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Introduction

The genus Paeonia was classified in the Ranunculaceae until the 20th. Recently, based on the characteristics of the stamen and specific chemical components, this genus was classified in separate family known as Paeoniaceae [1] and it’s the only genus in Paeoniaceae family. The species and varieties of this genus include perennials and herbaceous plants with about 33 species and 26 subspecies distributed mostly over temperate regions of northern hemisphere. The wild woody Paeonia species are found only in China, while the herbaceous species are widely spread in central and East Asia, as well as Northwest America [2]. In latest classification, the Paeonia genus divided into three groups; sect. Moutan, sect. Onaepia and sect. Paeonia [3].

The peony cultivation and using it as ornamental plant started first in China, which was then released into other East Asian countries such as Japan and Korea. In the 18th century, varieties of Chinese trees and herbaceous peonies became very popular and were transferred to Europe and North America. In the 19th century, by establishing breeding programs as well as considerable crossings, many new cultivars of this genus were released as ornamental plants. Herbaceous peony varieties have been introduced as a new cut flower and several large collections of peony cut flowers have been established around the world, such as in China, Holland, North America, and New Zealand. In 2011, China's ministry of health approved seed oil extracted from P. suffruticosa and P. ostii as a new food source, consequently oil peony planting rapidly expanded [2]. In this review, breeding history, phytochemical properties, horticultural utilization and distribution of Paeonia spp. in Iran are discussed.

The application of peony cultivars as ornamental plants, is included three main aspects landscape architecture, potted plants and cut flowers. The special peony gardens are the most famous in China and Japan. In Luoyang, Heze and Beijing, China, and Shimane, Japan, there are over 30 large special peony gardens, with the largest number in Luoyang [4]. In the international flower market, herbaceous peony is becoming more and more popular as a new cut flower. More than 25 countries are engaged in the production of herbaceous peony cut flowers, with the Netherlands being the largest global producer, annually producing more than 48 million herbaceous peony cut flowers [5]. The other utilization of Paeonia is the medicinal applications that will discuss this further.

Peony is usually propagated by division of a tuberous root with 3 to 5 vegetative and dormant buds [6]. Several studies have been carried out on the tissue culture of Peony. Although some progress has been made in this field, indirect shoot induction through callus is very difficult and requires a long time. One of the problems of callus production in peonies is excessive browning of the tissue. There are also few reports on peony somatic embryogenesis [7]. Tissue culture has been investigated in Paeonia mascula and the results showed that BAP, NAA and GA3 treatment increases branching [8].

Breeding history, phytochemical properties and distribution of Paeonia spp. in Iran is discussed in this review.

Genetic Breeding of Paeonia

With the expansion of the Paeonia industry around the world, the need to increase the number of suitable cultivars has urgently soared. However, Paeonia breeding is confronted with difficulties such as insufficient knowledge of the extent of germplasm resources, basic breeding techniques, fragmentary breeding knowledge, unclear breeding goals as well as low breeding efficiency [2].

Knowing the genetic characteristics of a plant can play an important role in its improvement. Weak self-compatibility, high chromosomal heterozygosity, and long juvenile period are the most important limiting factors in genetic studies of Paeonia. In recent years, some scientific institutions have paid more attention to Paeonia and some of its genetic mechanisms are gradually being investigated. Based on 33 species of Paeonia, more than 8000 varieties of this plant have been identified based on the color and type of flowers. Today, main methods of breeding techniques including selection and crossing are applied for breeding this plant [2].

Selection is still one of the most important methods of Paeonia breeding. This is a simple method in the breeding of Paeonia, which mainly focuses on the selection of stem and bud mutation. Before 1960 in China, most of the new cultivars were modified and introduced by this method. Molecular breeding is a very efficient method to overcome the shortcomings of traditional breeding, which shortens the breeding cycle. Currently, Paeonia tissue culture mainly uses embryos or buds to produce secondary buds by direct tissue culture method. For this plant, it is difficult to differentiate and produce callus and then produce stem. This limitation has caused the inability to edit genes in Paeonia. Although there are still many challenges in the success of molecular breeding of Paeonia, the mechanisms of several traits in this plant have been investigated, which have practical aspects in the production of this plant [2]. The history of Paeonia spp. identification and classification is showed in Table 1.

Biochemical Studies and Medicinal Applications

The root or bark of many species of this genus is usually used as a traditional medicine to treat various diseases. For example, Cortex Moutan is the dried bark of the P. sufruticosa root, which is called mudanpi in Chinese and is used to remove heat, cool the blood, improve blood circulation, and reduce blood stasis. Also, the seeds of some species have high amounts of unsaturated fatty acids and are a suitable source for use as edible oil. In 2014, P. suffruticosa seed oil was approved as a new food source by the Chinese Ministry of Health [4].

