OBJECTIVE: To evaluate the efficacy of black cohosh extracts (BCE) in improving the low estrogen status induced by postoperative gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis. METHODS: Randomized clinical controlled trial about the improvement of low estrogen status caused by GnRHa with the treatment of BCE in patients with endometriosis after laparoscopic surgery were retrieved from Medline (Ovid), PubMed, Cochrane Library, CNKI, CBMdisc, Wanfang and VIP databases before January 2020, and meta-analysis of included studies was performed by Revman 5.3 software. RESULTS: Seven randomized controlled trials involving 745 patients were included in this study. Meta-analysis results showed that the addition of BCE did not alter hormone levels of patients, including serum estradiol levels [ =1.24, 95% (-4.58, 7.08), >0.05] and luteinizing hormone levels [ =-0.02, 95% (-0.15, 0.11), >0.05]. BCE effectively improved the perimenopausal symptoms induced by low estrogen status:improving hectic fever and sweating [ =0.1, 95% (0.02, 0.47), < 0.01], reducing the occurrence of insomnia symptoms [ =0.23, 95% (0.13, 0.39), < 0.01], improving fatigue [ =0.09, 95% (0.04, 0.20), < 0.01], reducing the occurrence of vaginal dryness [ =0.04, 95% (0.01, 0.30), < 0.01]. BCE affected Kupperman's menopausal index (KMI) score 12 weeks after the surgery [ =-11.50, 95% (-20.09, -2.90), < 0.01] and KMI score 24 weeks after the surgery [ =-23.68, 95% (-39.66, -7.69), < 0.01]. CONCLUSIONS The limited evidence so far indicates that BCE could efficiently improve perimenopausal symptoms cause by low estrogen status of the patients recieved GnRHa treatment after surgery for endometriosis, but does not alter hormone levels of patients.
Cimicifuga ; Endometriosis ; Estrogens ; Female ; Humans ; Plant Extracts

OBJECTIVES: To investigate whether the cytotoxic effect of Cimicifuga rhizoma extract is associated with cell death in the human keratinocyte (HaCaT) and human melanoma cell lines (G361). METHODS: Apoptosis induced by Cimicifuga rhizoma extract was confirmed by water-soluble tetrazolium salts-1 (WST-1) assay, immunocytochemistry, and western blot. Additionally, the release of cytochrome c and apoptosis-inducing factor (AIF) was visualized by confocal laser scanning microscopy. RESULTS: The results showed that Cimicifuga rhizoma extract significantly reduced the viability of G361 cells with half-maximal inhibitory concentration (IC 50) of 200 µg/ml, and the apoptotic process was found to occur via the activation of caspase-3 and caspase-9 pathways. Besides, the release of cytochrome c and AIF was also detected. CONCLUSIONS: This study suggests that Cimicifuga rhizoma extract causes apoptosis of human melanoma cells through the intrinsic apoptotic pathway.
Apoptosis Inducing Factor ; Apoptosis ; Blotting, Western ; Caspase 3 ; Caspase 9 ; Cell Death ; Cell Line ; Cimicifuga ; Cytochromes c ; Humans ; Immunohistochemistry ; Keratinocytes ; Melanoma ; Microscopy, Confocal

In the market of botanical dietary supplements, Cimicifuga heracleifolia (CH) has always been considered as an adulterated species of Cimicifuga racemosa (CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized (OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography (Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry (GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.
Animals ; Cimicifuga ; chemistry ; classification ; Dietary Supplements ; analysis ; Drug Evaluation, Preclinical ; Female ; Humans ; Menopause ; blood ; drug effects ; Metabolomics ; Osteoporosis ; blood ; drug therapy ; Ovariectomy ; adverse effects ; Phytotherapy ; Plant Extracts ; administration & dosage ; blood ; Rats ; Rats, Sprague-Dawley

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.
Alzheimer Disease ; Arthritis, Rheumatoid ; Cardiovascular Diseases ; Cimicifuga ; Cytokines ; Dendritic Cells ; Immune System ; In Vitro Techniques ; Inflammation ; Interleukin-6 ; Interleukins ; Korea ; Primary Cell Culture ; Ranunculaceae ; Tumor Necrosis Factor-alpha

OBJECTIVES: The current overview aimed to present the effect of herbal medicines on cognitive function among menopausal women. METHODS: Two separate authors performed systematic search of the 3 databases of (the MEDLINE Scopus and the Cochrane Central Register Trials) from inception to January 2018. Methodological quality of each study was assessed using the AMSTAR. RESULTS: According to 2 reviews, soy seems to be effective in enhancing summary cognitive function and visual memory. The effect of isoflavones on cognition was affected by treatment duration as six weeks of treatment improved some dimensions of cognitive parameters, including mental flexibility and planning, and longer treatment period (6 months) improved category digit span test, digit symbol test, and visual scanning test score. The effect of phytoestrogen on cognitive function of menopausal women might be altered age, gender, ethnicity, menopausal status, dosage, and length of treatment, types of cognitive test, location, types of soy, and types of phytoestrogen. Combination of Gingko with ginseng could not improve sustained attention, episode memory, category generation or frontal lobe function. Gingko biloba had no significant effect on planning, memory and sustained attention, except for its limited effect on mental flexibility in late menopause. In addition, other herbal medicines like black cohosh showed no effective beneficial. CONCLUSIONS: Phytoestrogen, soy and isoflavones might have a limited beneficial effect on some aspects of cognition. The phytoestrogens affecting cognition might be modified by age, gender, ethnicity, menopausal status, dosage, and length of treatment, types of cognitive test, location, types of soy, and types of phytoestrogen.
Cimicifuga ; Cognition ; Female ; Frontal Lobe ; Ginkgo biloba ; Herbal Medicine ; Humans ; Isoflavones ; Memory ; Menopause ; Panax ; Phytoestrogens ; Pliability

