Anti-Inflammatory Effects of Acupuncture at ST36 Point: A Literature Review in Animal Studies
Oh & Kim · Frontiers in Immunology · 2022
Evidence Level
MODERATEOBJECTIVE
Review how acupuncture at the ST-36 point regulates inflammation and its mechanisms in animal studies
WHO
Preclinical studies in animal models of various inflammatory conditions
DURATION
Search through July 2021
POINTS
ST-36 (Zusanli) — primary point of anti-inflammatory research
🔬 Study Design
Studies in body fluids
n=43
acupuncture/electroacupuncture at ST-36
Digestive system studies
n=27
acupuncture/electroacupuncture at ST-36
Nervous system studies
n=17
acupuncture/electroacupuncture at ST-36
📊 Results in numbers
Studies included
Exclusion rate
Mechanisms identified
Systems studied
Percentage highlights
📊 Outcome Comparison
Distribution by systems studied
This scientific review analyzed 69 animal studies that investigated how acupuncture at the ST-36 point (located on the leg) can reduce inflammation. The results show that this specific point has anti-inflammatory effects through several mechanisms, including vagus nerve activation and reduction of inflammatory cytokines.
Article summary
Plain-language narrative summary
Acupuncture at the ST-36 point, known as Zusanli in traditional Chinese medicine, has been widely studied as a promising alternative therapy for the treatment of inflammatory conditions. This specific point, located in the anterior part of the leg, has aroused great scientific interest due to its consistent anti-inflammatory effects demonstrated in different experimental models. Although many studies have individually investigated the mechanisms by which acupuncture at ST-36 modulates inflammation, a comprehensive analysis that systematically organized all these findings to provide a complete picture of the anti-inflammatory effects of this ancient technique did not yet exist.
To fill this gap in scientific knowledge, researchers at Dongguk University in South Korea conducted a systematic review of the scientific literature published through July 2021. The main objective was to investigate how acupuncture at the ST-36 point regulates inflammation and which biological mechanisms underlie these effects. The researchers conducted a comprehensive search in the PubMed database using specific keywords such as "animal," "acupuncture," "ST36," "inflammation," and "immune," initially identifying 292 relevant studies. After applying rigorous selection criteria, which included studies conducted exclusively in animal models with a focus on the anti-inflammatory effects of acupuncture at ST-36, the authors selected 69 high-quality studies for detailed analysis.
These studies were then organized according to the anatomical regions investigated, allowing for a clearer understanding of how acupuncture affects different body systems.
The analysis revealed fascinating findings about the multiple mechanisms through which acupuncture at ST-36 exerts its anti-inflammatory effects. Forty-three studies examined changes in body fluids such as blood and plasma, demonstrating that acupuncture can significantly reduce levels of pro-inflammatory cytokines such as tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta. Twenty-seven studies focused on the digestive system, showing that acupuncture can protect the intestinal barrier, reduce inflammatory cell infiltration, and modulate the composition of the gut microbiota. Seventeen studies investigated the nervous system, revealing that acupuncture can reduce neuroinflammation and modulate glial cell activity.
Additionally, thirty studies examined other tissues and organs, including liver, lungs, joints, and muscle tissues, demonstrating consistent anti-inflammatory effects throughout the body.
The identified mechanisms include activation of the vagus nerve, which is a crucial neural pathway for the regulation of the systemic inflammatory response. Acupuncture at ST-36 demonstrated activation of what scientists call the "cholinergic anti-inflammatory pathway," in which neural signals can rapidly suppress the production of pro-inflammatory cytokines in organs such as the spleen. Another important mechanism involves modulation of the TLR4/NF-kB signaling pathway, which is central to the regulation of the innate immune response. Acupuncture also influences macrophage polarization, favoring the anti-inflammatory M2 phenotype over the pro-inflammatory M1 phenotype.
Additionally, the technique affects signaling pathways such as MAPK and the activation of cannabinoid receptors, contributing to its therapeutic effects.
These findings have significant clinical implications for both patients and healthcare professionals. For patients suffering from chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel diseases, or chronic pain, acupuncture at ST-36 offers a promising therapeutic option with the potential to reduce dependence on conventional anti-inflammatory medications. Nonsteroidal anti-inflammatory drugs, although effective, can cause significant side effects in the gastrointestinal, cardiovascular, and renal systems, especially with prolonged use. Acupuncture has a favorable safety profile, serving as a valuable alternative or complementary therapy.
For healthcare professionals, these findings provide a robust scientific basis for incorporating acupuncture into treatment protocols for inflammatory conditions, offering an integrative approach that can improve therapeutic outcomes.
