The use of medicinal herbs in gynecological and pregnancy-related disorders by Jordanian women: a review of folkloric practice vs. evidence-based pharmacology

Abstract

Context National statistical reports in Jordan indicate a decrease in the total fertility rate along with a parallel increase in contraceptive use. The folkloric use of medicinal herbs in gynecological disorders has been growing in Jordan, despite of deficient reports on the evidence-based safety and efficacy of these practices.

Objective The aim of this comprehensive article is to review medicinal plants with claimed ethnonpharmacological usage in various gynecological and pregnancy-related issues in Jordan, and to assess their evidence-based pharmacological studies as well as their phytochemistry.

Methods The published literature was surveyed using Google Scholar entering the terms “ethnopharmacology AND Jordan AND infertility AND gynecology OR gestation”. We included ethnopharmacological surveys in Jordan with available full-text.

Results Twelve articles were reviewed. Plant species which are commonly used for female gynecological issues such as Artemisia monosperma Del. and A. herba-alba Asso. (Asteraceae) have been found to exert an antifertility effect. Ricinus communis L. (Euphorbiaceae) and Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) had antifertility effects in male rats, but Nigella sativa oil L. (Ranunculaceae) and Cinnamon zeylanicum J. Presl (Lauraceae) were found to enhance it.

Conclusion Using plants for gynecological disorders is a common practice in Jordan. Many of them, whether utilised for gynecological or non-gynecological conditions equally, were found to have detrimental effects on female or male fertility. Thus, couples planning pregnancy should be discouraged from the consumption of these herbs. Further local studies are warranted to confirm the appreciable beneficial pharmacological effects and safety of these plants.

Keywords:

• Ethnopharmacology
• gynecology
• herbal remedies
• Jordan
• phytochemistry

Introduction

A gynecological disorder is a condition that affects female reproductive system, mainly breasts and organs in the pelvic area such as uterus, ovaries, follapian tubes, vagina, and vulva. Hence, the term encompasses a broad term of diseases that can affect female fertility such as pelvic inflammatory diseases and endometriosis. Unfortunately, there are no statistical reports about the prevalence of various gynecological disorders in Jordan. However, national statistics allude to a decrease in the total fertility rate (TFR) over the last few years. A 2012 report by the Jordan Population and Family Health Survey (JPFHS) showed a TFR decline from 3.8 in 2009 to 3.5 children/woman. This comes along with the increase in usage of various kinds of contraceptives, which rose by 2% over the same period. The use of modern contraceptive methods such as oral contraceptive pills and intrauterine devices has increased, contributing to 42% of total contraceptive use, while the use of traditional methods, including herbal medicine, increased from 17 to 19%.

Despite the deficiency in the evidence-based safety and efficacy of herbal medicine utilisation in gynecology and obstetrics, the use of medicinal herbs in gynecological disorders, female fertility and pregnancy-related issues has been increasing in the developing countries, including Jordan. According to a survey by Bardaweel et al. (2013), 61.1% of infertile couples seeking in vitro fertilisation units use herbs, indicating that herbs are the most widely used regimen for infertility treatment. Around 12% used herbs for alleviation of nausea, vomiting and heartburn of pregnancy (Khresheh 2011). Many plant species utilised historically for several gynecological disorders were described by Abu-Irmaileh and Afifi (2003) (Table 1). An ethnopharmacological survey of medicinal herbs in the North Badia region of Jordan (Alzweiri et al. 2011) showed that several medicinal herbs species, including Artemisia monosperma Del. and A. herba-alba Asso. (Asteraceae), Ricinus communis L. (Euphorbiaceae), Ankyropetalum gypsophiloides Fenzl (Caryophyllaceae), are used in folkloric medicine for gynecological, birth issues, menstrual problems and female infertility. A similar survey by Hudaib et al. (2008) in Mujeb Nature Reserve showed that women use Anchusa strigosa L. (Boraginaceae) to produce infertility. Al-Qura’n (2009) showed that Verbena officinalis L. (Verbenaceae) found in Showbak area is utilised commonly for folkloric ethnomedicine of menstrual flow and milk secretion. Whether these ehnopharmacological practices are supported by evidence-based literature is principally unknown. In addition, there are limited reviews in the literature that investigated the use of herbal medicine in gynecological disorders, or pregnancy-related issues. Therefore, the aim of this paper is to review the medicinal plants with claimed ethnonpharmacological use in various gynecological and pregnancy-related issues in Jordan, and hence, to assess whether or not these practices are supported by evidence-based pharmacological studies and medicinal reports.

Table 1. Selected medicinal herbal remedies with claimed ethnopharmacological abortive and female infertility uses in Jordan.

