White Peony

Metadata

Approved Indications

Chinese Pharmacopoeia

• Official drug in the Pharmacopoeia of the People’s Republic of China (all editions)
• Listed as: Paeoniae Radix Alba (Bai Shao), produced from the root of P. lactiflora by removing root bark and drying
• Traditional indications: Headache and dizziness, flank and abdominal pain, muscle spasms and cramps, dysmenorrhea, irregular menstruation, spontaneous sweating, night sweats
• TCM category: Blood-tonifying, Liver-calming, pain-relieving
• Quality standard: Minimum paeoniflorin content of 1.6% by HPLC

Kampo Official Formulas (Japan)

• Shakuyaku-kanzo-to (TJ-68, Peony-Licorice Decoction): One of the 148 Kampo extract formulas approved for prescription by Japan’s Ministry of Health, Labour and Welfare and covered under the National Health Insurance Drug Tariff. Indicated for acute muscle cramps and spasms.
• Tokishakuyakusan (Dang Gui Shao Yao San): Approved Kampo formula for menstrual irregularities, dysmenorrhea, menopausal complaints, and habitual miscarriage.
• Kamishoyosan (Jia Wei Xiao Yao San): Approved for menopausal syndrome, anxiety, and irritability.
• Shakuyaku (peony root) is a component in over 30 approved Kampo formulas.

Total Glucosides of Peony (TGP) — China

• Approved drug in China since 1998 by the China Food and Drug Administration (now NMPA) as an anti-inflammatory and immunomodulatory agent
• Trade name: Pa Fu Lin (帕夫林) capsules
• Approved indication: Adjunctive treatment of rheumatoid arthritis
• Standardization: 0.3 g capsules, each containing no less than 104 mg paeoniflorin

European Regulatory Status

• No Commission E monograph (Germany)
• No ESCOP monograph
• No EMA/HMPC monograph or assessment report
• Available in Europe only as a food supplement or traditional herbal product
• The absence of European monographs reflects the regulatory framework’s difficulty with TCM-origin herbs rather than a negative evaluation of the evidence

Agreement/Disagreement Between Bodies

• Strong East Asian recognition: Official drug in Chinese, Japanese, and Korean pharmacopoeias with extensive formulary inclusion
• Complete European absence: No European regulatory body has evaluated or adopted white peony
• Unique regulatory status of TGP: One of very few traditional herbal extracts approved as a pharmaceutical drug (not just a supplement) in China for a specific modern disease indication (RA)

Conditions Treated

Menstrual Disorders and Gynecological Conditions

• Dysmenorrhea: Primary traditional indication; Bai Shao is a key component of Dang Gui Shao Yao San and Si Wu Tang (Four Substances Decoction), the two most prescribed TCM gynecological formulas
• Irregular menstruation: Traditional use for both scanty and excessive menstruation, especially when attributed to “blood deficiency” or “Liver blood stasis” in TCM
• Menopausal symptoms: Component of Kamishoyosan (Jia Wei Xiao Yao San), studied for hot flashes and emotional symptoms
• Threatened miscarriage: Traditional use in combination formulas (Tokishakuyakusan)

Polycystic Ovary Syndrome (PCOS)

• Emerging indication with preclinical and early clinical evidence
• Paeoniflorin inhibits testosterone production through downregulation of CYP17A1 and CYP11A1 in theca cells (PMID: 30195059)
• Paeoniflorin promotes aromatase activity, shifting androgen-to-estrogen conversion (PMID: 1897494)
• Animal models show paeoniflorin attenuates DHEA-induced PCOS via TGF-beta1/Smads pathway inactivation, improving estrous cycle regularity and reducing ovarian fibrosis (PMID: 33638949)
• Clinical evidence primarily through combination formulas (e.g., Unkei-to containing peony reduced LH by 49.7% in PCOS patients)

Muscle Cramps and Spasms

• Shakuyaku-kanzo-to (peony-licorice decoction) is a well-established treatment in Japan for skeletal muscle cramps
• Used for cramps associated with hemodialysis, hepatic cirrhosis, lumbar spinal stenosis, and exercise
• Rapid onset: cramps resolved within 5.3 +/- 3.9 minutes in hemodialysis patients (PMID: 16685141)

Autoimmune Conditions

• Rheumatoid arthritis: TGP is an approved adjunctive therapy in China; multiple meta-analyses confirm efficacy when combined with DMARDs (methotrexate, leflunomide)
• Systemic lupus erythematosus (SLE): Meta-analyses of 14 RCTs (978 participants) show TGP combined with conventional treatment reduces SLEDAI scores, lowers prednisone requirements, and decreases infection episodes (PMID: 35237142)
• Sjogren’s syndrome: Preliminary evidence for TGP as adjunctive therapy
• Ankylosing spondylitis: Limited but emerging evidence

