Traditional herbal interventions for premenstrual syndrome management: A comprehensive literature review

Abstract

Premenstrual syndrome (PMS) causes severe physical and emotional health problems in many women. Due to concerns regarding the potentially harmful effects of conventional treatments, there has been an increased interest in exploring alternative medicines, mainly traditional herbal remedies. This comprehensive literature review employed a rigorous methodology involving extensive data collection from databases such as Scopus®, Web of Science®, and PubMed®, as well as respected publishers like Oxford University Press, Elsevier, Springer Nature, and others. The study examines the properties and potential benefits of Cyperus rotundus, Curcuma longa (turmeric), Aloe vera, Angelica sinensis (Dong Quai), Zingiber officinale (ginger), Crocus sativus (saffron), and Withania somnifera (Ashwagandha) in the context of PMS management. It is important to note that these traditional herbs offer diverse therapeutic properties, which can effectively address both the physical and emotional symptoms of PMS. These herbal interventions have notable analgesic and anti-inflammatory effects, as well as mood-enhancing and adaptogenic qualities. As promising and versatile alternatives to conventional medications, it is essential to conduct further research to prove their efficacy, safety, and ideal use fully. This calls for extensive clinical trials, mechanistic analyses to reveal their mechanisms of action, the creation of standardized formulations, and the adoption of a patient-centered strategy that considers unique preferences and needs. It is possible to significantly improve the holistic approach to PMS management by realizing the full potential of these conventional herbal treatments. This study highlights the vital importance of these herbal interventions in PMS management, ultimately providing women with safer options for PMS relief and an enhanced quality of life.

Full text

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 120
Traditional herbal interventions for premenstrual syndrome
management: A comprehensive literature review
Md Abul Hasan Roni 1,2*, Md Abu Bakar Siddique Jami 3,4, Rezwana Sultana 3,4,
Prethula Areefin 5, Safayet Hossain 6, Sahadat Hossen 7,
Rozina 8, Mohd Yusri Bin Mohd Yunus 1*
1 Faculty of Chemical and Process Engineering, Technology, Universiti Malaysia Pahang Al-Sultan
Abdullah (UMPSA), Gambang, Malaysia.
2 Bangladesh Army International University of Science and Technology, Cumilla, Bangladesh.
3 Department of Pharmacy, East West University, Dhaka, Bangladesh.
4 Department of Pharmacy, Faculty of Life and Earth Sciences, Jagannath University, Dhaka, Bangladesh.
5 Department of Pharmacy, Stamford University Bangladesh, Dhaka, Bangladesh.
6 Institute of Pharmaceutical Sciences, Kurukshetra University, Thanesar, Haryana, India.
7 Young Women’s College Preparatory Academy, Science Department, Houston, Texas, USA.
8 Mainamoti Medical College and Hospital, Cumilla, Bangladesh.
Abstract
Premenstrual syndrome (PMS) causes severe physical and emotional health problems in many women. Due to concerns
regarding the potentially harmful effects of conventional treatments, there has been an increased interest in exploring alternative
medicines, mainly traditional herbal remedies. This comprehensive literature review employed a rigorous methodology involving
extensive data collection from databases such as Scopus®, Web of Science®, and PubMed®, as well as respected publishers like
Oxford University Press, Elsevier, Springer Nature, and others. The study examines the properties and potential benefits of Cyperus
rotundus, Curcuma longa (turmeric), Aloe vera, Angelica sinensis (Dong Quai), Zingiber officinale (ginger), Crocus sativus
(saffron), and Withania somnifera (Ashwagandha) in the context of PMS management. It is important to note that these traditional
herbs offer diverse therapeutic properties, which can effectively address both the physical and emotional symptoms of PMS. These
herbal interventions have notable analgesic and anti-inflammatory effects, as well as mood-enhancing and adaptogenic qualities. As
promising and versatile alternatives to conventional medications, it is essential to conduct further research to prove their efficacy,
safety, and ideal use fully. This calls for extensive clinical trials, mechanistic analyses to reveal their mechanisms of action, the
creation of standardized formulations, and the adoption of a patient-centered strategy that considers unique preferences and needs.
It is possible to significantly improve the holistic approach to PMS management by realizing the full potential of these conventional
herbal treatments. This study highlights the vital importance of these herbal interventions in PMS management, ultimately providing
women with safer options for PMS relief and an enhanced quality of life.
Keywords: Premenstrual Syndrome, PMS, Dysmenorrhea, Herbal, Traditional medicine.
Full length article *Corresponding Author, e-mail: yusri@ump.edu.my, roni_chem@baiust.edu.bd
1. Introduction
Every healthy woman of reproductive age has
menstruation regularly, and it is essential for the uterine
lining to regenerate to get ready for conception. Premenstrual
syndrome (PMS) typically presents as a mix of physical,
behavioral, and emotional symptoms during the final week of
the luteal phase, frequently the week before menstruation,
which is when it typically manifests [1]. The American
International Journal of Chemical and Biochemical Sciences
(ISSN 2226-9614)
Journal Home page: www.iscientific.org/Journal.html
© International Scientific Organization

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Roni et al., 2024 121
College of Obstetricians and Gynecologists (ACOG) defined
PMS as a clinical disorder marked by the cyclic presence of
physical and emotional symptoms that appear in each of the
three previous menstrual cycles five days before menstruation
and disappear within four days of the start of menstruation.
These symptoms don't reappear until at least cycle day
thirteen [2]. The severe form of PMS is termed premenstrual
dysphoric disorder (PMDD). PMS and PMDD are clinically
extreme conditions and can severely impact a woman's
quality of life [3]. Even though 50–80% of women of
reproductive age report having at least mild premenstrual
symptoms, 30–40% report symptoms requiring medical
attention, and 3-8% of women experience PMDD and fulfill
the demanding DSM–IV criteria. However, the majority of
premenstrual symptomatic women suppress their symptoms
without receiving any proper diagnosis or treatment [4].
Though it is unsure what the actual prevalence of PMS is, it
has been estimated that between 70-90% of menstruating
women face some symptoms before their period [5]. Many
conventional treatment methods are available for treating
these symptoms, with which women often self-medicate
themselves. While traditional medicine offers a range of
treatments to alleviate PMS symptoms, the choice to self-
medicate raises essential considerations, especially in
underdeveloped countries [6]. However, traditional herbal
interventions have been studied for the management of
Premenstrual Syndrome (PMS) alongside conventional
medicinal treatment. It has been demonstrated that several
traditional and complementary therapies, including herbal
therapy, significantly reduce PMS symptoms [7].
1.1. Etiology and Symptoms
The exact etiology of premenstrual syndrome (PMS)
has not been established, but various theories have been
proposed involving alterations in neurotransmitters,
hormones, and neuroendocrine pathways [8]. However, prior
research has revealed that there may be some significant
elements underlying PMS, such as hormonal changes,
specific chemical changes, body weight, inadequate physical
activity, mental stress, food, postpartum depression, and other
things [9,10]. We have listed different etiological factors;
their short explanations are depicted in Table 1. However,
there still needs to be a clear pathophysiological explanation
for PMS in the literature. These theories need more rigorous
investigation and empirical evidence to establish a definitive
understanding [11-18]. In terms of symptoms, PMS
symptoms can vary widely among individuals [19-25]. PMS's
severity and recurrent nature have contributed to its
prevalence in women, impacting their everyday activities,
interpersonal relationships, and jobs and income [26-30]. A
patent was found that proposed treatments for various PMS
and PMDD symptoms. This invention listed symptoms like
muscle aches, bloating, cramping, acne, tender breasts,
bloating, fatigue, difficulty concentrating, decreased impulse
control, irritability, anxiety, tension, anger, depression,
insomnia, and rapid mood changes (mood swings), among
others [31]. According to an article from Hofmeister and
Bodden, PMS is a disorder marked by recurring physical and
psychological symptoms that happen in a cycle one to two
weeks before a woman's menstruation. Therefore, PMS can
be categorized into physical and emotional symptoms [32-
36]. We have listed some of the significant physical and
emotional symptoms of PMS found in the literature and their
short explanations in Table 2 [37-42].
1.2. Current Strategies for PMS Management
Current conventional strategies for managing
different premenstrual symptoms include both
pharmacological and non-pharmacological approaches [43-
50]. Cardiovascular exercise [51-55], dietary adjustments,
and cognitive-behavioral therapy are examples of common
non-pharmacological treatments [56-61]. For pain and
cramps, nonsteroidal anti-inflammatory drugs (NSAIDs)
such as ibuprofen can help relieve pain and reduce cramping.
Over-the-counter pain relievers like NSAIDs can help
alleviate headaches [62]. Wearing supportive clothing,
undergarments, and NSAIDs can alleviate breast discomfort
[63]. Reducing salt intake, increasing water consumption, and
avoiding gas-producing foods may help manage bloating
problems [64,65]. Mood swings can be controlled by daily
exercise, stress reduction methods (such as yoga and
meditation), and lifestyle adjustments [66]. Selective
serotonin reuptake inhibitors (SSRIs) like fluoxetine and
sertraline, benzodiazepines like alprazolam, and
gonadotropin-releasing hormone (GnRH) agonists are among
the medications used to treat behavioral and emotional
premenstrual symptoms [67,68]. If symptoms are severe, a
doctor may prescribe antidepressants or recommend therapy.
Maintaining a healthy diet, getting adequate sleep, and
exercising frequently can all help to control lethargy and its
accompanying symptoms [69]. Eating a balanced diet and
managing stress can help control cravings for unhealthy foods
[70]. Practicing good time management, getting sufficient
sleep, and using organizational tools can aid in managing
concentration difficulties [71]. Sleep quality can be improved
by keeping a regular sleep schedule, refraining from coffee
and electronic gadgets before bed, and developing a relaxing
bedtime routine [72,73]. However, some people may require
prescription medications. Skin issues like acne can be
controlled using over-the-counter or prescribed topical
medications containing benzoyl peroxide, salicylic acid, or
retinoids [74,75]. Maintaining a high-fiber diet, staying
hydrated, managing stress, and drugs like domperidone can
help regulate bowel movements [76–78]. Historically, oral
contraceptives (OCs) have had limited data to support their
efficacy. However, recent research has demonstrated that OC
containing the progestin drospirenone helps lower
premenstrual discomfort [79]. The management of
premenstrual symptoms often combines pharmacological and
non-pharmacological methods. The advantages of traditional
herbal treatments for treating these symptoms are not entirely
understood, however. The potential adverse effects of
medications like NSAIDs and SSRIs should be noted [80–
82]. Managing PMS symptoms is crucial, and while
conventional medication may be an option, it can come with
potential risks of several side effects. Traditional herbal
interventions, on the other hand, offer a potentially safer
alternative. However, their efficacy and safety need further
investigation, and there is limited literature on these
traditional herbals and their potential PMS management
activities. Therefore, this study aims to bridge this knowledge
gap by conducting a thorough exploration of the literature on
using conventional herbal substances to manage PMS
symptoms.

