Academic Blog • Jade Health Acupuncture

Acupuncture, Oxidative Stress, and Neurodegeneration: Insights from the Nrf2/ARE Pathway

Based on: Huang Y-Y et al., 2021 (PMC8096560)

1. Introduction

Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are two major neurodegenerative disorders characterized by progressive decline in cognitive or motor function. Increasing evidence suggests that oxidative stress—a state where the body cannot adequately counteract free-radical damage—plays a central role in both conditions.

A 2021 review by Huang et al. systematically examined animal-model studies exploring how acupuncture might reduce oxidative stress by activating the Nrf2/ARE antioxidant defence pathway.

This pathway is considered one of the body’s most important protective systems against oxidative injury, particularly relevant to neurodegeneration.

2. What is the Nrf2/ARE Pathway?

The Nrf2/ARE pathway functions as an internal “antioxidant switch”:

Nrf2 (Nuclear factor erythroid 2–related factor 2) is a transcription factor.
When activated, Nrf2 translocates into the nucleus and binds to ARE (Antioxidant Response Element).
This binding triggers expression of antioxidant and cytoprotective enzymes.

Key Nrf2/ARE-related enzymes include:

HO-1 (heme oxygenase-1)
NQO1 (NAD(P)H quinone dehydrogenase 1)
SOD (superoxide dismutase)

These enzymes help neutralize reactive oxygen species (ROS), reduce oxidative injury, and support neuronal survival.

3. Key Findings from Animal Studies

3.1 Acupuncture Upregulates Nrf2 Activation

Across multiple AD and PD animal models, acupuncture and electroacupuncture were reported to:

Increase Nrf2 protein expression
Promote Nrf2 translocation into neuronal nuclei
Enhance downstream ARE-related antioxidant enzymes (e.g., HO-1, NQO1)

These findings suggest that acupuncture may strengthen endogenous antioxidant defence mechanisms in the brain.

3.2 Reduction of Oxidative Stress Biomarkers

The review also summarized consistent reductions in oxidative stress markers after acupuncture:

Lower reactive oxygen species (ROS)
Decreased malondialdehyde (MDA)
Reduced lipid peroxidation products

In parallel, overall antioxidant capacity was improved in these animal models.

3.3 Improvements in Behavioural and Pathological Outcomes

Beyond biochemical markers, some studies reported functional and pathological benefits:

In PD models, acupuncture improved motor performance.
In AD models, it reduced amyloid-related pathology in selected experimental settings.
Mitochondrial function tended to stabilize, and neuroinflammation markers were reduced.

These outcomes support the idea that acupuncture might offer neuroprotective effects, at least in preclinical animal research.

4. Limitations

While the findings are promising, several important limitations must be emphasized:

Animal models only mimic certain aspects of AD and PD and cannot fully replicate human disease.
Acupuncture protocols (acupoints, frequency, duration, stimulation type) varied widely across studies.
High-quality human clinical trials specifically targeting the Nrf2/ARE mechanism are still limited.
Mechanistic improvements (e.g., oxidative markers) do not automatically translate into long-term clinical outcomes in patients.

5. Clinical and Research Implications

For integrative medicine and acupuncture practice, this review offers several key implications:

The Nrf2/ARE pathway provides a biologically plausible mechanism for acupuncture’s potential neuroprotective effects.
Acupuncture may be considered as an adjunctive approach within a broader care plan for patients at risk of, or living with, neurodegenerative conditions.
Clinicians can monitor functional outcomes (e.g., cognition, motor symptoms, sleep quality, mood) when applying supportive acupuncture in early or mild stages.
Future research combining acupuncture with biomarker tracking (oxidative stress, imaging, cognitive tests) may clarify its role in human neurodegenerative disease.

6. Conclusion

The reviewed evidence suggests a promising link between acupuncture and the body’s antioxidant defence network. In AD and PD animal models, acupuncture appears to modulate oxidative stress via activation of the Nrf2/ARE pathway, resulting in reduced oxidative damage and partial neuroprotection.

Although human data are still emerging, these mechanistic insights open interesting directions for future integrative neurology research and may help explain why some patients report improved clarity, mobility, or resilience with regular acupuncture care.

Reference

Huang Y-Y, Lin J-G, Chen Y-H, Hung Y-C, Chen Y-H. Effects of Acupuncture on Oxidative Stress Amelioration via Nrf2/ARE Pathway in Alzheimer’s Disease and Parkinson’s Disease Animal Models. 2021.

