Peony

Peony root is one of the principal herbs of Chinese medicine. It is classically regarded as specific for the Liver, soothing constrained Liver energy, and as one of the main blood-nourishing tonics for women, especially when paired with licorice ^{25Reference 25Bensky et al. · 2004Chinese Herbal Medicine: Materia Medica (3rd ed.)}.

White peony (bai shao) and red peony (chi shao) are used differently. White peony nourishes the blood and calms the Liver; red peony cools and moves the blood. Peony is preferred over dong quai where a condition involves “heat”, and dong quai where it involves “cold” ^{25Reference 25Bensky et al. · 2004Chinese Herbal Medicine: Materia Medica (3rd ed.)}.

In Kampo, peony root is combined with licorice as Shakuyaku-kanzo-to. It is used for muscle cramps and for crampy pain in the gut and the skeletal muscles ^{21Reference 21Takao et al. · 2015RCTShakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as treatment of painful muscle cramps in patients with lumbar spinal stenosis and its minimum effective dose — randomised controlled trialView study →}.

In China, Korea and Japan, a decoction of the dried root without its bark has been used for rheumatoid arthritis, lupus, hepatitis, painful periods, muscle cramps and fever ^{1Reference 1He et al. · 2011ReviewAnti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine — reviewView study →}.

Rheumatoid arthritis is peony’s main human indication, as total glucosides of paeony (TGP) added to standard antirheumatic drugs.

An overview of 11 systematic reviews, covering 7,012 participants in trials of TGP and of a second Chinese extract (Tripterygium glycosides), found that both improved ACR20, ACR50 and ACR70 response rates, swollen and tender joint counts, ESR and CRP. TGP also reduced liver toxicity, and its most common side effect was mild to moderate diarrhoea. The quality of the evidence ranged from low to moderate ^{3Reference 3Luo et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviews — systematic reviewView study →}.

A safety meta-analysis of 39 studies (3,680 participants) found fewer liver-related adverse effects and less leukopenia when TGP was added to standard therapy ^{4Reference 4Liu et al. · 2021Meta-analysisClinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis — meta-analysisView study →}. In one randomised trial of 80 patients, TGP plus leflunomide had a higher total effective rate than leflunomide alone (97.5% vs 85.0%) ^{5Reference 5Zhao et al. · 2006RCTClinical observation on effects of leflunomide and total glucosides of paeony on rheumatoid arthritis — randomised controlled trialView study →}.

A formal appraisal of 11 reviews rated the methodological quality of all of them as critically low on AMSTAR-2. Of 59 outcomes, none had high-quality evidence and 49 were rated low or very low ^{6Reference 6Zhu et al. · 2020Meta-analysisTotal glucosides of paeony for rheumatoid arthritis: a methodological and reporting quality evaluation of systematic reviews and meta-analyses — reviewView study →}.

In animal models of rheumatoid arthritis, a meta-analysis of 24 studies found TGP lowered TNF-α, IL-1β and IL-6 and raised IL-10 ^{7Reference 7He et al. · 2024Meta-analysisEffects of total glucosides of paeony on serum inflammatory cytokines in animal models of rheumatoid arthritis: a systematic review and meta-analysis — animal model, systematic reviewView study →}. Paeoniflorin, the most abundant component of TGP, is thought to carry most of its effect ^{1Reference 1He et al. · 2011ReviewAnti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine — reviewView study →}.

Gap: the trials are almost all from China, often open-label or small, and test TGP as an add-on. No high-quality trial has tested a whole-root tincture or decoction on its own.

Methotrexate plus leflunomide is an effective combination in rheumatoid arthritis but often raises liver enzymes.

In an open-label multicentre trial of 204 patients, liver enzyme rises at 12 weeks were less common with TGP added (9.5% vs 34.8%) ^{8Reference 8Chen et al. · 2013RCTReduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis — randomised controlled trialView study →}. In a second trial of 268 patients given 1.8 g/day of TGP, abnormal liver function within 12 weeks fell from 23.3% to 11.4%, and severe rises (over three times normal) from 7.8% to 1.6% ^{9Reference 9Xiang et al. · 2015RCTTotal glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritis — randomised controlled trialView study →}.

In mice on high-fat diets, paeoniflorin reduced fat build-up in the liver, lowered markers of oxidative stress and inflammation, and changed the gut microbiota ^{10,11Reference 10Wang et al. · 2026AnimalPaeoniflorin protects against NAFLD through antioxidant, anti-inflammatory effects and restoration of gut microbiota homeostasis — mouse in vivoView study →Reference 11Wei et al. · 2026AnimalPaeoniflorin alleviates metabolic dysfunction-associated steatotic liver disease by inhibiting hepatic lipogenesis and inflammation — mouse in vivoView study →}.

Gap: the human evidence is specific to drug-induced liver enzyme rises in rheumatoid arthritis. Fatty liver and fibrosis have been studied in animals only.

