Oriental Medicine Samhwangsasim-tang Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Th1 Cell Responses and Upregulating Treg Cell Responses

Abstract

Oriental medicine Samhwangsasim-tang (SHSST) has traditionally been used in East Asia to treat hypertension and its complications. However, little is known about its potential value regarding the treatment of chronic inflammatory diseases such as multiple sclerosis (MS). In this study, we investigated whether SHSST has a beneficial effect in treating myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Onset-treatment with SHSST was found to alleviate neurological symptoms as well as demyelination and glial activation in the spinal cords from the EAE mice. The SHSST also attenuated the mRNA or protein expression of pro-inflammatory cytokines (interleukin-1beta and tumor necrotic factor-alpha); chemokines (RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha); inducible nitric oxide synthase; and cyclooxygenase-2 in correspondence with the down-regulation of the nuclear factor-kappa B and mitogen-activated protein kinases signal pathways in the spinal cords from EAE mice. Interestingly, the protective effect of the SHSST was related to a decreased number of Th1 cells and an increased number of Treg cells in spinal cords from EAE mice. Taken together, our finding firstly suggested that SHSST could delay or mitigate EAE with a wide therapeutic time-window by suppressing Th1 cell responses and upregulating Treg cell responses. Also, our findings are strong enough to warrant further investigation of SHSST as a treatment for chronic autoimmune diseases including MS.

Neuroprotective effects of crude extracts, compounds, and isolated molecules obtained from plants in the central nervous system injuries: a systematic review

“…Ten studies evaluated the neuroprotective effects induced by crude extracts obtained from plants ( Sekiya et al, 2009 ; Guimarães-Santos et al, 2012 ; Badem et al, 2014 ; Zhang et al, 2015 ; Lee et al, 2017 ; Li et al, 2018 ; Martinez-Oliveira et al, 2018 ; Zhou et al, 2018 ; Huang et al, 2019 ; Kim et al, 2020 ), 2 studies used isolated molecules ( Kyung et al, 2006 ; Zhu et al, 2006 ), and 2 studies reported the effect of a compound ( Chen et al, 2012 ; Zhou et al, 2020 ).…”

“…The crude extracts, compounds, and/or isolated molecules were extracted from herbs in 4 studies, roots in 4 studies, leaves in 2 studies, rhizomes in 2 studies, fruit in 2 studies, flower in 1 study, tree in 1 study, and trunk in 1 study. Among the experimental models, 4 studies induced spinal cord injury ( Kyung et al, 2006 ; Chen et al, 2012 ; Zhang et al, 2015 ; Zhou et al, 2020 ), 5 studies analyzed multiple sclerosis ( Zhu et al, 2006 ; Lee et al, 2017 ; Li et al, 2018 ; Huang et al, 2019 ; Kim et al, 2020 ), 2 studies evaluated amyotrophic lateral sclerosis ( Sekiya et al, 2009 ; Zhou et al, 2018 ), 1 study induced spinal cord ischemia ( Badem et al, 2014 ), 1 study reproduced acute damage to the motor cortex ( Guimarães-Santos et al, 2012 ), and 1 study replicated Alzheimer-like disease damage in the hippocampus ( Martinez-Oliveira et al, 2018 ). Ten in vivo studies, 1 in vitro study, and 3 both in vivo and in vitro studies were selected.…”

“…Regarding the experimental model of CNS injuries, 5 studies reproduced multiple sclerosis ( Kyung et al, 2006 ; Zhang et al, 2015 ; Lee et al, 2017 ; Li et al, 2018 ; Huang et al, 2019 ; Kim et al, 2020 ), 4 studies induced spinal cord injury ( Kyung et al, 2006 ; Chen et al, 2012 ; Zhang et al, 2015 ; Zhou et al, 2020 ), 2 studies reproduced amyotrophic lateral sclerosis ( Sekiya et al, 2009 ; Zhou et al, 2018 ) and 3 studies evaluated spinal cord ischemia, excitotoxicity into the motor cortex, and Alzheimer’s disease ( Guimarães-Santos et al, 2012 ; Badem et al, 2014 ; Martinez-Oliveira et al, 2018 ).…”

“…Four studies used two plant parts: herb and the tree ( Chen et al, 2012 ); rhizome and the root ( Lee et al, 2017 ); root and the flower ( Zhang et al, 2015 ); leaf and the root ( Martinez-Oliveira et al, 2018 ). One study used only the root ( Sekiya et al, 2009 ), 3 studies used only herbs ( Li et al, 2018 ; Zhou et al, 2018 ; Kim et al, 2020 ), 2 studies used only the fruits ( Huang et al, 2019 ; Zhou et al, 2020 ), 1 used only leaves ( Badem et al, 2014 ), 1 used only rhizome ( Kyung et al, 2006 ), 1 study used only the stem bark ( Zhu et al, 2006 ), and 1 study used only the trunk ( Guimarães-Santos et al, 2012 ).…”

“…These extracts can be fractionated to obtain compounds, which in turn can be purified to obtain isolated molecules ( Altemimi et al, 2017 ). It has been recently observed that some crude extracts and compounds can inhibit the nuclear factor kappa B (NF-kB), which prevents the production of inflammatory cytokines and microglial activation in experimental models of some neurological disorders, such as spinal cord injury, multiple sclerosis and amyotrophic lateral sclerosis (ALS; Kyung et al, 2006 ; Zhu et al, 2006 ; Sekiya et al, 2009 ; Chen et al, 2012 ; Zhang et al, 2015 ; Lee et al, 2017 ; Li et al, 2018 ; Zhou et al, 2018 , 2020 ; Huang et al, 2019 ; Salehi et al, 2019 ; Kim et al, 2020 ; Sharifi-Rad et al, 2020 ).…”