Effect of Iranian herbal medicines in Dysmenorrhea phytotherapy

Abstract

Dysmenorrhea is one of the most prevalent medical disorders of gynecologic system that affects almost 50% of women with regular menstruation. Today, for the treatment and control of pain and symptoms, various methods such as herbal therapy, local heat, thiamin, vitamin E, fish oil supplements, acupuncture and transcutaneous nerve stimulation are used. In this study, the most important medicinal plants native to Iran, which are effective on pain are reported. Iranian herbs such as mint, platyloba,, black pepper and so on are used for dysmenorrhea.

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Journal of Chemical and Pharmaceutical Research, 2015, 7(2):519-526
Review Article
ISSN : 0975-7384
CODEN(USA) : JCPRC5
519
Effect of Iranian herbal medicines in Dysmenorrhea phytotherapy
Mahmoud Bahmani
1
, Zohreh Eftekhari
2
, Mahyar Jelodari
3
, Kourosh Saki
3
, Reza
Abdollahi
4
, Maedeh Majlesi
5
, Mahmoud Rafieian-Kopaei
6*
and Shahriar Rasouli
7
1
Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran
2
Institute of Biomedical Research, Postdoc of Veterinary Medicine, Tehran University, Tehran, Iran
3
Shahid
Beheshti University of Medical Sciences, Tehran, Iran
4
Deputy for Food and Drug, Urmia University of Medical Sciences, Urmia, Iran
5
Faculty of Nursery and Midwifery, Iran University of Medical Sciences, Tehran, Iran
6
Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
7
Ilam University of Medical Sciences, Ilam, Iran
_____________________________________________________________________________________________
ABSTRACT
Dysmenorrhea is one of the most prevalent medical disorders of gynecologic system that affects almost 50% of
women with regular menstruation. Today, for the treatment and control of pain and symptoms, various methods
such as herbal therapy, local heat, thiamin, vitamin E, fish oil supplements, acupuncture and transcutaneous nerve
stimulation are used. In this study, the most important medicinal plants native to Iran, which are effective on pain
are reported. Iranian herbs such as mint, platyloba, anise, valerian, thyme, mountain tea, ginger, lemon balm, sage,
vitakous, dill, cinnamon, chamomile, celery, saffron, anise, anise, cumin, borage, marshmallow, citron, yarrow,
black beans, buttercup, cardamom, oregano, black pepper and so on are used for dysmenorrhea.
Keywords: Dysmenorrhea, herbal medicine, herbs, Iran
_____________________________________________________________________________________________
INTRODUCTION
Dysmenorrhea is one of the most prevalent medical disorders of gynecological system
[1]
. Dysmenorrhea refers to
pain associated with menstrual cramping, which usually occurs in the lower abdomen. It is the most common type of
cyclic pain, depending on the anatomic pathology
[2,3]
. Dysmenorrhea clinically is divided into two categories.
Primary dysmenorrhea refers to menstrual pain without pelvic disorders and secondary dysmenorrhea refers to
menstrual pain due to pelvic diseases
[4,5]
.
Since 1970s, prostaglandins have been identified as a cause of primary dysmenorrhea and non-steroidal anti-
inflammatory drugs have been introduced as the choice treatment of primary dysmenorrhea
[6][7]
. Menstrual pain that
is associated with ovulation, cramps occur in the midline suprapubic and sometimes in the lower back and groin
spread
[8]
. The pain usually begins with the onset of bleeding and lasts 12 to 48 hours. It seems that the cause of
menstrual pain and associated symptoms such as nausea, vomiting, fatigue and headaches are related to the release
of prostaglandins during menstruation
[9]
.
Primary dysmenorrhea is due to uterine contractions and ischemia
[10-12]
. Another reason that researchers noted
include increasing the concentrations of prostaglandins, vasopressin, increasing levels of leukotrienes and
psychological factors which have been implicated in the development of primary dysmenorrhea
[13]
.
The most prevalence of pain is in the first 20 years of life and after the age of 35 years, it begins to decline.