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Roni et al., 2024 122
2. Methodology
This review article uses a meticulous and
comprehensive approach to examine the effectiveness of
herbal remedies in treating Premenstrual Symptoms. The data
is collected by carefully selecting primary sources, including
well-known databases such as SciVerse, Scopus®, Web of
Science®, and PubMed®. Additionally, the study includes
data from famous publishers such as Cambridge University
Press, Oxford University Press, Springer Nature, Routledge,
Elsevier, Peter Lang, Thomson Reuters, Blackwell, Sage,
MDPI, Frontiers, Wiley Online, and PLOS ONE, both in their
online and printed versions. The search criteria comprises of
various aspects related to Premenstrual Symptoms and herbal
remedies. It includes their local and scientific names such as
Cyperus rotundus (Nagarmotha/Motha), Withania somnifera
(Ashwagandha), Curcuma longa (Turmeric), Aloe vera
(Ghrit Kumari), Angelica sinensis (Dong quai/Female
Ginseng), Zingiber officinale (Ginger), and Crocus sativus
(Saffron). The study excludes non-English articles to
maintain focus. The selection rigor is ensured by thoroughly
reviewing the full manuscripts of relevant articles, including
titles, abstracts, and conclusive remarks, to verify their
suitability for inclusion in the study. This approach ensures
the paper's comprehensiveness in addressing the research
objectives.
3. Traditional herbal remedies for PMS symptom
management
3.1. Cyperus rotundus (Nagarmotha / Nut Grass)
Cyperus rotundus, which is locally also called “Nut
Grass,” “Nagarmotha,” or “Motha,” is a well-known
medicinal plant that is utilized worldwide [83]. Traditionally,
people used it in many countries to treat disease conditions
such as diarrhea, pyresis, diabetes, inflammation, stomach
and bowel disorders, and malaria [84]. However, little direct
research has been done on this herb regarding its ability to
cure PMS and its associated symptoms. Volatile oil from this
plant contains the crucial ingredients b-pinene, cyperene, a-
cyperone, b-cyperone, and acyperol. Triterpenes, flavonoids,
and alkaloids are also present. Its volatile oil has a somewhat
estrogenic effect, which may aid in treating menopause,
premenstrual syndrome (PMS), mood swings, depression,
and convulsions (Figure 1) [85].
3.1.1. Antispasmodic, antidiarrheal, anti-inflammatory
activity of Cyperus rotundus
A substance with antispastic, antidiarrheal, and anti-
inflammatory properties relieve physical symptoms like
abdominal bloating, cramps, and muscle pain during PMS. Its
effectiveness can also address emotional symptoms such as
mood swings, irritability, and anxiety, contributing to overall
relief from a range of PMS-related discomforts. A direct
relaxing activity on the smooth muscle was demonstrated by
the ethanol extract of Cyperus rotundus, which relaxed the
rabbit ileum and had a spasmolytic effect against contractions
brought on by acetylcholine, barium chloride, and 5-
hydroxytryptamine [86]. An aqueous extract of C. rotundus
was tested by Shamkuwar et al. (2012) for its ability to treat
mice with castor oil-induced diarrhea. At doses of 125 mg/kg,
250 mg/kg, and 500 mg/kg, C. rotundus extract showed
30.36%, 37.90%, and 45.45% inhibition of diarrhea, while
Loperamide (a widely prescribed drug to reduce the
frequency of diarrhea) at dose of 2 mg/kg showed 92.45%
inhibition of diarrhea. Researchers concluded that an
antisecretory mechanism was responsible for its antidiarrheal
effects [87]. In a different study, mice with castor oil-induced
diarrhea responded significantly to the oral administration of
C. rotundus rhizome methanol extract. The total number of
wet feces in 4 hours was 3.00 ± 0.55 and 1.8 ± 0.37,
respectively, for dosages of 250 and 500 mg/kg body weight
(P < 0.01) [88]. In another study, the methanolic extract of C.
rotundus rhizome effectively decreased castor oil-induced
diarrhea in mice when given orally at 250 and 500 mg/kg
body weight dosages. Several in vitro investigations assessed
free radicals, reactive oxygen species, and IC50 values of C.
rotundus rhizomes extract. The rhizome extract scavenges
superoxide anion radicals, hydroxyl radicals, nitric oxide
radicals, and hydrogen peroxide, chelating and reducing
abilities in a concentration-dependent manner [83]. There are
45 μg/g of chlorogenic acid in the ethanol extract of C.
rotundus. Topical administration of C. rotundus extract
lowered cellular infiltration and edema in acute and chronic
skin inflammation models. These results demonstrate C.
rotundus extract's topical anti-inflammatory and
antiproliferative action for the first time, suggesting that the
extract may someday be used as a cutting-edge therapeutic
strategy for the treatment of inflammatory skin problems,
which may demonstrate its effectiveness for PMS-related
acne and other skin problems [89]. Anti-inflammatory
compounds have been studied for their potential role in
managing symptoms such as pain and discomfort [90]. A
review article by Bhaskar Das et al. (2015) reported that, in
another animal model study, C. rotundus tuber extract was
used to assess the anti-inflammatory efficacy in adult albino
Wistar rats. Three equal amounts of the powder were
extracted and given to the test group in ether, ethanol, and
distilled water. The findings showed that the extract
significantly reduced inflammation when applied to
carrageenan-induced rat paw edema in mice [91].
3.1.2. Analgesic, sedative, tranquilizing activity of Cyperus
rotundus
Herbal substances with analgesic, soothing, and
tranquilizing activities can be crucial for alleviating physical
symptoms such as headaches, cramps, muscle pain, and joint
pain during PMS. Additionally, its effectiveness in promoting
relaxation and reducing irritability can address emotional
symptoms like mood swings, anxiety, and social withdrawal,
enhancing overall relief from PMS-related distress. In
previous research, the tail-flick technique was used on mice
to assess the crude extract of C. rotundus' analgesic
effectiveness. Compared to the control and conventional
medications, the natural extract at 300 mg/kg body weight
(dissolved in 0.9 percent saline solution) showed a substantial
and noticeable change in reaction time (5s ± 0.45) [84]. Imam
and Sumi conducted research using a C. rotundus hydro-
methanol extract and discovered that it had antinociceptive
ability against chemical- and heat-induced nociception. The
hydro-methanol extract demonstrated a substantial, fast, and
persistent antinociceptive action at 100 and 200 mg/kg doses
[92]. In a previous study, an acetic acid writhing test
indicated analgesic effects from the whole decocts of C.
rotundus rhizomes. Both the plant's essential oil and
petroleum ether extract have been shown to have analgesic
properties. Additionally, research on the sesquiterpene
isocurcumenol, which was isolated from the C. rotundus

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Roni et al., 2024 123
plant, has shown that it functions as a benzodiazepine
receptor agonist, favorably modulating GABAergic
neurotransmission by enhancing GABA's interaction with its
receptor in animals. An essential part of the GABA receptor
complex is the benzodiazepine receptor. These findings offer
a pharmacological rationale for using C. rotundus as a
sedative because GABA is an inhibitory neurotransmitter
[93]. The ethanolic extract of C. rotundus had strong sedative
effects in several experiments, including those that focused
on how it affected motor coordination, potentiated
pentobarbital narcosis, and reduced mice's spontaneous
muscle movements [94]. In a 2012 study, researchers
employed the forced swimming test (FST) and the tail
suspension test (TST), two traditional behavioral models for
antidepressant screening, to assess the antidepressant effects
of the iridoid glycosides isolated from C. rotundus. Few of
them have been shown to possess intense antidepressant
activity, according to the research findings [95]. FST and TST
were utilized by Hao et al. (2017) to investigate the
antidepressant effect of CR extract and discovered that C.
rotundus extract drastically reduced Monoamine Oxidize A
(MAO) activity across the rat's whole brain. The findings
showed that MAO inhibitory activity may dependently be
dependent on the antidepressant effect of C. rotundus extract
in the rat. However, the study only looked at the animal level,
not the clinical level or the intracellular process [95,96].
Intense and persistent menstrual cramps are known as
Dysmenorrhea [43]. Anti-dysmenorrhea effects of a
substance are vital in reducing menstrual cramps and
abdominal pain during PMS. An article by Prof. Dr Ali
Esmail Al-Snafi reviewed some lab trials. Mice were used to
investigate the anti-dysmenorrhea effects of the essential oil
from the rhizome of C. rotundus (EOC). Four groups of mice
were created: Group 1 acted as the control group, while
groups 2, 3, and 4 received low, intermediate, and high
dosages of EOC (0.01g/kg, 0.02g/kg, and 0.1g/kg,
respectively). To generate an animal model of dysmenorrhea,
the mice were initially intragastrically administered
diethylstilbestrol for 12 straight days (2 mg/kg/day). Over the
last three days, each group's mice received a different dose of
EOC and equivalent saline. The mice were intraperitoneally
treated with 0.1 ml of oxytocin injection 30 minutes after the
last medication treatment, and distortions were noted and
recorded after 15 and 30 minutes. Cyperus rotundus rhizome-
derived EOC was treated to column chromatography for
fractionation, yielding six fractions, denoted by F1–F6. After
intraperitoneal oxytocin administration, distortion durations
were significantly decreased by EOC and its fractions F2
through F6, with F4 performing the best as it contains
spathulenol, β-caryophyllene oxide, and isoaromadendrene
oxide, according to GC-MS analyses. As a result, substantial
anti-dysmenorrhea was seen in EOC and its fractions F2
through F6. The results of the GC-MS analysis of EOC and
its fractions F2 to F6 indicated that more than one component
was responsible for the anti-dysmenorrhea effect [97].
3.2. Curcuma longa (Turmeric / Haldi)
Turmeric is produced by the perennial plant
Curcuma longa, a member of the ginger family. The
yellowish hue of turmeric is caused by curcumin. The
primary active component of turmeric is curcumin, a yellow
polyphenol with the chemical name diferuloylmethane.
Curcumin has potent analgesic, anti-inflammatory, and
antioxidant properties. Vitamins E and C and curcumin have
similar antioxidant properties. Prostaglandins are inhibited by
curcumin [98]. Both the pathways, cyclooxygenase (COX)
and lipooxygenase (LOX), are the mechanisms that make up
the metabolism of arachidonic acid. The primary enzyme is
cyclooxygenase, which transforms arachidonic acid into
prostaglandins in the COX pathway (COX1 and COX2).
Curcumin prevents the synthesis of these prostaglandins [99].
By interfering with Nuclear factor kappa B (NF-B), the
inflammatory response of human endothelial cells that TNF-
α has activated is reduced by curcumin. It prevents the
synthesis of these inflammatory cytokines. Curcumin also
can suppress platelet-derived growth factors. In addition to
alleviating physical discomforts associated with PMS, its
efficacy can also treat mental symptoms like mood changes,
impatience, and anxiety (Figure 2) [100,101].
3.2.1. Analgesic, antioxidant & anti-inflammatory activity
of Curcuma longa
A double-anonymized, randomized, controlled
clinical trial was conducted by Tabari et al. They underwent
a two-month screening process during which participants'
demographic information, menstrual features, and the
severity of dysmenorrhea were documented. Verbal Multi-
Dimensional Scoring was employed to evaluate the severity
of dysmenorrhea after the two cycles. According to the
questionnaire, participants were classified as having grade 2
dysmenorrhea and randomly assigned to one of two treatment
groups: the curcumin group and a placebo group. 500 mg of
curcumin-containing drug was given for three days with food
throughout the first three menstrual cycle days. In both
successive cycles, the students used a visual analog scale
(VAS) to record their pain severity and duration before and
three hours after the intervention. Before taking the
medication, the average pain level in the drug group was
5.408 ± 3.001. However, three hours after taking the
medication, it was -5.017 ± 2.294. Therefore, this study
shows that curcumin can effectively reduce PMS-related
discomfort in terms of duration and severity of pain [102].
Another study was conducted by Arabnezhad et al. to observe
the effect of curcumin on PMS. This triple-blinded, placebo-
controlled, randomized study created a control group and an
experimental group of PMS and dysmenorrhea-afflicted
women. One capsule (500 mg of curcuminoid plus 5 mg of
piperine or placebo) was given to the test group daily during
three consecutive menstrual cycles, from approximately
seven days before menstruation to 3 days after menstruation.
The severity of menstrual cramps was assessed based on the
PSST questionnaire, ranging from 0 (no cramps) to 3 (severe
cramps). It was found that after taking this medication, the
severity of menstrual cramps reduced from 3 to 2 (moderate)
and 2 to 1 (mild), showing evidence of curcumin's analgesic
effect. Again, when compared to the placebo, curcumin
significantly raised average (IQR) serum levels of vitamin D
from 18.6 ng/ml (2.2-26.8) to 21.3 ng/ml (5.2-27.1; P =
0.017), up from 12.8 ng/ml (7.0-24.6) to 16.2 ng/ml (6.4-
28.8). A considerable increase in vitamin D levels was seen
after taking curcumin supplements by PMS and
dysmenorrhea-afflicted women [103]. According to another
pertinent study, the curcumin group's physical, behavioral,
and emotional scores were significantly lower following the
intervention than before. After the intervention, the mean
physical score in the placebo group considerably dropped