	-Species-Family-References for ethnopharmacological indication-Preparation method	Reported phytochemical constituents	Evidence based pharmacology for “gynecological” use and reproductive health related issues	Other experimental pharmacological properties
1	Artemisia monosperma Delile;-Asteraceae-Aerial parts decoction are indicated for gynecological and birth problems (Alzweiri et al. 2011)	A flavanone 7-O-methyleriodictyol (Abu-Niaaj et al. 1993); Taraxasterol, taraxasterol acetate, pseudotaraxasterol acetate, lupeol, β-sitosterol and 3′,5-dihydroxy-4′,6,7-trimethoxyflavone (Elgamal et al. 1997). Eudesmane sesquiterpenes (Stavri et al. 2004); 4,6-di-OH-3-[3'-methyl-2'-butenyl]-5-[4''-OH-3''-methyl-2''-butenyl]-cinnamic acid, the 3R,8R stereoisomer of the C17 polyacetylene dehydrofalcarindiol and a C10 polyacetylene glucoside, 1,3R,8R-trihydroxydec-9-en-4,6-yne, spathulenol and eriodyctiol-7-methyl ether (Stavri et al. 2005); Polyacetylene capillin (Whelan & Ryan 2004); 6-OH-7,8-dimethoxycoumarin (I) and 5-acetyl-2-[1'-(OH-methyl)ethyl]-2,3 dihydrobenzo[b]furan, 6-OH-5,7-dimethoxycoumarin (fraxinol), 5-OH-6,7-dimethoxycoumarin (tomentin) and methyl-β-d-fructofuranoside (Hammoda et al. 2008). Volatile components: α- and β-pinene, α-terpinolene, limonene, β-maaliene shyobunone (Khan et al. 2012) as well as diphenylamine and dibenzofuran (Hafnawy et al. 1990). Artemisinin (ElMaggar 2012).	Antispasmodic effects on rat smooth muscles with right-shift of oxytocin concentration on the uterus as well as inhibition of maximum contractions induced by acetylcholine or oxytocin (Abu-Niaaj et al. 1993). Contraindicated in pregnant women because of leaves’ ethanol extracts’ drastic effects on decreasing number of viable fetus implantation, increasing adsorbing sites with midterm abortion and delay of onset of delivery and failure of spontaneous parturition of pregnant rats (Hijazi & Salhab 2010).	Drastic dose- and time- dependent antilarval properties (Assar & el-Sobky 2003). Anticancer cytotoxicity with proapoptotic activity in colorectal and breast cancer cell lines (Whelan & Ryan 2004; Stavri et al. 2005). Moderate inhibition of lipoxygenase, along with antimicrobial efficacy (Stavri et al. 2005). Pest and cotton leaf worm control (Khatter 2010) with repellency effect against mosquitoes (El-Sheikh 2009) and larvicidal potential (Hafnawy et al. 1990). Anti-microbial (Hammoda et al. 2008) anti-inflammatory (Alzweiri et al. 2011) and antimalarial activities (ElMaggar 2012).
2	Artemisia herba-alba Asso; (syn.: A. inculta)-Asteraceae-Aerial parts and roots decoction for menstrual and nervous problems (Alzweiri et al. 2011)	Flavonoids (hispidulin and cirsilineol), herbalbin, cis-chryanthenyl acetate (Afifi-Yazar et al. 2011; Messaoudene et al. 2011; Moufid & Eddouks 2012); Sesquiterpene lactones (Mohamed et al. 2013). Phenolic content (Khlifi et al. 2013); Essential oil: oxygen containing monoterpenes camphor, α-thujone, chrysanthenone (Mohsen & Ali 2009; Belhattab et al. 2014).	Significant decrease in the relative ovarian weights and embryo weights in rats exposed to A. herba-alba in addition to reductions in percentage pregnancies and in the number of implantation site and viable fetus’s number. In effect A. herba-alba caused adverse effects on fertility and reproduction (Almasad et al. 2007).	Relaxant effect of its essential oil on rodent jejunum contractions (Aziz et al. 2012). Aniticoccidiosis effect in broilers (Messai et al. 2014). Immunomodulatory (Messaoudene et al. 2011), antioxidative (Aouadi et al. 2014) and insecticidal properties (Abbad et al. 2014) along with hypoglycemic activity (Afifi-Yazar et al. 2011; Awad et al. 2012). Anticancer and inflammatory (Khlifi et al. 2013) as well as phytotoxic and antimicrobial activities (Amri et al. 2013).
3	Ricinus communis L. (Syn. R. speciousus Burm. R. viridis Willd.; castor oil)-Euphorbiaceae-Seeds pulver for female contraceptive; abortive; purgative and wound healing (Alzweiri et al. 2011).	Alkaloids and flavonoids (Kang et al. 1985) triterpenes lupeol and erandone (Srivastava et al. 2014); ricinoleic acid is the major among other fatty acids content (European Pharmacopeia 2005).	Antifertility (Das et al. 2014). Male contraceptive efficacy (Nath et al. 2013) with reversible negative impact on male rats' reproductive functions via disruptions of testosterone secretions (Raji et al. 2006). Cervical priming and induction of labor (Kelly et al. 2013). Castor oil-diet initiating labor of pregnant rats (Gao et al. 1998, 1999) and in pregnancies at term (Mozurkewich et al. 2011; Dante et al. 2014) but with possible adverse effects of uterine rupture (Sicuranza & Figueroa 2003) and amniotic fluid embolism causing a cardiorespiratory arrest associated temporally with ingestion of castor oil in a full-term normal pregnancy (Steingrub et al. 1988).	Hepato-suppression by R. communis against CCl4 induced liver toxicity in rat (Pingale 2010). Anti-inflammatory (Lomash et al. 2010; Srivastava et al. 2014) with potential antimicrobial (Naz & Bano 2012) and anticarcinogenic properties of R. communis oil and potential use as natural remedy for topical treatment of infections (Zarai et al. 2012). Castor oil polymer induces bone formation with high matrix metalloproteinase-2 expression (Saran et al. 2014). It has antiinflammatory (Vieira et al. 2000) wound healing (Yari et al. 2014) and laxative (Apu et al. 2013) efficacies.