Pain Conditions

• Abdominal pain, flank pain, and headache (traditional TCM indications attributed to “Liver Qi stagnation”)
• Neuropathic pain (preclinical evidence for paeoniflorin)

Mechanism of Action

Key Active Compounds

Immunomodulatory Mechanisms (Th1/Th2 Balance)

White peony’s immunomodulatory action is bidirectional, modulating both overactive and underactive immune responses:

1. Th1/Th2 cytokine rebalancing: Paeoniflorin reduces Th1 pro-inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1beta) while promoting Th2 anti-inflammatory cytokines (IL-10, IL-13). This shift from Th1-dominant to balanced Th1/Th2 responses underpins its benefit in autoimmune conditions (PMID: 25971794)
2. Treg cell promotion: TGP upregulates TGF-beta1 and Foxp3 expression, enhancing regulatory T-cell function and immune tolerance
3. Macrophage polarization: Paeoniflorin exerts unique effects on macrophages, modulating both type I (pro-inflammatory) and type II (anti-inflammatory) macrophage activities (PMID: 26852260)
4. NF-kappaB pathway inhibition: Suppresses NF-kappaB nuclear translocation, reducing transcription of pro-inflammatory mediators
5. Dendritic cell modulation: Affects dendritic cell maturation and antigen-presenting function

Anti-inflammatory Mechanisms

1. Prostaglandin inhibition: Inhibits production of PGE2 and leukotriene B4
2. Nitric oxide suppression: Reduces inducible nitric oxide synthase (iNOS) expression and NO production
3. Intracellular calcium regulation: Inhibits intracellular Ca2+ influx, reducing inflammatory cascade activation
4. COX-2 inhibition: Downregulates cyclooxygenase-2 expression in inflammatory models
5. Synoviocyte suppression: In RA, suppresses fibroblast-like synoviocyte proliferation and inflammatory mediator production

Antispasmodic and Analgesic Mechanisms

1. Smooth and skeletal muscle relaxation: Paeoniflorin promotes potassium ion efflux and inhibits intracellular calcium influx via Ca2+-activated K+ channel inhibition, explaining the rapid relief of muscle cramps with Shakuyaku-kanzo-to
2. GABA-ergic activity: Some evidence for enhancement of GABAergic inhibitory neurotransmission
3. Adenosine receptor involvement: Paeoniflorin may exert analgesic effects partly through adenosine A1 receptor activation

Anti-androgenic Mechanisms (PCOS Relevance)

1. CYP17A1 downregulation: Reduces 17-alpha-hydroxylase activity in ovarian theca cells, decreasing androgen synthesis
2. Aromatase promotion: Enhances aromatase enzyme activity, promoting conversion of testosterone and androstenedione to estradiol and estrone
3. CYP11A1 suppression: Decreases cholesterol side-chain cleavage enzyme, reducing overall steroidogenesis
4. Ovarian fibrosis attenuation: Inhibits TGF-beta1/Smads signaling pathway, reducing PCOS-associated ovarian fibrosis

Clinical Evidence Summary

Shakuyaku-kanzo-to (Peony-Licorice Decoction) for Muscle Cramps

Key findings: Shakuyaku-kanzo-to demonstrates consistent rapid-onset efficacy for acute muscle cramps across multiple settings. The formula is widely prescribed in Japan (estimated >7 million prescriptions annually). Evidence quality is limited by the small number of formal RCTs, but the consistent clinical experience across decades of Japanese clinical practice is notable. Long-term use requires monitoring for pseudoaldosteronism due to the licorice (glycyrrhizin) component.

Total Glucosides of Peony (TGP) for Rheumatoid Arthritis

Key findings: Multiple meta-analyses consistently show that TGP improves clinical outcomes when added to standard DMARDs (methotrexate, leflunomide) for RA. A distinctive finding is the hepatoprotective effect: TGP appears to reduce the liver toxicity of conventional DMARDs rather than adding to it. The main limitation is that most included RCTs are Chinese-language studies with varying methodological quality.

TGP for Systemic Lupus Erythematosus (SLE)

Key findings: Consistent evidence across meta-analyses that TGP as adjunctive therapy improves SLE disease activity scores while potentially allowing dose reduction of corticosteroids and cytotoxic agents. The steroid-sparing effect is clinically significant. However, included study quality is variable and larger, more rigorous RCTs are needed.