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Roni et al., 2024 124
from 46.7 ± 26.8 to 38.50 ± 20.27 (p=0.0425). However, the
average scores for behavioral and mood following the
intervention did not differ substantially from the values
before the intervention. The total PMS score fell considerably
in the curcumin group from 102.06 ± 39.64 to 42.47 ± 16.37
(p<0.0001), although the same score in the placebo group did
not change significantly from (106.06 ± 44.12 to 91.60 ±
43.56, p=0.058) following the intervention [104]. A previous
study Talebpour et al. conducted a triple-blind, placebo-
controlled clinical trial with 76 young women experiencing
PMS and dysmenorrhea. Daily oral curcumin administration
for three consecutive menstrual cycles significantly reduced
high-sensitivity C-reactive protein (hsCRP) levels (an
inflammatory marker) compared to a placebo, with no
significant impact on iron profile. The median hsCRP levels
reduced in the curcumin group, with a p-value of 0.041, from
0.30 mg/L (0.0-1.10) to 0.20 mg/L (0.0-1.3). Comparing the
curcumin-treated group to the placebo group shows a
statistically significant decrease in hsCRP levels. As a result,
curcumin may help with PMS-associated inflammation
[105].
3.3. Aloe vera (Ghrit Kumari)
Ghrit Kumari is a crucial herb used as a medicinal
plant, Aloe vera (Linn.) Burm. F. of the Liliaceae family, also
known as Aloe barbadensis Mill. (Liliaceae), has a variety of
effects on the human body. Aloe vera's stemless plant has
rosettes of highly thick, meaty leaves [106]. A, C, and E
vitamins are present in this plant. As lipid peroxidation is
decreased, it gains antioxidant capabilities as well. Salicylic
acid, nutrients and minerals, enzymes, tannins, and several
polysaccharides are all present in Aloe vera (Figure 3) [107].
3.3.1. Analgesic activity of Aloe vera
An earlier study Sardashti et al. sought to ascertain
whether oral Aloe vera gel supplementation impacted
menstrual pain intensity. One hundred fifty single students
between the ages of 20 and 26 who had menstruation pain
participated in a randomized, single-blind clinical
intervention. With the help of the COX Menstrual Symptom
Scale (CMSC), the severity of the pain was assessed. There
were 60 participants in each group, and aloe vera gel pills
were distributed randomly to each participant. Until the pain
level was one or lower, the initial trial group consumed 10 mg
of Aloe vera gel four times daily. Three pills were given orally
three times per day to the control group. Participants' pain
intensity and duration changes in both groups were assessed
in the first and second months. It was found that the average
pain score in the Aloe vera group lowered from 2.81 ± 0.65
to 2.02 ± 0.34. The two groups' pain levels in the second
month of the trial were alike. Therefore, menstrual discomfort
can be effectively treated with Aloe vera gel pills, an
alternative natural pain reliever with no side effects [108].
An earlier study Khazaiyan et al. conducted a double-blind
clinical experiment with 80 female students who had primary
dysmenorrhea. The subjects in the control group received a
bottle containing 120 cc of placebos. In contrast, the
intervention group members received a bottle containing 120
cc of Aloe vera gels each cycle. Beginning two days before
menstruation and continuing for the first three days after the
start of the menstrual cycle, the patients took the prescribed
medication every day for two cycles. Using a verbal
multidimensional grading system, the effects of drugs on the
severity of dysmenorrhea were evaluated. Results revealed a
significant difference in the amount of bleeding, analgesic
application, and pain severity between the Aloe vera and
placebo groups (P < 0.05); however, no significant
differences were seen in the side effects (P > 0.05) [109].
3.4. Angelica sinensis (Dong quai / Dang Gui / Female
Ginseng)
The Chinese Pharmacopoeia describes the dried root
of Angelica sinensis (Oliv.) Diels as Angelica sinensis. (110),
which is a member of the family Umbelliferae. It is a
perennial with a height of 1 m (3ft. 3in.) and a width of 0.7 m
(2ft. 4in.). It is also known as Dong Quai, Danggui, or Female
Ginseng, and this herb is found in mainland China, Japan, and
Korea. The famous Chinese herbal remedy A. sinensis has
been used for centuries as a feeding and hematological agent
in treating gynecological issues [111]. A. sinensis has several
pharmacological properties, including heart protection,
immunological function enhancement, anti-arrhythmic, anti-
atherosclerotic, and myocardial infarction prevention [112].
N-butylidenephthalide, ligustilide, n-butyl-phthalide, ferulic
acid, nicotinic acid, and succinic acid are the main
therapeutic ingredients of A. sinensis (Figure 4) [113].
3.4.1. Antidepressant activity of Angelica sinensis
In a study involving 60 male Sprague-Dawley rats,
researchers investigated the potential antidepressant effects
of A. sinensis using a chronic unexpected mild stress (CUMS)
model. After one-week incubation, rat models were divided
into five different groups randomly: control (NS), model
(MS), positive control venlafaxine (VLF), high-dosage group
of A. sinensis (HAS), and low-dosage group of A. sinensis
(LAS). The HAS and LAS groups received 15 g and 7.5 g
herb/kg of A. sinensis, respectively, for 28 days, based on
established efficacious dosages. The VLF group received 35
mg/kg of venlafaxine. Venlafaxine was mixed with water at
3.5 mg/ml, while A. sinensis was diluted at concentrations of
0.72 and 0.36 g/ml. Results showed that A. sinensis had a
more potent antidepressant effect in the rat model of CUMS-
induced depression, probably due to activation of the BDNF
signaling pathway and increased expression of BDNF,
phosphorylated ERK 1/2, and CREB proteins in the
hippocampus tissue [114]. In a metabonomic study, treatment
with A. sinensis was found to regulate 26 biomarkers
associated with depression potentially. Among these
biomarkers, eight were previously linked to sphingolipid and
amino acid metabolic pathways, suggesting that A. sinensis
may also modulate energy metabolism in an anemic model.
A. sinensis appeared to alter energy metabolism in depression
by suppressing lactate dehydrogenase A (LDHA) and
pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-
1) activities. These findings indicate that A. sinensis's
antidepressant effects may be attributed, in part, to its
regulation of the blood system [115].
3.4.2. Anti-fatigue activity of Angelica sinensis
In a study by Yeh et al., mice models were divided
into four groups: (1) vehicle control, (2) exercise control, (3)
exercise control with A. sinensis therapy at 0.41 g/kg/day
(ExAS1), and (4) vehicle control with 2.05 g/kg/day
(ExAS5). The vehicle and A. sinensis were given oral
administration for six weeks. Forelimb grip strength, serum
lactate, exhausting swimming time, glucose, ammonia, and

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Roni et al., 2024 125
creatine kinase (CK) levels after a 15-minute swim were used
to measure the ergogenic and anti-fatigue effects. A. sinensis
treatment increased swimming endurance and blood glucose
levels while decreasing serum lactate, CK, and ammonia
levels, with the ExAS1 and ExAS5 groups showing
significant reductions in blood lactate by 14.5% (p = 0.0171)
and 23.6% (p = 0.0002), respectively. In addition, serum
ammonia levels in the ExAS1 and ExAS5 groups were lower
than those in the exercise control group by 19.3% and 26.1%,
respectively (p < 0.0001). A. sinensis supplementation
mitigated oxidative stress induced by exercise, supported
blood glucose utilization for energy during physical activity,
and enhanced glycogen deposition in the liver and muscles,
ultimately improving exercise performance. These findings
indicate that A. sinensis has anti-fatigue properties in mice by
modulating blood lactate and ammonia levels, promoting
glycogen storage, and enhancing physical endurance [116].
Another study investigated the anti-fatigue effects of A.
sinensis polysaccharides (APS) in mice. Four groups were
tested: standard control, low-dose APS (LAT), medium-dose
APS (MAT), and high-dose APS (HAT). APS was
administered orally for 28 days. APS-treated groups showed
significantly higher exhaustive swimming times (p < 0.05)
than the regular control group. Post-swimming, APS-treated
groups had significantly lower blood lactic acid and serum
urea nitrogen levels (p < 0.05). APS-treated groups also
exhibited higher liver glycogen levels (LAT, MAT, and
HAT) and muscle glycogen levels (MAT and HAT)
compared to the regular control group (p < 0.05). The study
used dried Dong quai (the root of A. sinensis) and
demonstrated APS's anti-fatigue effects [117].
3.4.3 Hormonal and Physiological Functions Regulation of
Angelica sinensis
A standardized ethanol extract of Angelica sinensis
root was administered orally to female Wistar rats (200 ± 21
g) at 100 and 300 mg/kg daily for seven days. The estradiol
benzoate was given subcutaneously at 0.1 µg/rat for seven
days. Controls received the vehicle alone. After the last dose,
the rats were weighed and killed, and blood samples were
collected for LH and FSH measurement. The 300 mg/kg dose
of A. sinensis extract significantly modified vaginal smear in
67% of treated rats. It stimulated uterine histoarchitecture,
induced vaginal epithelial cornification, and reduced serum
LH levels, indicating its estrogenic nature. This research
suggests that A. sinensis may exhibit positive estrogenic
activity, which could be explored for alleviating PMS
symptoms. Additionally, it has been shown that A. sinensis
contains anti-inflammatory activities that can help inhibit
excessive antibody response, lower allergies, and lessen
inflammation, all of which may help relieve several PMS
symptoms [118]. A. Sinensis contains volatile oil, organic
acid, polysaccharides, coumarin, and amino acids. It is
responsible for its extensive pharmacological activities,
including regulating the vascular system and blood flow,
hepatoprotective activity, anti-inflammatory effects,
antioxidant effects, and neurological protection [119].
3.5 Zingiber officinale (Ginger)
Zingiber officinale Roscoe, the scientific name for
ginger, is a member of the Zingiberaceae family. It is a
tropical plant that originates in Southeast Asia and grows to a
height of 1 meter. Z. officinale has traditionally been used to
treat a wide range of illnesses, including nausea, vomiting,
asthma, coughing, palpitations, inflammation, dyspepsia,
lack of appetite, constipation, indigestion, and pain in
Ayurveda, Siddha, Chinese, Arabian, African, and Caribbean
medical systems, among many others [120]. Ginger has been
reported to have biological properties, including anti-
inflammatory, antibacterial, antioxidant, and anticancer
properties [121]. Ginger has a high amount of phytochemical
components. Ginger is a promising herbal medicine to treat
many chronic conditions, such as PMS, menopausal
symptoms, and dysmenorrhea (Figure 5) [122].
3.5.1 Clinical trials on PMS management activity of
Zingiber officinale
In a three-month double-anonymized clinical study
conducted by Khayat et al., 70 participants with PMS were
identified through a daily record scale questionnaire over two
menstrual cycles. They were randomly divided into two
groups (n = 35 each). The first group received 250 mg of
ginger capsules every 12 hours, while the second group
received placebo capsules. Both treatments were given from
7 days before to 3 days after the start of menstrual bleeding.
The severity of symptoms was assessed using a daily record
scale questionnaire for three cycles. After one month of
intervention, ginger significantly reduced the total PMS
score, mood severity, and somatic and behavioral symptoms.
This suggests that ginger can be a safe and effective remedy
for PMS symptoms [122]. In a 2013 double-blinded, placebo-
controlled study on 70 female students, daily record
questionnaires were used to diagnose PMS based on DSM-
IV criteria. Participants with PMS were randomly assigned to
receive either ginger capsules (250 mg every 12 hours for
seven days before and three days after menstruation) or
placebos. After one month, ginger significantly reduced total
PMS scores (p < 0.001) compared to placebo, with pre-
intervention scores being almost similar (ginger: 106.7 ±
44.65, placebo: 110.2 ± 30.77) [122].
3.5.2. Activity for abdominal discomfort of Zingiber
officinale
Zingiber officinale has been studied in several
clinical trials to treat abdominal bloating. In a double-blind,
randomized controlled trial of 106 patients with functional
bloating, those who received KAASER, a supplement
containing ginger, three times a day for two weeks showed
significant improvements compared to the placebo and
dimethicone treatment groups. KAASER demonstrated
marked reductions in bloating frequency and severity (P <
0.001) as well as improvements in the frequencies of
defecation, eructation, and borborygmus (P = 0.03) across all
phases of follow-up among the patients who completed the
study [123]. Another clinical trial was conducted to compare
the effectiveness of a ginger and artichoke supplement with a
placebo in treating functional dyspepsia (FD) in adult male
and female patients. The study found that the group receiving
the ginger supplement showed a significant improvement in
their symptoms, including nausea (P<0.001), epigastric
fullness (P<0.001), epigastric pain (P=0.002), and bloating
(P=0.017), compared to the placebo group [124]. After a
cesarean section surgery, a ginger supplement was found to
be more effective than a placebo in reducing abdominal
distention severity in a randomized, double-blind, placebo-
controlled trial. In comparison to the placebo group, the

