Peony root – Paeoniae radix rubra (Paeonia lactiflora Pall. or Paeonia veitchii Lynch)
|Latin name of the genus:||Paeoniae radix rubra|
|Latin name of herbal substance:||Paeonia lactiflora pall. or paeonia veitchii lynch|
|Botanical name of plant:||Herbalref.com|
|English common name of herbal substance:||Peony root|
Latin name of the genus: Paeoniae radix rubra
Botanical name of plant: Paeonia lactiflora Pall. or Paeonia veitchii Lynch
English common name of herbal substance: Peony root
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Peony red root is not yet covered by the current European Pharmacopoeia 8th edition (2015). A draft monograph of the EUROPEAN PHARMACOPOEIA COMMISSION Pharmeuropa 27.1 defines the herbal substance. The herbal substance is described only in the Pharmacopoeia of the People´s Republic of China (2010) and the Taiwan Herbal Pharmacopoeia. Paeonia veitchii Lynch is not found in the Japanese Pharmacopoeia and not in the WHO monographs.
Pharmeuropa 27.1 (draft): PEONY ROOT, RED; Paeoniae radix rubra; Chishao; 赤芍 is the whole or fragmented, dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch or a mixture of the two, with rhizome and rootlets removed. Content: minimum 1.8% of paeoniflorin (C23H28O11; Mr 480.5) (dried herbal substance). The absence of Paeonol is part of the identification.
Pharmacopoeia of the People´s Republic of China (2010): Paeonia radix rubra; Red peony root is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch (Ranunculaceae). The herbal substance is collected in spring and autumn, removed from rhizome, rootlet and dried in the sun.
The pharmacopoeia of Japan XVI (2011): Peony Root is the root of Paeonia lactiflora Pallas (Paeonaceae).
The Taiwan Herbal Pharmacopoeia: PAEONIAE RUBRA RADIX 赤芍 Chih Shao / Chi Shao/ Red peony root is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch (Fam. Ranunculaceae).
WHO Monographs on Selected Medicinal Plants 1999: Radix Paeoniae is the dried root of Paeonia lactiflora Pallas (Paeonaceae) with reference to the Pharmacopoeia of Japan and the Pharmacopoeia of the People´s republic of China.
Main characteristic constituents of the herbal substance
According to Blaschek et al. (2013) the herbal substance contains monoterpenes and monoterpenes glycosides (as paeoniflorin, albiflorin, oxipaeoniflorin), gallotannines, triterpenoids as
There is a great variation in the content of constituents depending on the harvest period and usage of peeled or unpeeled herbal substance.
Paeonols are found in the root bark of P. suffruticosa, which is not part of this herbal substance.
Liu et al. (2009) separated and characterized the major constituents in Paeoniae radix rubra by fast
Potential confounding materials
Paeonia lactiflora var. trichocarpa Stern; Paeonia japonica (Makino) Miyabe & H. Takeda; Paeonia suffruticosa Andrews syn.; Paeonia moutan Sims (Herbal Medicines Compendium, 2013).
The Pharmeuropa 27.1 contains a test of
White peony is distinguished from red peony by the process of peeling, cooking in water and drying of the root of Paeonia lactiflora. (Bruneton, 1995).
Comminuted herbal substance (Pharmeuropa 27.1)
Potential confounding is possible as a lot of different definitions of “peony radix” exist in parallel and the published non clinical and clinical literature does not always gives exact information. For example the pharmacopoeia of Japan XVI (2011) and the WHO does not distinguish red and white peony.
In conclusion, in cases where publications refer to “white” ore “red” peony they are only cited in the respective monograph and supporting documents. In cases where the publications refers to “Paeonia lactiflora” or “peony root” in general, the literature is considered in both monographs and supporting documents.
•Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
1.2. Search and assessment methodology
A literature search was performed using the DIMDI (Deutsches Institut für Medizinische Dokumentation und
2. Data on medicinal use
2.1. Information about products on the market
2.1.1. Information about products on the market in the EU/EEA Member States
Information on medicinal products marketed in the EU/EEA
According to the information provided by the National Competent Authorities, in Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Italy, Latvia, Lichtenstein, Lithuania, Luxemburg, Malta, The Netherlands, Norway, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain and Sweden no authorised or registered medicinal products are on the market.
In the United Kingdom, one traditional herbal medicinal product containing an ethanolic tincture of red peony root was registered in 2011. The national decision took into account usage of herbal
preparations by herbal practitioners in the United Kingdom. Data available to the HMPC are not appropriate to include the herbal preparation in a European Union monograph.
Additionally, this ethanolic tincture is not a preparation reported to be used in TCM in China, where only aqueous extracts or the powder (decoction) are used. As it can be seen by the comparison of the indications of red and white peony root in Table 2, herbal practitioners used the tincture of peony root in an indication that is not mentioned in the Pharmacopoeia of the People´s Republic of China (2010).
The herbal substance is used in Traditional Chinese Medicine (TCM) combinations and homeopathic medicinal products, and, from the data available, they are not sufficient to fulfil the legal requirements of Directive 2004/24/EC as regards single active substances in traditional herbal medicinal products and according to the principles applied for the establishment of EU monographs.
Table 1: Overview of data obtained from marketed medicinal products
This overview is not exhaustive. It is provided for information only and reflects the situation at the time when it was established.
Information on relevant combination medicinal products marketed in the EU/EEA
Information on other products marketed in the EU/EEA (where relevant)
2.1.2. Information on products on the market outside the EU/EEA
Red peony root is traditionally used in various TCM combination products in China and Taiwan (up to 12 different substances). Table 2 shows that whole ore fragmented, dried root of Paeonia lactiflora (Paeoniae radix rubra) has a different use in the TCM compared with peeled, boiled and dried root (Paeoniae radix alba).
Klein et al. (2010) analysed prescription patterns of Chinese Medicinal Herbs in Switzerland from the database of Lian Chinaherb AG. Baishao (Paeoniae radix alba) was one of the most commonly used herbs and was used in 41.4% of the TCM prescriptions. Paeoniae radix rubra was reported to be used less frequently.
Table 2: Comparison of the
Feng et al. (2010) and Zhang JJ (2013a) reported, Paeoniae radix rubra and Paeoniae radix alba are both TCMs commonly used in China. Although being of similar origins, the clinical efficacies of the two medicines are regarded different. The two TCMs are regarded as two independent medicines.
