Peony (Paeonia spp.): A Comprehensive Reference
1. Identity and Botanical Classification
1.1 Botanical Names and Taxonomy
The genus Paeonia, which comprises approximately 52 shrubs or herbaceous perennials around the world, is the only genus of the family Paeoniaceae. In a medicinal context, several species are relevant, but the two most extensively studied and used are:
- Paeonia lactiflora Pallas — Chinese peony or white/red peony
- Paeonia suffruticosa Andrews — Tree peony or moutan peony
Paeonia lactiflora Pall., commonly known as Chinese peony, is a perennial flowering plant widely utilized in traditional Chinese medicine (TCM). Renowned for its therapeutic properties, P. lactiflora has been traditionally employed to treat a variety of ailments, including inflammation, pain, and blood disorders.
1.2 Common Names and Drug Forms
Paeonia lactiflora Pall. (also known as shaoyao) is a plant of the genus Paeonia, which is divided into Radix Paeoniae Rubra (RPR, also known as chishao or red peony root) and Radix Paeoniae Alba (RPA, also known as baishao or white peony root). The distinction between these two drug forms is largely one of processing:
- White peony root (Radix Paeoniae Alba / Baishao): Its dried root is harvested without the bark in the autumn from plants that are between 3 and 5 years of age.
- Red peony root (Radix Paeoniae Rubra / Chishao): Derived from the dried roots of Paeonia lactiflora Pall. or Paeonia veitchii Lynch from the Ranunculaceae family.
- Moutan cortex (Cortex Moutan / Mudanpi): Cortex Moutan, the dried root bark of the plant Paeonia suffruticosa Andrews, is a traditional Chinese medicine with a rich history of use spanning over 2000 years.
Paeonia has a long history of medicinal use, with moutan cortex (the root bark of Paeonia suffruticosa) being first documented in Shennong's Classic Materia Medica. Traditionally, moutan cortex is used for "clearing heat, cooling blood, and promoting blood circulation to resolve stasis." White peony root (the processed root of herbaceous peonies) is used for "nourishing blood and relieving spasms," and red peony root (the unprocessed root of herbaceous peonies) is used for "activating blood circulation and removing stasis."
1.3 Common Preparations
A decoction of the root has been used to treat painful or inflammatory disorders in traditional Chinese medicine. Modern preparations include:
- Total glucosides of paeony (TGP): A water/ethanol extract of the root known as total glucosides of peony (TGP), which contains more than 15 components.
- Standardized capsules: TGP capsule, branded as Pavli (also rendered as Pafulin), was approved by China Food and Drug Administration (CFDA) to treat rheumatoid arthritis (RA) in 1998.
- Dried root powder and fluid extracts for traditional decoctions.
- Peony may be used in decoction or tincture in traditional TCM formulae, or in combination with other herbs in Western botanical formulae.
2. Traditional and Historical Use
2.1 Traditional Chinese Medicine (TCM)
In China, Korea, and Japan, a decoction of the dried root without bark of Paeonia lactiflora Pall. has been used in the treatment of rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1200 years.
This plant has been used in traditional Chinese medicine for over 2000 years in Asia, with broad pharmacological activities (e.g., anti-inflammatory, analgesic, and antispasmodic effects) to treat conditions like rheumatism, menstrual disorders, and muscle pain.
The dried root of Paeonia lactiflora Pall., a classical Chinese herbal medicine, has been utilized clinically to treat hepatic disease over thousands of years.
Within TCM's theoretical framework, the two drug forms have distinct energetic characterizations. White peony root is used for "nourishing blood and relieving spasms," while red peony root is used for "activating blood circulation and removing stasis." Cortex Moutan (CM), the dried root bark of Paeonia suffruticosa Andrews, is named "mudanpi" in Chinese and functions to clear heat, cool the blood, promote blood circulation, and relieve blood stasis (Chinese Pharmacopoeia, 2020 edition).
2.2 TCM Gynecological Uses
Peony is used in traditional Chinese medicine, mainly in combination with other herbs, for the relief of gynaecological symptoms including hot flushes associated with the menopause, regulation of the menstrual cycle and alleviating anaemia caused by menorrhagia.