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Roni et al., 2024 126
ginger group performed better in terms of effectiveness in
reducing abdominal distention (91% vs 65.2%, p < 0.001). In
terms of quality of life, more patients in the ginger group were
able to eat than in the placebo group (59.6% vs. 43.8%, p =
0.035) [125]. Furthermore, a study evaluated the efficacy of
a traditional Japanese herbal medicine containing ginger
called Daikenchuto (DKT). Face scale measurements of the
intensity of the abdominal pain and bloating showed a
substantial reduction (P = 0.039 and P = 0.008, respectively).
The quality of life for individuals with persistent constipation
was enhanced with DKT therapy [126]. Overall, these studies
suggest that ginger, alone or in combination with other
ingredients, may effectively reduce abdominal bloating, a
prominent physical PMS symptom. One of the primary signs
of premenstrual syndrome is dysmenorrhea. Primary
dysmenorrhea is initiated by an excess of prostaglandins
produced by endometrial tissue, and prostaglandin inhibitors
can alleviate 80% of instances of dysmenorrhea. Changes in
the prostaglandin system have been suggested as one of the
causes of premenstrual syndrome. The metabolism of
cyclooxygenase and lipoxygenase is inhibited by ginger,
which stops the formation of prostaglandins [113].
3.5.3. Pain relieving activity of Zingiber officinale
In two double-masked, placebo-controlled,
randomized trials, Black et al. investigated the effects of
ginger supplementation on muscular pain. Study 1 involved
34 participants, while study 2 had 40 participants. During two
studies, participants consumed either 2 grams of raw or
heated ginger or a placebo for 11 days. Participants then
underwent 18 eccentric elbow flexor motions to induce
inflammation or discomfort, and the results showed that raw
ginger (25% reduction, -0.78 SD, P = 0.041) and heated
ginger (23% reduction, -0.57 SD, P = 0.049) significantly
reduced pain intensity compared to the placebo 24 hours after
exercise. Raw ginger reduced pain intensity by 25% (9.3 VAS
units), while heated ginger reduced it by 23% (8.6 VAS
units). Ginger's action involves desensitizing TRPV1
receptors, implicated in pain processing and nociception, by
compounds such as gingerols, shogaols, and zingerone. This
suggests that ginger supplementation may effectively reduce
muscular pain intensity, which may be associated with PMS
[127]. In a 2012 study by Rahnama et al., a double-blind,
placebo-controlled, and parallel-group trial with balanced
randomization (1:1) was conducted on 120 female dormitory
students in Iran aged over 18. There were two equal groups:
one received 500 mg of ginger thrice daily or a placebo. Both
groups were given two different treatment protocols at
monthly intervals. The study indicates that ginger may be a
safe and effective therapy for easing the pain in women with
primary dysmenorrhea. The treatment should be administered
at the onset of menstruation and three days prior to it [128].
Another placebo-controlled randomized trial was conducted
by Kashefi et al. with 150 high school students aged 15 to 18
in Iran. In this study, participants were randomly assigned to
one of three groups: zinc sulfate (n=48), ginger (n=56), or
placebo (n=46). The capsules provided to each group
contained either 250mg of ginger powder for the ginger
group, 220mg of zinc sulfate for the zinc sulfate group, or
lactose for the placebo group. The results showed that both
the ginger and zinc sulfate groups reported significant pain
relief (p<0.05) during the study compared to the placebo
group. Overall, the ginger and zinc sulfate groups showed a
significant reduction in primary dysmenorrheal pain for
young women [129].
3.6. Crocus sativus (Saffron)
For many years, especially in Asian countries,
saffron, or Crocus sativus L. (C. sativus), has been used
extensively as a food ingredient and a curative agent in
traditional medicine. Picrocrocin, safranal, and crocin are
three bioactive components in this spice that have therapeutic
effects on various illnesses, including cardiovascular,
pulmonary, gastrointestinal, neurological, mental, and
female-specific diseases. This herbal compound is said to
have anti-nociceptive, anti-inflammatory, and anti-oxidative
properties. Additionally, several studies have focused on the
potential function of saffron in modulating the serotonergic
system, which may help treat certain diseases that affect
women specifically, such as PMS, PPD, postmenopausal
symptoms, and sexual dysfunction [130]. Additionally,
saffron includes more than 150 volatile and aroma-producing
compounds and several non-volatile active substances such
as polysaccharides and carotenoids like zeaxanthin, lycopene,
and beta-carotene [131]. Because of the potential properties
of this valuable substrate, several patent products or
pharmaceutical formulations are now available in drug shops
in some countries as supplements (Figure 6) [132].
3.6.1. Clinical trials on PMS management activity of Crocus
sativus A study on the impact of saffron on PMS symptoms
was carried out in 2007 by Agha-Hosseini et al. The study
involved women aged between 20 and 45 who had regular
menstrual cycles and had been experiencing PMS symptoms
for at least six months. One group of women received saffron
supplements, while the other group received a placebo. After
taking 15 mg of saffron orally twice daily for two menstrual
cycles, 75% of participants reported a 50% decrease in the
severity of their PMS symptoms. Furthermore, 60% of those
in the saffron group reported a 50% decrease in their
depressive symptoms. Based on these findings, saffron may
work well as a complementary medicine for PMS [134]. In a
study conducted by Fukui et al., the effects of saffron odor on
premenstrual syndrome, dysmenorrhea, and irregular
menstruation were investigated. The study involved 35
women with an average sense of smell who were exposed to
saffron odor for 20 minutes. The results showed that saffron
odor had both physiological and psychological effects on
women, including an increase in cortisol levels, a decrease in
17-beta estradiol levels, and a decrease in the STAI score
(State-Trait Anxiety Inventory) during both the follicular and
luteal phases. The findings suggest that saffron odor may help
alleviate menstruation discomfort, particularly for PMS,
dysmenorrhea, and irregular menstruation. This study is the
first of its kind to demonstrate the potential benefits of saffron
odor for menstrual health [135]. In a 2013 randomized, triple-
blind controlled study by S. Pirdadeh Beiranvand et al.
involving 78 female students, saffron capsules (30 mg/day)
were administered to one group for two menstrual cycles,
while another group received placebos. Initially, both groups
had similar PMS severity (P = 0.81). However, at the study's
conclusion, the mean PMS severity significantly decreased in
both groups (P = 0.001 for the intervention group and P = 0.04
for the control group). The difference in PMS severity
changes between the two groups was substantial (P < 0.001).

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Roni et al., 2024 127
This suggests that saffron may reduce PMS symptoms, but
further research is needed to confirm its efficacy [136].
3.6.2. Antidepressant, anxiolytic, pain-relieving activity of
Crocus sativus
Two clinical studies have shown that taking saffron
capsules can be just as effective as taking fluoxetine capsules
in treating mild to moderate depression. The first study,
conducted by Noorbala et al., found that taking 30 mg of
saffron capsules for six weeks was as beneficial as taking 20
mg of fluoxetine capsules (F = 0.13, d.f. = 1, P = 0.71) [137].
The second study, conducted by Akhoundzadeh et al.,
compared the efficacy of saffron capsules with fluoxetine in
treating depressed patients in an 8-week pilot double-blind
randomized trial. The results showed that taking 30-mg
saffron capsules for six weeks was more effective than taking
a placebo in treating mild to moderate depression (F= 0.03,
d.f.= 1, P=0.84) [138]. In a 12-week double-blind, placebo-
controlled study, researchers assessed the effects of saffron
extract on anxiety and depression in 60 adult patients. At the
end of the 12 weeks, the group that received saffron
supplements had significantly better psychiatric scores (p <
0.001), as measured by the Beck Anxiety Inventory and the
Beck Depression Inventory, compared to the group that
received placebo. These results suggest that saffron may be
an effective treatment for anxiety and depression disorders.
However, more research is needed to assess the potential side
effects of saffron supplementation. [139]. Another study
combined saffron with two other herbal components to treat
primary dysmenorrhea. Each test capsule contained 500 mg
of SCA (saffron, celery seed, and anise extracts). One
hundred eighty individuals were randomly assigned to one of
three test groups: mefenamic acid (250 mg), placebo, or both.
For three cycles, all participants took one related capsule
every 8 hours from the first onset of menstruation or pain. At
months 2 and 3, the subjects' pain severity and duration were
assessed using a visual analog pain intensity scale. These
findings indicate that SCA is a safe and effective treatment
for primary dysmenorrhea, although the researchers
recommended more clinical trials [140].
3.7. Withania somnifera (Ashwagandha)
For many years, ashwagandha has been recognized
as a beautiful rejuvenator, a general health tonic, and a
treatment for various conditions. It has sedative, diuretic, and
anti-inflammatory properties and is well-known for
increasing energy endurance and acting as an adaptogen with
potent immunostimulatory and anti-stress effects [141].
Ashwagandha has been the subject of numerous
pharmacological research to confirm its efficacy as a
multifunctional therapeutic agent [142]. According to the
Indian Herbal System (Ayurveda), Ashwagandha is one of
the most significant herbs and the finest adaptogenic.
Cuseohygrine, anhydride, tropine, and anaferine are among
its constituents, as are glycosides, withanolide, starches, and
amino acids [141]. It has been used for an extended period for
all age groups, both sexes, and even during pregnancy, with
no adverse effects. Recently, WS has been utilized to prevent
the development of tolerance and reliance on certain
psychiatric medicines when administered chronically (Figure
7) [143].
3.7.1. Clinical trials on PMS management activity of
Withania somnifera
A clinical pilot study was conducted in India to
assess the effectiveness of a combination of ‘Ashwagandha
Vati’ and ‘Satvavajaya Chikitsa’ in managing premenstrual
syndrome. Ashwagandha Vati is a formulation prepared from
Withania somnifera, which aims to mitigate lousy digestion,
bloating, and constipation. Satvavajaya Chikitsa is a
structured ayurvedic psychotherapy that seeks to restructure
the mind. The study involved 30 female volunteers at a
tertiary Ayurveda hospital in a South Indian city. The
research participants experienced more psychological
symptoms than physical ones. They took two Ashwagandha
Vati (500 mg) orally twice daily with milk and underwent
four Satvavajaya Chikitsa sessions over a month (1 menstrual
cycle). After the combination treatment, there was a
significant improvement (P < 0.001) in cognitive,
affective/psychological, and behavioral symptoms. The study
concluded that the combination of Ashwagandha Vati and
Satvavajaya Chikitsa effectively managed PMS symptoms
[144]. A previous study Akhila M et al. conducted an
interventional study with 20 females aged 20-35 years
experiencing PMS. They were treated with ‘Punarnavadi
Kashayam’ (48 mL two times a day) and ‘Aswagandha
Choorna’ (3 grams two times a day) for three consecutive
menstrual cycles. The medications were administered 14 days
before menstruation and continued until the fourth day of
menstruation. Both treatments effectively improved
depressive symptoms, anxiety, exhaustion, irritability, pain,
sleep changes, and bloating, as measured by the premenstrual
scale. Additionally, the medications restored serum sodium
and potassium levels to normal. The study concluded that
Punarnavadi Kashayam and Aswagandha Choorna are highly
beneficial in treating PMS [145]. An open-label exploratory
clinical study was conducted with 35 participants who met
diagnostic criteria for PMS. The participants received
Ashwagandha Vati (500mg twice daily with milk) and
Satvavajaya Chikitsa (counseling, relaxation, yoga, and
pranayama). After treatment, significant improvements were
observed in various domains, including negative affect,
concentration, behavioral changes, arousal, control,
hydration retention, and autonomic response. The combined
therapy's efficacy may be attributed to Ashwagandha's
anxiolytic and adaptogenic properties, along with the calming
effects of Satvavajaya chikitsa. The lasting effect of
Satvavajaya, particularly the relaxation response and positive
recommendations, may have contributed to the sustained
benefits even after treatment cessation [146].
3.7.2. Anti-oxidant, anti-stress, anxiolytic activity of
Withania somnifera
A study conducted by the Institute of Basic Medical
Sciences at Calcutta University investigated the impact of
Ashwagandha on chronic stress in animals. The animals were
subjected to mild electric shocks on their feet for 21 days,
causing hyperglycemia, glucose intolerance, a rise in plasma
corticosterone levels, stomach ulcers, male sexual
dysfunction, cognitive impairment, immunosuppression, and
depression. Researchers found that mice given Ashwagandha
one hour before the foot shock experienced a considerably
lower stress level. These findings suggest that Ashwagandha
has a significant anti-stress adaptogenic impact. [147]. In a
prospective, randomized, double-blind, placebo-controlled