Due to the outstanding characteristics of plants of the Paeoniaceae family, complete phytochemical and medicinal research has been conducted on these plants for food and medicinal applications during the past few decades. Among the different parts of the Paeonia plant, the root is of special interest to phytochemists because of its medicinal uses. Although the leaves, flowers, and stems of the plant have been studied to investigate chemical compounds [4].

Plants of the Paeoniaceae family are known for producing monoterpene glycosidic compounds and other metabolic compounds such as flavonoids, tannins, stilbenes, triterpenoids, steroids, and phenolic compounds. New pharmacological research has shown that compounds and extracts obtained from plants of this genus have wide biological activities such as antioxidant, anti-inflammatory, anti-tumor effects, liver protection, cardiovascular protection, and neuron protection [4].

According to the latest findings, up to now 153 monoterpene glycosides, 59 flavonoids, 53 tannins, 15 stilbene, 49 triterpenoid and steroids, 61 phenolics, and more than 60 compounds, including alkyl hydrocarbons, fatty acids, fatty alcohols, L-amino acids, nucleotides, coumarin, anthraquinone, sugars, amygdalin, benzamide, and (Z)- hex-3-enal, have been isolated in the Paeonia genus [4] (Figure 1).

In particular, there are 3 key bioactive compounds in the plants of this genus that has been used therapeutically or have been clinically tested, which include total glucosides of peony (TGP), paeoniflorin, and paeonol. TGP includes paeoniflorin, paeonin, albiflorin, lactiflorin, and benzoylpaeoniflorin compounds, that paeoniflorin being the most important active component of this compound [18]. The two most important bioactive, paeoniflorin and paeonol are in the monoterpene glycosides and phenols categories, which will be discussed further.

Monoterpene Glycosides

To date, 153 monoterpene glycoside compounds have been reported in the genus Paeonia. This group of compounds is the dominant compound in all Paeonia plants. Most of these compounds are well known due to their cage-- like pinane skeleton, for example, paeoniflorin. While other monoterpene compounds are p-menthane, such as paeonilactone (A to C). Pinane and p-menthane compounds are types of monoterpenes and their glycosidic compounds are the characteristics of Paeonia plants. It should be explained that a small amount of osmane and myrceane types of monoterpenes have also been observed in this genus [4].

In the Paeonia, glycosidic monoterpene compounds exist due to various structural lies. First, the cage-- like pinane skeleton is the most abundant type of monoterpene glycoside in the genus Paeonia. Most of these compounds are mono-cargo dibenzoate monoterpene glycosides that differ in the substitution of their aromatic rings, such as galloyl, vanilloyl, hemisuccinyl, and hemiglutaryl. Paeoniflorin compound is the most important active compound present in almost all species of the Paeonia genus. Second, the pinane skeleton is highly unstable and highly variable. It has been reported that other monoterpene glycoside compounds such as lactiflorin and paeobrin have the same biosynthetic pathway as paeoniflorin [4].

Paeoniflorin (C23H28O11) belonged to the monoterpene glycoside compounds. The most important active substance in Paeonia is paeoniflorin (almost in all species) which has broad and powerful biological effects. There are found often in fresh unripe fruits and roots in the cortex. Paeoniflorin has some biological effects such as anti-inflammatory, immune system regulating, anti-tumor activity, cardiovascular protective, therapeutic effects on central nervous diseases, antioxidant, diabetes improvement, prevention of arterial thrombosis, liver oxidative protection, and liver cholesterol regulation [4]. Paeoniflorin is insoluble in water but soluble in ethanol and other organic compounds. However, due to its size, it cannot be separated by steam distillation [19]. Structure of paeoniflorin is shown in Figure 2.

Based on reported research, paeoniflorin biosynthesis pathway could be branched into three stages apart. During first step, isopentenyl pyrophosphate (IPP), and dimethylallyl diphosphate (DMAPP), as common precursors, are synthesized. Then the pathway continues into two routes for producing IPP and DMAPP. The first is the mevalonate (MVA) pathway located in the cytoplasm, and the second one is the 2-C-methyl-D-erythritol4-phosphate (MEP) pathway located in plastids [20]. Biosynthesis pathway of paeoniflorin is shown in Figure 3.

Also, it was reported that PoDPBT, an O-benzoyltransferase belonging to the BAHD family, can catalyze the benzoylation of 8-debenzoylpaeoniflorin to paeoniflorin in Paeonia ostii. The PoDPBT enzyme was identified as the first enzyme involved in the modification stage of paeoniflorin biosynthesis. These results suggested PoDPBT could utilize benzoyl-CoA and 8-debenzoylpaeoniflorin to synthesize paeoniflorin [21] (Figure 4).

Phenols

There are about 61 phenolic compounds and their analogs in all plants of the Paeonia genus, which are mostly present in the roots and root cortex. Some of these compounds such as phenethyl alcohol, gallic acid, and benzoic acid are widely found in plants of this genus [4]. One of the most important phenolic compounds in this genus is paeonol, which is often found in the root cortex and has wide medicinal uses.

