Effect of Cordyceps sinensis on the Treatment of Experimental Autoimmune Encephalomyelitis: A Pilot Study on Mice Model

Abstract

Background: As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE).

Methods: Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35-55to induce EAE, followed by an instant intragastric feeding with a low dosage of CS (low-CS group, n = 5), high dosage of CS (high-CS group, n = 5), or the same volume of normal saline (control group, n = 5). All the mice were observed for clinical assessment. Over the 30 days of CS treatment, flow cytometry was used to detect the frequency of helper T-cell (Th) subsets, Th1 and Th17, and CD4+ CD25+ regulatory T cells in the spleen and lymph nodes. Meanwhile, pathological changes in brain were determined using both hematoxylin-eosin and luxol fast blue staining. Data were analyzed using the one-way analysis of variance (ANOVA).

Results: Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high-CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low-CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high-CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low-CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively). At 30 days post-CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS-treated mice than that of control group.

Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.

Figure 1

Flow cytometry. Region 1 (R1) was selected to set the mononuclear cell gate according to the forward light scatter and side light scatter properties for analysis of the Th1 (a) and Th17 (b) frequency. Region 2 (R2) was used to set the second gate to separate CD4⁺ T-cells to analyze the frequency of CD4⁺ CD25⁺ FoxP3⁺ Treg (c). Staining with isotype control antibodies was used as a control to define the gate.

Figure 2

Changes in mean disease severity scores in the control (EAE; normal saline), low-CS (1 g·kg^-1·d^-1), and high-CS groups (5 g·kg^-1·d^-1). EAE: Experimental autoimmune encephalomyelitis; CS: Cordyceps sinensis.

Figure 3

Changes in body weight in the control (EAE; normal saline), low-CS (1 g·kg^-1·d^-1), and high-CS groups (5 g·kg^-1·d^-1). EAE: Experimental autoimmune encephalomyelitis, CS: Cordyceps sinensis.

Figure 4

Histological analysis. Degree of inflammatory cell infiltration (H & E, ×100) and demyelination (LFB, ×50) in the corpus striatum in the control (a and d), low-CS (b and e), and high-CS (c and f) groups. Less inflammatory infiltration (long red arrow) or demyelination (short red arrow) was present in both high-CS and low-CS groups than control group. CS: Cordyceps sinensis.