€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHEMICAL AND PHARMACEUTICAL BULLETIN***** Koeda M Aoki Y Sakurai N Nagai M Studies on the Chinese crude drug "shoma." IX. Three novel cyclolanostanol xylosides, cimicifugosides H-1, H-2 and H-5, from cimicifuga rhizome. In: Chem Pharm Bull (Tokyo) (1995 May) 43(5):771-6 ISSN: 0009-2363 Three new cyclolanostanol xylosides were isolated from a batch of commercial Cimicifuga Rhizome, cimicifugoside H-1 (1), C35H52O9, mp 260-262 degrees C, [alpha]D -43.5 degrees, cimicifugoside H-2 (2), C35H54O10, mp 227-229 degrees C, [alpha]D -38.8 degrees, and cimicifugoside H-5 (3), C35H52O10, mp 262-264 degrees C, [alpha]D - 22.9 degrees, together with known glycosides, actein and 27- deoxyactein. Their structures were determined on the basis of chemical and spectrometric evidence including an X-ray crystallographic analysis. The structure of cimicifugoside H-1 (1) was established as (20R,24R)-24,25-epoxy-11 beta-hydroxy-3-beta-(beta- D- xylopyranosyloxy)-9,19-cyclolanost-7-ene-16,23-dione. Cimicifugoside H-5 (3) is the 15-hydroxylated derivative of 1. Since 1 changed into cimicifugoside H-2 (2) on treatment with p- toluenesulfonic acid, 2 has a 24R,25-diol structure derived from 1 by opening its epoxy ring. Registry Numbers: 18642-44-9 (actein) 66176-93-0 (cimicifugoside) 79-63-0 (Lanosterol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kusano A Shibano M Kusano G Miyase T Studies on the constituents of Cimicifuga species. XIX. Eight new glycosides from Cimicifuga simplex Wormsk. In: Chem Pharm Bull (Tokyo) (1996 Nov) 44(11):2078-85 ISSN: 0009-2363 Eight new glycosides were isolated from Cimicifuga simplex (Ranunculaceae), and their structures were determined to be 23-O- acetyl-7-8-didehydroshengmanol-3-O-alpha-L-arabinopyranosi de (1), 24- epi-24-O-acetyl-7,-8- didehydrohydroshengmanol-3-O-beta-D- galactopyranoside (2), 7,8-didehydrocimigenol-3-O-beta-D- galacytopyranoside (3), 24-epi-24-O-acetylhydroshengmanol-3-O-beta-D- galactopyranoside (4), cimigenol-3-O-beta-D-galactopyranoside (5), 25- O-methylcimigenol-3-O-beta-D-galactopyranoside (6), 25-O- acetylcimigenol-3-O-beta-D-galactopyranoside (7) and 25-O- acetylcimigenol-3-O-beta-D-glucopyranoside (8). Genuine aglycones were obtained by the hydrolysis of 1--7 with lactase F[Amano] and of 8 with cellulase T[amano]4. Acerinol was prepared from 7,8- didehydrocimigenol and showed antilipemic effects. Registry Numbers: 57-88-5 (Cholesterol) 637-07-0 (Clofibrate) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Sakurai N Koeda M Inoue T Nagai M Studies on the Chinese crude drug "Shoma." VIII. Two new triterpenol bisdesmosides, 3-arabinosyl-24-O-acetylhydroshengmanol 15-glucoside and 3-xylosyl-24-O-acetylhydroshengmanol 15-glucoside, from Cimicifuga dahurica. In: Chem Pharm Bull (Tokyo) (1994 Jan) 42(1):48-51 ISSN: 0009-2363 Two new triterpenol glycosides were isolated from the rhizomes of Cimicifuga dahurica (Ranunculaceae): 3-arabinosyl-24-O- acetylhydroshengmanol 15-glucoside (1), C43H70O16, mp 222-223 degrees C, [alpha]D +21.0 degrees and 3-xylosyl-24-O-acetylhydroshengmanol 15- glucoside (2), C43H70O16, mp 208-210 degrees C, [alpha]D +9.5 degrees. On acidic hydrolysis, 1 afforded cimigenol (3) as an aglycone, and glucose and arabinose as sugars. On enzymatic hydrolysis with molsin, 1 afforded 24-O-acetylhydroshengmanol 15-O- glucoside (4). On the basis of chemical and spectral data, the structure of 1 was proposed to be (23R,24S)-24-acetoxy-3-O-alpha-L- arabinopyranosyloxy-16,23-e poxy-9,19- 15-O-beta-D-glucopyranoside. The other glycoside (2) showed, in its 13C-NMR spectrum, a pattern of chemical shifts very similar to that of 1. On acidic hydrolysis, 2 afforded cimigenol (3), xylose and glucose. On enzymatic hydrolysis with molsin, 2 afforded 4. From these results, the structure of 2 was proposed to be (23R,24S)-24-acetoxy-3-O-beta-D-xylopyranosyloxy-16,23- epoxy -9,19-cyclolanostane-15 alpha,16 xi,25-triol 15-O-beta-D- glucopyranoside. