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Jppres24.1989 - 12.6.1090 - Mashitah Et Al.

This systematic review evaluates the anti-obesity activity of Cymbopogon citratus (lemongrass) through various studies conducted from 2003 to 2023. The findings suggest that the anti-obesity effects are attributed to its polyphenol content, essential oils, and dietary fiber, which inhibit digestive enzymes, suppress appetite, and modulate lipid metabolism. The review highlights the need for further research to fully understand the mechanisms behind these effects.
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0% found this document useful (0 votes)
23 views21 pages

Jppres24.1989 - 12.6.1090 - Mashitah Et Al.

This systematic review evaluates the anti-obesity activity of Cymbopogon citratus (lemongrass) through various studies conducted from 2003 to 2023. The findings suggest that the anti-obesity effects are attributed to its polyphenol content, essential oils, and dietary fiber, which inhibit digestive enzymes, suppress appetite, and modulate lipid metabolism. The review highlights the need for further research to fully understand the mechanisms behind these effects.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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© 2024 Journal of Pharmacy & Pharmacognosy Research, 12 (6), 1090-1110, 2024

ISSN 0719-4250
https://jppres.com

DOI: https://doi.org/10.56499/jppres24.1989_12.6.1090

Review

Anti-obesity activity of Cymbopogon citratus (lemongrass):


A systematic review
[Actividad antiobesidad de Cymbopogon citratus (hierba limón): Una revisión sistemática]
Musthika Wida Mashitah1,2*, Nashi Widodo3, Nur Permatasari4, Achmad Rudijanto5
1Department of Nursing, Faculty of Health Sciences, Institute of Technology, Science and Health Dr. Soepraoen Hospital, Malang, 65147, Indonesia.
2Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia.
3Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, 65145, Indonesia.
4Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia.
5Division of Endocrinology and Metabolic Disease, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya/Dr. Saiful Anwar Hospital,

Malang, 65145, Indonesia.


*E-mail: [email protected]

Abstract
Context: Obesity represents a significant global health challenge. The limited efficacy and possible side effects of available anti-obesity agents highlight the
need to find new, effective, and safe agents. Lemongrass (Cymbopogon citratus) is an aromatic herbal plant traditionally used as an anti-obesity agent, but
previous review studies did not explain the mechanism in detail.
Aims: To evaluate the anti-obesity activity of C. citratus in vitro, in vivo, and in humans.
Methods: Full-text relevant articles published between 2003 and 2023 were searched through Google Scholar, PubMed, and Scopus. The American Dietetic
Association (ADA) quality criteria checklist was used to assess the risk of bias. Data were systematically analysed and presented in tables and flowcharts.
Results: Eighteen articles met the inclusion criteria. The anti-obesity activity of C. citratus could come from various parts of the plant (leaves, stalks, roots, or
whole plant). Its hydroalcoholic-based extract was rich in polyphenols, which had anti-obesity activity through inhibiting digestive enzymes, appetite
suppression, modulation of lipid metabolism, and adipogenesis inhibition. Its essential oil and citral had anti-obesity activity through energy expenditure
stimulation, lipid metabolism modulation, and adipogenesis inhibition. Dietary fibre from C. citratus had anti-obesity activity by inhibiting digestive enzymes
and modulating lipid metabolism.
Conclusions: The anti-obesity activity of C. citratus could come from its polyphenol content, essential oil, or fibre through the same or different mechanisms,
namely inhibition of digestive enzymes, suppression of appetite, modulation of lipid metabolism, inhibition of adipogenesis, and stimulation of energy
expenditure.
Keywords: anti-obesity; Cymbopogon citratus; lemongrass.

Resumen
Contexto: La obesidad representa un importante desafío para la salud mundial. La eficacia limitada y los posibles efectos secundarios de los agentes contra la
obesidad disponibles resaltan la necesidad de encontrar agentes nuevos, eficaces y seguros. La hierba limón (Cymbopogon citratus) es una planta herbaria
aromática utilizada tradicionalmente como agente contra la obesidad, pero estudios de revisión anteriores no explicaron el mecanismo en detalle.
Objetivos: Evaluar la actividad antiobesidad de C. citratus in vitro, in vivo y en humanos.
Métodos: Se buscaron artículos relevantes de texto completo publicados entre 2003 y 2023 a través de Google Scholar, PubMed y Scopus. Se utilizó la lista de
verificación de criterios de calidad de la Asociación Dietética Americana (ADA) para evaluar el riesgo de sesgo. Los datos fueron analizados sistemáticamente
y presentados en tablas y diagramas de flujo.
Resultados: Dieciocho artículos cumplieron los criterios de inclusión. La actividad antiobesidad de C. citratus podría provenir de varias partes de la planta
(hojas, tallos, raíces o planta entera). Su extracto de base hidroalcohólica era rico en polifenoles, que tenían actividad antiobesidad mediante la inhibición de
las enzimas digestivas, la supresión del apetito, la modulación del metabolismo de los lípidos y la inhibición de la adipogénesis. Su aceite esencial y citral
tenían actividad antiobesidad mediante la estimulación del gasto energético, la modulación del metabolismo de los lípidos y la inhibición de la adipogénesis.
La fibra dietética procedente de C. citratus tenía actividad antiobesidad al inhibir las enzimas digestivas y modular el metabolismo de los lípidos.
Conclusiones: La actividad antiobesidad de C. citratus podría proceder de su contenido en polifenoles, aceite esencial o fibra a través de los mismos o
diferentes mecanismos, a saber, inhibición de las enzimas digestivas, supresión del apetito, modulación del metabolismo lipídico, inhibición de la
adipogénesis y estimulación del gasto energético.

Palabras Clave: antiobesidad; Cymbopogon citratus; hierba limón.

ARTICLE INFO AUTHOR INFO


Received: February 11, 2024. ORCID: 0000-0001-8711-5318 (MWM) 0000-0002-1630-1380 (NP)
Accepted: June 2, 2024. 0000-0002-1126-498X (NW) 0000-0003-3380-3208 (AR)
Available Online: June 19, 2024.
Mashitah et al. Anti-obesity activity of Cymbopogon citratus