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Roni et al., 2024 128
trial, Ashwagandha root extract was tested for its stress-
relieving effects on 60 stressed healthy individuals. They
were divided into three groups: Ashwagandha extract 125
mg, Ashwagandha extract 300 mg, and placebo, taken twice
daily for eight weeks. Both 250 mg and 600 mg
Ashwagandha doses significantly reduced stress levels (P <
0.05 and P < 0.001, respectively) and lowered serum cortisol
levels (P < 0.0001). Participants who received Ashwagandha
reported improved sleep quality. The study concluded that
supplementing with Ashwagandha root extract for eight
weeks significantly reduced stress levels and improved
overall quality of life [148].
4. Discussion and future recommendations
The comprehensive literature review thoroughly
investigated the potential use of traditional herbal
interventions for managing Premenstrual Syndrome (PMS).
These reviews underscore the rich historical significance,
intricate botanical characteristics, and bioactive compounds
of the herbs, which collectively contribute to their potential
therapeutic effects on the multifaceted symptoms associated
with PMS. Cyperus rotundus (Nagarmotha / Nut Grass)
demonstrates a multifaceted range of activities that can
potentially alleviate various symptoms associated with PMS.
Its antispasmodic, anti-diarrheal and anti-inflammatory
properties hold promise in addressing physical discomfort,
including abdominal bloating, cramps, muscle pain, and joint
discomfort, frequently experienced during PMS. Moreover,
these properties extend to emotional well-being by potentially
reducing mood swings, irritability, and anxiety. The herb's
ability to relax smooth muscles and relieve digestive issues
further positions it as a natural remedy for PMS. Its analgesic,
sedative, and tranquilizing effects add to its potential in
managing headaches, muscle pain, and mood-related
symptoms like anxiety and irritability. Turmeric, also known
by its scientific name Curcuma longa, has much promise for
reducing PMS symptoms. Curcumin, its main active
ingredient, has potent analgesic, anti-inflammatory, and
antioxidant effects. Its efficiency in lowering the duration and
intensity of pain brought on by dysmenorrhea has been
demonstrated in clinical studies. Furthermore, curcumin has
the potential to lessen inflammation in women with PMS and
dysmenorrhea due to its capacity to raise serum vitamin D
levels and lower high-sensitivity C-reactive protein (hsCRP)
levels. Aloe vera, also known as Ghrit Kumari, has been
recognized for its potential to ease menstrual pain that comes
with PMS. It is rich in vitamins and bioactive compounds,
which provide antioxidant properties and analgesic effects.
Research studies have revealed that ingesting Aloe vera gel
can effectively reduce the intensity of menstrual pain in
young women, making it a natural and side-effect-free
solution for managing menstrual discomfort related to PMS.
Additionally, it also helps to maintain hormonal balance and
have skin protection activity by lessening acne. Angelica
sinensis, commonly known as Dong Quai or Female Ginseng,
is a versatile medicinal herb that shows great potential for
managing PMS symptoms. Its unique properties offer a
multifaceted approach to addressing both the emotional and
hormonal aspects of PMS. The herb's antidepressant
properties, anti-fatigue effects, and estrogenic properties
make it a valuable tool for combating mood swings, fatigue,
and hormonal imbalances. Additionally, its anti-
inflammatory attributes may help reduce excessive antibody
production and alleviate inflammatory reactions, contributing
to the relief of various PMS symptoms. Ginger, or Zingiber
officinale as it is named scientifically, is another treatment
option for PMS and its symptoms. Clinical studies have
demonstrated that ginger can successfully lessen the intensity
of PMS symptoms, including mood swings and physical pain.
Due to its anti-inflammatory and prostaglandin-inhibiting
qualities, ginger is an effective treatment for dysmenorrhea, a
painful condition that many women experience during their
period. Additionally, ginger can ease bloating and abdominal
discomfort, which are typical physical signs of PMS. Ginger
can provide relief to those looking for a holistic method of
treating PMS symptoms because it is a natural and secure
treatment. Saffron, also known as Crocus sativus, has been
found to be effective in treating PMS and its related
symptoms. Clinical trials have demonstrated that saffron can
significantly reduce the severity of PMS symptoms,
particularly those related to depression. Its anti-depressant,
anti-anxiety, and pain-relieving properties make it a versatile
herbal solution for mood disorders and discomfort.
Additionally, its impact on regulating hormones, primarily
cortisol and estradiol levels, highlights its potential in
alleviating PMS and menstrual irregularities. Withania
somnifera (Ashwagandha) emerges as a valuable candidate
for managing PMS, addressing psychological and physical
manifestations. Combining Ashwagandha with structured
Ayurvedic psychotherapy has successfully managed
cognitive, affective, and behavioral symptoms. Furthermore,
Ashwagandha's anti-stress and anxiolytic effects provide
relief from stress-related conditions. Its adaptogenic qualities
and role in regulating hormonal responses position it as a
holistic approach to PMS management. Future
recommendations include the need for larger-scale clinical
trials to establish efficacy, determine optimal dosages, and
assess long-term safety profiles conclusively. Mechanistic
studies are necessary to elucidate the underlying action
pathways, and standardized formulations would enhance
consistency and reproducibility. Exploring combination
therapies and patient-centered approaches tailored to
individual preferences will optimize PMS management.

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Roni et al., 2024 129
Table 1: Etiological factors of PMS
Etiological Factors
Explanation
References
Hormonal
Imbalances
PMS can result from fluctuations in estrogen and progesterone levels during the
menstrual cycle.
(12–14)
Serotonin Levels
Changes in serotonin levels in the brain may contribute to mood swings and emotional
symptoms.
(15,16)
Chemical Changes
Altered sensitivity to neurotransmitters and chemicals in the brain can influence PMS
symptoms.
(17,18)
Genetic
Predisposition
A family history of PMS or mood disorders may increase the likelihood of experiencing
PMS.
(19–21)
Lifestyle Factors
Poor diet, lack of exercise, and high stress can exacerbate PMS symptoms.
(22,23)
Environmental
Factors
Exposure to environmental toxins or pollutants may play a role in PMS development.
(24–26)
Psychological
Factors
Depression and anxiety are prevalent mental health conditions that might exacerbate
PMS symptoms.
(27,28)
Neuroendocrine
Factors
The interplay between the nervous and endocrine systems can affect PMS symptoms.
(14,29)
Figure 1: Effectiveness of Cyperus rotundus for Premenstrual Syndrome.

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Roni et al., 2024 130
Figure 2: Biological effects of Curcuma longa in PMS management.
Figure 3: Biological effects of Aloe vera in PMS management.

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Roni et al., 2024 131
Figure 4: Biological effects of Angelica sinensis in PMS management.
Figure 5: Biological effects of Zingiber officinale in PMS management.

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Roni et al., 2024 132
Figure 6: Pharmacological benefits of saffron (Crocus sativus) (133).
Figure 7: Ashwagandha (Withania somnifera) benefits for different PMS symptoms.

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Roni et al., 2024 133
Table 2: Symptoms of PMS
Physical Symptoms
Explanation
References
Breast Tenderness
Swelling and tenderness in the breasts.
(33–35)
Abdominal Bloating
The feeling of fullness and bloating in the lower abdomen.
(36,37)
Headache
Mild to severe headaches may occur.
(38–40)
Fatigue
Persistent tiredness and lack of energy.
(3,9,41)
Cramp and Muscle Pain
Muscle aches and pains, sometimes resembling mild flu-like symptoms.
(42–44)
Joint Pain
Pain and discomfort in the joints.
(3,5,44)
Skin Issues
Acne breakouts or other skin problems may worsen.
(36,37,45)
Sleep Disturbances
Insomnia or disrupted sleep patterns.
(41,46)
Emotional Symptoms
Explanation
Mood Swings
Rapid and extreme changes in mood.
(16,37,47)
Irritability
Increased sensitivity and irritability.
(27,35,47)
Anxiety
Feelings of nervousness or tension.
(27,48,49)
Depression
Feeling sad, hopeless, or experiencing a lack of interest in activities.
(27,50,51)
Crying Spells
Uncontrollable crying or heightened emotional response.
(3,36,52)
Difficulty Concentrating
Reduced ability to focus and concentrate.
(50,53,54)
Changes in Appetite
Food cravings or loss of appetite.
(55–57)
Social Withdrawal
Avoiding social interactions or isolating oneself.
(58–60)
A comprehensive and multidisciplinary approach,
including rigorous research and standardized protocols, is
essential to unlock the full potential of traditional herbal
interventions in PMS management.
5. Conclusions
This comprehensive literature review has shed light
on the potential of traditional herbal interventions as
promising approaches for managing the complex array of
symptoms associated with Premenstrual Syndrome (PMS).
These herbs, including Cyperus rotundus, Curcuma longa
(turmeric), Aloe vera, Angelica sinensis (Dong Quai),
Zingiber officinale (ginger), Crocus sativus (saffron), and
Withania somnifera (Ashwagandha), each offer unique
therapeutic attributes that address both physical and
emotional manifestations of PMS. From analgesic and anti-
inflammatory properties to mood-enhancing and adaptogenic
effects, these herbal remedies present potential alternatives to
conventional medications, which may carry side effects.
However, it's essential to emphasize the need for further
research, including large-scale clinical trials, mechanistic
investigations, standardized formulations, and consideration
of individual patient preferences. These steps are crucial in
establishing these herbal interventions' efficacy, safety, and
optimal usage, ultimately providing women with diverse and
potentially safer options for managing PMS symptoms. In
doing so, we can unlock the full potential of traditional herbal
remedies and enhance the holistic approach to PMS
management.
Funding Information
This study received no specific grant from any
funding agency, commercial or not-for-profit sectors.
Competing Interest
The authors declare that they have no competing
interest.
References
[1] R. Abu Alwafa, M. Badrasawi, R. Haj Hamad.
(2021). Prevalence of premenstrual syndrome and
its association with psychosocial and lifestyle
variables: a cross-sectional study from Palestine.
BMC Women's Health. 21(1): 233.
[2] N. Buddhabunyakan, S. Kaewrudee, C.
Chongsomchai, S. Soontrapa, W. Somboonporn, J.
Sothornwit. (2017). Premenstrual syndrome (PMS)
among high school students. International journal of
women's health. 501-505.
[3] R.F. Casper, W.F. Crowley Jr, Patient education:
Premenstrual syndrome (PMS) and premenstrual
dysphoric disorder (PMDD)(Beyond the Basics). In
2019.
Available from:
https://www.uptodate.com/contents/premenstrual-
syndrome-pms-and-premenstrual-dysphoric-
disorder-pmdd-beyond-the-
basics/print?search=sindrome
premenstrual&source=search_result&selectedTitle
=5~150&usage_type=default&display_rank=5.
[4] A. Ryu, T.-H. Kim. (2015). Premenstrual syndrome:
A mini review. Maturitas. 82(4): 436-440.
Available from:
https://www.sciencedirect.com/science/article/pii/S
0378512215300451.
[5] M. Zaka, K.T. Mahmood. (2012). Pre-menstrual
syndrome- A review. Journal of Pharmaceutical
Sciences and Research. 2012;4(1):1684–91.
Available from:
https://www.jpsr.pharmainfo.in/Documents/Volum
es/vol4Issue01/jpsr 04120109.pdf.
[6] M.A.B.S. Jami, K. Biswas. (2023). A cross-
sectional study regarding the knowledge, attitude
and awareness about self-medication among

