Chemical Components and Pharmacological Activities of Terpene Natural Products from the Genus Paeonia

Paeonia is the single genus of ca. 33 known species in the family Paeoniaceae, found in Asia, Europe and Western North America. Up to now, more than 180 compounds have been isolated from nine species of the genus Paeonia, including terpenes, phenols, flavonoids, essential oil and tannins. Terpenes, the most abundant naturally occurring compounds, which accounted for about 57% and occurred in almost every species, are responsible for the observed in vivo and in vitro biological activities. This paper aims to give a comprehensive overview of the recent phytochemical and pharmacological knowledge of the terpenes from Paeonia plants, and enlighten further drug discovery research.


Introduction
Natural products contribute significantly to drug discovery research with a rich source of compounds and provide inherently large-scale of structural diversity than synthetic compounds [1]. The genus Paeonia belongs to the family Paeoniaceae and consists of about thirty-three known species [2]. The roots of P. suffruticosa, P. obovata, and P. lactiflora are important sources of crude drugs in traditional Chinese medication with activities of nitric oxide production inhibitory effects [3,4], anti-tumor activity [5,6], anti-inflammatory effects [7], anti-influenza virus [8], hematopoietic effects [9], anti-aggregatoryand and anti-coagulative effects [10].

Plant Distribution
The genus Paeonia naturally distributes in the cold and temperate areas of the Northern Hemisphere. They are mainly distributed in Asia and Europe, and only a few native to Western North America. A total of 11 species are found in China, with wide distribution in southwestern and northwestern areas, central China, northern and northeastern China [11].
In detail, P. emodi grows in the western Himalayas between Nepal and Pakistan [12]. P. obovata naturally distributes in forests ranging from deciduous broad-leaved to coniferous forests and may be found at an altitude from 200 m to 2800 m. In China, it occurs in Anhui, Gansu, Guizhou, Hebei, and Heilongjiang et al. It also grows in Korea, Russia and Japan [13]. In addition, P. lactiflora occurs in northern and northeastern China, Korea, Japan, Mongolia, Russia Far East and Siberia [14]. P. veitchii

Anti-Oxidative Effects
Compounds 28 and 29 have potent radical-scavenging remarkable effects on DPPH, and compounds 16 have a weak radical-scavenging effect [60]. It is also demonstrated paeonins A (45) and paeonins B (46) exhibited inhibitory activities against lipoxygenase [40]. Paeonin C (47) has potent inhibitory potential against lipoxygenase in a concentration-dependent fashion [61]. Compounds 33 demonstrated a significant scavenging capacity against the DPPH free radical, ROS, the superoxide anion radical, and the hydroxyl radical [62].

Sedative and Analgesic
Paeoniflorin (15) could modulate sleep behaviors and the mechanisms involved, and increased NREM sleep by inhibiting the histaminergic system via A1 receptors [63]. In addition, it could inhibit formalin-induced nociceptive behavior in mice, these effects may be might be associated with modulation of NMDA receptors, specifically the NR2B subunit [64]. Shimizu et al. found that paeoniflorigenone (2) produced a blocking effect on neuromuscular junction in phrenic nerve diaphragm preparations of mice [65]. In addition, paeonilactone C (9) was showed to suppress stimulated muscle twitchings of frog sciatic nerve-sartorius muscle [66].

Conclusions
Paeonia is the only genus in the family Paeoniaceae and has significant medicinal importance in traditional Chinese medicine. Researchers have different views on the number of species that can be distinguished ranging from 25 to 40 [71,72], although the current consensus is thirty-three known species. Based on data available, this paper summarizes three types of terpene compositions and exhibited their bioactivities such as inhibitors of nitric oxide production, anti-tumor activity, anti-inflammatory effects, anti-oxidative effects, anti-aggregatoryand and anti-coagulative effects, sedative and analgesic activity. Taken together, the compounds from Paeonia plants have a great potential to be used as new chemical drugs in future. However, only nine species of the genus Paeonia have been chemically studied, it should be urgent to study other species for more potential bioactive components. In addition, the relationships between the species also need to be further clarified.