Full text available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC8096560/

學術交流 • Jade Health Acupuncture

針灸、氧化壓力與神經退化：來自 Nrf2/ARE 路徑的研究啟示

文章整理自：Huang Y-Y 等人，2021（PMC8096560）

一、前言

阿茲海默症（Alzheimer’s Disease, AD）與巴金森氏症（Parkinson’s Disease, PD）是兩大常見的神經退化性疾病，其典型表現為記憶、思考、動作等功能的逐漸下降。越來越多研究指出，氧化壓力（oxidative stress）在兩種疾病的發展與惡化過程中扮演關鍵角色。

2021 年，Huang 等人發表一篇綜述性論文，整理各種 AD、PD 動物模型的研究，探討針灸是否能透過活化 Nrf2/ARE 抗氧化防禦路徑，來減少神經系統的氧化損傷。

Nrf2/ARE 路徑被視為細胞最重要的內在抗氧化系統之一，對神經退化相關疾病尤其受到關注。

二、Nrf2/ARE 路徑是什麼？

Nrf2/ARE 路徑可以理解為身體啟動「抗氧化開關」的一個重要機制：

Nrf2（Nuclear factor erythroid 2–related factor 2） 是一種轉錄因子。
當 Nrf2 被活化後，會進入細胞核，並結合到 ARE（Antioxidant Response Element，抗氧化反應元素） 上。
進而啟動多種抗氧化與細胞保護相關的基因表達。

主要相關的抗氧化酵素包括：

HO-1（heme oxygenase-1，血基質氧合酶-1）
NQO1（NAD(P)H quinone dehydrogenase 1）
SOD（superoxide dismutase，超氧化物歧化酶）

這些酵素可以幫助清除活性氧（ROS），減少氧化傷害，維護神經細胞存活。

三、動物模型中的主要發現

3.1 針灸可促進 Nrf2 活化

在多種 AD、PD 動物模型中，無論是傳統針刺或電針，研究普遍發現：

Nrf2 蛋白表達量增加
Nrf2 更容易進入細胞核內發揮作用
ARE 下游的抗氧化酵素（如 HO-1、NQO1）表達提升

這些結果顯示，針灸可能增強大腦內在的抗氧化防禦能力，對抗神經氧化損傷。

3.2 降低氧化壓力生物標記

綜述中也指出，針灸常見的效果之一，是降低氧化壓力相關的指標：

活性氧（ROS）濃度下降
脂質過氧化產物，例如 MDA（malondialdehyde）減少

同時，整體抗氧化能力有改善的趨勢。

3.3 行為與病理結果的改善

除了生化指標外，部份研究也觀察到功能與病理上的正向變化，例如：

在 PD 模型中，針灸可改善動作協調與活動能力。
在 AD 模型中，部份研究顯示類澱粉相關病變有所減少。
粒線體功能相對穩定，神經發炎指標降低。

整體而言，這些結果支持「針灸可能具有神經保護效果」的假說，但目前證據仍多來自動物實驗。

四、研究限制與需要謹慎之處

儘管結果令人期待，但仍有幾個需要謹慎看待的點：

動物模型只能模擬人類疾病的一部分，無法完全等同於臨床情況。
各研究使用的針灸穴位、頻率、刺激時間、療程長度差異很大，不易直接比較或標準化。
目前以 Nrf2/ARE 機轉為主題的人體臨床試驗仍相對有限。
機轉上的改善（例如氧化壓力指標）並不一定直接代表長期臨床症狀的明顯好轉。

五、對臨床與研究的意涵

對於從事整合醫學與針灸實務的臨床工作者而言，這篇綜述帶來幾個值得參考的方向：

Nrf2/ARE 路徑為針灸提供了神經保護潛力的生物學基礎，讓我們在向患者解釋時不只停留在「放鬆、舒緩」，而是可以談到細胞層級的保護機制。
在 AD、PD 或其他神經退化相關疾病的照護中，針灸可被視為輔助性療法，搭配藥物、復健、生活調整等多面向介入。
臨床上可定期追蹤患者的記憶、注意力、步態、睡眠品質與情緒變化，作為觀察針灸支持性效果的實際指標。
未來若能結合生物標記（如氧化壓力相關檢驗）、影像與功能測試，將有助於更清楚針灸在神經退化疾病中的角色。

六、結語

綜合目前動物實驗的證據，針灸似乎能透過活化 Nrf2/ARE 抗氧化防禦路徑，降低大腦的氧化壓力與相關損傷，在 AD 與 PD 模型中展現一定程度的神經保護效果。

然而，這些結果仍屬於前臨床研究，人類臨床試驗仍在進行與累積中。對臨床醫師與治療師來說，更合理的態度是：將針灸視為具生物學合理性的整合療法之一，謹慎地與現代醫學治療併行，而非取代。

參考文獻

線上全文： https://pmc.ncbi.nlm.nih.gov/articles/PMC8096560/