4	Anchusa strigosa (Banks et Sol);-Boraginaceae-Arial parts decoction for female sterility (Hudaib et al. 2008)	Triterpenes, alkaloids (Abbas et al. 2009); 7,7'-bis-(4-OH-3,5-dimethoxyphenyl)-8,8'-di-OH-methytetrahydrofuran 4'-O-β-d-glucopyranoside, rosmarinic-, caffeic- and tormentic acids (28-O-β-d-glucopyranoside, euscaphic acid 28-O-β-d-glucopyranoside, euscaphic acid, and allantoin; pyrrolizidine alkaloids, carboxylic acid, phenolic and oleanane glycosides (Braca et al. 2003). Aliphatic hydrocarbons and polyphenols (Al-Snafi 2014).	None	Effective inhibition of aryl hydrocarbon hydroxylase activity as well as the binding of 3H-benzo[a]pyrene to rat liver microsomal protein and DNA and (Alwan et al. 1989 2007). Root aqueous extracts had pepsin inhibitor (Abuereish 1998) and preventive and therapeutic effects on ethanol induced gastric ulcer in lab animals (Disi et al. 1998). Antimicrobial and hypotensive qualities (Al-Snafi 2014). Antifeedant activity of its pyrrolizidine alkaloids (Sicilliano et al. 2005). Antidiabetic activity of its aqueous extract in STZ- diabetic rats (Muhammed & Ari 2012; Al-Snafi 2014).
5	Inula viscosa L. Aiton. (Syn. Dittrichia viscosa (L.) Greuter)-Compositae (Astraceae)- Water bath of leaves to produce abortion (Al-Khalil et al. 1992).-Decoction of flower heads (Afifi-Yazar et al. 2011)	Sesquiterpenes, sesquiterpene acids, azulenes, lactones, flavonoids and essential oils (Afifi-Yazar et al. 2011; Talib et al. 2012); chlorogenic- and caffeic acids, rutin, myricetin, quercetin, luteolin and kaempferol (Gökbulut et al. 2013); bi- and tri-cyclic sesquiterpene lactones; inuloxins A-D (Andolfi et al. 2013).	Midterm abortifacient and antiimplantation (Al-Dissi et al. 2001) and antifertility on reproductive system of female rats (Raj et al. 2011).	Antioxidative, fungicidal and phytoxic effects (Andolfi et al. 2013; Askarne et al. 2013; Gökbulut et al. 2013). Selecive antiproliferative and proapoptotic capacity in breast cancer cells; cytotoxic and genotoxic effect in A. cepa. Hypoglycemic properties via stimulation of glucose uptake (Zhang et al. 2010; Afifi-Yazar et al. 2011; Talib et al. 2012; Seca et al. 2014). Antimicrobial and anti-Helicobacter pylori efficacies (Karygianni et al. 2014; Masadeh et al. 2014).
6	Carum carvi L.-Apiaceae (Umbelliferae)-Seeds ingestion for uterus constriction (Lev & Amar 2002)	Flavon(ol)-O-glycoside and quercetin 3-O-caffeylglucoside, kaempferol 3-O- and isorhammetin-glycosides (Kunzemann & Herrmann 1977); Carvone (Aydin et al. 2013) unusual fatty acid-petroselinic acid and limonene (Laribi et al. 2010); carvacrol anethole and estragol (De Martino et al. 2009).	Significant antifertility in female rats for significant reductions in LH and FSH, blockage of estrus phase with increase in weights of ovaries, uterus and body (Thakur et al. 2009; Priya et al. 2014; Agrahari & Singh 2014). Caraway is considered among herbs commonly associated with galactogogue properties, but strongly contraindicated in pregnancy and breastfeeding due to its antispasmodic effects (Mannion & Mansell 2012). Caraway after C-section can speed the resumption of post-opertaive bowel motility (Yosefi et al. 2014). It is contraindicated in pregnancy as it may cause uterine contractions, miscarriages or premature labor (Shinde et al. 2012).	Hepatoprotective (Samojlik et al. 2010) with relaxant effect on dispersed intestinal smooth muscles of guinea pig (Al-Essa et al. 2010) and insecticidal potentialities (Fang et al. 2010). Antioxidant (Satyanarayana et al. 2004) and antibacterial activity of its essential oil (Iacobellis et al. 2005; Lixandru et al. 2010). Potential anticancer activity in neuroblastoma cell line (Aydin et al. 2013). Anti-inflammatory, spasmolytic, antimicrobial, antioxidant, carminative and immunomodulatory properties of caraway along with anticolitis (Keshavarz et al. 2013). Daily intake of caraway extract for gastrointestinal problems in obese subjects for 12 weeks has not adverse effects (Kazemipoor et al. 2014) with antiobesity effects in women (Kazemipoor et al. 2013); cholesterol and triglycerides lowering activities in normal and STZ diabetic rats (Lemhadri et al. 2006) were reported.

