Medicinal Plants with Abortifacient or Emmenagogue Activity: A Narrative Review Based on Traditional Persian Medicine

2.1. Manual Search

In this review, the most authoritative and well-known textbooks of Persian traditional medicine from the ninth to 18th century were investigated, such as Al-Qanun Fi at-Tibb (The Canon of Medicine) written by Ibn-e-Sina in 1025 Common Era (CE), Tuhfat-al-Momenin written by Mohammad Tonekaboni in 1670 CE, and Makhzan-ul-advia (Storehouse of Medicaments) written by Aghili Khorasani in 1771 CE (12-14). An essential search keyword was medicinal plants with abortifacient activity, which was equal to the Arabic term "mosqete janin." Other keywords, such as inducing menstruation, were also considered, equivalent to "modere heiz." After identifying the plants, their generic names were extracted from popular medicinal plants of Iran and rechecked in Google to confirm the accuracy.

2.2. Electronic Search

In the next step, electronic databases such as PubMed, Scopus, Web of Science, and Google Scholar were searched between January 1970 and April 2021. The main search keywords were "induced abortion" or "emmenagogue" and "herbal plants" in the title and abstract. In this search strategy, the articles in non-English languages were excluded.

Nonetheless, the overlapped plants between hand search and electronic search were briefly reviewed, and the scientific names of the plants, plant families, plants extracts, and active components and their efficacy and safety in animal and human studies were described.

3.1. Heracleum persicum

Heracleum persicum is a flowering plant of the Apiaceae family. This plant grows in Iran, Iraq, and Turkey (15). It is known as “Golpar” in Iran (16). Various natural chemicals such as volatile (terpenes, aliphatic esters, phenyl propenes, and carbonyls) and non-volatile (furanocoumarins, alkaloids, flavonoids, and tannins) constituents and several minerals were identified during phytochemical analysis (16). Dried fruits are used as contraceptive, lactagogue, emmenagogue, and pain killer agents. A study showed that H. persicum L. is teratogenic with abortifacient activity in mice (17). Therefore, it should be taken with caution during pregnancy.

3.2. Origanum vulgare

Origanum vulgare L. (Marzanjosh) is an important medicinal herb of the Lamiaceae family. Origanum vulgare was traditionally used to treat dysmenorrhea (18). The active chemicals are volatile (essential oil) and non-volatile phenolic compounds (phenolic acids and flavonoids). Others biologically active compounds are terpenoids, tannins, and sterols (19). It has been shown that high dosages of O. vulgare extract can increase the rate of abortion and fetal malformations in the fetus of mice (20).

3.3. Zataria multiflora Boiss

Zataria multiflora Boiss (Shirazi thyme) is an aromatic perennial shrub from the Lamiaceae family, which is native to Iran, Afghanistan, and Pakistan. It is full of phytochemical components and biological activities. Zataria multiflora is called "Avishane Shirazi" in Persian and is used as a seasoned flour in many foods in Iran. The chemical components of Z. multiflora include β-sitosterol, luteolin, apigenin, linalool, 6-hydroxyluteolin, thymol, carvacrol, γ-terpinene, and p-cymene (21). Zataria multiflora is effective in the treatment of primary dysmenorrhea (22). It is enriched by gamma-terpinene that may damage DNA (23, 24). However, thyme consumption in early pregnancy may lead to abortion due to its adverse effects on the placental diameter. Therefore, its use would be with caution during pregnancy (25).

3.4. Sesamum indicum L.

Sesamum indicum L. is from the Pedaliaceae family. It has been well known for over 5,000 years as an oilseed crop. Sesamum indicum L. is widely used in traditional medicine as oily seeds with emmenagogue activity (26) and facilitated delivery (27). Also, in the cases of oligomenorrhea with menstruation retard for more than two weeks, it may be an effective choice in inducing menstruation with ignorable side effects compared to hormonal therapies (28). In a clinical trial by Aghababaei et al., Sesame was efficient for removing retained products of conception with minor vaginal bleeding and pain than the control group (29).

3.5. Commiphora myrrha

Commiphora myrrha (Nees.) Engl. is a large shrub or small tree belonging to Sapindales, a family of Burseraceae and genus Commiphora, found in abundance in northeast Africa and the Middle East (30). Preliminary research has indicated that myrrh contained about 3 - 8% essential oil, 25 - 40% resins, and 30 - 60% water-soluble gum. It contains several bioactive metabolites such as flavonoids, terpenoids, steroids, lignans, carbohydrates, and long-chain aliphatic alcohol derivatives (31). It is a uterine stimulant with emmenagogue activity (32). Vafaei et al. assessed the efficacy of myrrh in patients with incomplete abortion. Meanwhile, the rate of successful complete abortion was 82.9% compared with 54.3% in the placebo group that was significantly different (33).