2.2. Information on documented medicinal use and historical data from literature
Red peony root is used in Chinese herbal medicines. Few European pharmacopoeias or accepted collections in the European countries have introduced red peony root. Referring to the medicinal use they hint to references on the uses as TCM or give a public statement for the European medicinal use in the EU.
Table 3: Overview of historical data
2.3. Overall conclusions on medicinal use
No herbal medicinal product or traditional herbal medicinal product with red peony root could be identified on the marked in the EU before 2011.
In conclusion, there is no single herbal preparation for which 15 years of medicinal use in the EU could be confirmed from literature or based on the regulatory status overview. The requirement laid down in Article 16a(1)(d) of Directive 2001/83/EC that “the period of traditional use as laid down on Article 16c(1)(c) has elapsed”, is not considered fulfilled according to available data and the principles applied for the establishment of European Union monographs.
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
3.1.1. Primary pharmacodynamics
Kimura et al. (1984) found blocking effects of paeoniflorigenone, isolated from cold aqueous extracts of peony root, on neuromuscular junctions of frogs and mice. The suppressing effect by paeoniflorigenone (300 µg/ml) was not reversed by neostigmine. Paeoniflorigenone (100 µg/ml) inhibited weakly acetylcholine (5 µg/ml) induced slow contractions. Paeoniflorigenone decompressed on heating, therefore, the authors concluded that it may not necessarily play a predominant role in the clinical therapy of muscle pain.
Total glycosides of Paeonia lactiflora Pall. root (TGP)
(ethanol reflux, ethylacetat extraction, dried powder, consists of 90% paeoniflorin)
Chang Y et al. (2009) showed that TGP (312.5 µg/ml) significantly inhibited the proliferation of synoviocytes, decreased the production of
Chen JY et al. (2012) showed that paeoniflorin inhibited proliferation of
Jiang B et al. (2012) examined the inhibitory effect of paeoniflorin on the inflammatory vicious cycle between adipocytes and macrophages. The authors concluded, paeoniflorin exhibits
Li et al. (2012) treated
(100 mg/kg) decreased arthritis score, relieved ankle and paw swelling, improved spleen histopathology and decreased the levels of IgA, IgM, IgG and
Wu et al. (2014) determinated paeoniflorin in rat plasma, following the oral administration of Paeoniae radix alba aqueous decoction, showing to be absorbed. In the pharmacological experiment paeoniflorin was administered for 4 weeks in a low, middle and high dose (0.5; 1 and 3 mg/kg per day) in rats with
Zheng YQ et al. (2007) studied the effects and mechanisms of paeoniflorin, a bioactive glucoside from peony root, on adjuvant arthritis in rats. Rats were treated with paeoniflorin (5, 10, 20 mg/kg) orally from day 14 to 20 after inducing adjuvant arthritis. Paeoniflorin an 10, 20 mg/kg per day suppressed rat AA at least partly by inhibiting abnormal proliferation of synoviocytes and the production of
Total glucosides of peony (TGP)
Zheng YQ and Wei (2005) found that TGP suppressed adjuvant arthritis in rats and intervenes
Zhu L et al. (2005) analysed the effect and mechanisms of TGP on joint damage in rat collagen- induced arthritis. TGP (25, 50, 100 mg/kg/d) was orally administered to rats from day 14 to 28 after immunisation. The therapeutic effect of TGP could be associated with its ability to ameliorate the secretion and metabolism of synoviocytes and to inhibit the abnormal proliferation and VEGF, bFGF,
Zhu L et al. (2006) found that TGP had inhibitory effect on hyper functional synoviocytes from rats with
Xu HM et al. (2007) analysed the effect and mechanisms of TGP on adjuvant arthritis in rats. Intragastric administration of TGP (50, 100 mg/kg bw) significantly decreased secondary inflammatory reaction in adjuvant arthritis rats. Suppressing the activity of
Lin J et al. (2012) found that TGP inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis. TGP treatment (150 mg/kg i.p.) significantly decreased percentage and number of Th1 and Th17 cells in CIA in mice. TGP treatment inhibited dendritic cells (DCs) maturation and reduced production of
Wei et al. (2013) administered orally TGP at 60 mg/kg bw for 3 months to New Zeeland rabbits with
The tested substance paeoniflorin is only one component of the root. The results do not highlight any specific activity for the aqueous extract of the whole root. For
The results of the study Lee KK et al. (2011) showed Paeoniae radix and Gentianae radix extracts orally administered, did not induce significant antinociception in
Zhang XJ et al. (2009) found that the analgesic effect of paeoniflorin in rats with neonatal maternal
The results for peony root extract (no further information) are contradictory regarding
Rawat and Malviya (2010) tested the antipyretic activity of aqueous root extract of Paeoniae radix (100 and 200 mg/kg orally, the percentage yield of the prepared extract was 12%±0.51 (w/w)) in rats. The root extract showed significant reduction in normal body temperature and
The tested extract concentrations 100 and 200 mg/kg orally correspond to approximately
Ethanolic extract, Paeonol, Paeoniflorin
Lee B (2008) analysed the
The results hint an
Chen Y et al. (2007) analysed the effects of paeoniflorin on the level of antibodies and cAMP produced by splenocytes in rats with adjuvant arthritis. Paeoniflorin 25, 50, and 100 mg/kg bw) were given by intragastric administration for 7 days from the 17 days after immunization. Paeoniflorin
(50 and 100 mg/kg bw) reduced the levels of circulating immune complexes,
Total glycosides of peony (TGP)
Li CL et al. (2013) examined the effects of total glucosides (100 mg /kg per day intragastrically) of peony for delaying onset of Sjogren’s syndrome in an animal study using
Total glycosides of peony (TGP)
Jia et al. (2012) showed, that TGP in 1562.5 µg/ml regulates cytokines production in lupus CD4+ T cells from systemic lupus erythematosus patients.
Zhao M et al. (2012) examined the molecular mechanism of TGP in prevention of autoimmune response. They found, TGP (1562.5 µg/ml) induces regulatory CD4(+)CD25(+) T cells by increasing Foxp3 demethylation in lupus CD4(+) T cells. The
Leem et al. (2004) tested Paeonia lactiflora root extracts on the secretions of chemokines as monocyte chemotactic
Tsuboi et al. (2004) investigated whether paeoniflorin induces DNA fragmentation in murine
T lymphocytes and human
Yang L et al. (2013) conducted a comparative study on bioactivities of Paeoniae radix alba and Paeoniae radix rubra. The authors concluded Paeoniae radix alba and its major compounds possess more significant bioactivities on J774 macrophage cells than Paeoniae radix rubra and its major compounds, and the herbal substances should be classified into different category in TCM.