The published literature was surveyed for medicinal plants with claimed ethnopharmacological indications in female infertility, gynecological and pregnancy-related issues in Jordan. Google Scholar was used as a data source entering the terms “ethnopharmacology AND Jordan AND infertility AND gynecology OR gestation”, which have resulted in 127 articles. We included ethnopharmacological surveys in Jordan with available full-text and this resulted in 12 articles to review. Then the ethnopharmacological practices were basically compared against all in vitro, preclinical and/or clinical studies of evidence-based pharmacology of the above-mentioned uses. Phytochemical constituents as well as other pharmacological properties and efficacies were also mentioned for reference (Tables 1 and 2).

Table 2. Selected medicinal herbal remedies with claimed ethnopharmacological indications in gynecological and pregnancy issues and male fertility in Jordan.

	-Species-Family-References for ethnopharmacologic indication-Preparation method	Reported Phytochemical constituents	Reported ethnopharmacologic “gynecological” use and reproductive health related issues	Other experimental pharmacological properties
1	Ankyropetalum gypsophiloides Fenzl (syn. Allochrusa gypsophiloides (Regel) Schischk) Shirsh halawa-Caryophyllaceae-Root decoction for women infertility (Aburjai et al. 2007; Alzweiri et al. 2011).	Tritepenoid saponins (Amanmuradov et al. 1965; Yucekutlu & Bildaci 2008; Khatuntseva et al. 2012; Korkmaz & Ozcelik 2011) and polysaccharides (Arifkhodzhaev & Rakhimov 1992).	None	Antipyretic, appetite stimulant, whooping cough, expectorant and wound healing and as a saponin-vaccine for sheep brucellosis (Aburjai et al. 2007; Alzweiri et al. 2011). Immunoadjuvant, anti-inflammatory and antifungal properties with low hemolytic activity and low oral and intraperitoneal toxicity were found for its saponins (Khatuntseva et al. 2012). Acaricidal, antibacterial, antiprotozoal, antiviral and antinsecticidal propensities (Ryabushkina et al. 2008).
2	Verbena officinalis L. (Syn. V. domingensis Urb., V. macrostachya F.Muell.) Rai Al-hamam-Verbenaceae-Infusion of the leaves and stem for menstrual flow and milk secretion (Al-Qura’n 2008)	Oxygenated monoterpene and triterpenoids (De Marino et al. 2009; Shu et al. 2013); flavones (Duan et al. 2011); secoiridoid glycosides (Xu et al. 2010); hastatoside verbenalin aucubin verbascoside (Lui et al. 2012); iridoids (Shu et al. 2014).	Contraindicated in pregnancies as it might cause miscarriages for its ant-early-pregnancy and abortifacient components (Zhang et al. 2000).	Detoxicating agent promoting blood circulation, and removing blood stasis (Lui et al. 2012). Antioxidant, antibacterial and antifungal activities (De Martino et al. 2009); antitumor (Kou et al. 2013) proapoptotic (De Martino et al. 2009) properties; phytotoxic and food preservative effects (de Almeida et al. 2010; Camele et al. 2012). Anti-inflammatory (Speroni et al. 2007) analgesic (Calvo 2006) and neuroprotective (Lai et al. 2006) propensities.
3	Matricaria aurea (Loefl.) Shultz-BipAl-Babonej Al-Zahabi, and/or Matricaria chamomilla L. (Syn. C. chamomilla (L.) Rydb., C. recutita (L.) Rauschert, M. recutita L.)-Compositae (Asteraceae)-Infusion of flowers or shoot for gynocological disorders (Abu-Irmaileh & Afifi 2003; Ali-Shtayeh et al. 2008; Hudaib et al. 2008).	Flavonoids, tanninsand sesquiterpenes (α-bisabolol and farnesene) (Minaiyan et al. 2010; Aboul et al. 2012; Afifi & Kasabri 2014); coumarins, phenolic compounds, polyacetylenes, flavones, flavonols and flavonones (Singh et al. 2011; Aboul et al. 2012); Essential oil (monoterpenes), triterpenes and fatty acids (Capuzzo et al. 2014).	Chamomile is used as anti-nausea and antiemtic in early pregnancy (Bishop et al. 2011; Matthews et al. 2014) or throughout pregnancy (Broussard et al. 2010; Holst et al. 2011). A higher incidence of threatening miscarriages and preterm labors was observed among regular pregnant users of chamomile (Cuzzolin et al. 2010). More conflicting reports on decreasing length of gestation and birth weight upon herb consumption (Facchinetti et al. 2012; Moussally & Berard 2010, 2012). Apigenin is reported to slow/prevent breast cancer progression (Harrison et al. 2014).	Antimicrobial, cytotoxic-apoptotic effect against cancerous cells, spasmolytic and anti-inflammatory capacities (Abu-Rabia 2005; Minaiyan et al. 2010; Al-Tabini et al. 2012; Aboul et al. 2012; Afifi & Kasabri 2014); analgesic effect (Al-Quran 2011; Qnais 2011). Management of skin wounds (Pazyar et al. 2014) with antioxidative and radical scavenging activities (Capuzzo et al. 2014). It may provide antidepressant, sedative and anxiolytic with sleep enhancement activities (Aboul et al. 2012; Amsterdam et al. 2012)
4	Nigella sativa L.-Ranunculaceae-Extract of the seeds for gynecological disorders, lactation deficiency (Abu-Irmaileh & Afifi 2003; Otoom et al. 2006)	Thymoquinone, carvacrol, alkaloids, saponins, thymol (Razavi & Hosseinzadeh 2014; Afifi & Kasabri 2014; Tembhurne et al. 2014).	Contraceptive and antifertility in female rats (Keshri et al. 1995) with metabolic impact on experimental menopause induced rats (Parhizkar et al. 2011). Prophylaxis against cyclophosphamide induced reduction in primary and secondary follicles and ovarian diameters in female mice (Kamarzaman et al. 2014). It increased pups weights during sucking period via stimulating milk production in nursing rats (Hosseinzadeh et al. 2013). Thymoquinone treatment during pregnancy in diabetic mice inhibited embryo malformations and increased the size and maturation of embryos (Al-Enazi 2007). Black seed oil is promoted as male fertility agent (Ghazeeri et al. 2012) and could ameliorate and reverse the nicotine induced reduction in sperm motility and morphology and affected testicular histology (Cho Ping et al. 2014) and improve hyperlipidemic male rat fertility and spermatogenesis (Bashandy 2007; Al-Saaidi et al. 2009; Mohammad et al. 2009; Parandin et al. 2012; Mansour et al. 2013; Marbat et al. 2013). Daily intake of N. sativa oil for 2-3 months improved abnormal semen quality in infertile men without any adverse effects (Kolahdooz et al. 2014).	Antidiabetic, hypotensive, antiobesity, anti-inflammatory, antioxidative, cytotoxic-proapoptotic, hypolipidemic, nephroprotective, antiepileptic with antimalarial and antifungal capacities (Develi et al. 2014; Razavi & Hosseinzadeh 2014; Afifi & Kasabri 2014; Tembhurne et al. 2014). Vasorelaxant in rat aorta (Niazmand et al. 2014) and antidepressant (Perveen et al. 2013).