Both white and red peony are commonly used for various women's health problems in TCM. There is evidence from preliminary clinical trials supporting their use in dysmenorrhea and polycystic ovary syndrome (PCOS).
2.3 Japanese Kampo Medicine
Peony root is a key ingredient in several classical Kampo (Japanese herbal medicine) formulas. The TCM formula toki-shakuyaku-san — containing white peony, Atractylodes lancea (red atractylodes) rhizome, Alisma plantago-aquatica (alisma; water plantain) rhizome, Poria cocos (hoelen) sclerotium, Cnidium monnieri (cnidium) rhizome, and Angelica dahurica (Chinese angelica) radix — has been reported to alleviate pain in patients with primary dysmenorrhea in one double-blind clinical trial.
2.4 Moutan Cortex and European Recognition
Moutan Cortex was firstly documented in Shennong's Herbal Classic (神农本草经), where the flavor of MC is described as pungent, and the property of MC is described as cold. P. × suffruticosa bark root — Moutan cortex — is a medicinal raw material formerly known from traditional Chinese medicine (TCM) but less common in official European medicine. It was introduced for the first time in the European Pharmacopoeia Supplement 9.4 in 2018.
TCM attributes Moutan cortex with the following effects: antipyretic, regulating menstrual disorders, accelerating the healing of ulcers, improving blood circulation and reducing swelling.
3. Key Constituents and Active Compounds
3.1 Overview of Phytochemistry
The medicinal value of P. lactiflora is attributed to its rich chemical composition, which includes over 180 identified compounds, such as monoterpenoids, sesquiterpenes, flavonoids, tannins, stilbenes, triterpenoids, steroids, and phenols.
Different compounds have been isolated from this plant. These include monoterpenoid glucosides, flavonoids, tannins, stilbenoids, triterpenoids and steroids, and phenols.
3.2 Paeoniflorin — The Primary Bioactive
The major bioactive component extracted from Radix Paeoniae Alba is paeoniflorin (PF), a monoterpene glycoside. As the main medicinal part, the root of P. lactiflora contains a variety of medicinal components, including glycosides, terpenoids, flavonoids, volatile oils, phenols and sugars, among which paeoniflorin is the most important bioactive substance.
The monoterpene glucoside paeoniflorin and its derivatives are the active compounds of the P. lactiflora roots. In China, TGP has been approved as a disease-modifying oral drug for RA since 1998 by the China Food and Drug Administration, with paeoniflorin accounting for 90% of its active components.
Paeoniflorin is one of the active components of the root of peony, which has powerful and diverse pharmacological activities. However, low membrane permeability and gastrointestinal effects severely limit its absorption and bioavailability.
3.3 Total Glucosides of Paeony (TGP)
A water/ethanol extract of the root is known as total glucosides of peony (TGP), which contains more than 15 components. Total glucosides of peony (TGP), extracted from RPA, consist of paeoniflorin (Pae), albiflorin, hydroxyl-paeoniflorin, benzoylpaeoniflorin, benzoyloxypeoniflorin, and others.
Total paeony glycosides (TPGs) are identified as the principal active constituents of Radix paeoniae rubra, comprising monoterpenoid compounds with a cage-like pinane structure and monoterpenoids with a lactone structure.
3.4 Additional Constituents
The chemical components in the aqueous extract of this plant root include paeoniflorin, albiflorin, oxypaeoniflorin and benzoylpaeoniflorin.
For Moutan Cortex (P. suffruticosa): The scientific studies indicated that the profile of raw material activity is mainly due to paeonol, paeoniflorin and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose. Moutan cortex, according to the requirements of the European Pharmacopoeia 10th ed., should contain a minimum of 2.2% paeonol and a minimum of 1.1% paeoniflorin.
Monoterpenoid glucosides are the main active constituents. Although many compounds have been isolated from Paeonia plants, the biological activities of only a few of these compounds (paeoniflorin, paeonol, and TGP) have been extensively investigated.