No experimental studies were conducted with the aqueous extract or tea preparations. The
Anticoagulant and antiplatelet activity
Aqueous extract of Paeonia lactiflora Pall.
Ishida et al. (1987) measured the plasma
Different fractions of a methanolic extract
Kang et al. (1991) analysed platelet
Ye J et al. (2001) evaluated the
Koo et al. (2010) analysed the platelet
Li JZ et al. (2013) found inhibitory effects of paeoniflorin on
Zhu Y et al. (2013) compared the chemical components between Baishao and Chishao aqueous extracts and their effects on proliferation of rat thoracic aorta smooth muscle cells. The results indicate the extracts have different chemical components and produce different biological effects. (Chinese, only English abstract)
Total glycosides of peony (TGP)
Li J et al. (2011) analysed the effects of total glucosides from peony (Paeonia lactiflora Pall.) roots (120 mg/kg, 240 mg/kg) intragastrically administered for 15 weeks on experimental atherosclerosis in rats. Compared to control, TGP significant lowered the serum level of total cholesterol, triglyceride,
Zhu HM et al. (2004) conducted an experimental study on preventive effect of Paeoniae radix rubra (no further information) to restenosis after carotid balloon injury in high
on the restenosis after carotenoid bollon injury in high
Aqueous extract from Paeonia veitchii Lynch and Paeonia lactiflora Pall.
Guo et al. (2006) analysed in an
Lin TJ et al. (2013) tested the
Methanolic extract from Paeoniae radix and its fractions
Im et al. (2012) evaluated the nitric oxide production inhibitory effect and antibacterial activity of the methanol extract and fractions from Paeoniae radix. As a result the ethyl acetate fraction of the methanol extract showed the highest antibacterial activity and the ethyl acetate fraction in the highest nitric oxide production inhibitory effect. The aqueous fraction showed no activity in all the tests performed.
Ngan et al. (2012a) examined the inhibiting effects of Paeonia lactiflora root steam distillate constituents and structurally related compounds on human intestinal bacteria. The yield of the oil was 0.01% on dry weight basis of the root. Paeonia lactiflora root steam distillate was proven to have high
Ngan et al. (2012b) found
No preclinical studies were conducted with the aqueous plant extract.
Ethanolic extract of Paeoniae radix
Kim et al. (2009) analysed the antifungal activity of seven herbal plant extracts against five different Candida species by agar diffusion assay. The ethanolic extract (100% ethanol) of Paeoniae radix showed no antifungal activity.
Aqueous extract of Paeonia lactiflora Pallas radix
Goto et al. (1999) examined the effect of PRE on endothelial function. The extract of Paeoniae radix was prepared by boiling in water. The yield was 11.0 g Paeoniae radix extract from 100 g of herbal substance. Male springue rats were divided in four groups: control group, high cholesterol diet group, low PRE group (high colesterol plus 60 mg /d PRE) and high Paeoniae radix extract group (high cholesterol plus 360 mg per day extract). After 10 weeks of treatment, the body weights in high cholesterol, low Paeoniae radix extract and high Paeoniae radix extract groups were significantly lower compared with that of the control group. Plasma total cholesterol level was significantly increased by about
Yang HO et al. (2004) isolated paeoniflorin from Paeonia lactiflora and analysed the antihyperlipidemic effect in experimentally induced hyperlipidemic rats. Paeoniflorin showed a lowering effect of total cholesterol, LDL and triglyceride levels compared with the control group at the dose of 200 and
400 mg/kg p.o. once a day for 4 weeks.
Lin HR (2013) evaluated the activity of paeoniflorin against LXR by the mammalian
Aqueous extract from Paeonia lactiflora
Goto et al. (1996) showed that an extract from Paeoniae radix relaxed prostaglandin F2a pre- contracted aortic ring preparations of isolated rat aorta that contained endothelium. The active component was gallotannin. Paeoniflorin and paeonol lacked a vasodilator effect.
Ethanol extract of Paeoniae radix rubra
Jin et al. (2012) analysed the vasodilatory effects of ethanol extract (70% aqueous ethanol, DER unknown) of Paeoniae radix rubrae and its mechanism of action in the rat aorta. The extract induced relaxation of the
Total glycosides of peony (TGP)
Long et al. (2012) analysed the cardio protective effect of total peony glycosides against isoprenaline- induced myocardial ischemia in rats. Compared with model rats, TGP treatment (269.4 mg/kg intragastralic administration for 3 days before ISO administration and 449 mg/kg for 3 days after ISO administration) exhibited significantly reduced activities of GOT, LDH and CK, increased activity of SOD and lower levels of MDA. The protective effect of TGP treatment was even better than that of propranolol.
Paeonol and Paeoniflorin
Nizamutdinova et al. (2008) investigated the effect of paeonol and paeoniflorin, the postulated main active principles of Paeonia albiflora, on myocardial ischemia/reperfusion injury in rats. Administration of
10 mg/kg paeoniflorin or paeonol i.p. 1 h prior to reperfusion injury resulted in a significant improvement of the hemodynamic parameters. The administration of paeoniflorin or paeonol reduced myocardial infarct size, through inhibition of apoptosis.
No preclinical studies were conducted with the aqueous plant extract. The experiments of Long J et al. (2012) were performed with the isolated TGP in high doses (269.4 mg/kg intragastralic administration corresponds to 19 g TGP in a 70 kg person). Results are not relevant for establishing a monograph.
Other plant extract: Fractions of methanolic extract of Paeonia lactiflora, radix rubra
Baumgartner et al. (2010) tested 11 fractions of a methanolic Paeoniae radix extract (no DER information) on their pharmacological activity in an enzyme based assey. Pentagalloylglucose was able to enhance insulin receptor phosphorylation at a concentration of 10 µmol, which could account to the
Ethanolic extract of the root of Paeonia lactiflora Pallas
Juan et al. (2010) examined the
Methanolic fraction of an Ethanolic extract of Paeoniae radix rubra
Juan et al. (2011) evaluated the insulin mimetic novel suppressors of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription from Paeoniae radix rubra extract (80% ethanol). The extract of Paeonia radix rubra suppressed PEPCK expression in H4IIE cells in an insulin receptor independent manner, in the presence of an insulin receptor antagonist
The results of Kong et al. (2013) showed effects of paeoniflorin on tumour necrosis
PPARγ expression, which improves insulin signalling pathway and increases adiponectin expression.