INTRODUCTION termine/topiramate, naltrexone/bupropion, setmela-


notide, liraglutide and semaglutide, and orlistat.
Obesity represents a critical global health chal- Phentermine is a sympathomimetic that stimulates
lenge, posing substantial risks to human health. The noradrenaline and suppresses appetite (anorexigenic
prevalence of obesity worldwide has increased in the mechanism). Topiramate is an antiepileptic, which is
last 50 years, reaching pandemic levels (Blüher, 2019). also used for migraine therapy. Naltrexone is an opi-
In 2016, more than 1.9 billion (39%) adults (≥18 years) ate antagonist that blocks the autoinhibitory opioid-
in the world were overweight, and 650 million (13%) mediated proopiomelanocortin (POMC) receptor and
were obese. Overweight and obesity are major risk bupropion selectively inhibits the reuptake of dopa-
factors for chronic diseases such as cardiovascular mine and noradrenaline thereby reducing food intake
disease, diabetes, musculoskeletal disorders, and and increasing energy release. Setmelanotide is a
some cancers. More than 4 million people died every melanocortin-4 receptor (MC4R) agonist that acts on
year from being overweight and obese in 2017 (WHO, the paraventricular nucleus of the hypothalamus and
2021). the lateral hypothalamic area to suppress appetite.
Obesity is excessive fat accumulation due to ener- Liraglutide and semaglutide are glucagon-like pep-
gy imbalance, where energy intake exceeds energy tide-1 (GLP1) receptor agonists with incretin effects
expenditure (WHO, 2021). When energy intake chron- interfering with glucose homeostasis, food intake, and
ically exceeds energy expenditure, almost all excess satiety. Orlistat inhibits pancreatic and gastric lipase,
energy is stored as triglycerides in white adipose tis- reducing fat absorption (Gjermeni et al., 2021; Lin and
sue (WAT). An increase in adipocyte mass can occur Li, 2021).
due to hypertrophy and hyperplasia of adipocytes, The limited efficacy, possible side effects, and drug
which subsequently causes adipocyte dysfunction, interactions of available anti-obesity agents highlight
including insulin resistance, production of adi- the need to find new effective and safe anti-obesity
pokines, free fatty acids, and inflammatory mediators agents (Lin and Li, 2021). Many nutraceutical and
(Ferranti and Mozaffarian, 2008; Jakab et al., 2021; botanical dietary supplements are used to modulate
Spiegelman and Flier, 1996). body weight and its associated complications because
Current management of obesity includes lifestyle they provide many benefits with few or no side ef-
modification (dietary interventions and physical ac- fects (Bertuccioli et al., 2021). Phytopharmaceutical
tivity), medication, and bariatric surgery. Lifestyle compounds and preparations, based on their natural
modification is recommended as a cornerstone of origin, easy availability, cost-effectiveness, and bene-
obesity management, but many patients do not ficial traditional use based on accumulated experi-
achieve long-term benefits due to difficulties with ence, have been extensively explored to reduce the
compliance. Pharmacotherapy plays a minor role global burden of obesity (Borah et al., 2021). In addi-
because of the side effects that can be caused; it is tion to identifying and quantifying potential bioactive
considered given to patients with a body mass index compounds and proving their efficacy at the cellular
(BMI) ≥30 kg/m2 and a BMI ≥27 kg/m2 with comor- and molecular level (Sandner et al., 2020).
bidities such as type 2 diabetes mellitus. Bariatric Lemongrass [Cymbopogon citratus (DC.) Stapf, Po-
surgery is indicated for severe obesity or with comor- aceae] is an aromatic herbal plant widely used in trop-
bidities and results in substantial and sustained ical countries and commonly used as a cooking ingre-
weight loss with resolution of diabetes mellitus. Still, dient (Ajayi et al., 2016; Olorunnisola et al., 2014). In
costs are high, and the risk of serious complications is Asia, South America, and Africa, C. citratus leaves are
small. The balance of benefits against risks of these traditionally used for tea, infusion, or decoction. The
methods needs to be considered for therapeutic deci- essential active substances in C. citratus are phenolics
sions (Gadde et al., 2018; Zhang et al., 2014). (flavonoids, phenols, tannins), alkaloids, terpenoids
In general, pharmacotherapy is aimed at increas- (essential oils), saponins, minerals, and vitamins (Ek-
ing satiety and decreasing hunger (suppressing appe- penyong et al., 2015; Oladeji et al., 2019). Citral is the
tite), inhibiting fat absorption, or increasing catabo- most abundant essential oil (65-85%) and a pharmaco-
lism (stimulating thermogenesis and fat mobilisation) logically and physiologically important component of
(Gjermeni et al., 2021; Gurevich-Panigrahi et al., 2009; C. citratus (Ekpenyong et al., 2014). Other essential
Zhang et al., 2014). The appetite suppressant is divid- oils are myrcene, geraniol, nerol, citronellol
ed into noradrenergic, serotoninergic, and mixed (cymbopogonol and cymbopogone), and limonene.
agents (Gurevich-Panigrahi et al., 2009). Currently, The leaves contain essential bioactive compounds that
there are six main anti-obesity drugs approved by the provide anti-obesity, anti-bacterial, anti-fungal, anti-
Food and Drug Administration (FDA), namely phen- nociceptive, antioxidants, anti-diarrheal, and anti-

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

inflammatory effects (Merchaoui et al., 2018; Oladeji tracts/phytochemicals from different plants were not
et al., 2019). included.
The previous reviews about C. citratus focused on
Search strategy
its general pharmacological activities and stated one
of them as anti-obesity but did not explain in detail Two reviewers independently searched the data-
the mechanism of its anti-obesity activity (Ekpenyong bases and identified literature through other sources
et al., 2015; Kiani et al., 2022; Oladeji et al., 2019; Olo- in Rayyan (http://rayyan.qcri.org), a web-based plat-
runnisola et al., 2014; Tibenda et al., 2022). Other pre- form for accelerating the initial screening of abstracts
vious review studies about medicinal plants for the and titles that incorporates a high level of usability as
treatment of obesity stated that C. citratus was includ- it filters duplicates (Ouzzani et al., 2016). Searches
ed but also did not explain the details of its anti- were exported from the database to Rayyan in "txt"
obesity mechanism (Cercato et al., 2015; de Freitas and "ris" formats. The reviewers independently screen
Junior and de Almeida, 2017). Therefore, this review the retrieved abstracts according to the specified crite-
aims to be the first systematic review investigating the ria. Specifically, the population, type of intervention,
anti-obesity activity of C. citratus and its phytochemi- and outcomes assessed will be assessed during the
cals from previously published studies in vitro, in vivo, selection process. Any disagreements were resolved
and in humans. through consensus among the other authors.

MATERIAL AND METHODS Selection process


All included studies underwent a three-stage as-
Information sources sessment to collect the necessary data. The first stage
The reviewers searched articles and extracted data of the selection process is collecting general infor-
from studies that met the criteria. Studies were re- mation about the year of publication, the country, and
trieved on Google Scholar, PubMed, and Scopus with the period during which the research was conducted.
the keywords: "Cymbopogon citratus" OR "lemongrass" In the second stage, each article was assessed regard-
OR "citral" AND "anti-obesity" OR "hypolipidemic" ing the research design: (i) the plant part of C. citratus
OR "adipocyte". Boolean operators (OR and AND) are used or its phytochemicals and preparations, (ii) for in
used to refine search results. Articles published be- vivo studies, the experimental animal model used
tween 2003-2023 were included, and to minimise re- (normal, obesity model, or hyperlipidaemia), how the
trieval of irrelevant articles, these keywords and method induction, and its comparison, (iii) for in vitro
MeSH terms were searched within the "Ti- studies, whether the research object is adipocyte cul-
tle/Abstract" category. ture cells, lipids, or enzymes involved in lipid metab-
olism, (iv) for in human studies, the research subjects
Eligibility criteria used and the comparison, (v) the duration of the in-
tervention. In the final stage, the reviewer document-
Study eligible for the current review was original ed the anti-obesity effects observed in each study.
research with (i) the population for in vivo studies was
normal animal, obesity, or hyperlipidaemia models; The data collection process and the items
for in vitro studies was a culture of adipocytes, lipids,
or enzymes involved in lipid metabolism; for in hu- All reviewers will gather data from the included
man studies was obese or hyperlipidaemia patients, studies. The results will be organised by identifiers,
(ii) intervened by C. citratus, (iii) as compared to those including author(s), year of publication, and country
without, (iv) observing the outcome if there was an where the research was conducted. The subsequent
anti-obesity effect. The specific inclusion criteria were data set will include detailed characteristics of each
(i) studies that used a randomised controlled trial study, including the plant part of C. citratus used or
design, (ii) administered C. citratus and its phyto- its phytochemicals, preparation, dose or concentra-
chemicals from various parts of the plant and various tion, research objectives, population, and duration of
preparations, (iii) showed anti-obesity activity as the intervention. Results from the intervention and con-
outcome, anti-obesity activity was focused on its rela- trol groups will be extracted and categorised based on
tion to lipid metabolism. Research with irrelevant observed anti-obesity effects, organised into groups
topics and incomplete manuscripts would be exclud- reflecting different anti-obesity mechanisms or activi-
ed from this review. Studies using models of obesity ties such as inhibition of digestive enzymes, appetite
or hyperlipidaemia accompanied by other metabolic suppression, inhibition of adipocyte differentiation, or
syndromes, such as diabetes and cardiovascular dis- regulation of lipid metabolism. Conclusions will be
ease, were excluded. C. citratus extract and its phyto- formulated based on the findings documented in the
chemicals in combination with ex- manuscript and validated by the reviewing team.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Study risk of bias assessment process allows all reviewers to access and correct data
synthesis results simultaneously, significantly reduc-
The included studies' quality and risk of bias were
ing the chances of errors in our collaborative data
assessed using the American Dietetic Association
synthesis.
(ADA) quality criteria checklist, which includes sepa-
rate sections for primary research on human subjects
and in vitro and in vivo research on non-human sub- RESULTS
jects. Each section contains 14 questions (Academy of
Nutrition and Dietetics). Two reviewers independent- Study selection
ly conducted this assessment and discussed their A total of 1031 studies were initially retrieved
findings with other reviewers before advancing to the through databases, specifically PubMed (n = 7), Sco-
subsequent review phase. Eligible research received a pus (n = 26), and Google Scholar (n = 998). After du-
positive (+) value, indicating that the study adequate- plicates were removed, 985 studies remained. Initial-
ly addressed issues of inclusion/exclusion, bias, gen- ly, screening was based on titles and abstracts, fol-
eralizability, and data collection and analysis. Studies lowed by a full-text review. Articles were included or
were rated negatively (-) if they failed to address and excluded based on specific criteria, and reasons for
neutrally (Ф) if they were neither particularly strong exclusion were documented, e.g., review article, not
nor weak in these areas (ADA, 2008). pertinent, wrong intervention, or dual/combination
intervention. Of these, 957 studies were excluded,
Effect measures, synthesis methods, reporting bias leaving 28 for detailed full-text screening. After fur-
assessment ther exclusions, 10 articles were excluded based on
Online data processing tools, like Google sheets, the exclusion criteria, e.g., abstract only, wrong out-
will be used to tabulate the data. This tool was chosen come, wrong intervention, or wrong study design.
for its unique feature of real-time collaboration. This Thus, 18 final articles were selected for inclusion in
this systematic review (Fig. 1).