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9, 19-cyclolanostane triterpenoid glycosides, which often exhibit extensive pharmacological activities. 9, 19-Cyclolanostane triterpenoid glycosides are distributed widely in genus Cimicifuga rather than in other members of the Ranunculaceae family. So far, more than 140 cycloartane triterpene glycosides have been isolated from Cimicifuga spp.. The aim of this review was to summarize all 9, 19-cyclolanostane triterpenoid glycosides based on the available relevant scientific literatures from 2000 to 2014. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.
Animals ; Cimicifuga ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Glycosides ; chemistry ; isolation & purification ; pharmacology ; Humans ; Photochemistry ; Triterpenes ; chemistry ; isolation & purification ; pharmacology

BACKGROUNDIt is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women.

METHODSThis was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment.

RESULTSIn comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check.

CONCLUSIONSIn early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.

Adult ; Breast ; drug effects ; Breast Neoplasms ; drug therapy ; Cimicifuga ; chemistry ; Estrogens ; therapeutic use ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Middle Aged ; Plant Extracts ; pharmacology ; Postmenopause ; Progestins ; therapeutic use ; Software

PURPOSE: The aim of this study was to investigate the therapeutic effects of a herbal formula, PerioH-035, containing Angelica sinensis, steamed Rehmannia glutinosa, Angelica dahurica, Cimicifuga heracleifolia, and Zanthoxylum piperitum on the periodontal breakdown in a well-established ligature-induced periodontitis model in rats. METHODS: Sprague-Dawley rats were randomly assigned to 1 of 4 groups: NL (non-ligatured), L (ligatured), P1 (ligatured and treated with 1 mg/mL PerioH-035), P100 (ligatured and treated with 100 mg/mL PerioH-035). Periodontitis was induced by placing a ligature around the mandibular first molars. PerioH-035 was topically applied to both sides of the first molar for 2 weeks. The right side of the mandibles was retrieved for micro-computed tomography (CT) and methylene blue staining to analyze alveolar bone loss. The left side of the mandibles was histologically analyzed by TRAP and H&E staining. The MMP-9 mRNA level in gingival tissue was investigated by RT-PCR. RESULTS: Alveolar bone resorption was significantly reduced in the PerioH-035-treated groups. The number of dense multi-nucleated cells found to be TRAP-positive by staining in the ligatured rats was markedly decreased by PerioH-035 application. In addition, periodontal tissue destruction, especially cementum demineralization, was ameliorated in the P1 and P100 groups. Moreover, gingival tissue from the PerioH-035-treated group showed a decrease in the MMP-9 mRNA level, resulting in recovery of collagen degradation. CONCLUSIONS: These results suggest that PerioH-035 has therapeutic effects on periodontitis, and thus, PerioH-035 shows promise as a treatment for periodontitis. GRAPHICAL ABSTRACT:
Alveolar Bone Loss ; Angelica ; Angelica sinensis ; Animals ; Bone Resorption ; Cimicifuga ; Collagen ; Dental Cementum ; Ligation ; Mandible ; Matrix Metalloproteinase 9 ; Methylene Blue ; Molar ; Osteoclasts ; Periodontitis* ; Plants, Medicinal ; Rats ; Rats, Sprague-Dawley ; Rehmannia ; RNA, Messenger ; Steam ; Zanthoxylum

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.
Animals ; Cimicifuga ; chemistry ; Humans ; Phytosterols ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Saponins ; chemistry ; isolation & purification ; pharmacology ; Triterpenes ; chemistry ; isolation & purification ; pharmacology

In order to identify Cimicifugae Rhizoma from its adulterants and to ensure its safe use, the internal transcribed spacer 2 (ITS2) sequence of Cimicifugae Rhizoma and its adulterants were amplified and bidirectionally sequenced by DNA barcoding technology. Sequence assembly and consensus sequence generation were performed by the CodonCode Aligner V3.7.1. The genetic distances were computed by MEGA 5.0. Identification analyses were performed using neighbor-joining (NJ) methods. The length of ITS2 sequence of the three origin plants of Cimicifugae Rhizoma include Cimicifuga heracleifolia, C. foetida, C. dahurica was 217, 219 and 219 bp, respectively. Their intraspecific genetic distance was much lower than the interspecific genetic distance with their closely related species. The NJ tree of ITS2 indicated that the three origin plants of Cimicifugae Rhizoma formed a monophyletic clade, Cimicifugae Rhizoma and its adulterants could be distinguished clearly. The authors proposed that ITS2 sequence was suitable for the authentication of Cimicifugae Rhizoma and its adulterants.
Base Sequence ; China ; Cimicifuga ; classification ; genetics ; DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; genetics ; DNA, Ribosomal Spacer ; genetics ; Drug Contamination ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; classification ; Molecular Sequence Data ; Phylogeny ; Quality Control ; Rhizome ; classification ; genetics