Dysmenorrhea and pain are associated with impaired quality of life and social activities for young women,

Mahmoud Rafieian-Kopaei et al J. Chem. Pharm. Res., 2015, 7(2):
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520
especially if the symptoms such as headache, fatigue, nausea and vomiting, diarrhea, irritability, chills, muscle
cramps and other symptoms occur
[14]
.
The prevalence of primary dysmenorrhea in different countries is 50 to 90 percent and in Iran is 74 to 84.4 percent
[15]
. Published reports have estimated that approximately 15% of women suffer from severe pain during menstruation
[16]
.
In America it has been reported that about 60 percent of teens suffer from dysmenorrhea who reveal different
degrees of pain, and 14% of patients are frequently absent from school
[17]
. This disease is the leading cause of
school absenteeism and workplace which is about 600 million hours per year and it costs about $ 2 billion annually
for US economy
[18][19]
. The disease does not pose a problem for women, but the effect on the productivity of the
national problem is known
[20]
.
Nowadays, for the treatment and control of pain and symptoms, various methods are applied such as local heat,
medicine, thiamin, vitamin E, fish oil supplements, acupuncture and transcutaneous nerve stimulation. Among the
most effective of these methods, inhibitors of prostaglandin synthesis by about 80%, are impressive. The side effects
of these drugs, such as mefenamic acid and ibuprofen, like all chemical medications, are numerous
[21-23]
. Especially
in synthetic drugs that are prescribed for a long-term, the side effects are notable. Nausea, stomach irritation, ulcers,
gastrointestinal, renal papillary necrosis and renal blood flow are the side effects of synthesis inhibitors of
prostaglandin
[24]
. Due to the side effects of these drugs, the use of alternative therapies such as herbs or nutrients in
the treatment of primary dysmenorrhea or other complications has received special attention
[25-32]
.
This review paper presents the native plants which are scientifically or traditionally are used in the treatment of
dysmenorrhea.
RESULTS
The present study demonstrated that people in different regions of Iran use from medicinal plants such as
Peppermint extract, Echinophora platyloba extract, Foeniculum vulgar extract, Valeriana officinalis root extract,
Zataria multiflora, Stachys lvandulifolia powder, Vitex plant, Cinnamomum zeylanicum, Anethum graveolens
extract, Zingiber officinale, Matricaria chamomilla tea and Apium graveolens
,Crocus sativus, Pimpinella anisume
Capsule to treat dysmenorrhea and its symptoms and complications. The results details of the study are summarized
in table 1.
DISCUSSION
Synthetic drugs, especially the ones prescribed for long-term reveal a few side effects, especially prostaglandin
inhibitors
[45]
. Herbs have always been a source of human drugs
[46-48]
. Medicinal herbs are widely used by people in
different regions
[49-53]
and possess various therapeutic effects
[54-61]
. Academic and industrial researches are in
progress to produce natural remedies from medicinal plants
[62-67]
.
Women especially tend to use the herbal medicines and commonly used to treat problems like frequent symptoms of
dysmenorrhea, menopause, menstrual disorders, mood disorders, prevention of osteoporosis and pregnancy
problems by using herbal medicines .Some plants such as Cinnamon, dill seeds and drops, Anethum graveolens,
Nannorrhops ritchiana, thyme, Pimpinella anisum, Ajwain, cumin, ginger, chamomile, fennel, saffron, borage,
marshmallow, Fenugreek, Citron, valerian, yarrow, Nigella , Buttercup, Hypericum perforatum, cardamom, oregano,
black pepper, peppermint, Gelder, Artemisia vulgaris be used in different regions [68].
In traditional medicine of Iran and ethnobotany, some plants are traditionally used to reduce menstrual pain and
dysmenorrhea. In the North West of Iran, in Arasbaran region, the effective plants on menstruation and
dysmenorrhea include sumac (Rhus coriaria L.), savory (Satureja hortensis), pursuant to (Juniperus commonis),
Tiger's Tail (Leonurus cardiaca), marjoram or oregano (Origanum vulgare), sage (Salvia sclarea L.), pennyroyal
(Mentha longifolia), Ballota nigra, mountain ash (Sorbus boissieri) and nettle (Urtica dioica L.).