Figure 1. Flow diagram of the systematic review.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Study characteristics mg/kg/day, and citral (Modak and Mukhopadhaya,


2011) starting at a dose of 10 mg/kg/day from C.
The characteristics of the studies reviewed are
citratus decreased body weight in normal mice (Ade-
summarised in Table 1. Of the 18 articles, there were
neye and Agbaje, 2007; Dimgba et al., 2017) and hiper-
11 in vivo studies, 5 in vitro studies, 1 was a human
lipidaemia or obese models (Abdelrahman and Omar,
study, and 1 combined in vivo and in vitro methods.
2023; Agbafor and Akubugwo, 2007; da Costa et al.,
The studies reviewed varied in the parts of the C.
2015; Modak and Mukhopadhaya, 2011).
citratus plant used, the extraction types, and the active
compound used. For in vivo studies, Somparn et al.
Effect of Cymbopogon citratus on suppressing appetite
(2018) utilised a whole plant water extract, Betancourt
et al. (2015) utilised a hydroalcoholic extract from In the study by Dimgba et al. (2017), aqueous
aerial parts, Adeneye and Agbaje (2007) and Dimgba leaves extracted from C. citratus suppressed appetite
et al. (2017) used an aqueous extract from leaves, in normal Wistar rats. The amount of food consumed
Agbafor and Akubugwo (2007) employed an ethanol by a treated group with C. citratus (150, 300, and 600
extract from leaves, Furtado et al. (2011) utilised a mg/kg) significantly decreased dose-dependent
hydroalcoholic extract from leaves, and Abbas et al. across treatment periods (21 days).
(2019) developed an aqueous extract from roots. Villa-
lobos et al. (2021) used total dietary fibre fermenta- Effect of Cymbopogon citratus on lipid metabolism
tion, and Abdelrahman and Omar (2023) used C. citra- In vivo research reviewed in this study showed
tus powder; however, the specific parts of the plant that leaves ethanol extract (Agbafor and Akubugwo,
used were not specified in either study. Costa et al. 2007), aerial hydroalcoholic extract (Betancourt et al.,
(2011) used essential oils from leaves, Kumar et al. 2015), leaves hydroalcoholic extract (Furtado et al.,
(2011) used essential oils without specifying the plant 2011), root aqueous extract (Abbas et al., 2019), total
part, and Modak and Mukhopadhaya (2011) used dietary fibre (Villalobos et al., 2021), powder (Abdel-
citral. Adeneye and Agbaje (2007), Dimgba et al. rahman and Omar, 2023), and essential oil (Costa et
(2017), and Somparn et al. (2018) used normal exper- al., 2011; Kumar et al., 2011) from C. citratus decreased
imental animals, while other studies used models of total cholesterol in the hyperlipidaemia model.
obesity or hyperlipidaemia. Leaves aqueous extract (Adeneye and Agbaje, 2007)
In an in vitro study, Da Ressurreição et al. (2022) and whole plant water extract (Somparn et al., 2018)
used aqueous leaf extract on micellar to study the of C. citratus also decreased total cholesterol in normal
solubility of cholesterol. Jo et al. (2019) used ethanol rats. C. citratus whole plant water extract reduced the
extract (part of the plant used was not stated), expression of the catalysator of endogenous choles-
Ngamdokmai et al. (2021) used essential oil from stalk terol synthesis (HMGR) in normal rats (Somparn et
and citral, Sri Devi and Ashokkumar (2018) used cit- al., 2018). An in vitro study by Da Ressurreição et al.
ral, while Sprenger et al. (2022) used citral and its (2022) showed that aqueous extracts of C. citratus
isomers, and all studies used 3T3-L1 cells. A human leaves and their polyphenols (flavonoids, tannin, lu-
study by Waheed et al. (2019) used C. citratus leaf teolin, luteolin-7-O, luteolin-6-C-glucoside) had micel-
powder on hyperlipidaemia non-smoker male pa- lar destruction activity so that they could prevent
tients. cholesterol absorption in the gut. An in vitro study by
Villalobos et al. (2021) showed that propionate was
Risk of bias in studies the predominant short-chain fatty acid (SCFA) pro-
duced fermentation from C. citratus total dietary fibre,
Quality assessment was carried out using the ADA
and propionate inhibited HMGR activity in vitro.
quality checklist (ADA, 2008). No articles were ex-
cluded based on the assessment results. All of the 18 C. citratus essential oil (Kumar et al., 2011), aerial
studies reviewed had positive ratings (Table 2). hydroalcoholic extract (Betancourt et al., 2015), and
leaves hydroalcoholic extract (Furtado et al., 20111)
Results of individual studies decreased serum triglycerides in the hyperlipidaemia
model. C. citratus leaves aqueous extract (Adeneye
Effect of Cymbopogon citratus on weight loss and Agbaje, 2007) and total dietary fibre (Villalobos et
In several in vivo studies reviewed, it was proven al., 2021) decreased LDL and VLDL in normal and
that leaves aqueous extract (Adeneye and Agbaje, hyperlipidaemia models. C. citratus aerial hydroalco-
2007; Dimgba et al., 2017) starting at a dose of 125 holic extract (Betancourt et al. (2015), roots aqueous
mg/kg/day, leaves ethanol extract (Agbafor and extract (Abbas et al., 2019), and powder (Abdelrah-
Akubugwo, 2007) starting at a dose of 100 man and Omar, 2023) decreased LDL levels in the
mg/kg/day, powder 7.5% (Abdelrahman and Omar, hyperlipidaemia model and whole plant water extract
2023), essential oil (Costa et al., 2011) at a dose of 100 (Somparn et al., 2018) decreased LDL in normal rats.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Table 1. Studies on the effects of Cymbopogon citratus on obesity.

Part used/
compound Study design (population,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ intervention, and comparison)
concentration

In vivo

Adeneye and Leaf aqueous To investigate the Normal Wistar rats were divided into Four groups 42 days Leaf aqueous extract of C. citratus significantly
Agbaje (2007) extract of C. citratus hypoglycaemic and a control group given typical saline (n = 6 per group) induced weight loss in treated rats, lower fasting
(daily oral dosing of hypolipidemic effects of 10ml/kg/day and three treatment plasma glucose and lipid parameters (total
125-500mg/kg). the single, daily oral groups with 125, 250, and cholesterol, LDL-c, and VLD-c) dose-dependently
dosing of 125–500 500mg/kg/day leaf aqueous extract while raising the plasma HDL-c level (p<0.05) in the
mg/kg of fresh leaf of C. citratus, respectively. same dose-related mode but with no effect on
aqueous extract of C. plasma triglycerides level.
citratus in normal, male
Wistar rats.