4. Mechanisms of Action
4.1 Anti-Inflammatory Mechanisms
The analgesic effect of TGP was confirmed in various animal models of pain, which may be mediated partly by adenosine A1 receptor. The direct anti-inflammatory effects of TGP were observed in animal models of both acute and subacute inflammation, by inhibiting the production of prostaglandin E2, leukotriene B4, and nitric oxide, and by suppressing the increase of intracellular calcium ion concentration.
Mechanistically, total glucoside of peony modulates intracellular signaling transductions, including JAK/STAT, NF-κB, MAPK, and PI3K/AKT/mTOR pathways.
4.2 Immunomodulatory Mechanisms
In vitro, dual effects of TGP were noted on the proliferation of lymphocytes, differentiation of Th/Ts lymphocytes, and the production of proinflammatory cytokines and antibodies. In vivo, TGP inhibited the delayed-type hypersensitivity in immuno-activated mice, and enhanced the delayed-type hypersensitivity in immuno-suppressed mice. In adjuvant arthritis rats, paeoniflorin exerted immunosuppressive effects.
Total glucoside of peony shows broad immunomodulatory effects on many immune cells, such as T cells, macrophages, and dendritic cells, by regulating their activation, proliferation, differentiation, and production of effector molecules.
Some further investigation in rat models and patients of SLE have revealed the mechanism that TGP inhibited autoimmunity possibly by downregulating ERα expression, inhibiting the IRAK1-NF-κB pathway, and enhancing DNA methylation of ITGAL promoter in CD4(+) T cells.
4.3 Neuroprotective Mechanisms
The pharmacological aspects of paeoniflorin and its possible mechanisms include restoration of mitochondrial function; inhibition of neuroinflammation, oxidative stress, and cellular apoptosis; activation of adenosine A1 receptor, cAMP response element-binding protein (CREB) and extracellular signal-regulated kinase 1/2 (ERK1/2); or enhancement of brain-derived neurotrophic factor and serotonin function, in the prevention of disorders such as cerebral ischemia, subarachnoid hemorrhage, vascular dementia, Alzheimer's disease, Parkinson's disease, depression, post-traumatic syndrome disorder, and epilepsy.
In a complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model, intrathecal injection of PF reduced the levels of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) and inhibited spinal microglial activation, likely downstream of inhibition of Akt–NF-κB signaling. PF displayed analgesic effects in a chronic constriction injury (CCI)-induced neuropathic pain rat model by inhibiting p38 mitogen-activated protein kinase (MAPK) activation, likely due to inhibiting ASK1 activation, as well as by blunting increased NF-κB activity.
4.4 Antidepressant Mechanisms
It was found that the antidepressant activity of paeoniflorin may be due to the over-expression of brain-derived neurotrophic factor (BDNF), the signal activation of ERK1/2, the inhibition of signal transduction of TLR4/NF-κB/NLRP3, the decrease of pro-inflammatory cytokines, the inhibition of pyroptosis of CASP-11-GSDND and the negative regulation of microglia activation.
4.5 Smooth Muscle Relaxant and Spasmolytic Mechanisms
Paeoniflorin has exhibited smooth muscle relaxant ability in in vitro models (rat stomach and uterus) and it has demonstrated in vivo activity, analgesic, and spasmolytic activity. It appears that this blend may exert its action against dysmenorrhea through preventing prostaglandin production.
5. Scientific Evidence by Area of Use
5.1 Rheumatoid Arthritis (RA)
This is the area with the strongest and most extensive body of human clinical evidence for peony-derived TGP.
In China, TGP has been approved as a disease-modifying oral drug for RA since 1998 by the China Food and Drug Administration and is now widely used to treat RA. Many experimental studies have shown the anti-inflammatory and immunoregulatory actions of TGP.
A 2017 meta-analysis of 8 RCTs (522 participants) assessed TGP plus methotrexate (MTX) versus MTX alone. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001).
A 2021 systematic review and meta-analysis specifically assessed safety across 39 studies involving 3,680 RA participants: A total of 39 studies involving 3,680 RA participants were included. There were 8 comparisons: TGP plus methotrexate (MTX) therapy versus MTX therapy, TGP plus leflunomide (LEF) therapy versus LEF therapy, TGP plus MTX and LEF therapy, and others. This meta-analysis indicated that TGP adjuvant therapy might alleviate the incidence of hepatic adverse effect and leukopenia for the RA treatment compared to non-TGP therapy.