In ethnobotany of Sīstān, located in the south east of Iran, fennel (Foeniculum vulgare Mill.) is used to control the
menstrual cycle
[77]
.

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521
Table 1. Effective dysmenorrhea native medicinal plants in Iran
Number The scientific
name of the plant Type of study, type of
dysmenorrhea Results References
1 Peppermint extract Human clinical trials Primary dysmenorrhea in both groups receiving supermint oil (peppermint extract) at a dose of 40 drops and ibuprofen 400 mg dose was reduced. [33]
2 Echinophora
platyloba extract Human clinical trials The mean pain intensity in the two months prior to drug administration in the treatment group and the placebo group was 10.86 ± 34.72 and 11.16
± 35.55 which the differences were not significant. After the treatment, the mean of group platyloba 7.33 ± 22.49 and 9.91 ± 28.93 in the control
group and the difference was significant. [34]
3 Foeniculum vulgar
extract Human clinical trials Fennel extract can reduce the severity of dysmenorrhea. Based on the findings of the two groups was statistically significant difference in pain
intensity. The symptoms of systemic disease with decreased compared to before treatment. (P <0/001), but this reduction was not statistically
significant between the two groups. Except in the case of lethargy variable statistical difference between the groups was significant at the threshold [35]
4 Valeriana
officinalis root
extract Human clinical trials
Mean pain intensity before taking the drug in the treatment group and control group were not significantly different but average pain intensity after
drug consumption decreased in both groups, but it's more treated groups and a reduction in the difference between the two groups was statistically
significant. Also, the total systemic symptoms severity scores a total of differences between groups in terms of dysmenorrhea were significantly
associated with decreased compared to before treatment, but this reduction of t (g) between the two groups in terms of statistical consumers also of
valerian and placebo was not significant. Except in the case of highly variable statistical differences between the two chapters of the Group was
significant.
[36]
5 Zataria multiflora Primary dysmenorrhea
Human clinical trials Primary dysmenorrhea pain scores using linear-visual pain scale in the placebo group, 1% thyme, thyme 2%, respectively, 1.6 ± 7.8, 1.5 ± 7.3 and
1.7 ± 7.5 were measured. [37]
6 Stachys
lvandulifolia
powder
Primary dysmenorrhea
Human clinical trials Pain before and after lvandulifolia significant difference was observed. Lvandulifolia using the traditional method can alleviate the pain of primary
dysmenorrhea, and no side effects. In addition to effective pain patterns that can better tolerate the pain. [38]
7 Vitex plant Primary dysmenorrhea
Human clinical trials
The results showed that pain intensity was reduced 60% in the first cycle of treatment and the severity of pain at the end of the third month of drug
use, to 70 percent. While the reduction in the control group was 1.2% in the first months of the end of the third month up to 6 per cent. Results
showed significant differences in mean pain intensity of the pain level 2 before and after treatment were observed. [39]
8 Cinnamomum
zeylanicum
Primary dysmenorrhea
, Human clinical trials
The severity of pain in the test group, taking the cinnamon, reduced from 2.15 before treat to the 1.04 after treatment in the second cycle or a
placebo of 2.14 before treatment to 1.67 after treat in the second cycle.
The total scores of symptoms of systemic disease decreased compared to before treatment. [40]
9 Anethum
graveolens extract Primary dysmenorrhea
Human clinical trials
Dill and mefenamic acid extracts were effective on pain. Mean pain intensity in both groups before intervention was not significant. After the
intervention, the three cycles and in both groups there was a decrease in pain and this reduction was higher in the group of mefenamic acid and in
the second and third cycles was significant. [41]
10 Zingiber officinale
، Primary
dysmenorrhea Human
clinical trials The 64% improvement in severity of pain with ginger, 66% with ibuprofen and mefenamic 58%, which was statistically significant. [42]
11 Matricaria
chamomilla tea Primary dysmenorrhea
،Human clinical trials
In the intervention group, a week before menstruation and menstrual 5 days, 2 cups of chamomile tea every day was given for a period of 3 months
of treatment was continued. Pain, anxiety, and feelings of the group, after a month of tea than in the control group was significant. The total mean
score of four questionnaires in the intervention group, after 1 and 3 months after taking chamomile tea has a significant difference compared to
control group.