Agbafor and Leaves ethanol To investigate the Albino rats were divided into four Four groups 7 days Leaves ethanol extract of C. citratus significantly
Akubugwo, (2007) extract of C. citratus hypocholesterolaemic groups. Two other groups were (n = 5 per group) lowered body weight and serum cholesterol in a
(100 and 200 mg/kg). effect of fresh leaves of negative and positive control (high dose-dependent manner compared with the
C. citratus in albino rats. egg yolk diet). Two other groups untreated group. The serum cholesterol level in the
were treated with a high egg yolk animals given the higher dose (200 mg/kg) was
diet and 100 mg/kg or 200 mg/kg almost at par with those of the animals that were
ethanol extract of C. citratus, never given the egg yolk diet (normal group).
respectively.

Costa et al. (2011) C. citratus essential To investigate the Mice were randomly assigned to two Five groups 21 days No significant changes in gross pathology, body
oil (1, 10, or 100 toxicity and control groups, saline- or Tween 80 (n = 33) weight, absolute or relative organ weights, histology
mg/kg). genotoxicity of this C. 0.01%-treated groups, or one of the (brain, heart, kidneys, liver, lungs, stomach, spleen,
citratus essential oil in three experimental groups receiving and urinary bladder), urinalysis, or clinical
male Swiss mice. C. citratus essential oil (1, 10, or 100 biochemistry were observed in treated mice relative
mg/kg). to the control groups. Blood cholesterol was reduced
after essential oil treatment at the highest dose
tested. During the 21-day acute toxicity treatment, a
slight weight loss was observed among the mice
treated with EO at 1 or 100 mg/kg, starting after 16
days of treatment.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
compound Study design (population,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ intervention, and comparison)
concentration

In vivo

Furtado et al. Leaves To evaluate the effect of Adult male Wistar rats were Five groups 24, 48, and 72 h Hydroalcoholic extract of C. citratus at 0.5 g/kg and
(2011) hydroalcoholic the hydroalcoholic randomised and divided into five (n = 6 per group) 1.0 g/kg reduced total cholesterol levels by 58% and
extract of C. citratus extract of C. citratus in groups. Group I-IV were induced 45% and triglycerides by 43% and 31%, respectively,
(0.5 g/kg and 1.0 hyperlipidaemic rats. hyperlipidaemia with Triton WR 1339 and increased the HDL fraction by 38%. and 45%,
g/kg). (tyloxapol) at a dose of 0.3 g/kg and respectively, in hyperlipidaemic rats after 48 h of
treated with saline, hydroalcoholic induction.
extract of C. citratus at 0.5 g/kg, 1.0
g/kg, and ciprofibrate, respectively.
Group 5 (saline) received only the
injection of 0.9% physiological NaCl
solution.

Kumar et al. C. citratus oil (100 and To evaluate the anti- Adult male Wistar albino rats were Five groups 8 days C. citratus oil (100 and 200 mg/kg, po.) treatment has
(2011) 200 mg/kg, po.). hyperlipidaemic activity divided into 5 groups. The first group (n = 6 per group) shown significant inhibition against dexamethasone
of C. citratus oil against of rats fed with a normal laboratory hyperlipidaemia by maintaining the serum level of
dexamethasone- diet alone served as standard cholesterol, triglycerides, and atherogenic index near
induced control. The second group of rats the normal levels.
hyperlipidaemia in rats. was administered with
dexamethasone (10 mg/kg, sc.) for 8
consecutive days and served as
pathogenic control. The third,
fourth, and fifth groups of rats
received dexamethasone (10 mg/kg,
sc.) and simultaneously treated
orally with 10 mg/kg atorvastatin,
100 mg/kg C. citratus oil and 200
mg/kg C. citratus oil, respectively, for
8 consecutive days.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
compound Study design (population,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ intervention, and comparison)
concentration

In vivo

Modak and Citral (10, 15, and To assess the effects of citral In five groups of male Sprague–Dawley Five groups 28 days Citral-treated groups showed a dose-dependent
Mukhopadhaya 20 mg/kg body – an inhibitor of rats, 4 were maintained on an energy- (n = 10 per group) reduction in body weight gain. They significantly had
(2011) weight). retinaldehyde intense, palatable, fat diet for– 42 days, lower fasting glucose levels, improved glucose tolerance,
dehydrogenase (the primary while 1 was the control. After obesity had higher metabolic rate (increased energy dissipation), and
enzyme metabolising been induced, 3 groups were treated smaller adipocytes (reduced lipid accumulation) after
retinaldehyde), on body with daily doses of citral (10, 15, and 20 citral administration.
weight, glucose tolerance, mg/kg body weight) for 28 days.
fasting plasma glucose and
insulin levels, metabolic
rate, adipocyte size, and
morphology in a diet-
induced model of obesity.

Betancourt et al. Hydroalcoholic To evaluate the lipid- Six experimental groups of C57BL/6J Six groups 24 and 48 h C. citratus extract at the doses studied in the model of
(2015) extract of C. lowering effect of C. citratus male mice were formed: Group I (n = 8 per group) acute hyperlipidaemia presents hypolipidaemic activity.
citratus aerial in a model of acute corresponded to the negative control, II Cholesterol, TAG, and VLDL variables for groups V and VI
part (400 and 600 hyperlipidaemia induced by to the control group of hyperlipidaemia, showed significant differences to the control group of
mg/kg). poloxamer 407, a non-ionic III and IV to control groups of simvastatin hyperlipidaemia (II) and behaved similarly to the control
detergent. and nicotinic acid, as well as, groups V groups of simvastatin (III) and nicotinic acid (IV).
and VI corresponded to the evaluated
doses of C. citratus extract.

Dimgba et al. Leaves aqueous To evaluate the appetite Twenty adults male Wistar rats were Four groups 21 days Aqueous extract of Cymbopogon citratus suppressed
(2017) extract of C. suppressing potential of divided into four groups of five rats per (n = 5 per group) appetite, reducing animal weight. The quantity of food
citratus (150, 300, aqueous leaf extract of C. group. Group I was the standard control consumed by the control group significantly increased
and 600 mg/kg). citratus in Wistar rats. and was only fed with normal rat feed across treatment periods. However, the amount of food
and water. Groups II-IV were orally consumed by the treated group with C. citratus
administered with 150, 300, and 600 significantly decreased dose-dependent across treatment
mg/kg bw, respectively. periods. The quantity of water consumed by the control
group significantly increased across treatment periods,
while a contrary observation was made on its treated
counterpart. Evaluation of the weight of rats
administered with varying doses of C. citratus indicated a
significant reduction in body weight over treatment
periods.

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Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
compound Study design (population, intervention,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ and comparison)
concentration

In vivo

Somparn et al. Whole plant C. To investigate the effects of Male Sprague-Dawley rats were divided into Five groups 30 days After treatment, the extract significantly decreased rats'
(2018) citratus water consuming C. citratus aqueous five groups of six rats each. The group I (control (n = 6 per total cholesterol, low-density lipoprotein, and
extract (250, extract on rats' atherogenic group) animals were orally administered group) atherogenic index. The expression of SREBP1c and HMGR
500, and 1000 index and antioxidant status. vehicle solution (distilled water) for 30 days. genes and proteins was also significantly lowered in the
mg/kg/day). The animals in groups II-IV were orally treated groups.
administered C. citratus water extract, which
was dissolved in distilled water, at doses of 250,
500, and 1000 mg/kg/per day for 30 days. The
animals in group V were orally administered
simvastatin dissolved in distilled water at 10
mg/kg daily.

Abbas et al. (2019) Aqueous roots To investigate the Five groups of albino mice (I: normal, II: Five groups 14 days Aqueous roots and flower extracts of C. citratus
and flower antilipidemic effect of the hyperlipidaemic control, III: positive control (n = 6 per significantly decreased cholesterol and LDL levels, and
extracts of C. aqueous extract C. citratus. with lovastatin, IV, IV, and V: hyperlipidaemic group) increased HDL levels decreased compared to the
citratus (500 with roots and flower extract, respectively). An cholesterol-induced group. Root extract had better anti-
mg/kg/day). atherogenic diet induces the hyperlipidaemic hypercholesterolemia activity.
model for 20 days or Triton for 48 hours.