No preclinical studies were conducted with the aqueous plant extract and no
Paeoniae radix extract (no information on plant species, DER, extraction solvent)
Abdelhamed et al. (2013) screened 138 medicinal plant extracts in a concentration of 1 µg/ml against
Fang S et al. (2012) reported that paeoniflorin may effectively modulate multidrug resistance of the human gastric cancer cell line SGC7901/vincristine via the inhibition of
regulation its target genes MDRI1,
According Kwon et al. (2007) a lot of examples (Paeonia radix alba) of the induction of apoptosis by nutritional supplements and herbs through the generation of reactive oxygen species exist. The authors concluded, however nutritional supplements and herbs must be used with caution, as few research studies have actually evaluated their safety and efficacy and no guidelines for dose and usage are available.
Aqueous extract of Paeonia lactiflora Pallas
Lee SM et al. (2002) examined the cell growth of HepG2 and Hep 3 B cells in the presence of various concentrations of Paeoniae radix extract (PRE). The Paeoniae radix extract inhibited hepatoma cells growth by inducing apoptosis in a p53 independent pathway at a concentration of 4.6 and 4.4 mg/ml. The PRE could induce the internucleosomal DNA fragmentation of HepG2 and Hep3B cells. The authors concluded it may be a promising anticancer agent for inhibiting the growth of
Washida et al. (2009) isolated a new monoterpenes glycoside
Total glycosides of peony (TGP)
Xu HY et al. (2012) analysed the antitumor activity of total peony glycoside against human chronic myelocytic leukaemia K562 cell lines
(25 mg/kg) was administered via intraperitoneal injection every 4 days. At 32 days TGP showed a significant decreased tumour volume and tumour weight in nude mice inoculated with k562 cells.
Xu W et al. (2013) studied the
Cerebral ischaemia and cognitive effects
significantly enhanced the ameliorating effect. No correlation to the natural concentration of the derivates in the plant was given. The authors assumed further clarification is necessary for (chemical) design of more potent candidates.
Xiao et al. (2005) examined the effects of paeoniflorin on the cerebral infarction, behavioural and cognitive impairments at the chronic stage of transient middle cerebral artery occlusion in rats. One day (10 mg/kg twice s.c.) or
Tang et al. (2010) tested the
Total glycosides of peony (TGP)
Liu et al. (2004) analysed the protective effect of TGP on complete cerebral ischemia reperfusion injury in rats. TGP (20 mg/kg) possessed protective effects on the histopathological changes of ischemia cerebral tissues in rats. (Chinese only English abstract)
Zhang AP et al. (1993) showed that TGP, (50 mg/kg 7d, ig) could enhance the episode duration of
Aqueous extract of peony root, paeoniflorin
Ohta et al. (1993) analysed the effect of four herbs Japanese angelica root, cnidium rhizome, peony root and rhemmania root on the scopolamine induced spatial working memory disruption in rats. Among the component herbs, peony root extract (0.25 and 1 g dried her/kg, orally) exhibited the most antagonizing effect on the scopolamine disruption of the choice accuracy. Paeoniflorin
Aqueous extract of peony root
Tsuda et al. (1997) evaluated the protective effects of peony root extract and its components on neuron damage in the hippocampus induced by the cobalt focus epilepsy model in rats. Neuron damage in the CA1 area of the hippocampus and frequent spike discharges induced by application of metallic cobalt to the cerebral cortex of rats were completely prevented when the extract was continuously administered orally at 1 g/kg per day for 30 days prior to cobalt application. The use of paeoniflorin alone had no effect. The gallotannin fraction had incomplete protective action. A combination of the gallotannin and paeoniflorin fraction showed complete action in the same way as peony root extract.
Total glycosides of peony (TGP)
Yang J et al. (2000a) analysed the protective effect of TGP against cerebral
Yang J et al. (2001) analysed the protective effects of TGP on cerebral ischemia mice. TGP could prolong gasp time of decapatative mice, lessen cerebral water content and decrease permeability of cerebral capillary significantly. (Chinese only English abstract)
Yang J et al. (2000b) analysed the improvement effects of TGP on ability of learning and memory in model mice induced by drugs. TGP could reduce irritated time, prolonged duration of safe staying, lessen the times of error and adjust latent duration. In model mice of spatial resolution TGP increased ratio of successful landing, reduced times of mistake and lessoned the time of landing. (Chinese only English abstract)
Neuron damage in the CA1 area of the hippocampus and frequent spike discharges induced by application of metallic cobalt to the cerebral cortex of rats were prevented when an aqueous extract was continuously administered orally. In disruption of the choice accuracy, peony root extract exhibited an antagonizing effect on the scopolamine. The doses correspond to
Ono et al. (2000) found that Pentagalloylglucose, an antisecretory component of Paeoniae radix, inhibits gastric H+, K±ATPase with an IC50 of 166 nmol/l and may be responsible for inhibition of acid secretion by Paeoniae radix.
Liver protective activity
Total glucosides of peony (TGP)
Results of a study in rats by Dai LM et al. (1993) showed that
(10, 20, mg/kg per day times 7 days, i.p.) diminished the
Wang H et al. (2005) evaluated effects of TGP (60 and 120 mg/kg, oral) on immunological hepatic fibrosis in rats. Histological results showed that TGP improved the human
Zheng LY et al. (2008) concluded by their study results, TGP (0.15 g/kg bw, 0.05 g/kg bw) may protect liver function and modulate serum lipid for the fatty liver rats caused by insulin resistance, and its action mechanism may be concerned with enhancing sensitivity and antioxidative ability, decreasing serum lipid.
Aqueous extract of Paeoniae radix rubra
Li R et al. (2011) studied the hepatoprotective action of Paeoniae radix rubra aqueous extract against
Paeonia radix rubra and Paeonia radix alba alcoholic extract
Wang R et al. (2012) found, that oral administered Paeonia radix rubra and Paeonia radix alba extract (12 g/kg for 6 days) attenuate CCl4
Li X et al. (2009, 2010) investigated the effects of paeoniflorin on hepatic fibrosis of mice infected with S. japonicum. Paeoniflorin was administrated orally on the 12th day (30 days of successive administration) after infection. Paeoniflorin (30 mg/kg per day) ameliorates schistosomiasis liver fibrosis through regulating
The results of Kuo et al. (2012) in the
Lu et al. (2012) performed a screening for identifying of hepatoprotective compounds in Paeoniae radix rubra. Fluorescein diacetate labelled and MTT assay were applied for screening the hepatoprotective fractions on HepG2 cells exposed to galactosamine. Three hepatoprotective fractions were founded, in which three compounds were identified as paeoniflorin, ethyl palmitate and ethyl linoleate.