5	Rosmarinus officinalis L.-Labiatae-Extract of the shoot is used in gynecological disorders and as female contraceptive (Abu-Irmaileh & Afifi 2003).	Phenolics (Elansary & Mahmoud 2014; Vallverdú-Queralt et al. 2014); Essential oil components: 1.8 cineole, camphor and α-pinene (da Silva Bomfim et al. 2015); Carnosic acid (Lipina & Hundal 2014).	Gynecological disorders, female contraceptive (Abu-Irmaileh & Afifi 2003). Male contraceptive via antiandrogenic effects (Vala-Heidari et al. 2013). A significant decline in testicular spermatogenesis was attributed to testosterone decrease in addition to testicular sperm motility and density marked decrease in rosemary treated males (Nusier et al. 2007). Embryotoxic and anti-implantation effect without interfering with normal development (Lemonica et al. 1996; Damasco & Lemonica 1999) thus increasing number of fetal resorptions in female rats impregnated by rosemary treated males, thus decreasing their fertility (Nusier et al. 2007). Antioxidative; rosemary supplementation improved sperm characteristics and fertility after cryopreservation (Malo et al. 2010).	Carsonic acid stimulation of skeletal muscle cells glucose uptake (Lipina & Hundal 2014) and attenuation of TNF-α mediated inflammation and insulin resistance in 3T3L1 adipocytes (Tsai et al. 2014) with anti-obesity and antiiflammatory capacities (Romo-Vaquero et al. 2014). Besides, it is inhibitory of dipeptidyl peptidase IV in the diabetes management (Bower et al. 2014) and its nephropathy and neuropathy complications (Martynyuk et al. 2014; Ramachandran et al. 2014). It had calcium regulated spamsolytic activity in guinea pig ileum (Ventura-Martinez et al. 2011) with antioxidative and antiproliferative capacities against HeLa, MCF-7 and Jurkat cancer cells in a dose-dependent matter (Elansary & Mahmoud 2014) mainly via modulating estrogen and EGFR (González-Vallinas et al. 2014). Essential oil had antifungal and hepatoprotective properties (Rašković et al. 2014; da Silva Bomfim et al. 2015). It is consumed as a functional food with antimicrobial capacity (Nguyen et al. 2014) and a phytomedicine for skin wound healing (Pazyar et al. 2014). It had inhibition of formalin-induced pain and inflammation in mice (Emami et al. 2013) and H2O2 induced oxidative DNA damage in human lymphocytes (Razavi-Azarkhiavi et al. 2014). It improved memory impairment via modulation acetylcholinesterase and butyrylcholinesterase activities in rat brain (Ozarowski et al. 2013).
6	Trigonella foenum-graecum L.-Leguminosae-Extract of the seeds for lactation deficiency (Abu-Irmaileh & Afifi 2003).	4-OH-isoleucine (Maurya et al. 2014). Detailed phytochemistry (Afifi & Kasabri 2014); saponins, alkaloids (trigonelline) steroids (diosgenin), flavonoids (luteolin), coumarins, mucilage (galactomannan), volatile constituents and fixed oils (Yadav et al. 2011; Dande & Patil 2012; Adedapo et al. 2014).	It effected significant reduction in FSH, LH, and ovarian folliculogenesis with significant increase in stradiol, progesterone and corpus luteum in female mice (Modaresi et al. 2012). It had antiestrogenic and antifertility activity in female rats via exerting declines in ovary and uterus weights (Sharma & Bhinda 2005) with antiimplantation and abortifacient activity (Dande & Patil 2012) though trigonelline lacked any abortifacient or teratogenic effects during rats’ pregnancy, thus affirming its safety (Aswar et al. 2009). Despite reports of its antifertility and antiandrogenic capacities in male rabbits, rats and mice (Kamal et al. 1993; Kassem et al. 2006; Al-Janabi 2011); fenugreek exerted reversal of lindane associated ROS-damage in male rats reproductive and accessory organs with restoration of fertility, testosterone levels and amelioration of functionality (Seshadri et al. 2011). It could reverse aspirin related changes in male mice testicular tissues (Chaloob et al. 2010) and mitigate cadium- and adriamycin-induced testicular damage in male rats (Sakr et al. 2012; Arafa et al. 2014). It is ascribed galactogogue properties but strongly contraindicated in pregnancy and breastfeeding due to its uterine stimulant efficacy (Mannion & Mansell 2012).	It had multi-therapeutic properties with culinary, medicinal and industrial properties as in anticancer, antibacterial, anthelmintic, anticholinergic, wound healing and hypocholesterolemic activities (Adedapo et al. 2014). Hypoglycemic (Swaroop et al. 2014) with multiple and broadly diverse pharmacological capacities (Afifi & Kasabri 2014). Amelioration of fatty acid induced insulin resistance and inflammatory response in skeletal muscle cells (Maurya et al. 2014). Inhibition of fat accumulation and amelioration of dyslipidemia in high fat diet induced obese rats (Kumar et al. 2014). Selective cytotoxic anticancer properties (Alsemari et al. 2014). Protective effects against deltamethrin induced toxicity (Abdel-Daim et al. 2014). Proven efficacy as an adjuvant to L-dopa in management of Parkinson patients (Nathan et al. 2014).