Abdelrahman and C. citratus To investigate the effect of Four groups of male albino rats of Sprague Four groups 30 days C. citratus powder 7.5% significantly decreased glucose
Omar (2023) powder (7.5%). Cymbopogon citratus and Dawley (I: negative control, II: high-fat diet (n = 6 per levels, atherogenic index, body weight, total cholesterol,
orlistat on hyperlipidaemia in group, III: high-fat diet +7.5% C. citratus group) TG, LDL, ALT, AST, ALP, and liver weight, and increased
rats fed on a high-fat diet. powder, IV: high-fat diet + orlistat 60 HDL level compared with the high-fat diet group.
mg/kg/body weight).

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Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
compound Study design (population,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ intervention, and comparison)
concentration

In vivo and in vitro

Villalobos et al. Total dietary To analyse dietary fibre (DF) C. citratus dietary fiber components were Three groups Two weeks TDF in C. citratus was 65.7 g/100g, and soluble DF was 2.8
(2021) fibre (TDF) components of C. citratus, analysed, TDF was fermented in vitro; the (n = 5 per group) g/100 g. A significant amount of propionate (10.9 mM/g
extracted from investigate the potential of the primary fermentation product was TDF) was produced after TDF fermentation; propionate
C. citratus significant product from total isolated for enzyme inhibitory assays; inhibited 20.4% amylase activity and 13.1% HMG-CoA
(propionate) dietary fibre fermentation to and the postprandial blood glucose- and reductase activity in vitro. In an animal model, total
(400 mg/kg inhibit amylase and HMG-CoA cholesterol-lowering potential of TDF dietary fibre from C. citratus exhibited antihyperglycemic
BW/day). reductase in vitro, critical was determined in Sprague-Dawley rats. and cholesterol-lowering potential. Dietary fibre
enzymes of diabetes mellitus Sprague-Dawley rats were modified to a prevented the rise in fasting blood sugar levels, lowered
and hypercholesterolemia, high cholesterol, high sugar diet for two the total cholesterol, and minimised the increase in
respectively, and determine weeks, then were divided into three LDL+VLDL levels.
the serum glucose- and groups (total dietary fibre from C.
cholesterol-lowering potential citratus, acarbose + pravastatin as
of total dietary fibre in an positive control, and saline as negative
animal model. control) for two weeks while high
cholesterol and sugar maintained.

In vitro

Sri Devi and Citral (30, 40, To investigate the inhibitory 3T3-L1 preadipocytes were incubated Four groups 8 days Cells were treated with citral significantly attenuated
Ashokkumar and 50 µM). effect of citral against with adipogenesis cocktail (DMEM with 3- (differentiated intracellular triglyceride accumulation, suppressed the
(2018) adipogenic genes in 3T3-L1 isobutyl-1-methylxanthine, control without expression of PI3K/AKT, adipogenic specific transcription
cells. dexamethasone, and insulin) for 2 days citral and with citral factors (PPARγ, SREBP-1c, and FAS), and inflammatory
and then replaced with DMEM containing 30, 40, 50 µM). biomarkers (TNF-a, IL-6, and MCP-1). The anti-obesity
insulin with or without citral (30, 40 and effects of citral decrease adipogenesis by modulating
50 µM) for 8 days. adipogenic transcriptional factors, PI3K/AKT signalling,
and inflammatory signalling.

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Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
compound Study design (population,
Author and year Research objectives intervention, and No. of subjects Duration Main outcomes/results
and dosage/ comparison)
concentration

In vitro

Jo et al. (2019) Ethanol To investigate the In the differentiation period, Five groups (negative control, 7 days Ethanol extracts of C. citratus inhibit adipocyte
extracts of C. effect of ethanol extract of 3T3-L1 preadipocytes were positive control, and treated group differentiation in 3T3-L1 cells. Ethanol extracts
citratus (50, C. citratus on treated with 50, 100, and 200 with 50, 100, and 200 µg/mL of C. of C. citratus effectively suppressed
100, and 200 adipogenesis and its µg/mL of C. citratus ethanol citratus ethanol extract. intercellular lipid accumulation at non-toxic
µg/mL). underlying mechanism in extract. concentrations. They were associated with the
3T3-L1 preadipocytes. down-regulation of adipocyte-specific
transcription factors, including C/EBPα and
PPARγ, and increased phosphorylation of
AMPKα. Ethanol extracts of C. citratus
increased p21 expression, while the expression
of CDK2, cyclin A, and cyclin B1 was reduced.
Ethanol extracts of C. citratus seem to induce
G0/G1 cell cycle arrest of 3T3-L1 cells. ERK and
Akt signalling pathways were not involved in
anti-adipogenesis by ethanol extracts of C.
citratus.

Ngamdokmai et C. citratus oil To investigate the activity To investigate the preventive C. citratus oil and nine other Preventive effect: C. C. citratus oil had preventive effects on
al. (2021) (12.5 and 25 of eight essential oils effect, the samples were essential oil (ginger, black pepper, citratus oil and citral adipogenesis in a dose-dependent manner. It
µg/mL) and (including C. citratus oil) added to the media on days 3, long pepper, turmeric, tea, were added to media demonstrated inhibition of lipid accumulations
citral (50 and and two water extracts 5, and 7 after the initiation of cassumunar ginger, kaffir lime, on days 3, 5, and 7 at a concentration of 12.5 µg/mL, which was 23
100 µg/mL). from the ingredients of differentiation induction. To coffee, and mixed oil) in 12.5-200 after the initiation ± 6%, which was the lowest effective
the herbal compress evaluate the treatment effect, µg/mL compared to negative differentiation concentration of all samples tested.
together with nine the samples were incubated control, caffeine, and adrenaline induction of 3T3-L1. Citral significantly inhibited lipid accumulation
monoterpenoid with the mature adipocyte on as positive control. Treatment effect: C. compared to the control cells in preventive and
constituents (including day 9 after the initiation, and Citral and eight other citratus oil and citral treatment ways.
citral) on the 3T3-L1 their effects were measured monoterpenoid constituents were incubated with
adipocytes for preventive on day 10. (camphor, camphene, 3-carene, the mature adipocyte
and treatment effect. limonene, myrcene, alpha-pinene, on day 9 after the
beta-pinene and terpinene-4-ol) in initiation and their
50 and 100 µg/mL compared to effects were
negative control, caffeine, and measured on day 10.
adrenaline as positive control.

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Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
Author and compound Study design (population, intervention,
Research objectives No. of subjects Duration Main outcomes/results
year and dosage/ and comparison)
concentration

In vitro

Sprenger et Citral (3,7-dimethyl- To investigate the effect of C. Citral was added, achieving a final Three groups: citral 96 h Citral significantly inhibited expression of
al., (2022) 2,6-octadienal), citral citratus essential oil major concentration of 1.25 × 10-3% following the (3,7-dimethyl-2,6- sterol response binding protein 2 (SREBP2),
dimethyl acetal (1,1- components citral in the development of morphological octadienal), citral cluster of differentiation 36 (CD36/FAT), fatty
dimethoxy-3,7- modulation of adipogenesis and characteristics of mature adipocytes (after dimethyl acetal (1,1- acid binding protein 4 (FABP4), and peripilin.
dimethylocta-2,6- genetic expression in adipocytes. 96 h differentiation induction). dimethoxy-3,7- These results indicate modulation of lipid
diene), and citral dimethylocta-2,6- accumulation through decreased lipid uptake,
diethyl acetal (1 ,1- diene), and citral increased lipolysis, decreased differentiation,
diethoxy-3,7- diethyl acetal (1 ,1- and downregulated lipid biosynthesis.
dimethylocta-2,6- diethoxy-3,7-
diene) (1.25 x 10-3%). dimethylocta-2,6-
diene).