[43]
12
Apium graveolens
+Crocus sativus
+Pimpinella
anisume Capsule
Primary dysmenorrhea
،Human clinical trials Herbal capsule consists of several plant was better than mefenamic acid in reducing the severity of primary dysmenorrhea. [44]

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In Shiraz which is located in southern Iran, flax (Linum album Ky. Ex Boiss.), Marrubium vulgare L., Nepeta
persica Boiss., Black cumin (Nigella ciliaris L.) and Senecio glaucus L. are used for treatment of menstrual cycle
problems
[69]
.
In Kazerun, in south of Iran, chameleon plant (brevilimbe Boiss. Heliotropium) and red clover (Trifolium repens L.)
are used to control menstrual pain
[70]
.
In Kerman, located in east of Iran, Achillea eriophora, Cuminum cyminum, flax (Linumus itatissimum), Salvia
macrosiphon and Teucrium polium are used for menstrual cramps
[71]
.
Mobarakeh is located in Isfahan in central of Iran, Achillea santolina, valerian (Valeriana officinalis L), cumin
(Cuminum cyminum L.) and sage (Salvia nemorosa L) are used to reduce menstrual cramps
[72]
.
In Urmia, North West of Iran, Achillea millefolium L., Centaurea behen L., Grammosciadium daucoide DC., Nettle
water (Polygonum hydropiper L.), Salix triandra L ., Stachys lavandulifolia Vahi. and Teucrium orientale L are
consumed for alleviating the menstrual pain
[73]
.
Different areas of Iran, depends on the type of plants, fauna and culture of this region, a few of medical plants are
used to treat the symptoms of dysmenorrhea.
Peppermint oil inhibits the contractions induced by cell depolarization and the calcium channels are blocked
[74]
.
Peppermint has antispasmodic effect on smooth muscle
[74]
. Mint has muscle relaxant, anti-inflammatory and
analgesic properties
[75]
. Echinophora platyloba contains flavonoids, alkaloids and saponins, Trans-B-Ocimene, 2-
Furanone, Myrcene, Linalool and is Cisocimene
[76]
. Platyloba has antispasmodic effect and reduces muscle
contraction
[76]
. It seems that the flavonoid, saponin and alkaloid compounds are effective and are involved in
reducing uterine contractions and decreasing dysmenorrhea problems
[76]
.
The fennel essential oil, due to anethol, can reduce spasms of the gastrointestinal tract
[78][77]
. Foeniculum vulgare
contains palmitic acid, oleic acid, linoleic acid, petrocilinic acid, comphen, fencho and anethol
[80][81]
. Valeriana
officinalis has sedatives, analgesics, and the regulation of menorrhea properties
[82][83]
. Valerian root is used as a
sedative and antispasmodic. Antispasmodic and anti-spasmodic and analgesic effects are ultimately it is because of
valerinic acid composition
[84-87]
.
Thyme, traditionally used as medical herbal, has anti-smooth muscle spasm properties
[88]
. Thymol and carvacrol are
the active ingredients of thyme
[89]
. Antispasmodic properties of plant are because of phenolic compounds that
thymol is the major part
[90]
. The flavonoid compounds of Thyme inhibit contraction of cell depolarization and block
the calcium channels
[91-92]
. Studies on mouse models showed anti-inflammatory and analgesic properties of thyme
[93]
. Bioactive compounds of plant extract and essential oil with specific mechanism is known to improve the
symptoms of dysmenorrhea.