Paeonol (C9H10O3) is a simple phenolic compound that has a phenolic hydroxyl group and methoxy group [19], and is a white crystalline powder, that has molecular weight 166.17 g/mol and melting point 52.5 °C [22]. Paeonol easily dissolves in hot water and polar organic solvents such as ethanol and methanol, but its solubility in cold water is very low. This is a volatile compound that can be isolated by steam distillation. Paeonol has wide pharmacological and physiological effects, including anti-inflammatory, anti-tumor, antioxidant activity, anti-allergic, anti-diabetic, platelet aggregation inhibition, anti-atherosclerosis, and cardiovascular protective activities [19]. Paeonol extracted from plants like Paeonia genus, Dioscorea japonica, and Arisaema erubescens [23]. Dioscorea japonica belongs to the Dioscoreaceae and is a folk remedy used in Korea to treat syndromes related to metabolic disorders such as diabetes. Plants of the genus Dioscorea have been reported to possess various pharmacological activities such as anti-inflammatory, anti-tumor and immunomodulatory effects [24]. Arisaema erubescens in traditional Chinese medicine, several biological diseases have been treated with this plant and it used in traditional Chinese medicine to clear wet mucus, prevent spasms, and help reduce hardening and swelling [25].

In paeonia, it is often found in the root cortex [22]. Structure of paeonol is shown in Figure 5.

There are many problems associated with paeonol's solubility and bioavailability that have hindered the development of the drug as a pharmacological agent. A variety of derivatives of paeonol were synthesized and studied to enhance its stability. For example, drug delivery one of the best methods to enhance paeonol bioavailability [22].

Paeonia Genus in Iran

There is little information about Paeonia genus in Iran. Until now, according to the latest classification all the species of the Paeonia genus that have been reported in Iran belonged to the Paeonia section. The number of reported species in Iran varies among different sources and different names have been used for them [26]. In some references it was reported that P. corallina Retz, with two varieties, var. tridentate (Pall.) Boiss and var. corallina, and P. wittmanniana recorded in Iran [27]. One reference reported that there is only one species of P. wittmanniana with two varieties, var. wittmanniana with hairy follicles, and var. nudicarpa Schipcz with glabrous follicles in Iran [28]. Other reference reported that P. cf. mlokosewitschi Lomark has been observed in Northwestern Iran [29]. Later, this species was considered as a new species which was named as P. wendelboi. Moreover, it was reported P. mascula L. subspecies mascula in western Iran [30].

During research on the diversity of the genus Paeonia in Iran until 2018, it has been determined that there were 4 species of Paeonia, including P. wendlboi, P. wittmanniana, P. tomentosa, and P. muscala subsp. Mascula [26]. However, the most recent survey identified a new species in Iran which was named P. archibaldii [31]. Therefore, until today, 5 species of the Paeonia genus have been reported in Iran, of which two are endemic to Iran; P. archibaldii and P. wendlboi. Pictures and descriptions of locations of Paeonia genus in Iran are presented in Figure 6 and Table 2, respectively.

In the case of P. wittmanniana, there has been a long debate among plant taxonomists. The first group, consider P. wittmanniana and P. tomentosa to be same species [32], while the other group consider them as two independent species [33]. These studies are often based on morphological traits that must be confirmed in detail by molecular investigations.

Important morphological traits in the Paeonia plant include floral traits such as petal color, petal and sepal size, filament and anther traits and carpel number as well as branching habits and leaf related traits [34]. Some morphological traits of Iranian Paeonia genus mentioned in Table 3.

Conclusion

To assess the distribution range of Paeonia spp in Iran and to survey their therapeutic potential, this study was conducted by collecting information via library and electronic search. Based on our knowledge, there is not much information about the Paeonia genus in Iran. So far, the most research work had been focused on the identification of species of Peaonia, without considering the genetic diversity and bio compound properties of this plant, especially the endemic species. Considering that so far there is not much information about the Paeonia genus in Iran, its genetic and phytochemical properties can improve the Paeonia breeding program and phytochemical studies. As stated, the selection is still one of the most important methods of Paeonia breeding. So, for selecting peony, it is necessary to study and evaluate plant genetic diversity in the world. It is possible to improve breeding resources using Iranian species due to the limited Paeonia germplasm available. For example, due to the lack of yellow color in the Paeonia genus, P.wendlboi can be used in breeding program.

No study was reported on the identification and extraction of important compounds such as Paeonol and paeoniflorin. These two compounds are the main bioactive compounds that have wide biological effect. They exist in almost all species. So, Iranian Paeonia genus can have significant amounts of these two valuable compounds. Due to the gaps in research, particular attention will be paid to Paeonia breeding studies and bio compounds characteristics as future research needs.

Acknowledgements

This research was financially supported by Tarbiat Modares University as a grant awarded for PhD study to Mohammad Fazli.

Conflict of Interest

The authors declare no conflict of interest.