Da Aqueous extracts of C. To optimise an inexpensive An assay was carried out on the effect of Delipidified and non- - C. citratus extracts and their polyphenols can
Ressurreição citratus leaf (5-400 colourimetric method to study in delipidified infusion, non-delipidified delipidified infusion prevent cholesterol absorption in the gut by
et al. (2022) µg/mL). vitro, the micellar solubility of infusion, phenolic, flavonoid, tannin, of C. citratus: 5-400 micellar destruction and its contribution to
Phenolic fractions, cholesterol was applied to plant luteolin, luteolin-7-O-glucoside, and µg/mL. cholesterol-lowering activity.
flavonoids, and extracts (C. citratus leaf extracts, luteolin-6-C-glucoside from C. citratus in Phenolic, flavonoid, For the fraction of flavonoids, the micellar
tannin fraction (0.001- phenolic fractions, and flavonoids various concentration on micellar solubility and tannin fraction: destruction was 92.74% at 1 µg/mL, and for the
200 µg/mL). were evaluated). of cholesterol. 0.001-200 µg/mL. tannin fraction, 99.45% at 25 µg/mL. Luteolin
Luteolin, luteolin-7-O- Luteolin, luteolin-7-O- presented a percentage of micelle destruction
glucoside, and glucoside, and of 94.83% in the concentration of 1 ng/mL,
luteolin-6-C-glucoside luteolin-6-C- followed by luteolin-7-O-glucoside with
(0.1-100 µg/mL). glucoside: 0.1-100 93.71% and luteolin-6-C-glucoside with 91.26%
µg/mL. at the concentrations of 25 ng/mL and 50
ng/mL, respectively.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Table 1. Studies on the effects of Cymbopogon citratus on obesity (continued...)

Part used/
compound Study design (population,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ intervention, and comparison)
concentration

In human

Waheed et al. C. citratus dried leaf To assess and compare the C. citratus powder was first subjected to Four groups 30 days C. citratus attenuated the serum lipid parameters
(2019) powder (4, 8 and 12 g). prospect of ameliorative proximate analysis. Then, nominated (n = 10 per dose-dependently. The most desirable cholesterol
potential of sundried C. citratus hyperlipidaemic, non-smoker males (age group). reduction was witnessed in G2 and G3. Levels of TG
leaf powder against lipid- 25-50 years) were divided into four groups diminished most significantly in G4 (statins). LDL
lowering drugs (statins) in (G1, G2, G3, and G4), and each faction reduction in both G2 and G3 were nearly the same.
hyperlipidaemic non-smoker included 10 subjects. The first three sets
male patients and to execute its were given deliberated amounts of C.
compositional analysis. citratus powder (4, 8, and 12 g,
respectively) for 30 days. G4 set was
prescribed the use of statins.
Akt: protein kinase B; ALP: alkaline phosphatase; ALT: alanine transaminase; AMPKα: AMP-activated protein kinase alpha; AST: aspartate transaminase; C/EBPα: CCAAT/enhancer-binding protein α; CD36: a cluster of differentiation 36; CDK2: Cyclin-
dependent kinase 2; ERK: extracellular signal-regulated kinase; FABP4: fatty acid binding protein 4; FAS: fatty acid synthase; FAT: fatty acid translocase; HDL: high-density lipoprotein; HMGR: HMG-CoA reductase; IL-6: interleukin-6; LDL: low-density
lipoprotein; MCP-1: monocyte chemoattractant protein-1; PI3K: phosphatidylinositol 3-kinase; PPARγ: peroxisome proliferator-activated receptor γ; SREBP1c: sterol regulatory element binding protein-1c; TAG=TG: triacylglycerols, triglycerides;
TNF-α: tumour necrosis factor-alpha; VLDL: very low-density lipoproteins; ACC: acetyl-CoA carboxylase; LPL: lipoprotein lipase; CE: cholesterolester; CETP: cholesteryl ester-transfer-protein; HL: hepatic lipase.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Table 2. Risk of bias assessment using the ADA quality criteria checklist for primary research.

Author and year Relevance questions Validity questions Quality


rating
1 2 3 4 1 2 3 4 5 6 7 8 9 10

In vivo

Adeneye and Agbaje Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +
(2007)
Agbafor and Akubugwo Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +
(2007)
Costa et al. (2011) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +

Furtado et al. (2011) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +

Kumar et al. (2011) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
Modak and Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +
Mukhopadhaya (2011)
Betancourt et al. (2015) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +

Dimgba et al. (2017) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +

Somparn et al. (2018) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +

Abbas et al. (2019) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
Abdelrahman and Omar Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +
(2023)

In vivo and in vitro

Villalobos et al. (2021) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +

In vitro

Sri Devi and Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
Ashokkumar (2018)

Jo et al. (2019) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
Ngamdokmai et al. Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
(2021)
Sprenger et al. (2021) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
Da Ressurreição et al. Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes Yes +
(2022)

In human

Waheed et al. (2019) Yes Yes Yes Yes Yes Yes Yes No No Yes Yes Yes Yes No +

Relevance questions

1. Would implementing the studied intervention, procedure or product (if found successful) improve outcomes for the

patients/clients/target population group? (NA for some Epi studies)

2. Did the authors study an outcome (dependent variable) or topic the patients/clients/target population group would care about?

3. Is the focus of the intervention, procedure product (independent variable) or topic of study a common issue of concern to dietetics

practice?

4. Is the intervention, procedure or product feasible for application in dietetic practice?

If the answers to the above relevant questions are "Yes," the report is eligible for designation with a plus (+) on the Evidence Quality Worksheet,
depending on answers to the following validity questions.

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Table 2. Risk of bias assessment using the ADA quality criteria checklist for primary research (continued...)

Validity questions

1. Was the research question clearly stated?

2. Was the selection of study subjects/units free from bias?

3. Were study groups comparable, or was an appropriate reference standard used?

4. Did the study describe the methods for handling data losses from the original sample (e.g., withdrawals)?

5. Was blinding used to prevent the introduction of bias?

6. Was the intervention/treatment regimen/exposure factor, procedure, process or product of interest and any detailed comparison(s)

described? Were intervening factors described?

7. Were outcomes, conditions, or interest status clearly defined, and were the measurements valid and reliable?

8. Was the statistical analysis appropriate for the study design and type of outcome indicators?

9. Do results with biases and limitations considered support conclusions?

10. Is bias due to the study's funding or sponsorship unlikely?

MINUS/NEGATIVE (-)
If most (six or more) of the answers to the above validity questions are "No," the report should be designated with a minus (-) symbol on the
Evidence Worksheet.

NEUTRAL (∅)
If the answers to validity criteria questions 2, 3, 6, and 7 are "Yes" but several other criteria indicate study weaknesses, the report should be
designated with a neutral (∅) symbol on the Evidence Worksheet.

PLUS/POSITIVE (+)
If most (six or more) of the answers to the above validity questions are "Yes" (including criteria 2, 3, 6, 7), the report should be designated with a plus
symbol (+) on the Evidence Worksheet.

When a validity criteria question is NA


Suppose any of the ten validity questions are NA. In that case, the report requires a majority of "Yes" answers (including 2, 3, 6, 7, as applicable) for
a plus (+) or a majority of "No" answers for a minus (-) rating.

