Saikokeishikankyoto (SKK)

What It Is

Definition / identity

• Saikokeishikankyoto (SKK) is a traditional Japanese (Kampo) herbal formulation.
• Its Chinese analog is Chaihu-Guizhi-Ganjiang Tang.

Ingredients / composition

According to the official package insert (Tsumura) for the SKK extract granules, one 7.5 g daily dose (divided) contains dried extracts from multiple crude herbs:

• Bupleurum root
• Scutellaria root
• Trichosanthes root
• Cinnamon bark
• Oyster shell
• Processed ginger
• Glycyrrhiza (licorice)

The Japanese Pharmacopoeia (JP) and Kampo prescription listings show similar proportions. Nikkankyo

Indications / traditional use

• In Kampo practice, SKK is used for a constellation of symptoms associated with a “weak constitution” and imbalance in autonomic / psychological state. The Tsumura insert indicates it is indicated for relief of symptoms in patients with slight oversensitivity to cold, slight anemia, palpitations, shortness of breath, nervousness, or autonomic imbalance (e.g. menopausal or neurosis-related symptoms, insomnia). Tsumura
• The Kampo.ca herbal formulary lists possible uses (in more general / symptomatic terms) such as anxiety, fatigue, neck/shoulder tension, dry mouth, cough, night sweats, insomnia, nervousness, depression. Kampo

Approved dosage and forms (Japan / Kampo context)

• In Japan, SKK is marketed as extract granules for “ethical use” (i.e. prescription) under standard Kampo practice. Tsumura
• The usual adult dosage is 7.5 g/day (in divided doses, typically 2 or 3 times) before or between meals, though adjustments may be made depending on body weight or patient age. Tsumura
• Another product listing (Teikoku) states a dose of 2.5 g three times daily (i.e. same total 7.5 g) as standard. 帝國製薬株式会社
• The package insert “Kampo Formulations for Prescription 2024” lists similar daily doses and ingredient breakdowns. Nikkankyo

How It Works (Mechanisms / Hypotheses / Evidence)

Because SKK is a multicomponent herbal formula used in traditional medicine, its precise mechanisms are not fully elucidated in conventional Western biomedical terms. But some preclinical, clinical, and theoretical insights exist:

Traditional (Kampo) rationale

• In Kampo theory, SKK is prescribed based on a patient’s SHO (a diagnostic pattern / constitution) — the idea is that the herbal combination helps correct imbalances in qi, harmonizes internal states, counteracts stagnation, or modulates autonomic reactivity.
• The prescription is not “one size fits all” — careful matching to the patient’s pattern (symptoms, constitution) is emphasized; if symptoms do not improve, extended use is discouraged. Tsumura

Biological / pharmacological findings

PTSD clinical trial evidence

• In a randomized, observer-blinded controlled trial of SKK for PTSD in survivors of the 2011 Great East Japan earthquake and tsunami, SKK significantly improved PTSD symptom scores (as measured by the Impact of Event Scale–Revised, IES-R) over two weeks compared to a control group. Europe PMC
• In that trial, subscales of avoidance, intrusion, and hyperarousal all improved in the SKK group. Europe PMC
• This suggests that SKK may exert effects on stress response, mood regulation, or neuroendocrine / autonomic pathways.

Molecular / animal / cell-based studies

• A 2021 study reported that hot-water SKK extracts could alleviate muscle atrophy in a diabetic / obesity mouse model, possibly via upregulating Sirt1 transcriptional activity. SpringerLink
• Some herbal components (e.g. Bupleurum, licorice) are known in pharmacology to have immunomodulatory, anti-inflammatory, or stress-response–modulating properties; some may influence cytokine levels (e.g. interleukin-6) or neurochemical systems. (This is more speculative in the SKK context.) Student Doctor Network

Safety / side effect evidence

• The package insert (Tsumura) notes that because SKK contains Glycyrrhiza (licorice root), care must be taken with potassium levels, blood pressure, and risk of pseudoaldosteronism (a syndrome characterized by sodium retention, hypokalemia, edema, hypertension). Tsumura
• Additionally, adverse reactions listed in Teikoku’s insert include possible interstitial pneumonia, myopathy (via hypokalemia), hepatic dysfunction, and hypersensitivity reactions. 帝國製薬株式会社

Thus, the “how it works” combines both traditional theoretical mechanisms (balance, pattern-based remedy) and emerging biomedical evidence (effects on stress, inflammation, metabolic pathways). But the mechanistic understanding remains incomplete.