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 134
Bangladeshi people. Health Policy and Technology.
100715.
Available from:
https://www.sciencedirect.com/science/article/pii/S
2211883722001228.
[7] C.L. Vandeleur, S. Rothen, Y. Lustenberger, J.
Glaus, E. Castelao, M. Preisig. (2017). Ayurvedic
Management Of Premenstrual Syndrome: A Case
Study. International Journal of Ayurveda and
Pharma Research. Volume 8:119–21.
[8] B.L. True, S.M. Goodner, E.A. Burns. (1985).
Review of the etiology and treatment of
premenstrual syndrome. Drug intelligence &
clinical pharmacy. 19(10): 714-722.
Available from:
https://doi.org/10.1177/106002808501901003.
[9] A. Mishra, G. Banwari, P. Yadav. (2015).
Premenstrual dysphoric disorder in medical students
residing in hostel and its association with lifestyle
factors. Industrial psychiatry journal. 24(2): 150.
[10] Women’s Health Concern. (2015). Premenstrual
Syndrome (PMS) [Internet].
Available from: https://www.womens-health-
concern.org/wpcontent/uploads/2015/02/WHC_FS
_PMS.pdf.
[11] S. Walsh, E. Ismaili, B. Naheed, S. O'Brien. (2015).
Diagnosis, pathophysiology and management of
premenstrual syndrome. The Obstetrician &
Gynaecologist. 17(2): 99-104.
[12] C. Roomruangwong, A.F. Carvalho, F. Comhaire,
M. Maes. (2019). Lowered plasma steady-state
levels of progesterone combined with declining
progesterone levels during the luteal phase predict
peri-menstrual syndrome and its major subdomains.
Frontiers in psychology. 10: 2446.
[13] R. Hamidpour, L. Rashan. (2017). An Herbal
Preparation that Relieves Symptoms of
Premenstrual Syndrome. Translational
Biomedicine. 8(3): 126.
[14] E.M. Mulligan, B.D. Nelson, Z.P. Infantolino, K.R.
Luking, R. Sharma, G. Hajcak. (2018). Effects of
menstrual cycle phase on electrocortical response to
reward and depressive symptoms in women.
Psychophysiology. 55(12): e13268.
[15] J.G. Hensler. (2010). Serotonin in mood and
emotion. In Handbook of behavioral neuroscience,
Elsevier: 2010; Vol. 21, pp 367-378. Available
from:
https://www.sciencedirect.com/science/article/pii/S
1569733910700904.
[16] K.G. Commons, Serotonin system function,
organization, and feedback. In Handbook of
Behavioral Neuroscience, Elsevier: 2020; Vol. 31,
pp 41-48.
Available from:
https://www.sciencedirect.com/science/article/pii/B
9780444641250000037.
[17] E. Bannister. (2019). There is increasing evidence to
suggest that brain inflammation could play a key
role in the aetiology of psychiatric illness. Could
inflammation be a cause of the premenstrual
syndromes PMS and PMDD? Post Reproductive
Health. 25(3): 157-161.
Available from:
https://doi.org/10.1177/2053369119875386.
[18] P. Liu, Y. Wei, Y. Fan, R. Li, Y. Liu, G. Wang, Y.
Wei, Y. Pang, D. Deng, W. Qin. (2018). Altered
brain structure in women with premenstrual
syndrome. Journal of Affective Disorders. 229:
239-246.
Available from:
https://www.sciencedirect.com/science/article/pii/S
0165032717314982.
[19] C. Vandeleur, S. Rothen, Y. Lustenberger, J. Glaus,
E. Castelao, M. Preisig. (2015). Inter-informant
agreement and prevalence estimates for mood
syndromes: direct interview vs. family history
method. Journal of Affective Disorders. 171: 120-
127.
Available from:
https://www.sciencedirect.com/science/article/pii/S
0165032714005370.
[20] K. Jansen, T. Cardoso, G. Fries, J. Branco, R. Silva,
M. Kauer‐Sant'Anna, F. Kapczinski, P. Magalhaes.
(2016). Childhood trauma, family history, and their
association with mood disorders in early adulthood.
Acta Psychiatrica Scandinavica. 134(4): 281-286.
[21] H. Berenbaum, K. Bredemeier, M.T. Boden, R.J.
Thompson, M. Milanak. (2011). Affective
instability, family history of mood disorders, and
neurodevelopmental disturbance. Personality
Disorders: Theory, Research, and Treatment. 2(3):
220.
[22] A. Daley, H. Stokes‐Lampard, A. Thomas, C.
MacArthur. (2014). Exercise for vasomotor
menopausal symptoms. Cochrane Database of
Systematic Reviews. (11).
Available from:
https://doi.org//10.1002/14651858.CD006108.pub4
[23] M.S. Hashim, A.A. Obaideen, H.A. Jahrami, H.
Radwan, H.J. Hamad, A.A. Owais, L.G. Alardah, S.
Qiblawi, N. Al-Yateem, M.e.A.-I.E. Faris. (2019).
Premenstrual syndrome is associated with dietary
and lifestyle behaviors among university students: a
cross-sectional study from Sharjah, UAE. Nutrients.
11(8): 1939.
[24] H. Sakai, K. Ohashi. (2021). Effects of past
environmental tobacco smoke exposure on the
menstrual cycle and menstrual phase‐related
symptoms: A cross‐sectional study. Journal of
Obstetrics and Gynaecology Research. 47(1): 243-
253.
[25] C. Delpierre, J. Lepeule, S. Cordier, R. Slama, B.
Heude, M.-A. Charles. (2016). DOHaD:
epidemiological researches. Medecine Sciences:
M/S. 32(1): 21-26.
[26] J. Guo, P. Tian, Z. Xu, H. Zhang. (2021).
Introduction to Environmental Harmful Factors.
Environment and Female Reproductive Health. 3-
19.
Available from: https://doi.org/10.1007/978-981-
33-4187-6_1.
[27] C.-H. Ko, C.-Y. Long, S.-Y.C.I.-J. Chen, T.-H.
Huang, J.-Y. Yen. (2013). Depression, irritability,
and anxiety in women with premenstrual dysphoric

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 135
disorder. The International Journal of Psychiatry in
Medicine. 46(1): 39-55.
Available from: https://doi.org/10.2190/PM.46.1.d.
[28] L. Riven. (1983). Premenstrual syndrome: A
psychological overview. Canadian Family
Physician. 29: 1919.
[29] A.J. Rapkin, A.L. Akopians. (2012).
Pathophysiology of premenstrual syndrome and
premenstrual dysphoric disorder. Menopause
international. 18(2): 52-59.
Available from:
https://doi.org/10.1258/mi.2012.012014.
[30] J.N. Kues, C. Janda, M. Kleinstäuber, C. Weise.
(2016). How to measure the impact of premenstrual
symptoms? Development and validation of the
German PMS-Impact Questionnaire. Women &
health. 56(7): 807-826.
Available from:
https://doi.org/10.1080/03630242.2015.1118734.
[31] M. Janssen, J.S. Edgar, E. Golan, Treatment of
menstrual cycle-induced symptoms. In Google
Patents: 2023.
Available from: https://lens.org/066-153-061-277-
567.
[32] S. Hofmeister, S. Bodden. (2016). Premenstrual
syndrome and premenstrual dysphoric disorder.
American family physician. 94(3): 236-240.
[33] A. Goyal. (2014). Breast pain. Vol. BMJ Clinical
Evidence.
[34] J. Scurr, W. Hedger, P. Morris, N. Brown. (2014).
The prevalence, severity, and impact of breast pain
in the general population. The Breast Journal. 20(5):
508-513.
[35] K. Winther, J. Campbell-Tofte, A.M. Motawei, F.
Pedersen, S.B. Roos, A.S.V. Hansen, G.G. Fornitz,
M. Killi, G. Gerhardsen. (2018). A double-blinded,
randomized, placebo controlled, parallel study of
pollen pistil extract (Sèrèlys) on women reporting
irritability as predominant PMS symptom. Journal
of Herbal Medicine. 12: 23-32.
Available from:
https://www.sciencedirect.com/science/article/pii/S
2210803318300101.
[36] C. Costanian, Z. Akiki, Z. Rabah, S. Daou, S.
Assaad. (2018). Factors associated with
premenstrual syndrome and its different symptom
domains among university students in Lebanon.
[37] A. Antai, A. Udezi, E. Ekanem, U. Okon, A.
Umoiyoho. (2004). Premenstrual syndrome:
prevalence in students of the University of Calabar,
Nigeria. African journal of biomedical research.
7(2).
[38] G. Moy, V. Gupta. (2022). Menstrual Related
Headache. Stat Pearls Publishing.
Available from:
https://www.ncbi.nlm.nih.gov/books/NBK557451/
?report=classic.
[39] G. Allais, I. Castagnoli Gabellari, C. Burzio, S.
Rolando, C. De Lorenzo, O. Mana, C. Benedetto.
(2012). Premenstrual syndrome and migraine.
Neurological Sciences. 33: 111-115.
Available from: https://doi.org/10.1007/s10072-
012-1054-5.
[40] J. Kiesner, V.T. Martin. (2013). Mid‐cycle
headaches and their relationship to different patterns
of premenstrual stress symptoms. Headache: The
Journal of Head and Face Pain. 53(6): 935-946.
Available from:
https://doi.org/10.1111/head.12082.
[41] P.-C. Lin, C.-H. Ko, Y.-J. Lin, J.-Y. Yen. (2021).
Insomnia, inattention and fatigue symptoms of
women with premenstrual dysphoric disorder.
International Journal of Environmental Research
and Public Health. 18(12): 6192.
[42] M. Begum, S. Das, H.K. Sharma. (2016). Menstrual
disorders: causes and natural remedies.
Journal of Pharmaceutical, Chemical and Biologica
l Sciences . 4(2): 307-20.
Available from:
http://jpcbs.info/2016_4_2_20_Monawara.pdf.
[43] S. Sivadasan, A.N. Ali, K. Marimuthu, Z.A. Nazer,
S. Chigurupati, R. Veerasamy. (2014). Menstrual
disorders among students–an overview. Research
Journal of Pharmacy and Technology. 7(6): 704-
711.
[44] D. Choi, D.-Y. Lee, P. Lehert, I.S. Lee, S.H. Kim,
L. Dennerstein. (2010). The impact of premenstrual
symptoms on activities of daily life in Korean
women. Journal of Psychosomatic Obstetrics &
Gynecology. 31(1): 10-15.
[45] S. Stolla, A.R. Shalita, G.F. Webster, R. Kaplan, S.
Danesh, A. Penstein. (2001). The effect of the
menstrual cycle on acne. Journal of the American
Academy of Dermatology. 45(6): 957-960.
Available from:
https://www.sciencedirect.com/science/article/pii/S
019096220123641X.
[46] M. Meers, J.L. Bower, C.A. Alfano. (2020). Poor
sleep and emotion dysregulation mediate the
association between epressive and premenstrual
symptoms in young adult women. Archives of
Women's Mental Health. 23: 351-359.
Available from: https://doi.org/10.1007/s00737-
019-00984-2.
[47] A. Labrum. (1983). Hypothalamic, pineal and
pituitary factors in the premenstrual syndrome. The
Journal of Reproductive Medicine. 28(7): 438-445.
[48] J.W. Bailey, L.S. Cohen. (1999). Prevalence of
mood and anxiety disorders in women who seek
treatment for premenstrual syndrome. Journal of
women's health & gender-based medicine. 8(9):
1181-1184.
[49] E.W. Freeman, S.M. Halberstadt, K. Rickels, J.M.
Legler, H. Lin, M.D. Sammel. (2011). Core
symptoms that discriminate premenstrual syndrome.
Journal of Women's Health. 20(1): 29-35.
[50] M.A.B.S. Jami, R. Sultana, M.M. Hasan, I.J.
Ananna. (2023). Menstrual health and prevalence of
menstrual disorders among modern society females
in Dhaka, Bangladesh: a cross-sectional study.
[51] S.K. Padhy, S. Sarkar, P.B. Beherre, R. Rathi, M.
Panigrahi, P.S. Patil. (2015). Relationship of
premenstrual syndrome and premenstrual dysphoric
disorder with major depression: Relevance to
clinical practice. Indian journal of psychological
medicine. 37(2): 159-164.

