19.ALPHA.-Hydroxyursane-Type Triterpenoids: Antinociceptive Anti-inflammatory Principles of the Roots of Rosa rugosa

Abstract

The roots of Rosa rugosa (Rosaceae) have traditionally been used to treat diabetes mellitus, pain, and chronic inflammatory disease in Korea.1) Previously, the hypoglycemic principle, catechin, 2) was isolated together with triterpenoids, along with the 28-glucosides of euscaphic acid, tormentic acid, and arjunic acid from this crude drug. 2,3) We have previously reported on triterpenoids with antinociceptive/antiinflammatory action, e.g., oleanolic acid, momordin Ic, 4) hederagenin, kalopanaxsaponin A, 5) and 23-hydroxyursolic acid, 6) from the botanical medicines, which are used to treat diabetes mellitus and inflammatory disease. Murakami et al. 7)reported the inhibitory activity of euscaphic acid and tormentic acid against mouse ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) and suggested that the two triterpenoids have antiinflammatory and mammalian DNA polymerase activities. Banno et al. 8) reported that tormentic acid isolated from Perilla frutescens has a potent antiinflammatory effect against TPA-induced inflammation in the ear of rats. However, their tumor promoter (TPA)-induced inflammation accompanied by fibroblast proliferation and granulation is different from the carrageenan-induced inflammation used in the present research.To isolate the antinociceptive principle from the roots of R. rugosa, the MeOH extract was fractionated and the fractionated extracts were used in a writhing assay. From the active EtOAc fraction, kaji-ichigoside F 1 (1) and rosamultin (2) ( Fig. 1) were isolated using column chromatography. The more active hydrolyzed fraction of the EtOAc extract was also subjected to silica gel column chromatography and yielded euscaphic (3) and tormentic acids (4) (Fig. 1). Although four isolates were present in this crude drug, the two triterpenes 3 and 4 were also obtained from the hydrolyzed fraction prepared for activity-guided fractionation and for in vivo investigations. The four compounds were 19a-hydroxyursane-type triterpenoids and their antinociceptive/antiinflammatory activities are described in this communication. MATERIALS AND METHODS Plant MaterialThe roots of R. rugosa were purchased from the Chun-Il Oriental Herbal Store in Wonju, Korea, and was identified by Prof. Sang-Cheol Lim (Department of Botanical Resources, Sangji University) and a voucher specimen (#natchem-25) was deposited in Sangji University.Extraction and Fractionation The dried and cut roots of R. rugosa (5 kg) were extracted three times for 5 h with MeOH under reflux. The extract was then filtered and evaporated in a rotatory evaporator under reduced pressure. The concentrated extract was then freeze-dried to give a solid extract (245 g), which (230 g) was suspended in H 2 O and partitioned with CHCl 3 . The CHCl 3 -soluble portion was concentrated in vacuo and freeze-dried to yield the CHCl 3 extract (74 g). The aqueous layer was successively partitioned with EtOAc and BuOH, respectively, and these layers were also evaporated in vacuo and freeze-dried to give the EtOAc (65 g) and BuOH extra...

Chemical composition and anti-inflammatory activity of the leaves of Byrsonima verbascifolia

“…Our results are in agreement with other numerous studies which demonstrated that polyphenols-rich extracts could inhibit the NO production in LPS-stimulated macrophages [49][50][51].…”

Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited LPS-induced iNOS, COX-2, and TNF-α expression through inactivation of the nuclear factor-κb pathway in RAW 264.7 macrophages

“…1) used for this study were isolated from the roots of R. rugosa as previously described [13]. These isolated compounds were determined by LC-MS and found to be 95% pure.…”

“…Furthermore, it has been demonstrated that TA has potent anti-inflammatory effects against TPA-and carrageenan-induced inflammation [13]. However, the molecular targets and the molecular mechanisms underlying the anti-inflammatory activities of TA are poorly understood.…”

Biological activity and composition of teas and tinctures prepared from Rosa rugosa Thunb.

“…Previous research has revealed the presence of many biologically active compounds in all parts of R. rugosa [1,[4][5][6][7]. Many of them act as potential natural antioxidants [8][9][10].…”

“…common cold [3]. Despite the great commercial potential of the R. rugosa, only a few reports have been published about the phytochemical content and biological activity of this plant; in particular, the knowledge of its roots and leaves remains limited, which is surprising considering that rose roots have been utilized by Asian folk medicine to treat conditions such as diabetes mellitus, pain and chronic inflammatory diseases [4].Previous research has revealed the presence of many biologically active compounds in all parts of R. rugosa [1,[4][5][6][7]. Many of them act as potential natural antioxidants [8][9][10].…”