3.6. Stachys lavandulifolia

Stachys lavandulifolia belongs to the Lamiaceae family and grows worldwide, although it is endemic in Iran. They are well known for their flavoring and therapeutic effects. It contains hydroxyl and phenolic compounds such as polyphenols, tannins, steroids, flavonoids, and terpenoids (34). Due to the presence of flavonoid compounds, it changes the function level of the hypothalamic-pituitary-gonadal axis. This plant can reduce the progesterone level by more than 20%; therefore, it leads to miscarriage and inability to preserve the fetus and risk of abortion depending on dosage in animals (35). Abortion can be caused by the use of S. lavandulifolia during pregnancy; therefore, it should be considered a contraindication or used with caution (35). Also, it is used to control premenstrual syndrome (PMS) and primary dysmenorrhea symptoms (36) and can be suggested as add-on therapy or even an alternative remedy to non-steroidal anti-inflammatory drugs (NSAIDs) with fewer side effects (37).

3.7. Peganum harmala

Peganum harmala L. from the Zygophyllaceae family is well-known for its seeds, root, and bark in traditional Persian medicine and is known as "Esfand," "Espand," and "Harmal" in Iran. The pharmacological and therapeutic effects of P. harmala are mainly from alkaloids (38-40).

An in-vivo study found that the hydroalcoholic extract of P. harmala had contractive effects on the uterus and stripped the myometrium via the external calcium flow by the voltage-dependent calcium channels (41). Quinazoline alkaloids vasicine and vasicinone have been attributed to the abortifacient activity (42, 43). Therefore, it is contraindicated during pregnancy (40).

3.8. Ruta graveolens L.

Ruta graveolens belonging to the Rutaceae family is an ever-green shrub distributed worldwide (44). Some of its chemical constituents are glycosides (flavonoids) and alkaloids (quinolones: coquisagenine, skimmianine, and graveoline) (45). Dried aerial parts of R. graveolens induce abortion through the mechanism of multiple organ damage and death. There is no estrogenic effect; however, it can interfere with implantation time (46). The aqueous extract interferes with the pre-implantation phase in mice (47).

In a study examining the abortion and estrogenic activity of ethanolic extract of Sodab on different days of pregnancy in female rats, abortion or stillbirth was not observed on one to six days, but fetal malformation was observed after use on 7 - 9 days of gestation (47). Besides, DNA replication and mitosis can also be prevented by Psoralens in Sodab (R. graveolens L.) (47). The alkaloids in the plant can reduce the number of fetal cells and decrease the transmission of fetuses from the oviduct to the uterine branches.

3.9. Crocus sativus

In Persian medicine, C. sativus, known as Saffron, has a hard, circular, meaty onion covered with thin, brown membranes (48). It contains several active and potent biological compounds, including crocin and croctin as the most active ones. An experimental study by Hosseini et al. (49) assessed the abortifacient and teratogenic effects of different doses of C. sativus in female mice. Their results showed that the numbers of resorbed and demised fetuses were more significant than in the control group. Saffron may affect embryonic implantation that results in abortion.

Indeed, high doses of Saffron may interfere with organogenesis that mostly happens in the second gestational trimester and leads to abnormalities such as decreased tail length and placenta weight and diameter in animal studies (49).

Tafazoli et al. evaluated the effect of Saffron on abortion and its side effects on BALB/c mice and indicated that the percentages of absorbed and abnormal embryos increased significantly in the Saffron group (50). In a prospective case-control study on pregnant female farmers during the harvesting season of Saffron, the abortion rate was significantly higher among female farmers who had Saffron exposure (51). In a clinical study, Darooneh et al. investigated the effect of C. sativus (Saffron) on cervical ripening and the progress of labor in primiparous women. Their results showed that Saffron could shorten the average length of the first and second labor stages and induce stimulation and intensification of uterine contractions, labor facilitation, and lower oxytocin use (52).

3.10. Opoponax chironium

The genus O. chironium is a member of the Apiaceae family and grows in the Mediterranean. It is yellow and consumed as food and medicine. It contains abortifacient activity, and its mixture with honey is used as a vaginal suppository, which is very effective as feticide and for expelling the product of conception (53).