The experiments of Wang R et al. (2012) were performed with ethanolic extracts in high doses
(12 g/kg corresponding to 840 g in a 70 kg person). TGP, what are isolated substances of peony, may protect liver function and modulate serum lipids
Lung protective activity
Paeoniae radix rubra (no further information on the plant extract)
Chen C et al. (2005) investigated the effect of Paeoniae radix rubra on expression of iNOS and eNOS in
Chen C et al. (2008) investigated the effect of pretreatment (i.v. injection of 30 mg/kg bw) of Paeoniae radix rubra (no further information on the plant extract) on acute lung injury induced by intestinal ischemia/reperfusion in rats and its protective mechanism. Under light microscope, the pathologic changes induced by ischemia/perfusion group were significantly attenuated by Paeoniae radix rubra. The protective effect in acute lung injury was related to its property of inducing
Zhang F et al. (2005) analysed the protective effects of
partial pressure of carbon dioxide in the Paeoniae radix rubra
Ji et al. (2013) found paeoniflorin attenuated
The experiments have methodological deficiencies as they were conducted with preparations of unknown composition /DER, i.v. injection or only from isolated substances. Results are not relevant for establishing a monograph.
Cao BY et al. (2010) evaluate a neuroprotective effect of paeoniflorin and found that paeoniflorin (50 µM) protects PC12 cells from MPP and acidic damage via autophagic pathway.
Lee SM et al. (2008) examined the protective effects of Paeonia lactiflora Pall. on hydrogen peroxide- induced apoptosis in PC12 cells. The total phenolic content was 89.65 mg per g of extract. After 2 h of cell exposure to 0.5 mM H2O2 a marked reduction in cell survival was observed in the MTT reduction assay and LDH release assay.
Chen T et al. (2011) found that Paeoniae alba radix extract (prepared of decoction) caused enhancement of the nerve growth
Liu DZ et al. (2005) examined the neuroprotective effect of paeoniflorin on transient ischemic model in rat by activating adenosine A1 receptor in a manner different from its classical agonists. The administration of paeoniflorin (2.5 and 5 mg/kg bw s.c.) produced a
Methanolic extract of peony root
Harada et al. (1984) analysed the effects of Japanese Angelica root and peony root extracts (3 g/kg) on uterine contraction in the rabbit in situ.
“Crude alcoholic extract”
Madari and Jacobs (2004) reported Paeonia officinalis was used in traditional medicine of ancient Persia as abortificient. A crude alcohol extract of the root of Paeonia officinalis produced uterine stimulation in rat confirming the traditional use as abortificant.
There is no information on the dosages used for abortification in the report of Madari (2004). The in- vivo experiments of Harada (1984) were conducted with very high doses 3 g/kg corresponding to 210 g herb for a 70 kg person, so no conclusions for clinical relevance can be drawn. The possible effect should be considered for safety reasons.
Chen T et al. (2011) analysed the protective effects of paeoniflorin extracted by Paeonia lactiflora Pall. against hydrogen
Im and Lee (2011) analysed the tyrosinase inhibitory activity and melanin production inhibitory activity of the extract and fractions from Paeoniae radix. The total polyphenol content of the extract was 73.45 mg/g. The tyrosinase inhibitory activity of the ethyl acetate fraction showed higher activity than arbutin used as a positive control. In nontoxic concentration range, the ethylacetate fraction showed strong melanin production inhibitory effect and the authors considered it could be applicable to functional materials for
The results of the experiments of Lee SC et al. (2005) showed, the oral administration of 50% ethanol extract of peony root (no DER information), gallic acid and methyl gallate potently inhibited the formation of micronucleated reticulocytes in the mouse peripheral blood induced by a KBrO3 treatment
Effect on renal tubulointerstitium in rats
Total glucosides of peony (TGP)
Fang F et al. (2008) administered TGP 50, 100, 200 mg/kg per day orally once a day for 8 weeks in diabetic rats. Increased indices for tubulointerstitial injury were significantly ameliorated by TGP treatment with 100 and 200 mg/kg bw. Elevated expression of osteopontin protein was inhibited with 100 and 200 mg/kg bw, and increased expression of
200 mg/kg bw.
Zhang P (2009) analysed the effect of TGP on the expression of nephrin in the kidneys from diabetic rats. TGP 50, 100, 200 mg/kg per day was administered orally once a day for 8 weeks in diabetic rats. Western blot analysis showed that the expression of nephrin protein was reduced in the kidneys of diabetic rats but significantly increased in the TGP treatment group. The expression of
Wu et al. (2009) analysed the renoprotective effect of TGP and its mechanism in streptozotocin- induced diabetic rats. The rats were treated orally with TGP for 8 weeks. Treatment at 50, 100 and 200 mg/kg significantly lowered 24 h urinary albumin excretion rate. 100 and 200 mg/kg reduced indices for tubolointerstitial injury in diabetic rats.
Wound healing effect
Malviya and Jain (2009) examined the wound healing activity of aqueous extract (no further information) of Paeoniae radix by incision, incision and dead space wound models on Wistar rats. The results indicated that radix Paeoniae extract accelerates the wound healing process by decreasing the surface area of the wound and increasing the tensile strength. The histological examination of the granulation tissue of treated group showed increased
Total glycosides of peony (TGP)
Mao et al. (2009) examined the effects of peony glycosides on mice exposed to chronic unpredictable stress. Chronic unpredictable stress induced depression, as indicated by increase in immobility time in the tail suspension test, was alleviated by s.c. administered TGP (160 mg/kg). The authors suggest the effect is probably mediated by inhibition of monoamine oxidation.
Mao et al. (2012a) found that peony glycosides (160 mg/kg, s.c.) reverse the effects of corticosterone on rats.
The experiments were performed with applied s.c. TGP. No
Zhang JJ et al. (2013b) conducted a comparative study on effects of blood enriching on mouse model of blood deficiency syndrome induced by compound method of bleeding, starved feeding and exhausting of Paeoniae radix alba and Paeoniae radix rubra (2 g/kg bw, no information about the extract) paeoniflorin and albiflorin. At the 7th day Paeoniae radix alba has a better effect of blood enriching than Paeoniae radix rubra. Albiflorin was more effective than paeoniflorin.