7	Mentha piperita L.-Lamiaceae-Water extract of leaves for nausea and vomiting of pregnancy (Khresheh 2011).	Essential oil: menthol, menthone, piperitenone oxide and carvone (Hussain et al. 2010), limonene, menthyl acetate, menthofuran and β-caryophyllene (Grulova et al. 2014); Polyphenols: OH-cinnamic acid derivatives and rosmarinic acid (Aprotosoaie et al. 2013; Vladimir-Knežević et al. 2014).	Despite its common use as an anti-emetic herbal remedy among pregnant women for pregnancy related health ailments (Westfall 2004; Moussally et al. 2009; Holst et al. 2011; Kenney et al. 2013); peppermint oil does not have the effect on anticipated pregnancy nausea and vomiting (Pasha et al. 2012) and did not significantly increase the risk of low birth weight or preterm birth (Moussally & Berard 2010, 2012). Prophylactic peppermint gel in breastfeeding women is associated with few nipple cracks and is more effective than lanolin (Melli et al. 2007); it has supportive evidence for use in dyspepsia (Koretz & Rotblatt 2004). Peppermint aromatherapy effectiveness on nausea in women post C-section is reported (Lane et al. 2012); it reduces the severity of pruritus in pregnant women (Akhavan Amjadi et al. 2012); it controls infantile colic via decreasing frequency and duration (Alves et al. 2012).	Ovicidal activity was recognised for its essential oil (Sinthusiri & Soonwera 2014); immunomodulatory and antiparasitic effects on Schistosomiasis (Dejani et al. 2014). Antimicrobial (Bouari et al. 2014), antibiofilm and antifungal effects (Saharkhiz et al. 2012) along with cytotoxic effect on cancer cells (Hussain et al. 2010; Berdowska et al. 2013) and anxiolytic (Kravchenko et al. 2012) capacities were reported. Its proapoptotic in yeast via cytosolic and mitochondrial ROS-mediated damage (Ferreira et al. 2014); acetylcholine esterase inhibitory and antioxiadtive (Vladimir-Knežević et al. 2014) with antiglycation (Ramkissoon et al. 2013) properties. Neuroprotective (Hassan et al. 2013) and antinociceptive activity (Taher 2012) were proved.
8	Cinnamomum (z)ceylanecum-Lauraceae-Extract of the bark for cleansing the female genital system (Lev & Amar 2002).	Polyphenols (Im et al. 2014; Vallverdú-Queralt et al. 2014); cinnamaldehyde (Piovezan et al. 2014); cinnamic acid, and cinnamate (Rao & Gan 2014).	It is indicated in postpartum conditions (Abu-Irmaileh & Afifi 2003). Cinnamon contains sedative and anti-inflammatory agents for the treatment of endometriosis related symptomatic discomfort (Fang et al. 2012). It could decrease muscle soreness significantly in athlete women without affecting exercise related oxidative stress (Mashhadi et al. 2013a, b). It can be used for reducing perineal pain and for improving healing of episiotomy incision, thus minimising vaginal tears during childbirth (Mohammadi et al. 2014). Also cinnamon supplementation improves menstrual cyclicity and significantly reduces insulin resistance in women with polycystic ovary syndrome Wang et al. 2007; (Kort & Lobo 2014). Enhancement of male fertility and alleviating impotency in diabetic rats via increasing testicular weight and ameliorating degenerative legions, increasing testosterone serum levels, improving semen quality and quantity (Hafez 2010; Shalaby & Mouneir 2010; Yuce et al. 2013; Fathiazad et al. 2013). It used to treat dysmenorrhea and delayed menses (Flores & Quinlan 2014).	It had antibacterial (Fraňková et al. 2014), antioxidant potential, hypoglycemic and hypolipidimic (Im et al. 2014) with antifungal effects (Sessou et al. 2013). Also, it is a relaxant for isolated porcine arteries (Raffai et al. 2014); it has anti-inflammatory (Durak et al. 2014) and anticancer capacities. Cardiovascular disease lowering effects (Rao & Gan 2014) were evidenced for cinnamon.It is as well reported to have activities against neurological disorders, such as Parkinson's and Alzheimer's diseases (Rao & Gan 2014). It could produce attenuation of ischemia induced endothelial cell swelling and mitochondrial dysfunction (Panickar et al. 2014).
9	Taraxacum officinale F.H.Wigg (Webber)-Asteraceae-Male fertitlity booster (Oran & Al-Eisawi 1998)	Coumarins (Budzianowski 1997); Cinnamic acids (Williams et al. 1996); Sesquiterpene glucosides (Kashiwada et al. 2001); Amino acids (Qureshi et al. 2014), phenolic content (Kenny et al. 2014); taraxasterol (San et al. 2014); di- and tri-substituted 4-OH-phenylacetic acid; inositol derivates (Kenny et al. 2014); cysteine rich peptides (Astafieva et al. 2013); mono- and di-caffeoylquinic acids, tartaric acid derivatives and flavonol glycosides (Schütz et al. 2005); flavones; luteolin and luteolin-7-O-glucoside (Hu & Kitts 2004)	Rather than being a fertility booster as prescribed by Jordanian herbalists Dandelion decreases male rat fertility by reducing significantly testis weight, sperm count, motility and normal morphology, pregnancy rate and diameter and wall thickness of seminiferous tubules. Distortion of morphology of the seminiferous tubules and arrest in spermatogenesis was observed. In addition, the percentage of sperm with damaged chromatin integrity was significantly higher (Tahtamouni et al. 2011). No negative effects were reported during pregnancy or lactation (Yarnell & Abascal 2009)	Anticancer (Sigstedt et al. 2008), antidiabetic (Yarnell & Abascal 2009), antifibrotic (Domitrović et al. 2010), antioxidative and anti-inflammatory activities (González-Castejón et al. 2012; San et al. 2014); hepatoprotective (Hfaiedh et al. 2014), antimicrobial (Kenny et al. 2014), antifungal (Astafieva et al. 2013), antiviral (Han et al. 2011) and antidepressant (Li et al. 2014) effects were reported of T. officinale. Reduction of adipogenesis and lipid accumulation in adipocytes (González-Castejón et al. 2014) with hypolipidemic effects in cholesterol fed rabbits (Choi et al. 2010) via pancreatic lipase and alpha glucosidase inhibitory activity (Onal et al. 2005; Zhang et al. 2008) were recognised for T. officinale.

