Traditional Chinese Medicine for Myasthenia Gravis Treatment

Traditional Chinese Medicine Formula Shows Promise for Myasthenia Gravis Treatment

Myasthenia gravis (MG) is a chronic autoimmune disease that disrupts communication between nerves and muscles, leading to symptoms such as muscle weakness, drooping eyelids, difficulty swallowing, and fatigue. In more severe cases, it can cause life-threatening breathing difficulties. MG is driven by autoantibodies that attack components of the neuromuscular junction (NMJ)—most commonly the acetylcholine receptor (AChR). This disruption weakens signal transmission from nerves to muscles.

The disease affects up to 350 people per million and is more prevalent in women. Current treatments, including glucocorticoids, immunosuppressants, biologics, and thymectomy, offer symptomatic relief but come with significant side effects, high costs, and a risk of relapse. As such, the need for alternative, low-toxicity therapies is increasingly urgent.

Traditional Medicine, Modern Insight

In China, Traditional Chinese Medicine (TCM) has long been used to treat MG. One such formulation is the Jianpi Yiqi Busui Prescription (JYBP)—a blend of herbs including Astragalus membranaceus, Codonopsis pilosula, and Rehmannia glutinosa. Although JYBP has shown clinical effectiveness, its mechanisms remained largely unknown—until now.

Researchers from Changchun University of Chinese Medicine have conducted a preclinical study exploring how JYBP works to alleviate MG symptoms, using an experimental autoimmune MG (EAMG) rat model that mimics the human disease.

Study Overview

To evaluate JYBP’s effects, researchers immunized female Lewis rats to induce MG-like symptoms. They divided the rats into several treatment groups—receiving low, medium, or high doses of JYBP, a prednisone group for comparison, and a control group. Key metrics such as body weight, muscle strength, fatigue resistance, and antibody levels were assessed over the course of treatment.

Key Findings: What the Study Revealed

1. Symptom Improvement

• JYBP significantly improved body weight, muscle strength, and fatigue resistance in EAMG rats.
• It reduced the Lennon clinical score, a measure of disease severity.
• High-dose JYBP effects were comparable to prednisone, a standard MG therapy.

2. Reduced Autoimmune Activity

• JYBP lowered levels of AChR antibodies in the bloodstream, which are key drivers of MG.

3. Immunomodulatory Effects on T Cell Subsets

• JYBP suppressed pro-inflammatory Th17 and Th1 cells.
• It increased anti-inflammatory Th2 and Treg cells, promoting a healthier immune balance.

4. Regulation of Key Cytokines

• It reduced the expression of inflammatory cytokines like IL-17, IL-6, TNF-α, and IL-1β.
• It also boosted TGF-β, an important anti-inflammatory cytokine.

Digging Deeper: The Mechanism Behind the Effects

What sets this study apart is its investigation of a specific signaling pathway: the TAK1/P38 MAPK/eIF-4E pathway. This pathway plays a critical role in Th17 cell differentiation—a process known to worsen MG by increasing IL-17 production.

The study found that JYBP:

• Inhibited the phosphorylation (activation) of TAK1, P38 MAPK, and eIF-4E proteins.
• Reduced IL-17 levels at both protein and gene expression levels.
• Likely suppressed mRNA translation of inflammatory signals through reduced eIF-4E activity.

These findings suggest that JYBP may block the cascade leading to harmful T-cell activation and cytokine release, which in turn could prevent or lessen disease symptoms.

Comparing JYBP to Standard Treatment

Interestingly, the medium and high doses of JYBP performed similarly to prednisone, but without the adverse effects often associated with long-term steroid use (e.g., weight fluctuations and symptom rebound).

This positions JYBP as a potentially safer alternative or complementary therapy for managing MG—especially in cases where steroids are not well-tolerated.

Practical Implications and Future Research

This research highlights how traditional formulations like JYBP can be validated using modern biomedical tools. The findings pave the way for:

• Developing integrated MG treatment plans that combine conventional and herbal therapies.
• Clinical trials to assess JYBP’s safety and efficacy in human patients.
• Exploring JYBP’s broader applications in other autoimmune diseases involving Th17-mediated inflammation.

The study also acknowledges its limitations, such as the need to study effects on other immune cells like B cells, and to dissect the roles of individual herbal compounds in JYBP.

Conclusion: A New Chapter for Myasthenia Gravis Management?

JYBP appears to exert significant immunoregulatory effects in MG, through modulation of T cell differentiation and inhibition of key inflammatory pathways. With comparable efficacy to prednisone and fewer apparent drawbacks, it may represent a viable, evidence-backed candidate for further development in MG therapy.

As autoimmune disorders become increasingly prevalent, studies like this offer a promising bridge between traditional knowledge and modern science.