Dang Gui Shao Yao San for Dysmenorrhea

Key findings: Evidence for Dang Gui Shao Yao San in dysmenorrhea is suggestive but limited by the small number of high-quality RCTs meeting inclusion criteria. The formula contains six herbs (Dang Gui, Bai Shao, Chuan Xiong, Bai Zhu, Fu Ling, Ze Xie), making it impossible to attribute effects to white peony alone. Traditional biomedical indications for this formula extend to dysfunctional uterine bleeding, polycystic ovaries, threatened miscarriage, pre-eclampsia, and infertility.

PCOS and Hyperandrogenism

Key findings: The anti-androgenic mechanism of paeoniflorin is well-characterized preclinically (CYP17A1 downregulation, aromatase promotion). However, clinical evidence specifically for white peony or paeoniflorin as a standalone treatment for PCOS remains limited. Most clinical data comes from combination formulas. This is a promising area for future standalone RCTs.

Safety Profile

Contraindications

• Pregnancy (first trimester): Traditional contraindication based on TCM classification; insufficient modern safety data. Some Kampo formulas containing Bai Shao (e.g., Tokishakuyakusan) are traditionally used in pregnancy for threatened miscarriage, but only under practitioner supervision.
• Known hypersensitivity to Paeonia species
• Bleeding disorders: Paeoniflorin has demonstrated antiplatelet and anticoagulant activity in vitro (prolongation of prothrombin and thrombin times) (PMID: 20824965)
• Pre-surgical: Discontinue at least 2 weeks before elective surgery due to potential antiplatelet effects

Drug Interactions

Adverse Effects

• Gastrointestinal: Most common adverse effect. In TGP clinical trials, adverse events occurred in approximately 13.3% of patients, predominantly mild diarrhea and loose stools, usually self-resolving within 1-2 weeks
• Nausea and stomach upset: Occasional, especially at higher doses
• Dizziness/lightheadedness: Rare, reported in some individuals
• No significant hepatotoxicity: TGP actually demonstrates hepatoprotective effects when combined with hepatotoxic DMARDs
• No significant nephrotoxicity signals reported

Shakuyaku-kanzo-to Specific Safety Concern

• Pseudoaldosteronism: The licorice component (glycyrrhizin) in Shakuyaku-kanzo-to can cause hypokalemia, hypertension, and edema with long-term use. This is NOT caused by the peony component but is an important safety consideration for this widely prescribed combination. Potassium levels should be monitored with regular use.

Pregnancy and Lactation

• Pregnancy: Category C. Traditional TCM sources caution against use in the first trimester. However, certain Kampo formulas containing Bai Shao (Tokishakuyakusan, Dangguishaoyaosan) have been traditionally used for threatened miscarriage during pregnancy under practitioner guidance. Insufficient modern safety data for definitive assessment. Precautionary avoidance recommended, especially in first trimester, unless under expert supervision.
• Lactation: Insufficient data. The LactMed database notes limited information on peony during breastfeeding. Traditional use does not flag lactation concerns, but modern evidence is lacking.

Overdose and Toxicity

• White peony root has a wide margin of safety. In animal toxicology studies, the LD50 of paeoniflorin via oral administration is very high (approximately 9.53 g/kg in mice), indicating low acute toxicity.
• Chronic toxicity studies of TGP at therapeutic doses show no significant organ damage.
• No reports of fatal or severe overdose in the clinical literature.

Clinical Dosage

TCM Decoction (Traditional)

TGP Extract (Modern Pharmaceutical)

Kampo Formula Dosing

Western Supplement Dosing

Important Dosage Notes

• No single standardized extract has been validated in Western RCTs (unlike, e.g., Vitex Ze 440 or Remifemin for black cohosh)
• TGP capsules are the closest to a validated pharmaceutical preparation but are primarily available in China
• Formula-based dosing (TCM/Kampo) should be guided by a qualified practitioner
• Maximum studied duration: Up to 5+ years for TGP in SLE patients without significant safety concerns