A meta-analysis found that compared with methotrexate and leflunomide, TGP combined with the above therapy for RA significantly decreased the disease activity score in 28 joints and the occurrence of liver dysfunction, leukopenia, diarrhea, nausea, and vomiting, which has a favorable efficacy and safety.
Evidence strength: Though TGP could mitigate the unanticipated adverse effects during the conventional treatment of RA, high-quality evidence-based meta-analysis data on this subject are still insufficient. Most trials are conducted in China, and methodological quality is variable.
5.2 Systemic Lupus Erythematosus (SLE)
A systematic review and meta-analysis (2022) identified 14 RCTs including 978 participants. A total of 14 RCTs were included, including 978 participants, 492 in the intervention group and 486 in the control group. Results showed that TGP plus conventional treatments (CTs) was superior to CTs alone in reducing disease activity.
The results also showed that TGP contributed to a betterment in improving other outcomes related to lupus activity, such as ESR, CRP, complement proteins (C3, C4), and immunoglobulins (IgA, IgM). In addition, TGP significantly decreased average daily glucocorticoid dosage and cumulative cyclophosphamide dosage, as well as disease recurrence rate.
In terms of safety, TGP may reduce the incidence of adverse reactions (RR = 0.51, 95% CI = 0.29 to 0.88, p = 0.01). The certainty of the evidence was assessed as moderate to low. TGP appears potentially effective and generally safe in reducing disease activity in SLE. However, in view of high risk of bias, the findings need to be confirmed in high-quality trials.
5.3 Primary Sjögren's Syndrome
TGP (Baishao in Chinese) has been successfully applied in clinical treatment of autoimmune diseases, such as rheumatoid arthritis, primary Sjögren's syndrome, and ankylosing spondylitis. Total glucoside of peony has been shown to inhibit inflammatory responses and disease progression in experimental models of multiple autoimmune diseases, including Sjögren's syndrome.
Evidence strength: A multi-center, randomized, double-blinded, placebo-controlled clinical trial has been conducted, and clinical data exist, but high-quality independent replication remains limited.
5.4 Dermatological Conditions (Psoriasis, Vitiligo)
In recent times, using TGP has been extended to the management of a wide range of dermatologic diseases encompassing vitiligo, psoriasis, contact dermatitis, lichen planus, Sjögren's syndrome and systemic lupus erythematosus.
TGP can promote the expression of antioxidant genes, suppress excessive proliferation of keratinocytes, and reduce inflammatory cell infiltration, thus alleviating the pathological progression of these diseases. Additionally, in psoriasis and other Th17 cell-dominant dermatologic diseases, TGP mitigates inflammation by regulating the STAT signaling pathway.
Evidence strength: Preliminary clinical data exist; at least one double-blind, randomized, placebo-controlled trial has assessed TGP for moderate-to-severe plaque psoriasis. There are still certain limitations in the scientific rigor of existing studies and in its clinical application.
5.5 Women's Health: Dysmenorrhea and PCOS
Clinical trials have demonstrated positive results in the treatment of dysmenorrhea owing to "qi and blood stasis" (with licorice root), a reduction in serum and free testosterone in women with PCOS (with licorice), and an improvement in clinical symptoms and reduction in size of fibroids in an open study of 100 women (with P. suffruticosa, Poria cocos, Cinnamomum cassia, and Prunus persica).
A 2017 RCT (122 participants) assessed combined lifestyle and herbal medicine (which included peony) in overweight women with PCOS. One hundred and twenty-two women gave their consent. At 3 months, women in the combination group recorded a reduction in oligomenorrhoea of 32.9% (95% confidence interval 23.3–42.6, p < 0.01) compared with controls, estimated as a large effect. Other significant improvements were found for body mass index (p < 0.01); insulin (p = 0.02) and luteinizing hormone (p = 0.04); blood pressure (p = 0.01); quality of life (p < 0.01); depression, anxiety and stress (p < 0.01); and pregnancy rates (p = 0.01). This trial provides evidence of improved effectiveness and safety for lifestyle intervention when combined with herbal medicines in women with PCOS.
