Anshen Dingzhi Ling (ADL)

What It Is

Nature / Type

• ADL is a TCM herbal prescription (a decoction or formula) used in Chinese medicine, especially in Jiangsu and affiliated hospitals, for the management of ADHD symptoms (inattention, hyperactivity, impulsivity) in children and in experimental models. Frontiers
• In the literature, the term often used is An Shen Ding Zhi Ling (ASDZL), which seems to be essentially the same or closely related to ADL in naming and function. Frontiers

Composition / Ingredients

• The formula is composed of multiple herbs — the version in a key animal-model study uses 12 herbs: Scutellariae Radix, Bupleuri Radix, Forsythiae Fructus, Curcumae Radix, Cassiae Semen, Bambusae Concretio Silicea, Uncariae Ramulus cum Uncis, Rehmanniae Radix, Acori Tatarinowii Rhizoma, Angelicae Sinensis Radix, Alpiniae Oxyphyllae Fructus, and Polygalae Radix. Frontiers
• Some earlier or variant studies also investigate how ADL acts on dopamine-related enzymes or receptors, indicating its “core formula” is modifiable or has multiple functional components. zgsyfjxzz.ijournals.cn
• One paper also mentions that ADL / Anshen Dingzhi Ling was formulated by Professor Xinmin Han and has been used clinically for over 20 years in certain TCM hospitals. Frontiers

Clinical / Empirical Use

• It is included in some Chinese Medical Clinical Pathway for treating ADHD protocols (in Jiangsu). Frontiers
• There are clinical observations (in China) of its use in children with ADHD; though rigorous randomized controlled trials (especially by Western standards) are more limited in availability in the public literature. Frontiers

How It Works (Proposed / Investigated Mechanisms)

Because TCM formulas are complex mixtures, the reported mechanisms are multiple and not fully settled. The studies mostly use animal models (especially spontaneously hypertensive rats, SHR) as models of ADHD. Below are main findings / hypotheses:

Reduction of Neuroinflammation

• ADL / ASDZL appears to reduce proinflammatory cytokines (IL-1β, IL-4, IL-6, TNF-α, MCP-1) and increase anti-inflammatory factors such as IL-10 in the prefrontal cortex and hippocampus in SHR models. Frontiers
• It also seems to reduce activation of glial and immune cells in the brain: microglia, astrocytes, and mast cells show reduced activation in treated animals. Frontiers
• The formula also is associated with protection of the blood-brain barrier (BBB) integrity, which is relevant because neuroinflammation often involves BBB disruption. Frontiers
• In terms of signaling, suppression of MAPK and NF-κB signaling pathways (common inflammatory pathways) has been observed in treated animals. Frontiers

Modulation of Dopaminergic / Dopamine System

• Because ADHD is often conceptualized (in part) as a disorder of dopamine signaling (insufficient dopamine in synapses, dysregulation of transporter or receptor function), ADL has been studied for its influence on these systems:
• In one study, ADL increased expression and activity of tyrosine hydroxylase (TH), dopa decarboxylase (DDC), and protein kinase A (PKA) in synaptosomes (i.e. in neurotransmitter release machinery), which are enzymes relevant to dopamine synthesis and signaling. This suggests ADL may increase the speed or capacity of dopamine synthesis. zgsyfjxzz.ijournals.cn
• Another study looked at dopamine transporter (DAT) expression: ADL (medium and high dose) reduced DAT mRNA and protein expression in striatum of SHR rats (DAT is the reuptake transporter which, when reduced, leads to more dopamine remaining in the synaptic cleft). Thus ADL may block reuptake of dopamine, allowing more dopamine in synapses. xueshu.baidu.com
• It also influences dopamine receptor expression. For example, a study measured DRD1 and DRD2 expression in prefrontal cortex and striatum in SHR rats with/without ADL treatment, showing that ADL may modulate those receptor levels. Peertechz Publications
• In a more recent mechanistic paper, the authors explored how ADL influences the BDNF / TrkB signaling pathway (brain-derived neurotrophic factor) in PFC and hippocampus synaptosomes. They found that ADL can increase levels of BDNF, TrkB, p75, JNK1, and NF-κB in synaptosome compartments. The authors propose that ADL mediates a balance between BDNF/TrkB (which promotes vesicle circulation / neurotransmitter release) and BDNF/p75/JNK1/NF-κB (which may inhibit vesicle circulation), thereby modulating dopamine release/availability in synaptic clefts. Semantic Scholar
• Through these mechanisms, ADL aims to increase the concentration of dopamine in the synaptic cleft, improve dopamine signaling / neurotransmission, and thereby mitigate ADHD-like behaviors. Semantic Scholar

Behavioral / Cognitive Effects in Animal Models

• In SHR animals, ADL treatment over weeks reduced hyperactivity and impulsivity, and improved spatial memory, as assessed by open field tests and Morris water maze tests, compared to untreated SHR controls. Frontiers
• The behavioral improvement is taken as a correlate to its biochemical effects above.

