Jppres24.1989 - 12.6.1090 - Mashitah Et Al.
Jppres24.1989 - 12.6.1090 - Mashitah Et Al.
ISSN 0719-4250
https://jppres.com
DOI: https://doi.org/10.56499/jppres24.1989_12.6.1090
Review
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.
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.
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).
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.
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.
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.
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).
Part used/
compound Study design (population,
Author and year Research objectives No. of subjects Duration Main outcomes/results
and dosage/ intervention, and comparison)
concentration
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.
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.
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.
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.
Table 2. Risk of bias assessment using the ADA quality criteria checklist for primary research.
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)
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
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?
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.
Table 2. Risk of bias assessment using the ADA quality criteria checklist for primary research (continued...)
Validity questions
4. Did the study describe the methods for handling data losses from the original sample (e.g., withdrawals)?
6. Was the intervention/treatment regimen/exposure factor, procedure, process or product of interest and any detailed comparison(s)
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?
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.
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-
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).
https://jppres.com J Pharm Pharmacogn Res (2024) 12(6): 1105
Mashitah et al. Anti-obesity activity of Cymbopogon citratus
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
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-
https://jppres.com J Pharm Pharmacogn Res (2024) 12(6): 1107
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
weight loss in Brazil: Is there potential for obesity treatment? J
of the anti-obesity effects of C. citratus in humans Ethnopharmacol 176: 286–296.
encourage the need for proof in randomised con- https://doi.org/10.1016/j.jep.2015.10.038
trolled trials on humans. C. citratus has the potential Chan DC, Pang J, Watts GF (2016) Dyslipidemia in Obesity. In:
to be developed as a functional food or nutraceutical Ahima RS (eds) Metabolic Syndrome. Springer, Cham.
product as an anti-obesity agent. https://doi.org/10.1007/978-3-319-11251-0_30
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:
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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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