Evidence strength: Preliminary. Most studies use peony in combination formulas (e.g., with licorice), making it difficult to isolate peony's individual contribution. The evidence is suggestive but not definitive for peony as a single agent.
5.6 Neuroprotection (Parkinson's Disease, Alzheimer's Disease)
Evidence in this area is largely preclinical (animal models). Paeoniflorin (PF), the major active component of Paeonia alba Radix, has demonstrated neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Subcutaneous administration of PF (2.5 and 5 mg kg⁻¹) for 11 days could protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by MPTP.
Pretreatment with an adenosine A1 receptor antagonist reversed the neuroprotective and anti-neuroinflammatory effects of PF. In conclusion, this study demonstrated that PF could reduce the MPTP-induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.
Evidence strength: Predominantly preclinical (animal and cell models). No well-powered human clinical trials for neurological indications have been established to date. Although the anti-inflammatory and neuroprotective effects of PF have been reported in a large number of studies, the feasibility, and effectiveness of PF in clinical treatment of neurodegenerative diseases are still relatively scarce.
5.7 Recurrent Aphthous Ulcers
There has been a lack of treatments available to lower the frequency of recurrent aphthous ulcers (RAUs) until now. Total glucosides of paeony (TGP) is a botanical drug extracted from the dried roots of Paeonia lactiflora Pall. In one double-blind, randomized, placebo-controlled trial, patients were randomly assigned to the TGP or placebo group and treated with 1.8 g/day for 24 weeks. Participants were observed for a total of 36 weeks and were asked to record ulcer severity, medication, and adverse reactions. The primary outcome was the monthly ulcer-free interval. A total of 79 individuals were enrolled, with 40 assigned to the TGP group and 39 to the placebo group.
Evidence strength: Single-center trial; evidence is preliminary and requires replication.
5.8 Pancreatitis
The red peony root derived from Paeonia lactiflora has been applied to treat human inflammatory diseases. To investigate its therapeutic potential in treating moderately severe acute pancreatitis (MSAP), this study was designed as a double-blinded, placebo-controlled, randomized clinical trial. A total of 60 MSAP patients were enrolled and randomly divided into an experimental (n = 30) group and a control group (n = 30), who received a coloclyster of 15 g of red peony root or placebo granules dissolved in 150 mL of water.
Evidence strength: Preliminary; single trial, small sample size.
5.9 Liver Protection
Paeonia lactiflora Pall., a traditional Chinese herbal medicine, is a member of the Paeoniaceae family which exhibits protective effects against liver diseases through antioxidation and free radical scavenging mechanisms. Paeonol, an active ingredient found in Moutan Cortex, exhibits significant therapeutic effects on liver protection and has shown promising effects in treating liver diseases, particularly non-alcoholic steatohepatitis (NASH).
Evidence strength: Largely preclinical, with some observational clinical data embedded within RA and SLE trials demonstrating hepatoprotective effects as secondary findings.
6. Body Systems and Health Areas of Association
- Immune system / Rheumatology: RA, SLE, Sjögren's syndrome, ankylosing spondylitis — with the most robust clinical evidence.
- Dermatology: Psoriasis, vitiligo, contact dermatitis, lichen planus.
- Reproductive / Endocrine system: Dysmenorrhea, PCOS, uterine fibroids, hyperprolactinemia.
- Nervous system: Neuroprotection in Parkinson's and Alzheimer's disease models, depression, epilepsy — predominantly preclinical.
- Gastrointestinal / Hepatic system: Liver protection, acute pancreatitis, recurrent aphthous ulcers.
- Cardiovascular system: TGP possesses a variety of biological effects, including immunomodulatory, anti-inflammatory, hepatoprotective, nephroprotective, antidepressant, and cell proliferation regulatory activities. In recent years, clinical research has demonstrated favorable therapeutic effects of TGP on disorders of the liver, cardiovascular, nervous, endocrine, and skeletal systems.