In animal models of acute and subacute inflammation, TGP reduced the production of prostaglandin E₂, leukotriene B₄ and nitric oxide ^{1Reference 1He et al. · 2011ReviewAnti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine — reviewView study →}. It had both stimulating and suppressing effects on lymphocytes in vitro, and relieved pain in animal models, partly through adenosine A1 receptors ^{1Reference 1He et al. · 2011ReviewAnti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine — reviewView study →}.

Paeoniflorin lowers COX-2 and iNOS, and paeonol inhibits NF-κB activation ^{2Reference 2Tan et al. · 2020ReviewEfficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae Alba — reviewView study →}. The animal meta-analysis found consistent falls in inflammatory cytokines in experimental arthritis ^{7Reference 7He et al. · 2024Meta-analysisEffects of total glucosides of paeony on serum inflammatory cytokines in animal models of rheumatoid arthritis: a systematic review and meta-analysis — animal model, systematic reviewView study →}.

Gap: there is no dedicated human inflammation endpoint; the human data come through the rheumatoid arthritis, Sjögren’s and psoriasis trials.

Primary Sjögren’s syndrome is an autoimmune disease that dries the eyes and mouth.

In a double-blind, placebo-controlled pilot trial, 45 patients took TGP or placebo for 24 weeks. The main outcome, the ESSPRI patient-reported symptom score, did not differ between the groups ^{12Reference 12Zhou et al. · 2016RCTClinical and immunological consequences of total glucosides of paeony treatment in Sjögren’s syndrome: a randomised controlled pilot trial — randomised controlled trialView study →}. In the TGP group, dry-mouth scores improved in patients with moderate scores, stimulated salivary flow rose, ESR fell compared with placebo, and some B-cell markers fell ^{12Reference 12Zhou et al. · 2016RCTClinical and immunological consequences of total glucosides of paeony treatment in Sjögren’s syndrome: a randomised controlled pilot trial — randomised controlled trialView study →}.

A meta-analysis of seven trials (632 participants) found that TGP added to hydroxychloroquine improved dry mouth and eyes, salivary flow, the Schirmer tear test and immunoglobulin levels compared with hydroxychloroquine alone ^{13Reference 13Zhang et al. · 2023Meta-analysisCombined use of total glucosides of paeony and hydroxychloroquine in primary Sjögren’s syndrome: a systematic review — meta-analysisView study →}.

Gap: the samples are small, and the meta-analysis combines TGP with hydroxychloroquine, so peony’s own contribution is hard to separate.

In mice fed a high-fat, high-sugar diet for 10 weeks, paeoniflorin raised superoxide dismutase and lowered malondialdehyde, a marker of lipid peroxidation, in the liver and colon ^{10Reference 10Wang et al. · 2026AnimalPaeoniflorin protects against NAFLD through antioxidant, anti-inflammatory effects and restoration of gut microbiota homeostasis — mouse in vivoView study →}. TGP protected cells against oxidative stress ^{1Reference 1He et al. · 2011ReviewAnti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine — reviewView study →}.

Gap: no human study has measured an antioxidant endpoint for peony.

In frog and mouse nerve–muscle preparations, paeoniflorin and glycyrrhizin from licorice together blocked muscle twitches at concentrations that had no effect when either was used alone. The 1:2 ratio found in Shakuyaku-kanzo-to was the most potent, and oxypaeoniflorin also worked with glycyrrhizin ^{20Reference 20Kimura et al. · 1984In vitroBlocking effects of blended paeoniflorin or its related compounds with glycyrrhizin on neuromuscular junctions in frog and mouse — in vitro/animalView study →}.

In an open randomised comparison in patients with painful muscle cramps from lumbar spinal stenosis, Shakuyaku-kanzo-to halved cramp frequency in 13 of 16 patients, against 4 of 14 on the muscle relaxant eperisone ^{21Reference 21Takao et al. · 2015RCTShakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as treatment of painful muscle cramps in patients with lumbar spinal stenosis and its minimum effective dose — randomised controlled trialView study →}. Taken as needed, 2.5 g worked as well as 7.5 g/day taken regularly ^{21Reference 21Takao et al. · 2015RCTShakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as treatment of painful muscle cramps in patients with lumbar spinal stenosis and its minimum effective dose — randomised controlled trialView study →}.

Gap: the cramp evidence is for the combination formula, and licorice’s glycyrrhizin carries its own risks of low potassium, high blood pressure and oedema ^{21Reference 21Takao et al. · 2015RCTShakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as treatment of painful muscle cramps in patients with lumbar spinal stenosis and its minimum effective dose — randomised controlled trialView study →}.

A 2025 meta-analysis of 36 randomised trials (3,140 participants) found that adding TGP to conventional psoriasis treatment, such as acitretin or narrow-band UVB, improved PASI 60 and PASI 50 response rates and may have reduced adverse events ^{14Reference 14Li et al. · 2025Meta-analysisAdd-on effects of total glucosides of paeony on conventional therapies for psoriasis: a systematic review and meta-analysis of randomised controlled trials — meta-analysisView study →}.