Results and discussion

Our search resulted in a total of fifteen plants used in Jordan for the fertility, gynecological and pregnancy-related disorders identified. Results are summarised in Tables 1 and 2.

Herbal remedies with female antifertility and abortificiant effects

Most of the evidence-based pharmacologies for female fertility are derived from preclinical studies in experimental rats. In the lieu of ethical issues with regard to the administration of medicinal products during pregnancy, this scenario is the most likely too. Plant species including A. monosperma, A. herba-alba, R. communis, Inula viscosa L. Aiton. [Syn. Dittrichia viscosa (L.) Greuter)] Compositae (Astraceae), Ballota undulate (Fresen.) Bentham [Labiatae (Lamiaceae)], Citrullus colocynthis (L.) Schrad (Cucurbitaceae), Globularia arabica Jaub. & Spach (Globulariaceae), Carum carvi L. (Umbelliferae), Verbana officinalis L. (Verbanaceae) have been found to exert antifertility effect in experimental rats (Farnsworth et al. 1975; Ammar et al. 2003; Benariba et al. 2013). The mechanism by which these antifertiliy properties were exerted is, however, different among the different species. In addition to oxytocin-like effects on rat uterus (Abu-Niaaj et al. 1993), the ethanolic extracts of A. monosperma leaves exhibitied drastic effects on decreasing number of viable fetus implantation, increasing adsorbing sites with midterm abortion and delay of onset of delivery and failure of spontaneous parturition of pregnant rats (Hijazi & Salhab 2010). Artemisia herba-alba, on the other hand, causes a significant decrease in the relative ovarian weights and embryo weights in rats in addition to reductions in percentage pregnancies and in the number of implantation sites and viable fetus number (Almasad et al. 2007; Qazan et al. 2007, Priya et al. 2014). Carum carvi and Trigonella foenum-graecum L. (Fabaceae) exert their antifertility effect by significant reduction of Leutinzing Hormone (LH) and Follicle Stimulating Hormone (FSH), blockage of estrus phase with increase in weights of ovaries, uterus and body (Thakur et al. 2009; Agrahari & Singh 2014; Priya et al. 2014). Accordingly, pregnant women or those who would like to conceive should be discouraged from the consumption of these herbs.

Of interest, many plant species such as B. undulata, C. colocynthis, G. arabica, and Salvia fruticosa Mill. (Lamiaceae) are used in folklore for various purposes. Nevertheless, evidence from preclinical studies showed that the aforementioned plant species have adverse effects on female fertility, and can even have abortive action. For example, B. undulata has no reported use for gynecological disorders. However, the long-term treatment by B. undulata might lead to diversified negative effects on fertility and pregnancy in female rats (Qazan 2008), as in decrease in ovarian weights and in number and weights of viable fetuses, and significant reduction in percentage of pregnancies and number of implantation sites, arrestment of developing ovarian follicles at primary and secondary stages in addition to degeneration and hypercellularity in medulla (Priya et al. 2014), as well as contraceptive properties (Pradhan et al. 2012). The chronic treatment with C. colocynthis might lead to diversified negative effects on fertility and pregnancy in female rats, as decreasing ovarian weights in addition to decrease in number and weights of viable fetuses, and significant reduction in percentage of pregnancies and number of implantation sites (Qazan et al. 2007), thus increasing mortality rate in pregnant mice in a dose-dependent manner (Dehghani et al. 2008). It is shown to be abortifacient (Pravin et al. 2013). Salvia officinalis L. (Lamiaceae) is an essential oil-containing plant. Traditionally, the decoction of this plant is widely used by the Jordanian population as a hot beverage for stomach and intestinal disturbances. Herba salvia and its extracts have reportedly many pharmacologic propterties. It can be used as an antiseptic agent, in the inflammation of the oral cavity and gingivitis and also as antihydrotic agent for stomach. It is widely utilised in the cosmetics and food industry in Europe (Daniela 1993). A study has been conducted to evaluate the reproductive toxicity of this medicinal plant. Ingestion of various extracts of S. fruticosa L. (Labiatae) were proved to exert negative effects on fertility in female rats. For example, ingestion of ethanolic extract of S. fruticosa for 30 consecutive days by adult female rats had no effect on the occurrence of pregnancy. However, it reduced the number of viable fetuses and increased the number of resorptions in the pregnant rats.

Herbal remedies of fertility, pregnancy-related issues, and breastfeeding

In a pilot study by Mannion and Mansell (2012), C. carvi (Caraway), a herb commonly associated with galactogogue properties, is strongly contraindicated in pregnancy and breastfeeding due to its antispasmodic effects. Nevertheless, the use of caraway after C-section can speed the resumption of post-opertaive bowel motility (Yosefi et al. 2014). It is also contraindicated in pregnancy as it may cause uterine contractions, miscarriages or premature labour (Shinde et al. 2012). Trigonella foenum-graecum (Fenugreek), a galactogogue, is also strongly contraindicated in pregnancy and breastfeeding due to its uterine stimulant efficacy (Mannion & Mansell 2012). Cinnamomum zeylanecum (Cinnamon) is commonly used in postpartum conditions (Abu-Irmaileh & Afifi 2003). Cinnamon containing sedative and anti-inflammatory agents is the most commonly prescribed Chinese herbal formula mainly for the treatment of endometriosis-related symptomatic discomfort (Fang et al. 2012). It could decrease muscle soreness significantly in athlete women without affecting exercise-related oxidative stress (Mashhadi et al. 2013a, b). It can also be used for reducing perineal pain and improving healing of episiotomy incision, thus minimising vaginal tears during childbirth (Mohammadi et al. 2014). Furthermore, cinnamon supplementation improves menstrual cyclicity and significantly reduces insulin resistance in women with polycystic ovary syndrome (Wang et al. 2007; Kort & Lobo 2014). It used to treat dysmenorrhea and delayed menses (Flores & Quinlan 2014). Clinical studies showed that Matricaria aurea (Chamomile) is used for nausea and vomiting intervention in early pregnancy (Bishop et al. 2011; Matthews et al. 2014) or throughout pregnancy (Broussard et al. 2010; Holst et al. 2011). A higher incidence of threatening miscarriages and preterm labors was observed among regular pregnant users of chamomile (Cuzzolin et al. 2010). Also, there are more conflicting reports on chamomile consumption leading to decreased length of gestation and birth weight (Facchinetti et al. 2012; Moussally & Berard 2010, 2012). Nigella sativa L. (Ranunculaceae) (Black seed) was found to provide prophylaxis against cyclophosphamide induced reduction in primary and secondary follicles and ovarian diameters in female mice (Kamarzaman et al. 2014).