It is unclear which herbal preparation or whether the crude herbal substance was administered. The dose of 2 g/kg corresponds to 140 g for a 70 kg person and is higher as traditionally (TCM) used dosage ranges.
Effect on colitis
Zhou et al. (2010) found that paeoniflorin increases
3.1.2. Secondary pharmacodynamics
3.1.3. Safety pharmacology
3.1.4. Pharmacodynamic interactions
The preclinical studies were often performed with isolated substances as paeoniflorin or TGP. Wang C et al. (2012) reported, when administered orally, paeoniflorin was absorbed poorly in gastrointestinal
tract, leading to a very low bioavailability of
No conclusions can be drawn from preclinical experiments and pharmacological data. No therapeutic posology in humans is known for the use in Europe. In summary, available data are not adequate to support establishment of a European Union monograph.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Dong et al. (2009) showed that the absorption of paeoniflorin was linear at different intestine segments and dosages. The square of degrees correlation coefficient exceed 0.9, which is consistent with a zero order rate process. The Kα of paeoniflorin showed a
Pharmacokinetic comparison between Paeoniae radix rubra and Paeoniae radix alba
Wang CH et al. (2008) conducted a comparative pharmacokinetic study of paeoniflorin after oral administration of decoction of Paeoniae radix rubra and Paeoniae radix alba in rats. There was a significant difference between the pharmacokinetic characteristics of Paeoniflorin alone, Paeoniae radix rubra and Paeoniae radix alba (3.24%, 4.26% and 1.82%). The results suggested that the bioavailability of paeoniflorin in rats after oral administration was very low, about 3%. The Tmax, AUC 0- ∞, Cmax were increased after oral consumption of Paeonia radix rubra compared to Paeoniae radix alba.
Feng et al. (2010) reported a significant difference between the pharmacokinetic characteristics of Paeoniae radix rubra and Paeoniae radix alba, by the
The increase of AUC suggested, paeoniflorin was absorbed better from the decoction of Paeoniae radix rubra than of Paeoniae radix alba. The longer Tmax and T1/2 implied the delay of absorption and slower of elimination of paeoniflorin.
Hsiu et al. (2003) investigated the metabolism and pharmacokinetics of paeoniflorin by oral administration in rats. The paeoniflorin levels in serum were below the detection limit through the study. In conclusion paeoniflorin was not absorbed per se, whereas its aglycone paeoniflorigenin was absorbable and circulating in the bloodstream.
Tang and Eisenbrand reported in the Handbook of Chinese Medicinal Plants, Chemistry, Pharmacology, Toxicology (2011) that paeoniflorin seemed to be poorly absorbed from the gastrointestinal tract, resulting in an extremely low bioavailability.
Wang C et al. (2012) reported, according to previous studies, when administered orally, paeoniflorin was absorbed poorly in gastrointestinal tract, leading to a very low bioavailability of
Chen LC (1999) administered orally peony root extracts to mice (24.6 g dry extract obtained from 200 g crude material, extraction solvent aqua) at a dose of 10 mg/kg paeoniflorin for quantification of paeoniflorin. The calibration curve for paeoniflorin was linear over the concentration range
Cao C et al. (2006) determined the paeoniflorin concentration in the cortex of normal and cerebral
Liang et al. (2013) analysed the profiling and identification of the absorbed constituents and metabolites of Paeoniae radix rubra (PRR) decoction in rat plasma and urine by the
Sun et al. (1996) reported glycosidases, produced in E. coli as a cytoplasmic protein, convert natural glycosides to bioactive compounds. Paeoniflorin was biotransformed to paeonimetabolins I and II. While paeoniflorin shows depressant, antispasmodic and
Decoct of Paeoniae radix rubra
Jiang F et al. (2012) conducted a comparative pharmacokinetic study of paeoniflorin and albiflorin after oral administration of Paeoniae radix rubra decoct in normal rats and the acute cholestasis hepatitis rats. Particularly at the high dose group, paeoniflorin and albiflorin eliminated much more slowly in the cholestasis hepatitis rats group and the concentration increased in the plasma (higher AUC
longer). The results showed that acute liver injury could alter the pharmacokinetic parameters.
Chen LC et al. (2002) analysed the pharmacokinetic interactions between carbamazepine and Paeoniae radix (Paeonia lactiflora) extracts (300 mg/kg; 24.6 g extract weighting from 200 g of raw material by decoct and drying) in rats. The significant decrease of Tmax indicated that simultaneous oral administration of PR contributes to more rapid absorption of carbamazepine. A significant decrease in protein binding rate was found (62.7 and 68.1%), what was considered probably free from clinical consequences because the wide fluctuations in carbamazepine concentrations between doses. There were no changes in AUC, T 1/2, Cmax.
Chen LC et al. (2001) analysed the pharmacokinetic interactions between phenytoin and Paeoniae radix (Paeonia lactiflora) extracts (300 mg/kg; 24.6 g extract weighting from 200 g of raw material by decoct and drying) in rats. The significant increase of Tmax indicated that simultaneous oral administration of PR delayed the absorption of phenytoin. No significant decrease in protein binding rate was found. There were no changes in AUC, T1/2, Cmax, MRT, CL/F of phenytoin.
Dong et al. (2009) showed, paeoniflorin is a substrate of
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
3.3.1. Single dose toxicity
3.3.2. Repeat dose toxicity
Ethanolic extracts of Paeonia lactiflora Pallas and Paeoniae radix rubra (P. albiflora var. hortensis Makino): Chang et al. (1989) examined 40 Chinese herbal drugs for mutagenicity in the SOS chromotest (E. coli PQ37) and in the SOS umu test. The ethanolic herbal extracts in 4 mg/ml showed no mutagenicity.
Aqueous extracts of Paeonia lactiflora Pallas and Paeoniae radix rubra (P. albiflora var. hortensis Makino): Chang et al. (1989) examined 40 Chinese herbal drugs for mutagenicity in the SOS chromotest (E. coli PQ37) and in the SOS umu test.