Sources

• He DY, Dai SM. “Anti-Inflammatory and Immunomodulatory Effects of Paeonia Lactiflora Pall., a Traditional Chinese Herbal Medicine.” Front Pharmacol. 2011;2:10. (PMC3108611)
• Luo J et al. “Total glucosides of paeony for rheumatoid arthritis: A systematic review of randomized controlled trials.” Complement Ther Med. 2017;34:46-56. (PMID: 28917375)
• Xiang N et al. “A systemic review and meta-analysis of the clinical efficacy and safety of total glucosides of peony combined with methotrexate in rheumatoid arthritis.” Biomed Rep. 2017;7(2):137-145. (PMID: 28748514)
• Chen Z et al. “The Efficacy and Safety of the Combination of Total Glucosides of Peony and Leflunomide for the Treatment of Rheumatoid Arthritis: A Systemic Review and Meta-Analysis.” Evid Based Complement Alternat Med. 2016;2016:9852793. (PMID: 27143990)
• Feng Z et al. “Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis.” BMC Complement Med Ther. 2021;21(1):95. (PMID: 33771151)
• Fan YS et al. “The effectiveness and safety of total glucosides of paeony in systemic lupus erythematosus: A systematic review and meta-analysis.” Medicine. 2022;101(50):e32234. (PMID: 36544850)
• Zhu L et al. “Total Glucosides of Paeonia lactiflora for Safely Reducing Disease Activity in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.” Front Pharmacol. 2022;13:834947. (PMID: 35237142)
• Ota K et al. “Effect of Shakuyaku-kanzo-to in patients with muscle cramps: A systematic literature review.” J Gen Fam Med. 2020;21(3):56-62. (PMID: 32489757)
• Hyodo T et al. “Immediate effect of Shakuyaku-kanzo-to on muscle cramp in hemodialysis patients.” Nephron Clin Pract. 2006;104(1):c28-32. (PMID: 16685141)
• Sun L et al. “Herbal medicine (Danggui Shaoyao San) for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.” Maturitas. 2016;85:19-26. (PMID: 26857875)
• Takeuchi T et al. “Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production.” Am J Chin Med. 1991;19(1):73-78. (PMID: 1897494)
• Ye T et al. “Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells.” J Ethnopharmacol. 2018;229:144-151. (PMID: 30195059)
• Qiu Z et al. “Paeoniflorin attenuates DHEA-induced polycystic ovary syndrome via inactivation of TGF-beta1/Smads signaling pathway in vivo.” Aging (Albany NY). 2021;13(5):6854-6875. (PMID: 33638949)
• Zhang L, Wei W. “Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony.” Pharmacol Ther. 2020;207:107452. (PMID: 32172753)
• Arentz S et al. “Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings.” BMC Complement Altern Med. 2014;14:511. (PMID: 25515024)
• Tan Y et al. “Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa.” Pharmazie. 2010;65(8):600-605. (PMID: 20824965)
• Wu M et al. “Unique immunomodulatory effect of paeoniflorin on type I and II macrophages activities.” J Pharmacol Sci. 2016;130(3):143-150. (PMID: 26852260)
• Liu Y et al. “Immunoregulatory Effects of Paeoniflorin Exerts Anti-asthmatic Effects via Modulation of the Th1/Th2 Equilibrium.” Inflammation. 2015;38(6):2017-2025. (PMID: 25971794)
• Peony Monograph. Alternative Medicine Review. 2001;6(5):495-499.
• Jiang H et al. “Efficacy, Chemical Constituents, and Pharmacological Actions of Radix Paeoniae Rubra and Radix Paeoniae Alba.” Front Pharmacol. 2020;11:1054. (PMC7365904)

Connections

• Dong Quai: The most important pairing partner for Bai Shao in TCM gynecology. Together they form the core of Si Wu Tang (Four Substances Decoction) and Dang Gui Shao Yao San. While Dong Quai “moves blood,” Bai Shao “nourishes blood” — complementary actions in TCM theory. White peony has substantially more modern pharmacological validation than Dong Quai.
• Licorice: Combined with peony root in Shakuyaku-kanzo-to, the simplest and most studied formula containing white peony. The paeoniflorin-glycyrrhizin synergy for antispasmodic action is pharmacologically characterized. Licorice’s glycyrrhizin component is the source of pseudoaldosteronism risk with long-term SKT use.
• Vitex Chasteberry: Both herbs address menstrual irregularities and hormonal imbalances, but through different mechanisms. Vitex acts centrally via dopaminergic modulation of prolactin and gonadotropins; white peony acts peripherally via direct effects on ovarian steroidogenesis (CYP17A1, aromatase). Vitex has stronger standalone Western clinical evidence for PMS and cycle regulation.
• Red Clover: Both herbs have emerging relevance to PCOS and hormonal conditions. Red clover provides phytoestrogens (isoflavones), while white peony modulates androgen production. Different mechanisms that could theoretically be complementary.
• Boswellia: Both are used for inflammatory and autoimmune conditions. TGP for RA can be compared to Boswellia’s use in RA and inflammatory joint disease, though they work through distinct anti-inflammatory pathways.