A human study by Waheed et al. (2019) showed Effect of Cymbopogon citratus on inhibiting adipogenesis,
that C. citratus leaf powder decreased total cholester- lipogenesis, and increasing lipolysis
ol, triglycerides, and LDL in hyperlipidaemia sub-
In an in vivo study, whole plant water extract of C.
jects.
citratus reduced the expression of SREBP-1c, which
C. citratus leaves aqueous extract (Adeneye and promotes lipogenesis in normal rats (Somparn et al.,
Agbaje, 2007) increased HDL levels in normal rats. C. 2018). In vitro studies proved that citral (Sprenger et
citratus leaves hydroalcoholic extract (Furtado et al., al., 2022; Sri Devi and Ashokkumar, 2018) and ethanol
2011), roots aqueous extract (Abbas et al., 2019), and extract (Jo et al., 2019) from C. citratus inhibited adi-
powder (Abdelrahman and Omar, 2023) increased pogenesis in 3T3-L1 preadipocytes. Sri Devi and
HDL in the hyperlipidaemia model. C. citratus essen- Ashokkumar (2018) study proved that 3T3-L1 preadi-
tial oil (Kumar et al., 2011) and powder (Abdelrah- pocytes treated with citral on differentiation process
man and Omar, 2023) decreased the atherogenic in- showed decreased expression of transcription factors
dex in the hyperlipidaemia model. C. citratus whole and genes involved in adipogenesis, namely PPARγ,
plant water extract decreased atherogenic index in SREBP-1c, and FAS. Citral also suppressed the ex-
normal rats (Somparn et al., 2018) pression of PI3K/AKT (a signalling pathway in-

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

volved in differentiation, inflammation, and prolifera- eral studies have characterised the C. citratus prepara-
tion) (Sri Devi and Ashokkumar, 2018). tions. Results of the characterisation of aqueous whole
plant extract by Somparn et al. (2018) C. citratus water
The study of Jo et al. (2019) showed that ethanol
extract contains polyphenols, including gallic acid,
extract of C. citratus reduced the expression of PPARγ
isoquercetin, quercetin, routine, catechin, and tannic
and C/EBPα. Ethanol extract of C. citratus also in-
acid. Rutin, isoquercetin, catechin, and quercetin are
creased AMPK activity as an important regulator of
the flavonoids with the most content. Da Ressurreição
cellular energy metabolism and regulated adipocyte
et al. (2022) also showed that the phenolic compounds
differentiation. Sprenger et al. (2022) proved that cit-
present in aqueous extracts of C. citratus leaves are
ral and its isomers reduced adipocyte differentiation
phenolic acid (p-coumaric acid, caffeic and ferulic
by decreasing FABP4 expression, decreased lipid
acid derivatives), flavonoids (flavone type, namely C-
uptake by decreasing SREBP-2 expression, decreased
and O-glycosylated derivatives of luteolin), and tan-
lipogenesis by decreasing peripilin expression, and
nins (mostly the condensed type, namely, type B pro-
increased lipolysis by decreasing CD36/FAT expres-
cyanidins and derivatives of apigeniflavans and lute-
sion on 3T3-L1 preadipocytes.
oliflavans). The results of phytochemical screening by
Citral reduced lipid accumulation and adipocyte Betancourt et al. (2015) from hydroalcoholic extract of
size in obesity model mice (Modak and Mukho- C. citratus aerial parts also showed the presence of
padhaya, 2011). C. citratus essential oil (Ngamdokmai flavonoids, triterpenes, phenolics and tannins. Phyto-
et al., 2021), citral (Ngamdokmai et al., 2021; Sri Devi chemical analysis by Jo et al. (2019) showed the pres-
and Ashokkumar, 2018), and ethanol extract (Jo et al., ence of the polyphenols caffeic acid and isoorientin in
2019) reduced lipid accumulation in 3T3-L1 adipo- C. citratus ethanol extract. The essential oil from C.
cytes. Jo et al. (2019) also showed that C. citratus etha- citratus leaves obtained through hydrodistillation
nol extract induced G0/G1 cell cycle arrest of 3T3-L1 extraction predominantly contains the monoterpenes
cells by increasing zp21 and p21 expression and de- citral (a mixture of geranial and neral stereoisomers),
creasing CDK2, cyclin A, and cyclin B1 expression. beta myrcene, and geraniol (Costa et al., 2011). Re-
search by Villalobos et al. (2021) shows that propio-
Effect of Cymbopogon citratus on energy expenditure nate is the dominant SCFA content of total dietary
Administration of citral to obese mice models in- fibre C. citratus fermentation products using fresh
creased the metabolic rate, suggesting more signifi- human faecal inoculum. Based on these, it can be
cant energy dissipation (Modak and Mukhopadhaya, concluded that the anti-obesity effect of C. citratus can
2011). come from its polyphenol, essential oil, or fibre con-
tent through the same or different mechanisms.
Effect of Cymbopogon citratus on glucose level In general, different mechanisms of anti-obesity
An in vitro study by Villalobos et al. (2021) showed action are associated with inhibiting digestive en-
that propionate from C. citratus total dietary fibre zymes, stimulating energy expenditure, suppressing
fermentation reduced α-amylase activity (an enzyme appetite, inhibiting adipocyte differentiation, regulat-
that causes the degradation of starch molecules to ing lipid metabolism, and modulation of gut microbi-
release glucose subunits). C. citratus leaves aqueous ota (Singh et al., 2020). Hydroalcoholic-based extract
extract (Adeneye and Agbaje, 2007) and total dietary from C. citratus is rich in polyphenols, which have
fibre (Villalobos et al., 2021) lowered fasting plasma anti-obesity activity through inhibition of digestive
glucose in normal rats and rats with high fat and glu- enzymes (Somparn et al., 2018), appetite suppression
cose diets. Administration of citral to obese models (Dimgba et al., 2017), modulation of lipid metabolism
reduced fasting plasma glucose and increased glucose (Abbas et al., 2019; Adeneye and Agbaje, 2007;
tolerance (Modak and Mukhopadhaya, 2011). C. citra- Agbafor and Akubugwo, 2007; Betancourt et al., 2015;
tus powder decreased glucose levels in rats with a Somparn et al., 2018), and adipogenesis inhibition
high-fat diet (Abdelrahman and Omar, 2023). (Somparn et al., 2018; Jo et al., 2019). C. citratus essen-
tial oil and citral as its major components have anti-
DISCUSSION obesity activity through stimulation of energy ex-
penditure (Modak and Mukhopadhaya, 2011), modu-
This review showed that the potential of C. citratus lation of lipid metabolism (Costa et al., 2011; Kumar
as an anti-obesity agent could come from various et al., 2011), and adipogenesis inhibition
parts of the plant (leaves, stalks, roots, or whole plant) (Ngamdokmai et al., 2021; Sprenger et al., 2022; Sri
and various preparations or extractions (aqueous Devi and Ashokkumar, 2018). Dietary fibre from C.
extract, ethanol extract, powder, dietary fibre, or es- citratus has anti-obesity activity by inhibiting diges-
sential oil). This method, of course, affects the phyto- tive enzymes and modulation of lipid metabolism
chemical content, which has anti-obesity effects. Sev- (Villalobos et al., 2021) (Fig. 2).
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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

Figure 2. Potentials of anti-obesity activity of Cymbopogon citratus.


AMPK: AMP-activated protein kinase alpha; C/EBPα: CCAAT/enhancer-binding protein α; FABP4: fatty acid binding protein 4; FAS: fatty acid
synthase; FAT: fatty acid translocase; HDL: high-density lipoprotein; HMGR: HMG-CoA reductase; LDL: low-density lipoprotein; PI3K/Akt:
phosphatidylinositol 3-kinase/ protein kinase B; PPARγ: peroxisome proliferator-activated receptor γ; SREBPs: sterol regulatory element
binding proteins; VLDL: very low-density lipoproteins.