Why It’s Important / What It Offers

Alternative / Complementary to Existing ADHD Treatments

• Many conventional ADHD treatments (e.g. stimulants like methylphenidate, non-stimulants) have side effects, and not all patients respond well. A TCM adjunct or alternative like ADL may provide a complementary approach, especially in settings (China, TCM hospitals) where integration of herbal medicine with conventional medicine is practiced.

Multi-target and Multi-mechanism

• As an herbal formula with many components, ADL can act on multiple pathways (inflammation, dopamine synthesis, transport, receptor expression, neurotrophic factors). This “systems” or network effect is appealing in complex brain disorders where multiple dysregulated pathways coexist.

Focus on Neuroinflammation

• Emerging research suggests neuroinflammation plays a role in various psychiatric / neurodevelopmental conditions, including ADHD. ADL’s anti-inflammatory properties in the CNS may address aspects of ADHD pathophysiology not targeted by standard stimulant therapies. Frontiers

Regulation of Synaptic Dopamine Homeostasis

• By modulating the balance of dopamine synthesis, reuptake, receptor sensitivity, and synaptic release (via BDNF pathways), ADL has the potential to more finely “tune” dopaminergic signaling rather than bluntly pushing dopamine levels upward, which might reduce side effects.

Cultural / Clinical Relevance in Chinese Medicine Context

• In Chinese clinical practice, formula-based herbal medicine is integrated routinely. Having a formula like ADL that is recognized and used in TCM hospitals and clinical pathways lends it relevance where patients are already seeking combined (integrative) therapies.

Considerations, Limitations, & Cautions

While the research is promising, there are many caveats and limitations to keep in mind:

Evidence Level & Human Clinical Trials

• Much of the mechanistic and efficacy evidence comes from animal models (especially SHR rats). Translating these findings to humans is nontrivial. Frontiers
• The human clinical evidence is more limited. There are observational / “clinical observation” reports (in children) of ADHD symptom improvement, but few high-quality randomized, double-blind, placebo-controlled trials published (especially in English) to firmly establish efficacy and safety. Semantic Scholar
• The methodologies of existing human studies are often not well documented in public literature, making critical assessment challenging.

Formulation Consistency and Standardization

• Herbal formulas can vary in exact herb sources, quality, processing, dosages, extraction methods, etc. This introduces variability in potency, bioavailability, and safety.
• The translation of dosages from animal models (often very high per kg) to safe human-equivalent doses is nontrivial.

Complex Mixture and Potential Interactions

• Because ADL involves many herbs, it may interact (synergistically or antagonistically) with conventional medications (e.g. stimulants, antidepressants, antipsychotics, or other CNS-active drugs). These interactions are not well studied in the public literature.
• Herbal formulas may also have components that stress the liver, kidney, or other organs, or cause allergic or idiosyncratic reactions. Adequate toxicology profiling is essential before wide clinical use.

Safety, Toxicity, and Long-Term Effects

• Long-term safety (especially in children) is largely unknown in rigorous studies.
• Some herbal formulas, if misprepared or contaminated, may carry risks (heavy metals, adulteration, contamination). Quality control is crucial.

Regulatory and Ethical Issues

• In many countries, herbal formulas are regulated differently from pharmaceuticals. Their claims may not be tightly controlled, and oversight of manufacturing standards may vary.
• In clinical settings outside of China, integrating ADL would require navigating regulatory, institutional, and evidence-based medicine standards.

Patient Selection and TCM Diagnosis

• In TCM practice, formulas are often prescribed not solely on disease label but on pattern differentiation (i.e. the specific “syndrome” in the TCM framework). ADL may be more effective in patients whose TCM diagnosis matches a pattern for which ADL is indicated.
• Not every ADHD patient would “fit” the TCM pattern for which ADL is optimal; a one-size-fits-all use may reduce effectiveness or increase adverse effects.

Comparison to Conventional Therapies

• It remains uncertain how ADL compares with standard ADHD medications in terms of effect size, onset speed, side effect profile, and durability of benefits.
• Combining ADL with standard therapies might offer synergistic benefits but also could lead to unforeseen interactions.