Peony

This is peony’s strongest human indication, and it is really the indication of total glucosides of paeony (TGP) used as an add-on to conventional antirheumatics rather than the root itself. An overview of systematic reviews covering roughly 7,000 participants found that TGP improved ACR20/50/70 response rates, swollen- and tender-joint counts, ESR and CRP when added to standard therapy, and reduced the incidence of hepatotoxicity ^{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 meta-analysis focused on safety reached similar conclusions for TGP as adjuvant 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 →}, and a representative RCT of TGP plus leflunomide reported 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 →}. The honest counterweight: a formal appraisal rated the methodological quality of these reviews as critically low on AMSTAR-2 with low GRADE certainty ^{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 →}, and an animal meta-analysis confirms the cytokine-lowering mechanism but underscores how much of the base is preclinical ^{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 is the presumed active.

Gap: trials are almost all China-based, open-label or small, and test the standardised TGP extract as an adjunct — there is no high-quality RCT of whole-root tincture or decoction as monotherapy.

Two multicentre randomised trials give this a real human footing, though in a narrow context: in patients with active RA on methotrexate plus leflunomide — a combination that reliably raises liver enzymes — adding TGP significantly reduced the incidence and severity of hepatotoxicity ^{8,9Reference 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 →Reference 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 →}, one enrolling 268 patients ^{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 →}. Mechanistically, paeoniflorin protects rodent liver against high-fat-diet steatosis (NAFLD/MASLD) through antioxidant and anti-inflammatory action and restoration of gut-microbiota balance ^{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 →}. A pharmacology review collates the broader hepatoprotective profile of the root ^{2Reference 2Tan et al. · 2020ReviewEfficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae Alba — reviewView study →}.

Gap: the solid human evidence is specifically about protecting against drug-induced liver enzyme rises in RA; general hepatoprotection (fatty liver, fibrosis) is animal-only, and the marketed preparation is TGP, not the crude root.

Anti-inflammatory activity is the through-line under most of peony’s autoimmune indications and is the best-characterised mechanism. TGP and paeoniflorin suppress NF-κB signalling and downstream COX-2, and lower pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while nudging regulatory-T-cell/Th17 balance; the crude-root analgesic effect appears to be mediated 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 →}. An animal-model meta-analysis confirms consistent reductions in serum inflammatory cytokines in experimental RA ^{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 →}, and a comparative review maps the same activity across white and red peony root ^{2Reference 2Tan et al. · 2020ReviewEfficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae Alba — reviewView study →}.

Gap: as a standalone claim this is preclinical/mechanistic — the human read-out is indirect, arriving through the RA, Sjögren’s and psoriasis trials rather than a dedicated inflammation endpoint.

In primary Sjögren’s syndrome (the autoimmune sicca — dry eyes and dry mouth — disorder), a randomised, double-blind, placebo-controlled pilot trial (n=45) found TGP improved patient-reported symptom indices and some immunological measures over 24 weeks ^{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 later systematic review and meta-analysis of TGP combined with hydroxychloroquine reported improvements in sicca symptoms, immunoglobulin levels and inflammatory markers ^{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 →}. Activity is consistent with peony’s paeoniflorin-driven immunomodulation.

Gap: samples are small, the meta-analysis pools TGP with hydroxychloroquine so the independent contribution of peony is hard to isolate, and again the preparation is TGP.

Antioxidant activity is well replicated at the preclinical level and is the plausibility bridge to peony’s hepatoprotective and anti-ageing claims. paeoniflorin activates the Nrf2/antioxidant-response pathway, raises endogenous antioxidant-enzyme activity and lowers lipid peroxidation in liver and other tissue models ^{10Reference 10Wang et al. · 2026AnimalPaeoniflorin protects against NAFLD through antioxidant, anti-inflammatory effects and restoration of gut microbiota homeostasis — mouse in vivoView study →}, and the pattern recurs across the pharmacology literature for both white and red peony root ^{2Reference 2Tan et al. · 2020ReviewEfficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae Alba — reviewView study →}.

Gap: there is no human study measuring an antioxidant endpoint for peony; the score reflects consistent but entirely preclinical (cell and rodent) evidence.

