Yaqing Guo1, Tong Yin2, Xiaoming Wang3, Fan Zhang4, Guixiang Pan5, Hong Lv6, Xianrui Wang7, John Owoicho Orgah8, Yan Zhu9, Honghua Wu10. 1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin International Joint Academy of Biomedicine, Tianjin 300457, PR China. Electronic address: guoyaqing1012@foxmail.com. 2. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin International Joint Academy of Biomedicine, Tianjin 300457, PR China. Electronic address: tong__yin@126.com. 3. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: xiaoming_w@yeah.net. 4. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: zhang_fan1102@163.com. 5. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: guixiangp@tjutcm.edu.cn. 6. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin International Joint Academy of Biomedicine, Tianjin 300457, PR China. Electronic address: 18153657004@163.com. 7. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin International Joint Academy of Biomedicine, Tianjin 300457, PR China. Electronic address: 1015020457@qq.com. 8. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: john_orgah@yahoo.com. 9. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: yanzhu.harvard@icloud.com. 10. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China. Electronic address: wuhonghua2011@tjutcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Cimicifuga have long been used as an ethnomedicine in China, Europe, and North America for its high medicinal value and health benefits. Their dried rhizomes are widely used for treating wind-heat headache, toothache, aphtha, sore throat, measles, spot poison, archoptosis, and uterine prolapse. In addition, it is used as a dietary supplement for preventing women menopausal symptoms and osteoporosis. AIM OF THE REVIEW: This paper aims to provide up-to-date information on the genus Cimicifuga, including botanical characterization, medicinal resources, traditional medicinal uses, phytochemistry, quality control, pharmacological research as well as the toxicology. The possible structural-activity relationships and molecular mechanisms of the bioactive constituents are discussed in ways that contribute to the structural optimization and preclinical safety assessment for further drug design. MATERIALS AND METHODS: The relevant information on Cimicifuga was collected from scientific databases (such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, CNKI, Baidu Scholar, Web of Science, China Knowledge Resource Integrated Database), Chinese herbal classics, ethnobotanical books, PhD and MSc dissertations, Chinese Pharmacopoeia, published articles in peer-reviewed journals, local magazines, and unpublished materials. In addition, the Plant List (TPL, www.theplantlist.org) was also used to validate the scientific names and synonyms of this plant. The literature cited in this review dated from 1953 to 2017. RESULTS: The majority of chemical constituents of this plant include triterpenoid glycosides, phenylpropanoids, nitrogenous compounds, chromones, flavonoids and 4α-methyl steroid. Among them, the primary bioactive constituents are believed to be present in the triterpene glycoside fraction. To date, investigation of seven Cimicifuga spp. plants led to the identification of more than 457 compounds. Years of pharmacological research proved that the crude extracts and certain pure compounds obtained from Cimicifuga exhibited menopausal syndrome-treatment, anti-osteoporosis, antiviral, antitumor, antioxidant and antiangiogenic activities. On the other hand, Cimicifuga plant-induced toxicities of liver, cardiovascular, central and peripheral nervous systems have also been reported. Therefore, safety consideration should be placed into a high priority for herbal medicine Cimicifuga therapy in the early stages of development and clinical trials. CONCLUSIONS: This review presents information on botany, medicinal resources, and traditional medicinal history of some Cimicifuga plants. Modern pharmacology researchers have validated many traditional uses of Cimicifuga species. As the quality control and safety assessment of Cimicifuga plants is still incomplete, only a small part of the plant is permitted to be used as medicines. Expansion of medicinal resources in Cimicifuga is urgently needed to enable its full use. Currently research primarily focuses on the triterpenoid glycosides but there are many other types of compounds which may possess new biological activities however the systematic studies of these compounds are lacking. Extensive study is required on Cimicifuga plant before it can be fully used in clinics as a potent drug candidate.
ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Cimicifuga have long been used as an ethnomedicine in China, Europe, and North America for its high medicinal value and health benefits. Their dried rhizomes are widely used for treating wind-heat headache, toothache, aphtha, sore throat, measles, spot poison, archoptosis, and uterine prolapse. In addition, it is used as a dietary supplement for preventing women menopausal symptoms and osteoporosis. AIM OF THE REVIEW: This paper aims to provide up-to-date information on the genus Cimicifuga, including botanical characterization, medicinal resources, traditional medicinal uses, phytochemistry, quality control, pharmacological research as well as the toxicology. The possible structural-activity relationships and molecular mechanisms of the bioactive constituents are discussed in ways that contribute to the structural optimization and preclinical safety assessment for further drug design. MATERIALS AND METHODS: The relevant information on Cimicifuga was collected from scientific databases (such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, CNKI, Baidu Scholar, Web of Science, China Knowledge Resource Integrated Database), Chinese herbal classics, ethnobotanical books, PhD and MSc dissertations, Chinese Pharmacopoeia, published articles in peer-reviewed journals, local magazines, and unpublished materials. In addition, the Plant List (TPL, www.theplantlist.org) was also used to validate the scientific names and synonyms of this plant. The literature cited in this review dated from 1953 to 2017. RESULTS: The majority of chemical constituents of this plant include triterpenoid glycosides, phenylpropanoids, nitrogenous compounds, chromones, flavonoids and 4α-methyl steroid. Among them, the primary bioactive constituents are believed to be present in the triterpene glycoside fraction. To date, investigation of seven Cimicifuga spp. plants led to the identification of more than 457 compounds. Years of pharmacological research proved that the crude extracts and certain pure compounds obtained from Cimicifuga exhibited menopausal syndrome-treatment, anti-osteoporosis, antiviral, antitumor, antioxidant and antiangiogenic activities. On the other hand, Cimicifuga plant-induced toxicities of liver, cardiovascular, central and peripheral nervous systems have also been reported. Therefore, safety consideration should be placed into a high priority for herbal medicine Cimicifuga therapy in the early stages of development and clinical trials. CONCLUSIONS: This review presents information on botany, medicinal resources, and traditional medicinal history of some Cimicifuga plants. Modern pharmacology researchers have validated many traditional uses of Cimicifuga species. As the quality control and safety assessment of Cimicifuga plants is still incomplete, only a small part of the plant is permitted to be used as medicines. Expansion of medicinal resources in Cimicifuga is urgently needed to enable its full use. Currently research primarily focuses on the triterpenoid glycosides but there are many other types of compounds which may possess new biological activities however the systematic studies of these compounds are lacking. Extensive study is required on Cimicifuga plant before it can be fully used in clinics as a potent drug candidate.