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 136
[52] S. Kumari, A. Sachdeva. (2016). Patterns and
predictors of premenstrual symptoms among
females working in a psychiatry hospital.
Scientifica. 2016.
Available from:
https://doi.org/10.1155/2016/6943852.
[53] D. Kustriyanti, H. Rahayu. (2020). Prevalence of
premenstrual syndrome and quality of life among
health science college student. International Journal
of Public Health Science (IJPHS). 9(1): 15-19.
[54] N. Nisar, N. Zehra, G. Haider, A.A. Munir, N.A.
Sohoo. (2008). Frequency, intensity and impact of
premenstrual syndrome in medical students. Journal
of College of Physicians and Surgeons Pakistan.
18(8): 481-4.
[55] S. Alshayeb, F. Kahal, O. Al Helwani, A. Al
Helwani, A. Torbey, S. Kadri, A. Aldarra, A.
Alsaadi, S. Al-Habal, M. Moufti. (2022). The
prevalence of various menstrual disorders and its
association with psychological stress in medical
faculties students. A Cross-sectional study.
[56] E.J. Frackiewicz, T.M. Shiovitz. (2001). Evaluation
and management of premenstrual syndrome and
premenstrual dysphoric disorder. Journal of the
American Pharmaceutical Association (1996).
41(3): 437-447.
[57] E.W. Freeman, S.M. Halberstadt, K. Rickels, J.M.
Legler, H. Lin, M.D. Sammel. (2011). Core
symptoms that discriminate premenstrual syndrome.
Journal of Women's Health. 20(1): 29-35.
Available from:
https://doi.org/10.1089/jwh.2010.2161.
[58] D.E. Rizk, M. Mosallam, S. Alyan, N. Nagelkerke.
(2006). Prevalence and impact of premenstrual
syndrome in adolescent schoolgirls in the United
Arab Emirates. Acta obstetricia et gynecologica
Scandinavica. 85(5): 589-598.
[59] F.A. Quintana-Zinn, B.W. Whitcomb, A.G.
Ronnenberg, C. Bigelow, S.C. Houghton, E.R.
Bertone-Johnson. (2017). Premenstrual symptom
patterns and behavioral risk factors in young
women: a cross-sectional study. Journal of Women's
Health. 26(10): 1099-1105.
Available from:
https://doi.org/10.1089/jwh.2016.5921.
[60] R.L. Robinson, R.W. Swindle. (2000). Premenstrual
symptom severity: impact on social functioning and
treatment-seeking behaviors. Journal of women's
health & gender-based medicine. 9(7): 757-768.
Available from: https://doi.org/10.1016/S0020-
7292(00)82807-6.
[61] R. Kroll, A.J. Rapkin. (2006). Treatment of
premenstrual disorders. Journal of Reproductive
Medicine. 51(4 Suppl):359–70.
[62] Y. Khelemsky, A. Malhotra, K. Gritsenko. (2019).
Academic Pain Medicine: A Practical Guide to
Rotations, Fellowship, and Beyond. Springer: pp.
Available from: https://doi.org/10.1007/978-3-030-
18005-8_13.
[63] E.C. Yiannakopoulou. (2015). Aspirin and NSAIDs
for breast cancer chemoprevention. European
Journal of Cancer Prevention. 24(5): 416-421.
Available from:
https://journals.lww.com/eurjcancerprev/fulltext/20
15/09000/aspirin_and_nsaids_for_breast_cancer.7.
aspx.
[64] W. Marcason. (2012). What Is the FODMAP Diet?
Journal of the Academy of Nutrition and Dietetics.
112(10):1696.
Available from:
https://doi.org/10.1016/j.jand.2012.08.005.
[65] L. Hooper, C. Bartlett, G.D. Smith, S. Ebrahim.
(2002). Systematic review of long term effects of
advice to reduce dietary salt in adults. Bmj.
325(7365): 628.
Available from:
http://www.bmj.com/content/325/7365/628.1.abstr
act.
[66] S.K. Pandit. (2022). Role of meditation and yoga in
treating Stress,Anxiety &Depression. Indian Journal
of Psychiatry. 64(Suppl 3).
Available from:
https://journals.lww.com/indianjpsychiatry/fulltext/
2022/64003/role_of_meditation_and_yoga_in_treat
ing.271.aspx.
[67] J.F. Mortola. (1992). Issues in the diagnosis and
research of premenstrual syndrome. Clinical
obstetrics and gynecology. 35(3): 587-598.
Available from:
https://journals.lww.com/clinicalobgyn/Fulltext/19
92/09000/Issues_in_the_Diagnosis_and_Research_
of.19.aspx.
[68] J.F. Mortola. (1994). A risk-benefit appraisal of
drugs used in the management of premenstrual
syndrome. Drug Safety. 10(2): 160-169.
Available from: https://doi.org/10.2165/00002018-
199410020-00005.
[69] L. Scheffers, I. Vos, E. Utens, G. Dieleman, S.
Walet, J. Escher, L. van den Berg, R.E. Team.
(2023). Physical training and healthy diet improved
bowel symptoms, quality of life and fatigue in
children with inflammatory bowel disease. Journal
of Pediatric Gastroenterology and Nutrition.
Available from:
https://journals.lww.com/jpgn/fulltext/2023/08000/
physical_training_and_healthy_diet_improved_bo
wel.16.aspx.
[70] K. Gemesi, S.L. Holzmann, B. Kaiser, M.
Wintergerst, M. Lurz, G. Groh, M. Böhm, H.
Krcmar, K. Gedrich, H. Hauner. (2022). Stress
eating: an online survey of eating behaviours,
comfort foods, and healthy food substitutes in
German adults. BMC Public Health. 22(1): 391.
Available from: https://doi.org/10.1186/s12889-
022-12787-9.
[71] M. Kabakibi, K.A. Macauley. (2019). A Web-based
Stress Reduction Program for Occupational Health.
The International Journal of Health, Wellness and
Society. 9(2): 29.
[72] Z. Ubaidillah, R.K. Rosul, R. Ilmiasih. (2023).
Benson's Relaxation Techniques to Improve Sleep
Quality in Diabetes Mellitus Patients. KnE
Medicine. 343–356-343–356.

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 137
Available from:
https://knepublishing.com/index.php/KnE-
Medicine/article/view/13069.
[73] H.T. Pham, H.-L. Chuang, C.-P. Kuo, T.-P. Yeh,
W.-C. Liao. (2021). In Electronic device use before
bedtime and sleep quality among university
students, Healthcare. MDPI. p 1091.
[74] S. Li, X. He, Z. Zhang, X. Zhang, Y. Niu, A. Steel,
H. Wang. (2023). Efficacy and safety of a facial
serum and a mask containing salicylic acid and
lipohydroxy acid in acne management: A
randomized controlled trial. Journal of Cosmetic
Dermatology.
Available from: https://doi.org/10.1111/jocd.15746.
[75] G. Kosmoski, D. Miller, C. Coret, E. Atillasoy.
(2022). A Topical Combination Regimen of
Benzoyl Peroxide and Retinol Moisturizer for Mild
to Moderate Acne. Journal of Drugs in
Dermatology: JDD. 21(12): 1340-1346.
[76] Y. Funakami, E. Itoh, T. Hata, T. Wada, S. Ichida.
(2010). Specific alternation of rhythm in
temperature (SART) stress-induced irritable bowel
syndrome-like changes in mice and effects of drugs.
Biological and Pharmaceutical Bulletin. 33(9):
1545-1549.
[77] M.R. Lappin, A. Zug, C. Hovenga, J. Gagne, E.
Cross. (2022). Efficacy of feeding a diet containing
a high concentration of mixed fiber sources for
management of acute large bowel diarrhea in dogs
in shelters. Journal of Veterinary Internal Medicine.
36(2): 488-492.
Available from: https://doi.org/10.1111/jvim.16360.
[78] M.G. Puoti, A. Assa, M. Benninga, I.J. Broekaert,
F.J.M. Carpi, M.D. Saccomani, J. Dolinsek, M.
Homan, E. Mas, E. Miele. (2023). Drugs in focus:
Domperidone. Journal of Pediatric
Gastroenterology and Nutrition. 77(2): e13-e22.
Available from:
https://journals.lww.com/jpgn/fulltext/2023/08000/
drugs_in_focus__domperidone.4.aspx.
[79] B. Das, D. Pal, A. Haldar. (2019). Premenstrual
syndrome: a review of the literature. Gynecology.
21(2):38–43.
Available from:
https://gynecology.orscience.ru/2079-
5831/article/view/33475.
[80] J.M. Ferguson. (2001). SSRI antidepressant
medications: adverse effects and tolerability.
Primary care companion to the Journal of clinical
psychiatry. 3(1): 22.
[81] A. Davis, J. Robson. (2016). The dangers of
NSAIDs: look both ways. Vol. 66, The British
journal of general practice:The journal of the Royal
College of General Practitioners. England. p. 172–
3.
[82] J.C. De Jong, P.B. Van Den Berg, H. Tobi, L.T. De
Jong. (2003). Combined use of SSRIs and NSAIDs
increases the risk of gastrointestinal adverse effects.
British journal of clinical pharmacology. 55(6):
591-595.
[83] R. Srivastava, A. Singh, S. Shukla. (2013).
Chemical investigation and pharmaceutical action of
Cyperus rotundus-a review. Journal of Biologically
Active Products from Nature. 3(3): 166-172.
[84] A.M. Peerzada, H.H. Ali, M. Naeem, M. Latif, A.H.
Bukhari, A. Tanveer. (2015). Cyperus rotundus L.:
Traditional uses, phytochemistry, and
pharmacological activities. Journal of
ethnopharmacology. 174: 540-560.
Available from:
http://dx.doi.org/10.1016/j.jep.2015.08.012.
[85] N. Nuning, J. Jamsari, H.T. Djong, B. Hendr.
(2016). Skeleton Development Of Mice (Mus
Musculus L) Threated With Nutgrass (Cyperus
rotundus) Extract. In: The USR International
Seminar On Food Security. Bandar Lampung,
Lampung, Indonesia. p. 245–52.
Available from:
http://repository.lppm.unila.ac.id/2528/1
[86] N. Singh, B. Pandey, P. Verma, M. Bhalla, M. Gilca.
(2012). Phyto-pharmacotherapeutics of Cyperus
rotundus Linn.(Motha): an overview.
Available from:
https://api.semanticscholar.org/CorpusID:4586837
6.
[87] P.B. Shamkuwar, A.H. Hoshamani, I.D. Gonjari.
(2012). Antispasmodic effect of Cyperus rotundus
L.(Cyperaceae) in diarrhoea. Der Pharmacia Lettre.
4(2): 522-524.
[88] S. Uddin, K. Mondal, J. Shilpi, M. Rahman. (2006).
Antidiarrhoeal activity of Cyperus rotundus.
Fitoterapia. 77(2): 134-136.
[89] F.G. Rocha, M. de Mello Brandenburg, P.L.
Pawloski, B. da Silva Soley, S.C.A. Costa, C.C.
Meinerz, I.P. Baretta, M.F. Otuki, D.A. Cabrini.
(2020). Preclinical study of the topical anti-
inflammatory activity of Cyperus rotundus L.
extract (Cyperaceae) in models of skin
inflammation. Journal of ethnopharmacology. 254:
112709.
Available from:
https://doi.org/10.1016/j.jep.2020.112709.
[90] E.S. Fernandes, E.S. Ferro, G. Simão, G. Alves de
Góis, J. Arbiser, S.K. Pereira Costa. (2022). Current
challenges in inflammation and pain biology: The
role of natural and synthetic compounds. Frontiers
in Physiology. 13: 1008538.
[91] B. Das, D. Pal, A. Halder. (2015). A review on
Cyperus rotundus as a tremendous source of
pharmacologically active herbal medicine.
International Journal of Green Pharmacy (IJGP).
9(4).
[92] M.Z. Imam, C.D. Sumi. (2014). Evaluation of
antinociceptive activity of hydromethanol extract of
Cyperus rotundus in mice. BMC complementary
and alternative medicine. 14(1): 1-5.
[93] N. Singh, B. Pandey, P. Verma, M. Bhalla, M. Gilca.
(2012). Phyto-pharmacotherapeutics of Cyperus
rotundus Linn.(Motha): an overview.
[94] N. Singh, V. Kulshrestha, M. Gupta, K. Bhargava.
(1970). A pharmacological study of Cyperus
rotundus. The Indian journal of medical research.
58(1): 103-109.
[95] F. Wang, S. Zhang, J. Zhang, F. Yuan. (2022).
Systematic review of ethnomedicine,