3.11. Lowsonia inermis

Lowsonia inermis is known as Henna in Persian medicine (54). This plant contains quinones, phenylpropanoids, flavonoids, terpenoids, phenolic compounds, and fatty acids. Apigenin is a flavonoid that exists in aromatic vegetables like Henna. Lowsonia inermis may be teratogen and should be used cautiously during pregnancy (55). Jafarzadeh et al. investigated the teratogenicity of this plant, showing that the L. inermis plant could create abnormalities in mice, and its teratogenic effects were dose-dependent (56). Also, Esteki and Miraj investigated the abortifacient effects of hydroalcoholic extract of L. inermis on female mice. Their results showed that L. inermis could significantly increase estrogen and decrease progesterone levels; besides, induced abortion was significantly lower in the experimental groups (57).

3.12. Plumbago rosea

Plumbago rosea L., mostly known as Rakta Chitrak, is mainly growing in the wild and abundantly in India. Quinones, polyphenols, alkaloids, and flavonoids are the significant phytochemicals reported from the plant. Plumbagin, hydroxy-1, 4-napthaquinone, sitosterol glycoside, fatty alcohol, and tannins are the active constituents in this plant. Sheeja et al. worked on the antifertility activity of P. rosea stem in female albino rats using different solvent extracts like petroleum ether, chloroform, acetone, and ethanol, confirming the significant estrogenic and anti-estrogenic activity of acetone extracts (58).

The plant's roots possess anti-tumor, anti-teratogenicity, anti-fertility, and uterine activities (59). The extracts of this plant can be further explored for contraceptive use (59). The possible presence of the utero-active compound in this plant was indicated by inhibiting oxytocic agents causing uterine motility. Furthermore, unwanted pregnancy can be avoided by supporting the accredited traditional use of pronounced fetotoxic and mild abortifacient potentials observed at higher doses in pregnant mice (60).

3.13. Juniperus sabina

Juniperus sabina is called Abhal in Arabic and Savin in English. This plant is one of the plants used for abortion in the past (61). Its extract or infusion is used as a medicine to increase menstruation. In Persian medicine, its essential oil and extract are used for their abortive and laxative qualities (62). It also contains lignans such as deoxypodophyllotoxin and terpene. The major components of the terpene part include sabinyl acetate and Sabinene. Sabinyl acetate is a terpenoid compound, comprising about 50% of this plant and accounting for its abortive and presumably poisonous qualities.

Oils rich in sabinyl acetate are considered dangerous (63). The abortive qualities are generally attributed to essential oils, particularly sabinyl acetate, which effectively prevents implantation. A study conducted by Mortazavi Gazar et al. assessed the effects of alcoholic extracts of J. sabina on oogenesis in mice. They showed that J. sabina could cause corpus luteum and atrophic follicles to increase and Graafian follicle and primary follicle to decrease, which can have undesirable effects on implantation and the number and size of the ovum (61).

3.14. Matricaria chamomilla

Chamomile is from the Asteraceae family, the primary source of which is the Mediterranean, but nowadays, it is widespread in Europe, the temperate regions of Asia, and even the United States (64). Their flowers include multiple phenolic compounds, primarily the flavonoids apigenin, quercetin, patuletin, luteolin, and their glucosides terpenoids α-bisabolol and its oxides and azulenes, including chamazulene.

In an experimental study, Mirzakhani assessed the abortive effect of this plant in 80 adult female rats and showed a significant increase in the number of aborted fetuses and follicle atresia and decreases in the serum levels of estrogen, progesterone, luteinizing hormone (LH), and follicular stimulation hormone (FSH) (65). It also causes uterine contraction invoking miscarriage in pregnant women and decreasing the labor pain intensity (66). The abortifacient medicinal plants that overlap in traditional and modern medicine are listed in Table 2.

4.1. Conclusions

The abortifacient activity of L. inermis L. (Henna), O. chironium L. (Jooshir), P. rosea (Stumbag, Shitraj), and J. sabina (Abel or Abhal) have been proven in both traditional medicine and recent studies. The properties of many traditional plants with abortifacient activity are unknown in modern medicine; however, they should not be used in pregnant women. However, it may have the power to be entered into modern medicine. Identifying the pharmacology and their action mechanisms may be helpful to introduce them as a potential alternative for chemical agents in the management of induced or incomplete abortion with possibly lower side effects.