Probably, the extract has inhibitory effect by blocking voltage-dependent calcium channels and inhibition of calcium
release from intracellular sources revealing its therapeutic effect
[94]
.
Studies have shown that plants lvandulifolia and Hypericum perforatum may inhibit the production of
prostaglandins that mediate pain
[95]
and expose anti-inflammatory effects
[96]
and analgesic activity
[97]
. Cinnamon
has amidoun, mucilage, tannins, a dye, calcium oxalate, sugar, cinamomin, essential oils and resins. The
physiological effects of essential oils and tannins of cinnamon in folk medicine induce the energy sector, sedative,
antispasmodic, anti-inflammatory and is used to reduce menstrual pain
[98][99]
.
Its antispasmodic effect is due to cinnamaldehyde in cinnamon. The eugenol can also prevent the biosynthesis of
prostaglandins and reduce inflammation. Pharmacology and toxicology studies in humans did not show any
particular risk to Cinnamon
[100]
.
Anethum graveolens has a volatile oil that reveals anti-spasmodic effect
[101]
, regulates the irregular menstrual
[102]
and is effective on amenorrhea
[103]
.
The researches on antispasmodic effect of Anethum graveolens extract on rat uterine contractions showed that the
extract induced its contractile effect by blocking voltage-dependent calcium channels and the dysfunction in actions
of oxytocin
[94]
. Anethum graveolens essence has volatile oil containing limonene and Karun that more than 90% of
the essence oil has antispasmodic effects
[101]
.

Mahmoud Rafieian-Kopaei et al J. Chem. Pharm. Res., 2015, 7(2):519-526
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Gingerols and liabilities of Ginger (Zingiber forming compounds) are potent inhibitors of prostaglandin by
inhibiting cyclooxygenase (] Facts and Comparisons Publishing Group. In clinical trials in patients with knee pain
due to osteoarthritis analgesic effect of ginger has been reported
[105]
. In some of the traditional resources, ginger is
consumed in the treatment of dysmenorrhea
[106]
. Chamomile plant possesses anti-inflammatory effect,
antispasmodic, sedative and anti-agitation activies
[107]
.
Saffron plant has sedative and regulation of menorrhea effect. Chemical compounds in saffron contain glycoside
crocin, crocetin, picrocrocin and volatile essential oil
[108]
. Celery has chemical compounds including apigraveann,
apiometin, Celenin,bergaptene and ambliophrone which have different properties including sedative, diuretic,
promiscuous binding, anti-inflammatory and anti-depression activities
[109]
.
Native medicinal plants in Iran, presented in this study due to their quality ingredients and proven mechanism of
action can be effective in the treatment of pain and dysmenorrhea and can be produced effective natural remedies
from them.
Although inhibition of cyclooxygenase is considered to be the main factor for the effect of these plants in alleviation
of dysmenorrhea, however, the exact mechanism is not clear. Oxidative stress is involved in pain and dysmenorrhea
and most of these plants have been shown to possess antioxidant activity
[110-129]
. Therefore, the antioxidant activity
of
CONCLUSION
Because of the known side effects of synthetic drugs and the long history of herbal medicine and public confidence
in the therapeutic effects of medicinal plants, they can be a good alternative to treat disorders such as dysmenorrhea.
It should be noted that different plants contain very bioactive compounds that some of them have properties
effective on dysmenorrhra. In fact, plants are complex chemical cocktails with different properties. It means that just
one mechanism of a plant action on cancer in dysmenorrhra and it may act by several mechanisms. The rationale for
using a combination of medications to control pain is based on two important principles, single drug is often
accompanied by low effect, and over time causes unwanted effects, but using a combination of drugs and reducing
the dosage, the side effects might be reduced more effective. The best solution is to use multi-herbal treatment for
dysmenorrhea which has multiple and stronger effect, for instance anti-inflammatory, sedative and analgesic effects.
Acknowledgements
The authors would like to appreciate financial support of Deputy for Food and Drug, Urmia University of Medical
Sciences, Iran. Grant number of the research work is 9134.
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