Gap: the effect is as an add-on only, in Chinese trials of limited methodological quality ^{14Reference 14Li et al. · 2025Meta-analysisAdd-on effects of total glucosides of paeony on conventional therapies for psoriasis: a systematic review and meta-analysis of randomised controlled trials — meta-analysisView study →}.

In an open study, 34 Japanese women with polycystic ovarian disease took 7.5 g/day of Shakuyaku-kanzo-to for 24 weeks. Serum testosterone and free testosterone fell within 4 weeks, and the LH/FSH ratio fell by 24 weeks ^{15Reference 15Takahashi et al. · 1994Clinical trialEffect of TJ-68 (shakuyaku-kanzo-to) on polycystic ovarian disease — human clinical studyView study →}. The authors proposed that the formula raises aromatase activity in the ovary ^{15Reference 15Takahashi et al. · 1994Clinical trialEffect of TJ-68 (shakuyaku-kanzo-to) on polycystic ovarian disease — human clinical studyView study →}.

In rat ovary tissue, paeoniflorin, glycyrrhizin and glycyrrhetic acid each lowered testosterone production. Only glycyrrhetic acid, from licorice, raised the estradiol-to-testosterone ratio ^{16Reference 16Takeuchi et al. · 1991In vitroEffect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production — rat ovary tissue, in vitroView study →}.

In mouse theca cells, a paeoniflorin extract reversed excess testosterone output by lowering CYP17A1 ^{19Reference 19Ong et al. · 2019In vitroPaeoniflorin extract reverses dexamethasone-induced testosterone over-secretion through downregulation of cytochrome P450 17A1 expression in primary murine theca cells — in vitroView study →}. From the root, 6’-O-galloylalbiflorin and pentagalloylglucose bound the androgen receptor strongly, while paeoniflorin and albiflorin did not ^{18Reference 18Washida et al. · 2009In vitroAndrogen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, Japan — in vitroView study →}. A review lists Chinese peony among plant anti-androgens for promoting the conversion of testosterone to estrogen ^{17Reference 17Grant et al. · 2012ReviewAn update on plant derived anti-androgens — reviewView study →}.

Gap: the one human study is small, old and uncontrolled, and uses the combination formula.

Paeoniflorin reduced depression-like behaviour in chronically stressed mice through ERK1/2 signalling ^{22Reference 22Tang et al. · 2021AnimalPaeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathway — mouse in vivoView study →}. It had rapid and lasting antidepressant-like effects in mice that depended on the ghrelin receptor in the gut ^{23Reference 23Zhang et al. · 2021AnimalThe ghrelin/growth hormone secretagogue receptor system is involved in the rapid and sustained antidepressant-like effect of paeoniflorin — animal modelView study →}. In a mouse model of spinal and bulbar muscular atrophy, it increased clearance of the mutant androgen receptor ^{24Reference 24Tohnai et al. · 2014In vitroPaeoniflorin eliminates a mutant AR via NF-YA-dependent proteolysis in spinal and bulbar muscular atrophy — in vitro/mouseView study →}.

Gap: there are no human trials for mood or neurodegeneration.

Side effects. Across the TGP trials in rheumatoid arthritis the most common side effect was mild to moderate diarrhoea ^{3Reference 3Luo et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviews — systematic reviewView study →}. Adding TGP to standard drugs lowered liver-related adverse effects and leukopenia ^{4Reference 4Liu et al. · 2021Meta-analysisClinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis — meta-analysisView study →}.

Licorice. Peony is often taken with licorice in Shakuyaku-kanzo-to. The glycyrrhizin in licorice can cause low potassium, high blood pressure and oedema ^{21Reference 21Takao et al. · 2015RCTShakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as treatment of painful muscle cramps in patients with lumbar spinal stenosis and its minimum effective dose — randomised controlled trialView study →}, so long-term use of the formula needs the usual licorice precautions.

Drug metabolism. In rats, paeoniflorin given for a week moderately inhibited CYP3A and also slowed CYP1A2 and CYP2C11; no study has tested this in people ^{29Reference 29Li et al. · 2021AnimalEffects of paeoniflorin on the activities and mRNA expression of rat CYP1A2, CYP2C11 and CYP3A1 enzymes in vivo — rat in vivoView study →}. A second rat study found that paeoniflorin sped up CYP1A2 instead, while again slowing CYP2C11, and both effects were modest and seen only at high doses ^{30Reference 30Chen et al. · 2026AnimalEvaluation of the effects of paeoniflorin on cytochrome P450 isozymes in rats — rat in vivoView study →}.

In human liver preparations, the root compound 4-O-galloylalbiflorin inhibited CYP3A, CYP2C9 and CYP2D6 ^{31Reference 31Sun et al. · 2021In vitroSun, Y., He, M., Sun, Y., et al. (2021). 4-O-galloylalbiflorin inhibits the activity of CYP3A, 2C9, and 2D in human liver microsomes — in vitro. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/34082641/View study →}.

Anticoagulants. A caution about combining peony with anticoagulants is often repeated, but no direct clinical interaction data have been published.