Peony’s smooth-muscle-relaxant and antispasmodic reputation has a clear mechanism and a supporting cramp trial, but almost always as the two-herb Shakuyaku-kanzo-to (peony + licorice) combination rather than peony alone. Classic work showed paeoniflorin, together with glycyrrhizin from licorice, blocks transmission at the neuromuscular junction in frog and mouse preparations — the pharmacological basis of the peony–licorice synergy ^{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 →}. A randomised trial in patients with painful muscle cramps from lumbar spinal stenosis found Shakuyaku-kanzo-to effective and defined a minimum effective dose ^{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 →}, and the crude root carries analgesic activity in animal pain models ^{1Reference 1He et al. · 2011ReviewAnti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine — reviewView study →}. albiflorin accompanies paeoniflorin in the root.

Gap: the cramp evidence is for the combination formula (and licorice’s glycyrrhizin carries its own hypokalaemia/hypertension risk), so the antispasmodic effect cannot be credited to peony as a solo herb.

A 2025 systematic review and meta-analysis of randomised trials found that adding TGP to conventional psoriasis therapies (e.g. acitretin, narrow-band UVB) improved efficacy and reduced adverse events versus conventional therapy alone ^{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 →}. The direction is consistent with peony’s paeoniflorin-mediated anti-inflammatory and immunomodulatory activity.

Gap: strictly an adjunct effect from Chinese RCTs with the usual quality caveats; no evidence for peony (or TGP) as standalone psoriasis treatment.

Peony’s use for hyperandrogenism and PCOS is long-standing but thinly evidenced, and most of it involves the peony–licorice pairing. An early open study of Shakuyaku-kanzo-to (TJ-68) in 34 women with polycystic ovarian disease reported significantly reduced serum testosterone ^{15Reference 15Takahashi et al. · 1994Clinical trialEffect of TJ-68 (shakuyaku-kanzo-to) on polycystic ovarian disease — human clinical studyView study →}, and in rats paeoniflorin plus glycyrrhizin lowered ovarian androgen production ^{16Reference 16Takeuchi et al. · 1991AnimalEffect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production — rat in vivoView study →}. Mechanistic support includes androgen-receptor-binding gallotannins isolated from peony root — notably pentagalloylglucose ^{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 placing peony among plant-derived anti-androgens ^{17Reference 17Grant et al. · 2012ReviewAn update on plant derived anti-androgens — reviewView study →}, and cell work showing paeoniflorin downregulates CYP17A1 to curb testosterone over-secretion in theca cells ^{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 →}.

Gap: the one human study is small, old and uncontrolled, uses the combination formula, and the page’s earlier claim that peony is a “reliable aromatase inducer” is not supported — the data point to reduced androgen synthesis, not aromatase induction.

Neuroprotective and antidepressant activity is entirely preclinical. paeoniflorin reduced depression-like behaviour in chronically stressed mice via 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 →} and produced rapid antidepressant-like effects through the ghrelin/GHS-R system in rodents ^{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 →}, and it promoted clearance of a mutant androgen receptor in a model of spinal-and-bulbar muscular atrophy ^{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: no human trials of any kind for mood or neurodegeneration; these findings are hypothesis-generating and do not yet justify clinical claims.

Peony root and its standardised extract (total glucosides of paeony, TGP) are generally well tolerated; the most common adverse effect in clinical trials is mild, dose-related gastrointestinal upset such as loose stools or diarrhoea, which is usually transient ^{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 →}. Notably, TGP has hepatoprotective rather than hepatotoxic activity — in randomised trials it reduced the liver-enzyme rises caused by methotrexate and leflunomide in rheumatoid-arthritis patients ^{8,9Reference 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 →Reference 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 →}. The main practical cautions are theoretical or extrapolated rather than well documented: peony is often given with licorice (Shakuyaku-kanzo-to), and it is licorice’s glycyrrhizin — not peony — that drives the hypokalaemia, fluid retention and raised blood pressure seen with that combination ^{20,21Reference 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 →Reference 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 commonly repeated caution about combining peony with anticoagulants is not supported by direct clinical interaction data.