Why It’s Important (Potential Uses / Value / Significance)

Adjunct or alternative option in stress / trauma contexts

• Because psychiatric and psychological services (e.g. therapists) may be in short supply (especially in disaster-affected regions), SKK offers a potential complementary approach for treating PTSD or trauma-related symptoms in certain settings. The trial after the Great East Japan earthquake is a notable example. Semantic Scholar PDFs

Symptomatic relief in stress / autonomic / menopausal / neurosis-like conditions

• In clinical Kampo practice, SKK is important for patients who present with symptoms such as mild autonomic imbalance, sleep disturbance, mild anxiety / neurosis, palpitations, and “weak constitution.” Its role is to offer a more holistic (multisystem) remedy rather than isolated symptom targeting.

Multicomponent, systems-level effect

• Because SKK is herbal and contains multiple active constituents, it might modulate multiple pathways (neuroendocrine, immune, metabolic) simultaneously. This so-called “network pharmacology” aspect can be advantageous in complex disorders (e.g. stress, mood, metabolic dysfunction).

Potential novel discoveries / leads

• Preclinical findings (e.g. the Sirt1 effect on muscle atrophy) hint that SKK or its components might be sources for new therapeutic leads or deeper mechanistic insights into aging, metabolic disease, or stress resilience.

Cultural and integrative medicine value

• In Japan and other East Asian medical contexts, SKK is part of a broader system (Kampo) integrated into conventional health care; thus it has institutional legitimacy, regulatory approval, and transparency in dose/formulation — making it more accessible and standardized compared to many “herbal supplements.”

Considerations (Risks, Limitations, Gaps, Cautions)

While SKK shows promise, there are many caveats and important considerations:

Limited high-quality evidence / small trials

• The clinical trial in PTSD involved only 43 participants and a short duration (2 weeks). Semantic Scholar PDFs
• Its power to detect long-term efficacy, safety, and comparison to standard pharmacotherapy or psychotherapy is limited.
• More, larger-scale randomized controlled trials (with longer follow-up, diverse populations, rigorous methodology) are needed before SKK can be broadly recommended.

Safety and adverse effects

• Because SKK contains licorice (Glycyrrhiza), risk of pseudoaldosteronism is real: hypokalemia, sodium retention, edema, hypertension. Monitoring of serum electrolytes (especially potassium) and blood pressure is advisable. Tsumura
• Myopathy risks may increase under low potassium conditions. 帝國製薬株式会社
• Hepatic dysfunction and allergic reactions are also possible and noted in package inserts. 帝國製薬株式会社
• Interstitial pneumonia is mentioned as a possible adverse in Teikoku’s insert: if fever, cough, dyspnea appear, discontinuation and evaluation are warranted. 帝國製薬株式会社
• In combination with other Kampo formulas or herbal medicines, duplication of crude drugs, or interactions, can compound risks (especially for components like licorice). Tsumura

Patient selection (“SHO” matching) is crucial

• SKK is not universally suitable — in Kampo philosophy, it must match the patient’s SHO or pattern. Use without careful diagnostic alignment may reduce efficacy or increase risk of adverse effects.
• Moreover, in the package insert for SKK, there is a caveat that if no improvement is seen, continuous use should be avoided. Tsumura

Contraindications / careful use

• Pregnant or lactating women: safety not well established; use only if benefit outweighs risk. 帝國製薬株式会社
• Children: safety is not established. 帝國製薬株式会社
• Patients with existing liver disease, renal dysfunction, chronic respiratory disease are often excluded in trials or advised caution. RCT Portal
• Use with drugs that affect potassium (e.g. diuretics, corticosteroids, digoxin) must be monitored closely.

Quality control, standardization, and reproducibility

• As with many herbal formulas, batch-to-batch consistency, purity, contamination (heavy metals, pesticides), and standardization of active components are ongoing challenges. Even though SKK is manufactured under regulated Kampo systems in Japan, when used outside that context, quality may vary.

Regulatory and integration barriers

• In many countries, SKK may not be approved or may be classified as a dietary supplement / herbal medicine, not a prescription drug, which limits its use, oversight, and insurance coverage. Clinical adoption outside Japan / East Asia may face regulatory, cultural, or evidence-barrier challenges.

Unknown long-term effects

• Because most studies are short-term, the long-term safety, efficacy, interactions, and potential cumulative toxicity remain unclear.