7. Dosage Forms and Reported Dosages
The following dosages are those reported in clinical studies; they are not recommendations.
- TGP Capsules (Pafulin/Pavlin): In a RCT for recurrent aphthous ulcers, the dose was 1.8 g/day for 24 weeks. The capsule was 0.3 g per capsule, containing 130 mg of paeoniflorin.
- RA adjuvant therapy: Clinical trials in the RA meta-analyses typically used TGP in capsule form. TGP capsules, also known as Pafulin, are extracted from the dry roots of the traditional Chinese medicine plant Paeonia lactiflora, and have been developed as a drug for the treatment of RA and are widely used in the clinic in China.
- Red peony root (pancreatitis): Patients received a coloclyster of 15 g of red peony root granules dissolved in 150 mL of water.
- Paeoniflorin (animal models): Subcutaneous administration of PF at doses of 2.5 and 5 mg kg⁻¹ for 11 days was used in MPTP mouse models of Parkinson's disease. (Preclinical; not transferable to human dosing.)
- Standardization for commercial extracts: White peony root extract is often standardized to paeoniflorin content; however, dosage ranges from clinical trials are what inform evidence-based use.
8. Safety Considerations and Interactions
8.1 General Safety Profile
Modern pharmacological studies have shown the diverse effects of TGP, such as anti-inflammatory, antioxidant, immunomodulatory, hepatoprotective, and analgesic, accompanied by mild adverse effects.
The adverse events of TGP were mainly gastrointestinal tract disturbances, mostly mild diarrhea. More specifically, gastrointestinal issues are another commonly reported side effect of TGP. Some users have experienced symptoms such as nausea, vomiting, diarrhea, and abdominal discomfort. These symptoms can vary in intensity and may be more pronounced when TGP is taken on an empty stomach.
8.2 Hepatic Safety
Notably, TGP has been studied for its protective effects on the liver in the context of RA treatment. This meta-analysis indicated that TGP adjuvant therapy might alleviate the incidence of hepatic adverse effect and leukopenia for the RA treatment compared to non-TGP therapy. However, liver toxicity is a potential side effect that warrants attention, although it appears to be relatively rare. Some studies have indicated that high doses or prolonged use of TGP could lead to elevated liver enzymes, which are markers of liver damage.
8.3 Immunomodulatory Caution
One of the primary concerns with TGP is its immunomodulatory effects. While these effects can be beneficial in managing autoimmune disorders, they may also pose risks. For instance, suppressing the immune system too much could make individuals more susceptible to infections. This is particularly crucial for people with weakened immune systems or those already prone to infections.
8.4 Allergic Reactions
Allergic reactions to TGP, though uncommon, can occur. Symptoms of an allergic reaction may include rash, itching, swelling, dizziness, and difficulty breathing.
8.5 Drug Interactions
Although many Paeonia species have been widely used in folk medicine, the extracts of these plants were not used alone in clinical trials but were often used as a part of the prescriptions. This makes isolating interaction profiles complex.
Given its known immunomodulatory activity, caution is appropriate when TGP is used alongside immunosuppressants. Comprehensive plant quality control, and toxicology and pharmacokinetic studies are needed in future studies. The bioavailability of paeoniflorin is further modulated when combined with other herbal constituents: the addition of glycyrrhizin from licorice potentiates paeoniflorin's spasmolytic effects in both in vitro and in vivo settings, which underlies the traditional pairing of peony with licorice root in formulae such as Shakuyaku-kanzo-to.
8.6 Limitations of Evidence
In vitro and in vivo pharmacological studies of plant extracts have demonstrated partial traditional uses of several species, including P. suffruticosa, P. ostii, P. lactiflora, and P. emodi, while the active ingredients and mechanisms of these effects are not fully clear.
Though TGP could mitigate the unanticipated adverse effects during the conventional treatment of RA, high-quality evidence-based meta-analysis data on this subject are still insufficient. The majority of clinical trials are conducted in China, often without standardized outcome measures or sufficient blinding, and independent high-quality replication from non-Chinese research settings is limited.
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