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF PHARMACOBIO-DYNAMICS***** Hemmi H Kitame F Ishida N Kusano G Kondo Y Nozoe S INHIBITION OF THYMIDINE TRANSPORT INTO PHYTOHEMAGGLUTININ-STIMULATED LYMPHOCYTES BY TRITERPENOIDS FROM CIMICIFUGA SPECIES In: J Pharmacobiodyn (1979) 2(6):339-349 A study was made of naturally occurring triterpenoids from Cimicifuga sp that show an inhibitory effect on the lymphocyte blast formation induced by phytohemagglutinin (PHA). Study of 24 triterpenoids indicated that activity depends on a hemiacetal group in the side chain, the configuration at the C25 position, an acetoxy group or a hydroxy group at the C12 or C(15)-beta position, and a cyclopropane ring on the B ring. Cimicifugocide, one of the strongest inhibitors of thymidine-3H uptake, has all of these characteristics except an oxygenated group on C(15)-beta. As little as 4 nanog/ml cimicifugocide caused a 50% inhibition of thymidine 3H uptake. Its addition to mouse lymphosarcoma L-5178Y cell cultures significantly inhibited nucleoside incorporation without causing cytotoxicity, inhibition of cell growth, or inhibition of leucine and glucosamine incorporation. It was suggested that inhibition of thymidine uptake by cimicifugocide and related compounds may be due to inhibition of membrane transport of nucleosides or nucleoside trapping mechanisms rather than inhibition of DNA synthesis. (35 Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MATURITAS***** Einer-Jensen N Zhao J Andersen KP Kristoffersen K Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats. In: Maturitas (1996 Oct) 25(2):149-53 ISSN: 0378-5122 OBJECTIVES: The natural medicines, Cimicifuga and Melbrosia, are widely sold. Cimicifuga is an extract of Cimicifuga racemosa (L.), and Melbrosia is a mixture of Gelee Royale, perga-pollen and pollen. Cimicifuga and Melbrosia are used through self-medication to relieve symptoms of hot flushes and other menstrual or menopausal discomfort in many of the Danish women consulting private gynaecologists. A gynaecologist tends to treat these symptoms with oestrogen, so the present experiments were therefore made to investigate whether Cimicifuga and Melbrosia have oestrogenic effects as defined by the classical biological methods: uterine growth in immature mice and vaginal cornification in ovariectomized rats. METHODS: Vehicle, 6, 60 or 600 mg/kg Cimicifuga or 30, 300 or 3000 mg/kg Melbrosia was administered orally for 3 days to groups of 10 immature mice and the uterus weight measured on the fourth day. Similarly, vehicle, 6, 60, 600 mg/kg Cimicifuga or 3, 30, 300 mg/kg Melbrosia was injected subcutaneously in groups of 12 ovariectomized rats for 3 days and vaginal smears investigated for signs of cornified cells. All experiments were repeated once. RESULTS: No signs of an oestrogenic effect connected with the preparations were found in any of the experiments. CONCLUSIONS: It can be concluded that the eventual beneficial effects on menstrual or menopausal discomfort connected with Cimicifuga and Melbrosia self-medication cannot be explained as a traditional oestrogenic effect as measured in biological experiments. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHYTOCHEMISTRY***** Li CJ Li YH Xiao PG Mabry TJ Watson WH Krawiec M An unusual cycloartane triterpenoid from Cimicifuga foetida. In: Phytochemistry (1996 May) 42(2):489-94 ISSN: 0031-9422 A new cycloartane triterpenoid glycoside has been isolated from the rhizomes of Cimicifuge foetida L. The spectroscopic characteristics of the new compound are different from previously described cycloartane triterpenoids because of the loss of the 24-isopropyl group as well as the presence of a 11 beta-OH group. Based on spectroscopic evidence, including a series of 2D-NMR analyses, the structure of the new triterpene is assigned as 24-des-isopropyl-7-ene- 23-one-9,19; 16,24-dicycloart-3 beta,11 beta,16 alpha,24 alpha- tetraol 3-O-beta-D-xylopryanoside, named here as neocimiside. The structure of the aglycone of neocimiside was confirmed by X-ray analysis. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Duker EM Kopanski L Jarry H Wuttke W Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. In: Planta Med (1991 Oct) 57(5):420-4 ISSN: 0032-0943 Remifemin is an ethanolic extract of the rhizome of Cimicifuga racemosa (C.r.) and is used to relieve climacteric hot flushes. In the present study the effects of this preparation on LH and FSH secretion of menopausal women were investigated. After an 8 weeks treatment, LH but not FSH levels were significantly reduced in patients receiving the Cimicifuga extract. To further characterize the endocrinologically active principles of this plant extract, a lipophilic extract of C.r. was prepared and subjected to Sephadex chromatography. Fractions obtained were tested for their ability to reduce LH secretion in ovariectomized (ovx) rats and to compete in vitro with 17 beta-estradiol for estrogen receptor binding sites. Three types of endocrinologically active compounds were obtained: (1) Constituents which were not ligands for the estrogen receptor but suppress LH release after chronic treatment, (2) constituents binding to the estrogen receptor and also suppressing LH release, and (3) compounds which are ligands for the estrogen receptor but without an effect of LH release. It is concluded that the LH suppressive effect of C.r. extracts observed in menopausal women and ovx rats is caused by at least three different synergistically acting compounds. Registry Numbers: 9002-67-9 (LH) 9002-68-0 (FSH) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hirabayashi T Ochiai H Sakai S Nakajima K Terasawa K Inhibitory effect of ferulic acid and isoferulic acid on murine interleukin-8 production in response to influenza virus infections in vitro and in vivo. In: Planta Med (1995 Jun) 61(3):221-6 ISSN: 0032-0943 We investigated the effect of ferulic acid (FA) and isoferulic acid (IFA), which are active components of the rhizoma of Cimicifuga species used frequently as anti-inflammatory drugs in Japanese Oriental medicines, on murine interleukin-8 (IL-8) production in response to influenza virus infections in vitro and in vivo by antibody-sandwich enzyme-linked immunosorbent assay. In the in vitro study, the murine macrophage cell line RAW 264.7 was infected with influenza virus at a dose of 10 plaque forming units (PFU)/cell and cultured in the presence or absence of drugs. Both FA and IFA reduced the IL-8 levels in the 20-h conditioned medium in comparison with control in a dose-dependent manner. The effect of IFA was greater than that of FA: IL-8 levels were reduced to 43% and 56% of the control in the presence of 100 micrograms/ml of IFA and FA, respectively. In the in vivo study, mice were infected with 1,000 PFU of virus and received daily oral administrations of Cimicifuga heracleifolia extract (5 mg/mouse/day), FA (0.5 mg/mouse/day), IFA (0.125 mg/mouse/day), or phosphate buffered saline. The three drugs showed a tendency to reduce IL-8 levels in bronchoalveolar lavage (BAL) obtained 2 days after infection. Moreover, both FA and IFA also significantly reduced the number of exuded neutrophils into BAL. However, the drug administrations did not affect the virus yields in BAL. These data suggest that FA and IFA are novel and potent inhibitors of murine IL-8 production and might act as one of the main components of anti-inflammatory rhizoma of Cimicifuga species. Registry Numbers: 1135-24-6 (ferulic acid) 537-73-5 (isoferulic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAKUGAKU ZASSHI. JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN***** Sakurai N Nagai M [Chemical constituents of original plants of Cimicifugae rhizoma in Chinese medicine] In: Yakugaku Zasshi (1996 Nov) 116(11):850-65 ISSN: 0031-6903 (Published in Japanese) Cimicifugae Rhizoma have been used as an anti-inflammatory, analgesic and antipyretic remedy in the traditional Chinese medicines. Many 9,19-cyclolanostane glycosides have been isolated from Cimicifuga and related genera. Two biogenetically key compounds, acetylshengmanol xyloside and cimicifugoside H-1, were isolated and their chemical structures were elucidated by our group. The former compound seems to be the parent component of the other glycosides such as cimigenol xyloside from C. dahurica, C. iaponica and C. acerina. The latter glycoside, cimicifugoside H-1 was isolated together with cimicifugosides H-2-H-6 from commercial Cimicifugae Rhizoma. They are novel glycosides having a hydroxyl group ay C-11, and cimicifugosides H-3, H-4 and H-6 were trinor-triterpenol glycosides. Cimicifugoside H- 1 changed into H-2, H-3 and H-4 under acidic or alkaline conditions. In this review, the structure elucidation of the above glycosides and their chemical transformation into other Cimicifuga glycosides are described. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€