analysis, the test results showed that HCV contained HSD at about 4% w/w. Moreover, HSD 1 and 10 μM, HST 10 μM, and HCV 1 μg/ml showed inhibition of pseudovirus entry in 293/hACE2 cells with percentages inhibition 25.92, 37.40, 27.32, and 38.97 %, respectively. Despite HCV 1 μg/ml showing about 6 % lower inhibitory activity than HSD 1 μM in pseudovirus entry assay, it holds potential as a supplement or source of raw material for HSD as a SARS-CoV-2 antiviral.

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Acute toxicity evaluation and immunomodulatory potential of hydrodynamic cavitation extract of citrus peels

Cited by 8 publications

References 0 publications

Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line

Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line

Anti-apoptotic and anti-inflammatory properties of grapefruit IntegroPectin on human microglial HMC3 cell line

The effect ofCitrus reticulatapeel extract containing hesperidin on inhibition of SARS-CoV-2 infection based on pseudovirus entry assays

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