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 138
phytochemistry, and pharmacology of Cyperi
Rhizoma. Frontiers in pharmacology. 13: 965902.
[96] G.-f. Hao, M.-q. Tang, Y.-j. Wei, F.-y. Che, L.-j.
Qian. (2017). Determination of antidepressant
activity of Cyperus rotundus L extract in rats.
Tropical Journal of Pharmaceutical Research.
16(4): 867-871.
[97] A.E. Al-Snafi. (2016). A review on Cyperus
rotundus A potential medicinal plant. International
Organization of Scientific Research : Journal of
Pharmacy. 6(7): 32-48.
[98] F. Shoaee, M. Pouredalati, S. Dadshahi, P. Parvin,
M. Bolourian, A. Kiani, A. Tavakolian, F. Vafisani.
(2020). Evaluation of non-pharmacological
strategies, therapeutic and cognitive-behavioral
interventions in the treatment of premenstrual
syndrome: a review study. International Journal of
Pediatrics. 8(2): 10929-10939.
[99] P. Basnet, N. Skalko-Basnet. (2011). Curcumin: an
anti-inflammatory molecule from a curry spice on
the path to cancer treatment. Molecules. 16(6):
4567-4598.
[100] A. AloK, I.D. Singh, S. Singh, M. Kishore, P.C. Jha.
(2015). Curcumin–pharmacological actions and its
role in oral submucous fibrosis: a review. Journal of
Clinical and Diagnostic Research: JCDR. 9(10):
ZE01.
[101] K. Shimizu, M. Funamoto, Y. Sunagawa, S.
Shimizu, Y. Katanasaka, Y. Miyazaki, H. Wada, K.
Hasegawa, T. Morimoto. (2019). Anti-inflammatory
action of curcumin and its use in the treatment of
lifestyle-related diseases. European Cardiology
Review. 14(2): 117.
Available from:
https://doi.org/10.15420/ecr.2019.17.2.
[102] N.S. Tabari, M. Kheirkhah, F. Mojab, M. Salehi.
(2020). An investigation of the effect of curcumin
(turmeric) capsule on the severity and duration of
dysmenorrhea in students of Iran University of
Medical Sciences. Journal of evolution of medical
and dental sciences. 9(46): 3444-3451.
[103] L. Arabnezhad, M. Mohammadifard, L. Rahmani, Z.
Majidi, G.A. Ferns, A. Bahrami. (2022). Effects of
curcumin supplementation on vitamin D levels in
women with premenstrual syndrome and
dysmenorrhea: a randomized controlled study. BMC
complementary medicine and therapies. 22(1): 19.
[104] N. Maleki-Saghooni, F.Z. Karimi, Z.B. Moghadam,
K.M. Najmabadi. (2018). The effectiveness and
safety of Iranian herbal medicines for treatment of
premenstrual syndrome: A systematic review.
Avicenna journal of phytomedicine. 8(2): 96.
[105] A. Talebpour, M. Mohammadifard, R. Zare
Feyzabadi, S. Mahmoudzadeh, H. Rezapour, M.
Saharkhiz, M. Tajik, G.A. Ferns, A. Bahrami.
(2023). Effect of curcumin on inflammatory
biomarkers and iron profile in patients with
premenstrual syndrome and dysmenorrhea: A
randomized controlled trial. Physiological Reports.
11(13): e15763.
[106] Sheba MD, S N V. (2021). Exploring the Pharmaco-
Therapeutic Efficacy of Kumari (Aloe Vera L.) on
the Reproductive System. World
Journal of Pharmacy and Pharmaceutical.
10(4):1593.
Available from: www.wjpr.net.
[107] A. Manouchehri, S. Abbaszadeh, M. Ahmadi, F.K.
Nejad, M. Bahmani, N. Dastyar. (2023). Polycystic
ovaries and herbal remedies: A systematic review.
JBRA assisted reproduction. 27(1): 85.
[108] S. Sardashti, T.S.H. Abadi, S.S.H. Abadi, R.
Raznahan. (2020). Investigation the effect of oral
Aloe Vera gel pills supplementation on the intensity
of primary menstrual pain (Dysmenorrhea). Balneo
Research Journal. 11(2): 120-124.
[109] S. Khazaiyan. (2012). The effect of oral aloe vera
gel on the intensity of primary dysmenorrhea.
Medical-Surgical Nursing Journal. 1(1): 49-54.
[110] J. Nai, C. Zhang, H. Shao, B. Li, H. Li, L. Gao, M.
Dai, L. Zhu, H. Sheng. (2021). Extraction, structure,
pharmacological activities and drug carrier
applications of Angelica sinensis polysaccharide.
International Journal of Biological Macromolecules.
183: 2337-2353.
[111] P. Zeng, J. Li, Y. Chen, L. Zhang. (2019). The
structures and biological functions of
polysaccharides from traditional Chinese herbs.
Progress in molecular biology and translational
science. 163: 423-444.
[112] W.-L. Wei, R. Zeng, C.-M. Gu, Y. Qu, L.-F. Huang.
(2016). Angelica sinensis in China-A review of
botanical profile, ethnopharmacology,
phytochemistry and chemical analysis. Journal of
ethnopharmacology. 190: 116-141.
[113] M.S. Butt, M.T. Sultan. (2011). Ginger and its health
claims: molecular aspects. Critical reviews in food
science and nutrition. 51(5): 383-393.
[114] J. Shen, J. Zhang, M. Deng, Y. Liu, Y. Hu, L. Zhang.
(2016). The antidepressant effect of Angelica
sinensis extracts on chronic unpredictable mild
stress-induced depression is mediated via the
upregulation of the BDNF signaling pathway in rats.
Evidence-based complementary and alternative
medicine. 2016.
[115] W. Gong, S. Zhu, C. Chen, Q. Yin, X. Li, G. Du, Y.
Zhou, X. Qin. (2019). The anti-depression effect of
angelicae sinensis radix is related to the
pharmacological activity of modulating the
hematological anomalies. Frontiers in
pharmacology. 10: 192.
[116] T.-S. Yeh, C.-C. Huang, H.-L. Chuang, M.-C. Hsu.
(2014). Angelica sinensis improves exercise
performance and protects against physical fatigue in
trained mice. Molecules. 19(4): 3926-3939.
[117] Q. Liu, Y. Li. (2018). Anti-fatigue Effects of
Polysaccharide from Angelica sinensis. IOP
Conference Series: Materials Science and
Engineering. 392(5).
[118] J.M. Bokelmann. (2022). Dong Quai (Angelica
sinensis): Root. Medicinal Herbs in Primary Care.
Editor. Elsevier. p. 309–15. Available from:
https://www.sciencedirect.com/science/article/pii/B
9780323846769000404.
[119] H. Chang, H. Han, P. Tu. (1999). Chemical
constituents and pharmacological effects of

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 139
safflower. Xiandai Yaowu Yu Linchuang. 14: 201-
203.
[120] J. Dhanik, N. Arya, V. Nand. (2017). A review on
Zingiber officinale. Journal of Pharmacognosy and
phytochemistry. 6(3): 174-184.
[121] Q.-Q. Mao, X.-Y. Xu, S.-Y. Cao, R.-Y. Gan, H.
Corke, T. Beta, H.-B. Li. (2019). Bioactive
compounds and bioactivities of ginger (Zingiber
officinale Roscoe). Foods. 8(6): 185.
[122] S. Khayat, M. Kheirkhah, Z. Behboodi Moghadam,
H. Fanaei, A. Kasaeian, M. Javadimehr. (2014).
Effect of treatment with ginger on the severity of
premenstrual syndrome symptoms. International
Scholarly Research Notices.
[123] Z. Mahmoudpour, J. Shokri, M. Kamalinejad, N.
Meftah, S. Khafri, S.A. Mozaffarpur, H. Shirafkan.
(2019). The efficacy of a Persian herbal formulation
on functional bloating: A double-blind randomized
controlled trial. Journal of Integrative Medicine.
17(5): 344-350.
Available from:
https://www.sciencedirect.com/science/article/pii/S
2095496419300731.
[124] A. Giacosa, D. Guido, M. Grassi, A. Riva, P.
Morazzoni, E. Bombardelli, S. Perna, M.A. Faliva,
M. Rondanelli. (2015). The effect of ginger
(Zingiber officinalis) and artichoke (Cynara
cardunculus) extract supplementation on functional
dyspepsia: a randomised, double-blind, and
placebo-controlled clinical trial. Evidence-based
complementary and alternative medicine. 2015.
Available from:
https://doi.org/10.1155/2015/915087.
[125] W. Tianthong, V. Phupong. (2018). A randomized,
double-blind, placebo-controlled trial on the
efficacy of ginger in the prevention of abdominal
distention in post cesarean section patients.
Scientific reports. 8(1): 6835.
https://doi.org/10.1038/s41598-018-25200-6.
[126] M. Yuki, Y. Komazawa, Y. Kobayashi, M.
Kusunoki, Y. Takahashi, S. Nakashima, G. Uno, I.
Ikuma, T. Shizuku, Y. Kinoshita. (2015). Effects of
Daikenchuto on abdominal bloating accompanied
by chronic constipation: a prospective, single-center
randomized open trial. Current Therapeutic
Research. 77: 58-62.
Available from:
https://www.sciencedirect.com/science/article/pii/S
0011393X15000065.
[127] C.D. Black, M.P. Herring, D.J. Hurley, P.J.
O'Connor. (2010). Ginger (Zingiber officinale)
reduces muscle pain caused by eccentric exercise.
The journal of pain. 11(9): 894-903.
[128] P. Rahnama, A. Montazeri, H.F. Huseini, S.
Kianbakht, M. Naseri. (2012). Effect of Zingiber
officinale R. rhizomes (ginger) on pain relief in
primary dysmenorrhea: a placebo randomized trial.
BMC complementary and alternative medicine. 12:
1-7.
[129] F. Kashefi, M. Khajehei, M. Tabatabaeichehr, M.
Alavinia, J. Asili. (2014). Comparison of the effect
of ginger and zinc sulfate on primary dysmenorrhea:
a placebo-controlled randomized trial. Pain
Management Nursing. 15(4): 826-833.
[130] S. Bagheri, L. Kashani. (2021). Therapeutic
Application of Saffron for Improvement of
Women’s Health: A Review of Literature. Journal of
Iranian Medical Council.
[131] M. Irani, A. Rahmanian, N. Soltani. (2023). Efficacy
of Saffron (Crocus sativus L.) in Premenstrual
Syndrome, Labor, Childbirth, and Menopause: A
Systematic Review of Clinical Trials. Modern Care
Journal. 20(3).
[132] S.F. Omidkhoda, H. Hosseinzadeh. (2022). Saffron
and its active ingredients against human disorders:
A literature review on existing clinical evidence.
Iranian Journal of Basic Medical Sciences. 25(8):
913.
[133] A. Hosseini, B.M. Razavi, H. Hosseinzadeh. (2018).
Saffron (Crocus sativus) petal as a new
pharmacological target: A review. Iranian Journal of
Basic Medical Sciences. 21(11): 1091.
[134] M. Agha‐Hosseini, L. Kashani, A. Aleyaseen, A.
Ghoreishi, H. Rahmanpour, A. Zarrinara, S.
Akhondzadeh. (2008). Crocus sativus L.(saffron) in
the treatment of premenstrual syndrome: a double‐
blind, randomised and placebo‐controlled trial.
BJOG: An International Journal of Obstetrics &
Gynaecology. 115(4): 515-519.
[135] H. Fukui, K. Toyoshima, R. Komaki. (2011).
Psychological and neuroendocrinological effects of
odor of saffron (Crocus sativus). Phytomedicine.
18(8-9): 726-730.
[136] S.P. Beiranvand, N.S. Beiranvand, Z.B. Moghadam,
M. Birjandi, S. Azhari, E. Rezaei, A.N. Salehnia, S.
Beiranvand. (2016). The effect of Crocus sativus
(saffron) on the severity of premenstrual syndrome.
European Journal of Integrative Medicine. 8(1): 55-
61.
[137] A. Noorbala, S. Akhondzadeh, N. Tahmacebi-Pour,
A. Jamshidi. (2005). Hydro-alcoholic extract of
Crocus sativus L. versus fluoxetine in the treatment
of mild to moderate depression: a double-blind,
randomized pilot trial. Journal of
ethnopharmacology. 97(2): 281-284.
[138] A.A. Basti, E. Moshiri, A.-A. Noorbala, A.-H.
Jamshidi, S.H. Abbasi, S. Akhondzadeh. (2007).
Comparison of petal of Crocus sativus L. and
fluoxetine in the treatment of depressed outpatients:
a pilot double-blind randomized trial. Progress in
Neuro-Psychopharmacology and Biological
Psychiatry. 31(2): 439-442.
[139] M. Mazidi, M. Shemshian, S.H. Mousavi, A.
Norouzy, T. Kermani, T. Moghiman, A. Sadeghi, N.
Mokhber, M. Ghayour-Mobarhan, G.A. Ferns.
(2016). A double-blind, randomized and placebo-
controlled trial of Saffron (Crocus sativus L.) in the
treatment of anxiety and depression. Journal of
Complementary and Integrative Medicine. 13(2):
195-199.
[140] K. Nahid, M. Fariborz, G. Ataolah, S. Solokian.
(2009). The effect of an Iranian herbal drug on
primary dysmenorrhea: a clinical controlled trial.
Journal of midwifery & women's health. 54(5): 401-
404.

International Journal of Chemical and Biochemical Sciences (IJCBS), 25(18) (2024): 120-140
Roni et al., 2024 140
[141] M. Umadevi, R. Rajeswari, C.S. Rahale, S.
Selvavenkadesh, R. Pushpa, K.S. Kumar, D.
Bhowmik. (2012). Traditional and medicinal uses of
Withania somnifera. The pharma innovation. 1(9,
Part A): 102.
[142] L.-C. Mishra, B.B. Singh, S. Dagenais. (2000).
Scientific basis for the therapeutic use of Withania
somnifera (ashwagandha): a review. Alternative
medicine review. 5(4): 334-346.
[143] G.L. Gupta, A. Rana. (2007). PHCOG MAG.: Plant
review Withania somnifera (Ashwagandha): A
review. Pharmacognosy Reviews. 1(1): 129-136.
[144] M. Adiga, S. Kumar. (2022). Management Of Pre
Menstrual Syndrome With Combined Ayurveda
Interventions (Ashwagandha Vati And Satvavajaya
Chikitsa)-An Open Label Single Arm Clinical
Study. Annals of Ayurvedic Medicine. 11(1): 48-
48.
[145] H. Kour, I. Kaur. (2017). International Journal of
Ayurveda and Pharmaceutical Chemistry. 7(3):15–
21.
[146] A. VACHASPATI. (2017). Clinical Study on
Efficacy of Ashwagandha Vati and Satvavajaya
Chikitsa in the Management of Chittodvega in Pre
Menstrual Syndrome.
Available from:
https://search.proquest.com/openview/10bfa16e177
e7cb4eeb06515d35d6220/1?pqorigsite=gscholar&c
bl=2026366&diss=y.
[147] A.K. Sinha. (2020). Chemical Analysis Of
Ashwagandha With Its Applications Especially As
Antioxidant & Anti Stress Agent. 7(10):3191–6.
[148] J. Salve, S. Pate, K. Debnath, D. Langade, D.G.
Langade. (2019). Adaptogenic and anxiolytic effects
of ashwagandha root extract in healthy adults: a
double-blind, randomized, placebo-controlled
clinical study. Cureus. 11(12).