The results of the aqueous extracts of Paeonia lactiflora were not presented. The authors assumed, no of the 40 Chinese herbal drugs seem to exhibit mutagenic activities under the experimental conditions. The aqueous extracts of Paeoniae radix rubra (P. albiflora var. hortensis Makino) in 4 mg/ml and
50 mg/ml showed no mutagenicity in the SOS umu test
var. hortensis Makino) exhibited an antimutagenic activity against mitomycin C and aflatoxin B1 in SOS umu test.
Yu et al. (2004) examined the toxicological safety and stability of the components of an irradiated Korean medical herb, Paeoniae radix. The mutagenicity of the aqueous extract was examined triplicatedly in Salmonella reversion assay at 5 dosages from 62 to 5000µg/plate. The number of revertant colonies of each strain in test group did not increased comparing with negative control group. The increase of the colony formation by irradiate sample was not appreciated in both direct non- activate and indirect activated tests. The extract did not show cytogenetic toxicity in the culture of the Chinese hamster ovary cells. The authors concluded, chronic toxicity tests are needed for public acceptance in the application of irradiation for the hygienic technology of the herbs.
3.3.5. Reproductive and developmental toxicity
3.3.6. Local tolerance
3.3.7. Other special studies
Harada et al. (1984) analysed the effects of Japanese Angelica root and Peony root extracts (3 g/kg, no DER information) on uterine contraction in the rabbit in situ.
Only limited toxicological data are available from literature. Adequate tests on genotoxicity, carcinogenicity, reproductive and developmental toxicity and local tolerance are not available. There are some hints for abortificient effects. Consequently, the use in pregnants should be contraindicated (also in the combination preparations of the TCM) for safety reasons.
3.4. Overall conclusions on
Numerous publications on Paeoniae radix or constituents exist, however, often an appropriate description of herbal substance or herbal preparations used are missing. Available data are not sufficient to establish a European Union monograph.
4. Clinical Data
4.1. Clinical pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Total glucosides of peony (TGP)
Lin J et al. (2012) treated 10 patients with diagnosis of rheumatoid arthritis (RA) with TGP by oral administration of 15 mg/kg per day more than 3 months, while another 10 patients did not take TGP. Peripheral blood mononuclear cells were obtained from the patients by
Wang ZJ (1994) reported improvements in immune function by total glycosides of peony in rheumatoid arthritis patients. (No further information, Chinese, only English abstract).
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Wang C et al. (2012) reported TGP contain more than 90% of paeoniflorin. Paeoniflorin was absorbed poorly in gastrointestinal tract, leading to a very low bioavailability
4.2. Clinical efficacy
According the review article “Peony” in Herbal Medicines (2013), there is limited reliable clinical information available for the pharmacological effects and its main constituents. Many studies are available where peony is combined with other herbs in TCM or Traditional Japanese Medicine (TJM) or given with conventional treatment, so that clinical information on the action of peony alone is generally not available and therefore the effects found cannot always be attributed to peony.
4.2.1. Dose response studies
4.2.2. Clinical studies (case studies and clinical trials)
Patients with active rheumatoid arthritis
Total glucosides of peony (TGP) of Paeonia lactiflora Pallas
Zhao YX and Liu (2006) conducted a clinical observation on effects of leflunomide (no information on dose) and TGP on patients with rheumatoid arthritis. Forty persons were treated with TGP and leflunomide and the control group of 40 persons was treated with leflunomide alone for 12 weeks. The total effective rate was higher in the treatment group than in the control group (97.5% vs 85.0%) without significant difference in adverse reactions.
Chen Z et al. (2013) analysed in a
Du and Dong (2005) analysed the clinical efficacy of methotrexate combined with TGP on rheumatoid arthritis for 3 months. 30 patients were only administered orally methotrexate, while 31 patients were treated with methotrexate plus TGP (no dose information). The total effective rate was 90%, 94% 100% in the methotrexate plus TGP group and 87%, 90% 94% in the methotrexate group at 4, 8 and 12 weeks. (Chinese, only English abstract)
Wang Y and Xing (2007) conducted a clinical observation on the effect of TGP combined with methotrexate on rheumatoid arthritis for 24 weeks. Two hundred and sixty patients were assigned to two groups; the treated group (180 cases) was orally administered with methotrexate and TGP (no information on dose) and the control group (80 cases) with methotrexate plus sulfasalazine. The total effective rate at the 4th, 8th, 12th,24th week of the treatment was 70%, 81%, 94%, 98% in the treated group and 60%, 85%, 93% and 94% respectively. The authors concluded TGP combined methotrexate treatment shows a quicker initiation with less side effects. (Chinese, only English abstract).
Zhang W and Dai (2012) reported, a preparation of TGP was approved by State Food and Drug Administration of China to enter market as a
Patients with psoriatic arthritis
Total glucosides of peony (TGP)
Wang YN et al. (2014) analysed the beneficial effect of TGP on psoriatic arthritis links to circulating Tregs and Th1 cell function in clinical observation study. Nineteen patients received in a
Patients with chronic urticaria
Long et al. (2010) conducted a clinical observation on the treatment of chronic urticaria with TGP capsules combined with cetirizine to assess the effect and adverse reaction. A total of 120 patients were assigned to two groups by lottery, 65 in the treated group and 55 in the control group. They all were orally treated with cetirizine tablet 10 mg per day, but to the treated group, additional 0.2 g TGP was given three times per day. The therapeutic course for both groups was 4 weeks. The effectiveness of treatment was observed, and the changes of total symptom score, serum levels of
There were two dropout cases in the treated group and seven in the control group. Thus the study was accomplished on 63 patients in the treated group and 48 patients in the control group. The total effective rate was assessed at 73.02% (46/63) in the treated group, which was significantly higher than 47.92% (23/48) in the control group (P<0.01). After treatment, the total symptom score decreased in both groups, but the decrement in the treated group was more significant (P<0.05).
Serum levels of
The authors recommended more than 4 weeks medication, as through the observation in the first two weeks no relevant differences were between the groups. The symptom improving began in the latter two weeks of the treatment.
Patients with alopecia areata
Total glycosides of peony (TGP)
Yang DQ et al. (2012) conducted a randomised controlled trial comparing TGP capsule and a compound glycyrrhizin tablet for alopecia areata 3 months long. A total of 86 outpatients were randomised into two groups. The TGP group of 44 patients received 10 mg Vitamin B2 and three times 600 mg TGP daily. The control group received 3 times daily 50 mg glycyrrhizin. In the treatment group the cured and markedly effective rate was 36.36%, 50.00% and 68.18% at the end of the first, second and third month of treatment, versus 38.10%, 57.14% and 71.43% respectively. There was no statistic difference between the groups.