 

The translation of the preceding English text in Chinese:

 

中医药配方在重症肌无力治疗中展现希望

重症肌无力（Myasthenia Gravis，MG）是一种慢性自身免疫性疾病，会干扰神经与肌肉之间的信号传递，导致肌肉无力、眼睑下垂、吞咽困难和疲劳等症状。在严重的情况下，还可能引发危及生命的呼吸困难。MG 是由于自身抗体攻击神经肌肉接头（NMJ）中的关键成分所致，最常见的是乙酰胆碱受体（AChR），从而削弱神经向肌肉的信号传导。

该病影响高达每百万人中350人，女性发病率更高。目前的治疗方法包括糖皮质激素、免疫抑制剂、生物制剂及胸腺切除术，虽可缓解症状，但副作用大、成本高、易复发，因此迫切需要毒性较低的替代疗法。

传统医学与现代见解的结合

在中国，传统中医长期以来用于治疗MG。其中一种常用方剂为“健脾益气补髓方（JYBP）”，由黄芪、党参、生地黄等多种草药组成。尽管JYBP 在临床中显示出一定疗效，其作用机制此前尚不清楚——直到最近。

来自长春中医药大学的研究人员进行了一项前临床研究，探索JYBP 缓解MG 症状的作用机制，使用实验性自身免疫性MG（EAMG）大鼠模型模拟人类疾病。

研究概述

为了评估JYBP 的疗效，研究人员使用Lewis雌性大鼠进行免疫诱导，使其出现类似MG的症状。大鼠被分为多个治疗组，分别接受低剂量、中剂量、高剂量的JYBP，另设有强的松（Prednisone）组和对照组。研究评估了体重、肌肉力量、抗疲劳能力和抗体水平等关键指标。

主要发现：研究揭示了哪些内容？

      症状改善

• JYBP 明显改善了EAMG 大鼠的体重、肌肉力量和抗疲劳能力。

• 降低了疾病严重程度评分（Lennon临床评分）。

• 高剂量JYBP 的效果与标准治疗药物强的松相当。

      自身免疫活性降低

• JYBP 减少了血液中AChR 抗体水平，这是MG 的关键致病因素。

      对T细胞亚群的免疫调节作用

• 抑制促炎性的Th17 和Th1细胞。

• 增加抗炎性的Th2 和Treg细胞，促进免疫平衡。

      关键细胞因子的调控

• 降低炎性因子如IL-17、IL-6、TNF-α 和IL-1β 的表达。

• 增加抗炎因子TGF-β 的水平。

更深层次的机制探究

该研究的亮点在于对特定信号通路的探讨：TAK1/P38 MAPK/eIF-4E通路。该通路在Th17细胞分化中发挥重要作用，而Th17细胞通过提升IL-17水平使MG 恶化。

研究发现JYBP：

• 抑制了TAK1、P38 MAPK 和eIF-4E 蛋白的磷酸化（活化）；

• 降低了IL-17 蛋白水平和基因表达；

• 可能通过降低eIF-4E 活性抑制炎症信号的mRNA 翻译。

这些结果表明，JYBP 可阻断导致有害T细胞激活及细胞因子释放的级联反应，进而可能预防或减轻MG 症状。

JYBP 与标准治疗的对比

有趣的是，中高剂量的JYBP 与强的松治疗效果相当，但未出现长期使用类固醇常见的不良反应（如体重波动、症状反弹）。

因此，JYBP 有望作为一种更安全的替代疗法或辅助疗法，尤其适用于无法耐受类固醇的MG患者。

现实意义与未来研究方向

该研究表明，传统配方如JYBP 可借助现代生物医学手段加以验证。这一发现为以下方向铺平了道路：

• 制定融合中西医的MG 综合治疗方案；

• 开展JYBP 在人类患者中的临床试验以评估其安全性和疗效；

• 探索JYBP 在其他Th17介导的自身免疫疾病中的潜在应用。

研究也指出了自身局限性，如尚需研究对B细胞等免疫细胞的作用，并进一步解析JYBP 各种草药成分的具体作用机制。

结语：重症肌无力治疗的新篇章？

JYBP 在MG中展现出显著的免疫调节作用，其机制涉及T细胞分化的调控及关键炎症通路的抑制。在疗效可媲美强的松的同时，其副作用更小，具备作为治疗MG 的有前景、循证基础的候选药物的潜力。

随着自身免疫疾病日益增多，此类研究有望为传统医学与现代科学之间架起一座希望之桥。

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Reference:

Zhuming Chen, Jing Lu, Tianying Chang, Dongmei Zhang, Yibin Zhang, Miao Liu, Tong Wu, Peng Xv, Jian Wang

Jianpi Yiqi Busui prescription alleviates myasthenia gravis by regulating Th17 through the TAK1/P38 MAPK/eIF-4E signaling pathway.

Biomol Biomed [Internet]. 2025 Feb. 7 [cited 2025 Apr. 10];

Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/11546

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