It is important to recognize some limitations of this review. First, all analyzed studies were conducted in animal models, mainly rodents, which may limit the direct extrapolation of results to humans due to physiological differences between species. Second, there was considerable variability in the acupuncture protocols used among the studies, including different frequencies of electrical stimulation, duration of treatment, and application techniques, which can influence the results obtained. Third, although the identified mechanisms are biologically plausible, many studies investigated only specific aspects of the inflammatory response, not providing a complete view of how all these mechanisms interact in real clinical conditions.
Controlled clinical studies in humans are necessary to confirm these findings and establish optimized treatment protocols. Despite these limitations, this review represents a significant advance in understanding the anti-inflammatory mechanisms of acupuncture at ST-36, providing a solid foundation for future clinical investigations and offering valuable insights into how this ancient practice can be effectively integrated into modern medicine for the management of inflammatory conditions.
Strengths
- 1Comprehensive analysis of 69 studies
- 2Multiple mechanisms identified
- 3Consistent evidence across different models
- 4Systematic organization by body systems
Limitations
- 1Preclinical studies only
- 2Heterogeneity of protocols
- 3Need for clinical validation
- 4Limited to animal models
Expert Commentary
Dr. Marcus Yu Bin Pai
MD, PhD · Pain Medicine · Physical Medicine and Rehabilitation · Medical Acupuncture
▸ Clinical Relevance
Understanding the anti-inflammatory mechanisms of the ST-36 (Zusanli) point repositions acupuncture in the management of chronic inflammatory conditions beyond traditional empiricism. For the physiatrist who deals daily with rheumatoid arthritis, inflammatory low back pain, and pain syndromes with a neuroinflammatory component, having a consistent mechanistic map — reduction of TNF-alpha, IL-6, and IL-1 beta, modulation of the TLR4/NF-kB pathway, and activation of the vagal cholinergic anti-inflammatory reflex — transforms the choice of ST-36 into a rational and sustainable decision. The favorable safety profile makes this approach especially pertinent in patients with contraindications to prolonged NSAIDs, such as elderly patients with elevated cardiovascular or gastrointestinal risk, and those with inflammatory bowel disease where modulation of the mucosal barrier and microbiota represents an additional therapeutic target.
▸ Notable Findings
Among the most relevant findings of this review of 69 preclinical studies, the convergence of evidence in favor of the cholinergic anti-inflammatory pathway stands out: stimulation of ST-36 activates the vagus nerve and systemically suppresses the production of pro-inflammatory cytokines via splenic signaling — a neuroimmune mechanism with response speed that no conventional oral anti-inflammatory drug replicates by the same route. The influence on macrophage polarization, shifting the M1 phenotype toward M2, is particularly relevant in conditions of chronic tissue inflammation. The protection of the intestinal barrier and modulation of the microbiota, demonstrated in 27 studies of the digestive system, opens an interesting therapeutic window for conditions such as irritable bowel syndrome with an inflammatory component. The consistency of effects across multiple systems — body fluids, nervous system, liver, lungs, joints — reinforces that ST-36 operates on fundamental inflammatory pathways, not on tissue-specific mechanisms.
▸ From My Experience
In my practice in the musculoskeletal pain clinic, ST-36 is rarely used in isolation — it is almost always integrated into multipoint protocols in which systemic modulation of inflammation is the secondary objective, while the primary target is segmental points or local trigger points. I have observed that patients with mild to moderate inflammatory polyarthralgia, or with chronic low back pain with a documented inflammatory component, respond visibly after 4 to 6 sessions of electroacupuncture, with maintenance cycles every 3 to 4 weeks after the intensive phase of 8 to 12 sessions. The profile that responds best, which I have identified throughout my career, is the patient with real systemic inflammatory burden, not just pure mechanical pain — the one with slightly elevated CRP, associated fatigue, and worse conditioned pain modulation. I avoid indicating the technique in isolation in severe acute inflammatory conditions, in which pharmacological control is irreplaceable; there, acupuncture enters as an adjuvant after stabilization. The mechanistic detail of this review confirms what empirically already guided our protocol choices.
Full original article
Read the full scientific study
Frontiers in Immunology · 2022
DOI: 10.3389/fimmu.2021.813748
Access original articleScientific Review

Marcus Yu Bin Pai, MD, PhD
CRM-SP: 158074 | RQE: 65523 · 65524 · 655241
PhD in Health Sciences, University of São Paulo. Board-certified in Pain Medicine, Physical Medicine and Rehabilitation, and Medical Acupuncture. Scientific review and curation of every entry in this library.
Learn more about the author →Medical disclaimer: This content is for educational purposes only and does not replace consultation, diagnosis, or treatment by a qualified professional. Some information may be assisted by artificial intelligence and is subject to inaccuracies. Always consult a physician.
Content reviewed by the medical team at CEIMEC — Integrated Centre for Chinese Medicine Studies, a reference in Medical Acupuncture for over 30 years.
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