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Botanicals and Their Bioactive Phytochemicals for Women's Health 1521-0081/68/4/1026–1073$25.00 http://dx.doi.org/10.1124/pr.115.010843 PHARMACOLOGICAL REVIEWS Pharmacol Rev 68:1026–1073, October 2016 Copyright © 2016 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: ERIC BARKER Botanicals and Their Bioactive Phytochemicals for Women’s Health Birgit M. Dietz, Atieh Hajirahimkhan, Tareisha L. Dunlap, and Judy L. Bolton University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois Abstract ...................................................................................1028 I. Introduction . .............................................................................1028 A. Women’s Health as a Function of Age . ...............................................1028 B. Pharmaceutical Treatments . ...........................................................1028 1. Premenstrual Syndrome. ...........................................................1028 2. Urinary Tract Infections. ...........................................................1029 3. Pregnancy. .......................................................................1029 4. Lactation. .......................................................................1030 Downloaded from 5. Menopausal Symptoms.. ...........................................................1030 C. Botanicals as Alternatives for Women’s Health .........................................1030 D. Current Approaches and Techniques in Botanical Research .............................1031 1. Identification and Procurement of Plant Material. ...................................1031 2. Identification of Bioactive Compounds. ..............................................1032 3. The Selection and Implementation of Appropriate Screening Bioassays.. ............1033 by guest on September 23, 2021 4. Interactions between Phytochemicals in Botanical Extracts. ........................1034 5. In Vivo Studies; Pharmacokinetic Profile. .........................................1035 II. Botanicals Used by Premenopausal Women . ...............................................1035 A. Premenstrual Syndrome ...............................................................1035 1. Vitex agnus-castus (Chasteberry). ...................................................1035 2. Angelica sinensis (Dong Quai). .....................................................1036 3. Viburnum opulus and Viburnum prunifolium (Cramp Bark and Black Haw). ......1036 4. Zingiber officinale (Ginger). .........................................................1036 5. Valeriana officinalis (Valerian). .....................................................1037 6. Oenothera biennis (Evening Primrose). ..............................................1037 B. Urinary Tract Infections ...............................................................1037 1. Vaccinium macrocarpon (Cranberry).. ...............................................1037 2. Arctostaphylos uva-ursi (Bearberry). ...............................................1037 III. Botanicals Used during Pregnancy/Lactation ...............................................1038 A. Nausea . .............................................................................1038 1. Zingiber officinale (Ginger). .........................................................1038 B. Lactation . .............................................................................1038 1. Trigonella foenum-graecum (Fenugreek). .........................................1038 2. Silybum marianum (Milk Thistle). ...............................................1039 IV. Botanicals Used by Menopausal Women....................................................1040 A. Menopausal Symptoms ................................................................1040 1. Serotonergic Mechanism. ...........................................................1040 a. Actaea/Cimicifuga racemosa (black cohosh). ....................................1040 b. Valeriana officinalis (valerian). ...............................................1040 This work was supported in part by the National Institutes of Health Office of Dietary Supplements (ODS) and National Center for Complementary and Integrated Health (NCCIH) [Grants P50 AT000155 and T32 AT007533]. Address correspondence to: Dr. Judy Bolton, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood St., M/C 781, Chicago, IL 60612-7231. E-mail: [email protected] dx.doi.org/10.1124/pr.115.010843. 1026 Phytochemicals for Women’s Health 1027 2. Estrogenic Mechanism. ...........................................................1041 a. Isoflavones. .....................................................................1041 i. Glycine max (Soy). ..........................................................1041 ii. Trifolium pratense (Red Clover). .............................................1042 iii. Pueraria lobata (Kudzu). ....................................................1042 iv. Eriosema laurentii (Guinea-Bissau). .........................................1043 b. Humulus lupulus (hops). .....................................................1043 c. Glycyrrhiza species (licorice). ....................................................1043 d. Rheum rhaponticum (rhubarb). ...............................................1045 e. Vitex agnus-castus (chasteberry). ...............................................1045 f. Linum usitatissimum (flaxseed). ...............................................1046 g. Epimedium species (horny goat weed). .........................................1046 h. Lepidium meyenii (maca). .....................................................1046 i. Oenothera biennis (evening primrose). .........................................1047 j. Medicago sativa (alfalfa). .....................................................1047 3. Unknown Mechanism. ...........................................................1047 a. Dioscorea villosa (wild yam)......................................................1047 b. Angelica sinensis (dong quai).....................................................1047 B. Osteoporosis ...........................................................................1048 1. Isoflavones.. .......................................................................1048 2. Others. .............................................................................1048 V. Botanicals for Breast Cancer Prevention ...................................................1048 A. Hormonal Pathway . .................................................................1049 B. Chemical Pathway .....................................................................1049 C. Inflammatory Pathway ................................................................1049 D. Epigenetic Pathway. .................................................................1049 E. Isoflavone-containing Botanicals (Red Clover, Soy). ....................................1049 1. Hormonal Pathway. ................................................................1050 2. Chemical Pathway. .................................................................1053 3. Inflammatory Pathway.. ...........................................................1054 4. Epigenetic Pathway. ................................................................1055 F. Humulus lupulus (Hops) ...............................................................1056 1. Hormonal Pathway. ................................................................1056 2. Chemical Pathway. .................................................................1057 3. Inflammatory Pathway.. ...........................................................1057 4. Epigenetic Pathway. ................................................................1058 G. Glycyrrhiza Species (Licorice) ..........................................................1058 1. Hormonal Pathway. ................................................................1058 2. Chemical Pathway. .................................................................1058 3. Inflammatory Pathway.. ...........................................................1059 4. Epigenetic Pathway. ................................................................1059 H. Silybum marianum (Milk Thistle) . .....................................................1059 1. Hormonal Pathway. ................................................................1059 2. Chemical Pathway. .................................................................1060 3. Inflammatory Pathway.. ...........................................................1060 4. Epigenetic Pathway. ................................................................1060 ABBREVIATIONS: AhR, arylhydrocarbon receptor; ARE, antioxidant response element; BaP, benzo(a)pyrene; BGF, bioactivity guided fractionation; BW, body weight; CNS, central nervous system; COX-2, cyclooxygenase 2; DMBA, 7,12-dimethylbenz[a]anthracene; DNMT, DNA methyltransferase; E2,17b-estradiol; ER, estrogen receptor; ERE, estrogen response element; EROD, ethoxyresorufin-O-deethylase; G. glabra, Glycyrrhiza glabra; G. inflata, Glycyrrhiza inflata; G. uralensis, Glycyrrhiza uralensis; HER2, human epidermal growth factor 2; HT, hormone therapy; 5-HT, 5-hydroxytryptamine (serotonin); IC50, concentration associated with 50% inhibition of the maximal activity; IKKa/b, inhibitor
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