From inhibiting digestive enzymes, C. citratus research to examine the mechanism of citral in stimu-
whole plant water extract (Somparn et al., 2018) re- lating energy expenditure.
duced the expression of HMGR (catalysator of endog-
In the study by Dimgba et al. (2017), the aqueous
enous cholesterol synthesis) in normal rats. In vitro,
leaf extract of C. citratus suppressed appetite in nor-
the study by Villalobos et al. (2021) showed propio-
mal Wistar rats. The mechanism of appetite suppres-
nate as the predominant SCFA-produced fermenta-
sion by C. citratus had not been explained. Further
tion from C. citratus total dietary fibre inhibited
research can be carried out regarding the effect of C.
HMGR and α-amylase (an enzyme that causes the
citratus water extract on neurological and hormonal
degradation of starch molecules to release glucose
processes that control appetite.
subunits) activity in vitro. SCFA products from fer-
mented C. citratus total dietary fibre can influence gut The fundamental cause of obesity is overconsump-
microbiota, contributing to anti-obesity. However, tion of energy or lack of energy expenditure. Exces-
this review did not include and explore the article sive food or energy intake causes adipose tissue ex-
regarding the influence of C. citratus on the gut mi- pansion, including an increase in the number (adipo-
crobiota. genesis/hyperplasia) and size (hypertrophy) of adi-
pocytes. Thus, modulating the adipogenesis process is
A study by Modak and Mukhopadhaya (2011)
a potential therapeutic method to treat obesity (Sri
proved that citral administrated to obese mice in-
Devi and Ashokkumar, 2018; Zhao et al., 2022). Adi-
creased the metabolic rate, suggesting more signifi-
pogenesis is a complex multi-step process involving a
cant energy expenditure. This mode of action had not
cascade of transcription factors that regulate gene
been explained. It opens up opportunities for future

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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

expression, forming adipocytes. The transcription Omar, 2023), and citral (Modak and Mukhopadhaya,
factors SREBP, C/EBPα, and PPARγ are important 2011) reduced plasma glucose levels in vivo. The ad-
determinants of adipocyte terminal differentiation by ministration of citral to 3T3-L1 preadipocytes reduces
regulating the expression of genes involved in adipo- the inflammatory cytokines (Sri Devi and Ashokku-
genesis and lipogenesis, such as FABP4, acetyl-CoA mar, 2018). This result shows the potential of C. citra-
carboxylase (ACC), and FAS (Ku et al., 2022; Sri Devi tus in preventing the metabolic consequences of obesi-
and Ashokkumar, 2018). ty.
Lipid metabolism abnormalities are common in As far as the author knows, research on C. citratus
obesity. Lipid abnormalities in obesity include in- as an anti-obesity agent in humans is still limited.
creased serum triglycerides, VLDL, LDL, and de- Further research, utilising a randomised controlled
creased HDL (Chan et al., 2016; Feingold, 2023; Klop trial on humans, is needed to explore the potential of
et al., 2013). When lipid accumulation exceeds the C. citratus in both in vivo and in vitro research. There is
storage capacity of adipocytes, it results in increased a need for further research regarding other mecha-
delivery of free acids to the liver. This process causes nisms of C. citratus as an anti-obesity agent, namely
hepatic triglyceride accumulation and increases its mechanism for increasing energy expenditure and
VLDL synthesis by the liver, which inhibits chylomi- suppressing appetite. This review also showed the
cron lipolysis due to competition, especially for lipo- potential for developing C. citratus as an anti-obesity
protein lipase (LPL) levels, with an increase in residu- functional food product, considering that all parts of
al TG transported to the liver. Lipolysis is further the plant can provide therapeutic effects and, in gen-
impaired in obesity with reduced levels of LPL eral, the community uses only the stalks and roots of
mRNA expression in adipose tissue and reduced LPL C. citratus. There is also a need to develop nutraceuti-
activity in skeletal muscle. Hypertriglyceridemia fur- cal products from C. citratus based on its polyphenol,
ther induces an increased cholesterol ester (CE) and essential oil, and total dietary fibre content.
TG exchange between VLDL, HDL, and LDL by cho-
lesteryl ester-transfer-protein (CETP). This condition Strengths and limitation
then causes a decrease in HDL-C concentration and
This article is the first comprehensive systematic
TG content in LDL. In addition, hepatic lipase (HL)
literature review on the anti-obesity activity of C.
removes TG and phospholipids from LDL for the
citratus, as the authors know. As far as the authors are
final formation of small, dense LDL (Feingold, 2023;
concerned, they only found one study on the anti-
Klop et al., 2013).
obesity effects of C. citratus in humans. This review
Hypertrophic adipocytes release chemokines that did not include articles regarding the effects of C.
induce macrophage recruitment from the blood- citratus on gut microbiota, which is one of the poten-
stream, increasing infiltration and inflammation with tial anti-obesity mechanisms. This review also did not
increased production of pro-inflammatory cytokines include the effects of C. citratus on obesity, which are
such as TNF-α and IL-6. This increase in residual tri- related to other metabolic syndromes or consequences
glycerides transported to the liver is achieved by in- of obesity, such as diabetes or cardiovascular disease.
creased FFA release and dysregulation of leptin, adi-
ponectin, and resistin secretion. Adipokines derived CONCLUSION
from macrophages and adipose tissue act in a para-
The anti-obesity activity of Cymbopogon citratus,
crine or autocrine, exacerbating adipose tissue in-
flammation. Altered adipokine secretion at the sys- commonly known as lemongrass, could come from
various parts of the plant (leaves, stalks, roots, or
temic level may decrease muscle and liver insulin
sensitivity through increased ectopic lipid deposition whole plant) and various preparations or extractions
(aqueous or hydroalcoholic extract, powder, dietary
and inflammation. This effect causes an increase in
fibre, or essential oil). Hydroalcoholic-based extract
hepatic glucose production (via gluconeogenesis and
from C. citratus was rich in polyphenols, which had
glycogenolysis). In contrast, muscle metabolism is
anti-obesity activity through inhibiting digestive en-
altered to a pattern of low glucose uptake and low
zymes, appetite suppression, modulation of lipid
FFA oxidation (with increased levels of the glycerol
metabolism, and adipogenesis inhibition. C. citratus
substrate for hepatic gluconeogenesis). This event
causes an increase in plasma glucose and a subse- essential oil and citral as its primary component had
anti-obesity activity through energy expenditure
quent increase in insulin resistance (Coelho et al.,
stimulation, lipid metabolism modulation, and adi-
2013; Rezaee and Dashty, 2013).
pogenesis inhibition. Dietary fibre from C. citratus had
Administration of C. citratus dietary fibre (Villa- anti-obesity activity by inhibiting digestive enzymes
lobos et al., 2021), hydroalcoholic base extract (Aden- and modulating lipid metabolism. However, further
eye and Agbaje, 2007), powder (Abdelrahman and research is needed regarding the molecular mecha-
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Mashitah et al. Anti-obesity activity of Cymbopogon citratus

nisms of C. citratus's influence in suppressing appetite Cercato LM, White PAS, Nampo FK, Santos MRV, Camargo EA
(2015) A systematic review of medicinal plants used for
and stimulating energy expenditure. Limited studies
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Coelho M, Oliveira T, Fernandes R (2013) Biochemistry of adipose
tissue: An endocrine organ. Arch Med Sci 9(2): 191–200.
CONFLICT OF INTEREST https://doi.org/10.5114/aoms.2013.33181
The authors declare no conflicts of interest. Costa CARA, Bidinotto LT, Takahira RK, Salvadori DMF, Barbisan
LF, Costa M (2011) Cholesterol reduction and lack of genotoxic
or toxic effects in mice after repeated 21-day oral intake of
ACKNOWLEDGMENTS lemongrass (Cymbopogon citratus) essential oil. Food Chem
Toxicol 49(9): 2268–2272.
The author would like to thank LPDP, Ministry of Fi- https://doi.org/10.1016/j.fct.2011.06.025
nance of the Republic of Indonesia, through BPI scholarship
da Costa GFF (2015) Cymbopogon citratus and its polyphenols as
(SKPB-7063/LPDP/LPDP.3/2023) for supporting the re- potential phytotherapeutic products: an in vivo approach.
search and publication. Doctoral Thesis in Pharmacy. Faculty of Pharmacy, University
of Coimbra.
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AUTHOR CONTRIBUTION:

Contribution Mashitah MW Widodo N Permatasari N Rudijanto A

Concepts or ideas x x x x

Design x x x x

Definition of intellectual content x x x x

Literature search x x

Experimental studies x x

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Data analysis x x x x

Statistical analysis

Manuscript preparation x x x x

Manuscript editing x x x x

Manuscript review x x x x

Citation Format: Mashitah MW, Widodo N, Permatasari N, Rudijanto A (2024) Anti-obesity activity of Cymbopogon citratus (lemongrass): A
systematic review. J Pharm Pharmacogn Res 12(6): 1090–1110. https://doi.org/10.56499/jppres24.1989_12.6.1090

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