In the TGP group occurred 12 adverse reactions: 2 times abdominal pain, 6 times loose stool and
4 times increase of stool frequency. In the glycyrrhizin group occurred 14 adverse reactions: 2 times hypokalemia, 3 times increased blood pressure, 5 times edema, 2 times increased weight, 1 decrease in muscle strength.
Total glycosides of peony (TGP)
Zhang HF et al. (2007) conducted a retrospective clinical observation on effect of TGP in treating patients with
Patients with systemic lupus erythematosus
Zhang HF, Xiao and Hou (2011) conducted a clinical study of TGP in patients with systemic lupus erythematosus. Twenty nine patients of the TGP1 group took orally TGP for 5 or more years. 47 patients took TGP for more than one year (TGP2 group). 20 Patients served as control. The average daily dose of prednisone, total CTX dose and SLE disease activity index were lower in the TGP1 group than in the TGP2 group. The average daily dose of prednisone, total CTX dose were lower in the TGP2 group than in the control group. The authors concluded TGP could reduce the average daily dose of prednisone and the total CTX dose especially for the medication of more than five years.
Red peony root decoction
Zhang M et al. (2008) analysed red peony root decoction in treatment of severe acute pancreatitis in a randomised controlled trial. The treatment group (48 cases) received red peony root decoction
Table 4: Clinical studies on humans, in in rheumatoid arthritis
4.3. Clinical studies in special populations (e.g. elderly and children)
4.4. Overall conclusions on clinical pharmacology and efficacy
Clinical pharmacological data of peony root decoction/preparations are not available. The published studies were often conducted with total glycosides of peony (TGP, which contains approximately 90% paeoniflorin). No placebo controlled studies were available. The prospective controlled clinical studies were often conducted with a low number of patients and comedication was used.
In summary, the available clinical data are not considered sufficient to fulfil the requirements of a well- established medicinal use with recognised efficacy and to be eligible for a marketing authorisation according to Art. 10a of Directive 2001/83/EC. .
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
Chen Z et al. (2013) analysed in a
He and Dai (2011) reported in a review article the first prospective double blind trial of TGP was conducted 1993 in 450 patients with rheumatoid arthritis. They were randomized to receive TGP 1.8 g per day or methotrexate 810 mg per week) for 12 weeks. Therapeutic response was achieved in 71.7 of
Yang DQ et al. (2012) conducted a randomised controlled trial comparing TGP capsule and compound glycyrrhizin tablet for alopecia areata 3 month long. A total of 86 outpatients were randomised into two groups. The TGP group of 44 patients received 10 mg Vitamin B2 and three times 600 mg TGP daily. The control group received 3 times daily 50 mg glycyrrhizin. In the TGP group occurred 12 adverse reactions: 2x abdominal pain, 6x loose stool and 4x increase of stool frequency. In the glycyrrhizin group occurred 14 adverse reactions: 2x hypokalemia, 3x increased blood pressure, 5x edema, 2x increased weight, 1 decrease in muscle strength.
5.2. Patient exposure
5.3. Adverse events, serious adverse events and deaths
Timmermans et al. (2009) reported a case of contact dermatitis due to peony in a
Ward (2005) reported in “The Essential Guide to Clinical Safety” that a statement, bai shao or chi shao were found to be hepatotoxic, was based on one reference that had been incorrectly interpreted and no further evidence supported this. The Traditional Remedies Surveillance Team has repeatedly stated that no single ingredient has been implicated in the cases of hepatic reactions to herbs. There is still a lack of incidence data to fully define this problem, which is not unique to Chinese herbal medicine.
Ahmad et al. (2012) reported from the traditional TCM use adverse reactions as blistering of mouth and throat, diarrhoea, dizziness, fainting, gastroenteritis, haematuria, nausea, salivation, stomach pain, vomiting and/or possible death were known.
5.4. Laboratory findings
5.5. Safety in special populations and situations
No data available.
5.5.1. Use in children and adolescents
No data available.
No data available.
5.5.3. Special warnings and precautions for use
No data available.
5.5.4. Drug interactions and other forms of interaction
According to Landmark (2008) antiepileptic drugs have a high propensity to interact with concomitant medications. The administration of phenytoin in combination with Paeoniae Radix increased phenytoin Tmax
Chen LC et al. (2000) evaluated clinical interactions between the antiepileptic medicinal product valproic acid and Paeoniae Radix. The pharmacokinetics of VPA were investigated in a randomised,
(ii)one 200 mg VPA tablet alone on day 7
The mean maximum plasma concentration of VPA was attained at within 6 h after oral administration VPA alone and
In the Alternative medicine Review (2001) it was assumed, peony may not be combined with antibiotics. Damage to the gut flora by antibiotics might interfere with the process for cleaving the aglycons of peony and theoretically decreasing peony´s efficacy.
5.5.5. Fertility, pregnancy and lactation
Zhang and Dai (2012) report, that traditional use of peony root in TCM indicated that Radix Paeoniae may have abortifacient activity, so the use is contraindicated in pregnancy for safety reasons.
No data available.
5.5.7. Effects on ability to drive or operate machinery or impairment of mental ability
No data available.
5.5.8. Safety in other special situations
No data available.
5.6. Overall conclusions on clinical safety
Available data are not sufficient to establish a European Union monograph.
6. Overall conclusions
No clinical studies support the
The requirements for TU
A public statement is suggested. In conclusion, the following requirements for the establishment of a European Union herbal monograph on traditional or
–the requirement laid down in Article 10a of Directive 2001/83/EC that the active substance has a recognised efficacy and an acceptable level of safety and that the period of
–the requirement laid down in Article 16a(1)(b) of Directive 2001/83/EC that the herbal substance or herbal preparation is “exclusively for administration in accordance with a specified strength and posology”
–the requirement laid down in Article 16a(1)(d) of Directive 2001/83/EC that “the period of traditional use as laid down on Article 16c(1)(c) has elapsed”
–the requirement laid down in Article 16a(1)(e) of Directive 2001/83/EC that “the data on the traditional use of the medicinal product are sufficient; in particular the product proves not to be harmful in the specified conditions of use and the pharmacological effects or efficacy of the medicinal product are plausible on the basis of
– the HMPC acknowledges the existence of numerous publications on Paeoniae radix or constituents; however, often an appropriate description of herbal substance or herbal preparations used are missing. Available data are not sufficient to establish a European Union monograph.