Table 1.

Quercetin effects on preclinical and clinical models of MS.

Author and year	Type of Study	Model of MS	Number of samples	Drug therapeutic dose and method of injection	Treatment period	Outcomes
Ahmadi et al., 2023	In-vitro	PBMC isolated from RRMS patients	8	100 μm in cell culture	48 h	Immunomodulatory effects of Quercetin Penta Acetate on Th17 cells of MS patients are more effective than Quercetin.
Tan et al., 2021	In vivo	Vascular dementia demyelination model in mice	40	60 mg/kg/day by intraperitoneal (i.p) injections	14 days	Quercetin facilitated microglia transformation into M2 phenotype, decreased production of proinflammatory factors (TNF-α and IL-1β) and enhanced microglial engulfment ability of myelin fragments.
Yu et al., 2020	In vivo	Cuprizone induced demyelination model in C57BL/6 J mice	50	50 and 100 mg/kg/day	35 days	Quercetin (50 and 100 mg/kg) could decrease demyelination in corpus callosum and increase remyelination via enhancing MBP and Olig2 expression.
Mirzazadeh et al., 2019	In vivo	EAE model in Wistar rat	30	10 mg/kg/day by intraperitoneal (i.p) injection	24 days	Quercetin decreased myeloperoxidase activity, nitric oxide and lipid peroxidation level in the serum.
Naeimi., 2019	In vivo	Lysolecithin induced demyelination model in optic chiasm of rat	_	25 and 50 mg/kg/day, oral gavage	7 and 14 days	Quercetin decreased the P1–N1 latency, increased the amplitude of VEPs waves and myelin repair was improved. Also, Quercetin moderated glial activation and reduced expression of GFAP and lba1 in optic chiasm.
Carvalho et al., 2018	In vivo	Ethidium bromide induced demyelination model in Wistar rat	80	50 mg/kg/day, oral gavage	7 and 21 days	Quercetin could protect the function of Na+,K + -ATPase in the pons and cerebellum in the both demyelination and remyelination phases. Also, Quercetin could protect the function of AChE activity in whole blood and lymphocytes in both demyelination and remyelination phases and regulate redox state.
Hashemian., 2018	In vivo	Lysolecithin demyelination model in optic chiasm of rat	_	25 mg/kg/day by intraperitoneal (i.p.) injections	7 and 14 days	Quercetin-loaded NPs reduced the extent of demyelination areas, attenuated glial activation and inflammation.
Naeimi et al., 2018	In vivo	Lysolecithin demyelination model in optic chiasm of rat	–	25 mg/kg, 50 mg/kg/day, by oral gavage	–	Quercetin reduced the delay of visual signals, alleviated the level of glial activation, decreased the extent of demyelination areas and increased the remyelination process and PLP expression.
Ghasemi-kasman., 2017	In vivo	Lysolecithin induced demyelination model in optic chiasm of rat	_	50 and 100 mg/kg/day, ip injection	7 and 14 days	Quercetin reduced the P1–N1 latency, increased the amplitude of VEPs waves, reduced the expression of GFAP, improved myelin repair. Also, Quercetin ameliorated astrocytes activation of optic chiasm.
Backman et al., 2014	In vivo	Ethidium bromide induced demyelination model in Wistar rat	80	50 mg/kg/day, oral gavage	7 and 21 days	Quercetin promoted locomotor recovery, decreased demyelination, increased remyelination, promoted AChE activity and inhibited lipidic peroxidation.
Liuzzi et al., 2011	In vitro	Cell culture of rat astrocyte activated with LPS Sera of RRMS patient	1 × 105 cells/m 14	1–25 μg/ml in cell culture 50 μg/ml, in cell culture	overnight overnight	In LPS treated astrocytes the levels of MMP2 and MMP-9 were increased. Quercetin treatment of astrocytes could not inhibit the MMP-2 and MMP-9 levels in LPS activated astrocytes. Quercetin was able to significantly inhibit the gelatinolytic activity up to 81 % in the serum of RRMS Patients.
Sternberg et al., 2008	In-vitro	PBMC isolated from RRMS patients	23	5–50 μM in cell culture	–	Quercetin, in a dose-dependent manner, reduced the proliferation of PBMC and regulated the level of IL-1β and TNF-α. Also, reduced the MMP-9/TIMP-1 ratio by reduce the MMP-9 production.
Muthian et al., 2004	In vivo	EAE model in SJL/J mice	–	50 and 100 μg/day by intraperitoneal (i.p) injection	25 days	Quercetin treatment indicated that in both in vivo and in vitro models could block IL-12 and led to the inhibition of T cell proliferation and Th1 differentiation.
Hendriks et al., 2003	In vitro	Myelin content of adult mice	–	300 μg in cell culture of macrophage and myelin	90 min	Quercetin could completely inhibit myelin uptake by macrophages and diminish ROS production.