It increased pups weights during sucking period via stimulating milk production in nursing rats (Hosseinzadeh et al. 2013). Thymoquinone treatment during pregnancy in diabetic mice inhibited embryo malformations and increased the size and maturation of embryos (Al-Enazi 2007).

Considering chamomile and black seed clinical studies, there is limited documentation on their safety and efficacy during pregnancy. According to Khreshesh (2011), the use of mixed herbs, eating cucumber, eating lentil seeds or dry tea leaves was one of the home remedies used by Jordanian women to alleviate pregnancy heartburn. Nevertheless, there were no evidence-based studies to support such ethnopharmacological use. Importantly, as midwives are important caregivers for pregnant women, they should strive to give evidence-based advice on herbal use in pregnancy. If 'traditional use' is the only available information, the pregnant woman should be made aware of this to enable her to make an informed decision about the eventual use (Holst et al. 2011).

Herbal remedies of male fertility/infertility issues

Preclinical studies in male rats showed that Ricinus communis resulted in disruptions of testosterone secretions (Raji et al. 2006). In addition, C. colocynthis was found to exert antiandrogenic effects via 5α-reductase inhibitory activity (Nahata & Dixit 2014), as well as antispermatogenic effects in male rats (Mali et al. 2001) with reduction in serum testosterone. It also induces reversible antifertility and antiandrogenic nature in male rats (Chaturvedi et al. 2003) and showed contraceptive properties in male rats (Sharma et al. 2014). Despite reports of its antifertility and antiandrogenic capacities in male rabbits, rats and mice (Kamal et al. 1993; Kassem et al. 2006; Al-Janabi 2011), fenugreek exerted reversal of lindane-associated reactive oxygen species (ROS)-damage in male rat’s reproductive and accessory organs with restoration of fertility, testosterone levels and amelioration of functionality (Seshadri et al. 2011). On the other hand, N. sativa oil is promoted as a male fertility agent (Ghazeeri et al. 2012) and could ameliorate and reverse the nicotine-induced reduction in sperm motility and morphology and affected testicular histology (Cho Ping et al. 2014). It was also found to improve hyperlipidemic male rat fertility and spermatogenesis (Bashandy 2007; Al-Saaidi et al. 2009; Mohammad et al. 2009; Parandin et al. 2012; Mansour et al. 2013; Marbat et al. 2013). Thus, daily intake of N. sativa oil for 2–3 months improved abnormal semen quality in infertile men without any adverse effects (Kolahdooz et al. 2014). Cinnamum zeylanicum was found to enhance male fertility and alleviate impotency in diabetic rats via increasing testicular weight and ameliorating degenerative legions, increasing testosterone serum levels, improving semen quality and quantity (Hafez 2010; Shalaby & Mouneir 2010; Yuce et al. 2013; Fathiazad et al. 2013). Interestingly, some plants could exhibit pharmacological effects that were quite opposite to their anticipated traditional use. For example, while Taraxacum officinale F.H.Wigg (Webber) (Asteraceae) (Dandelion) was promoted as a male fertility booster in Jordanian traditional medicine (Oran & Al-Eisawi 1998). A study in male rats (Tahtamouni et al. 2011) showed that the administration of the aqueous extract of the whole plant exerts antifertility effect. The extract causes a decrease in the testes weight, sperm count, motility and altered morphology. As mentioned earlier, various plant species have adverse effects on male fertility but they have never been ethnopharmacologically used for that purpose specifically. Citrullus colocynthis has antiandrogenic propertiy via 5α-reductase inhibitory activity (Nahata & Dixit 2014), antispermatogenic effects in male rats (Mali et al. 2001) with reduction in serum testosterone. It exerted reversible antifertility and antiandrogenic properties (Chaturvedi et al. 2003), and was found to be a contraceptive in male rats (Sharma et al. 2014). Conversely, G. arabica is found to be fetotoxic in rats (Elbetieha et al. 2000), but Globularia alypum L. (Plantaginaceae) leaf extract in male rats activated spermatogenesis and androgenic properties (Fehri et al. 2012).

Miscellaneous herbal remedies

The phytochemical constituent β-caryophyllene, when administered for 21 days in rat model of endometriosis, was found to suppress the growth of endometriotic implants by 52.5% compared with controls, without affecting the fertility. β-Caryophyllene is found in large quantities in miscellaneous plants such as Cannabis sativa L. (Cannabaceae), Origanum vulgare L. (Lamiaceae), Cinnamomum spp., Eugenia caryophyllata L. Merrill & Perry (Myrtaceae) (syn. Syzygium aromaticum), Zingiber nimmonii (J.Graham) Dalzell (Zingiberaceae) and Piper nigrum L. (Piperaceae) (Abbas et al. 2013).

Conclusion

Our review showed that there are many plant species in Jordan traditionally used for gynecological disorders. While for some of these plants there were preclinical and clinical studies to support the ethopharmacological indication, the evidence mostly comes from international studies rather than from local ones. Knowing that the phytoconstituents of plants can vary from one region to another, local studies are warranted. Besides, the ethnopharmacological use did not always specify the exact type of the gynecological condition. Contrary, there were plant species, utilised equally for gynecological or non-gynecological conditions, with negative effects on female fertility and can, even worse, cause abortions. Therefore, pregnant women or their healthcare providers should be aware of these harmful consequences of consuming herbal supplements to conceive or to maintain pregnancy or for family planning purposes.

Disclosure statement

All authors contributed equally to this work and report no declaration of interest.