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Review Article
Effects of Moringa oleifera Leaf Extract on Liver
Histopathology: A Systematic Review
Titing Nurhayati ,
1
,
2
Muhamad Farrel Ridho ,
2
Putri Teesa Radhiyanti Santoso ,
1
Setiawan Setiawan ,
1
Hanna Goenawan ,
1
and Vita Murniati Tarawan
1
1
Department of Biomedical Science, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
2
Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
Correspondence should be addressed to Titing Nurhayati; titing.nurhayati@unpad.ac.id
Received 28 September 2023; Revised 10 June 2024; Accepted 20 June 2024
Academic Editor: Eric Gumpricht
Copyright ©2024 Titing Nurhayati et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Introduction. Moringa leaves (Moringa oleifera), which are members of the Moringaceae family, are one of the herbal plants that
are widely known in Indonesia. Phytochemical contents of moringa leaf, such as avonoid, quercetin, and phenolic acid, are
believed to have an eect on improvement of NAFLD. erefore, moringa leaf is considered as one the herbal plants that can be
used as supplementation in the form of adjuvant therapy to NAFLD. e study objective of our research is to review the eect of
giving moringa leaf to the liver, especially the histopathologic features. is study will be conducted on literature review research
design, more specically in the form of a systematic review. Research Method. Five major electronic web databases, including
PubMed, Cochrane Library, Google Scholar, Scopus, and ScienceDirect, were used in identifying literature from 2014 to 2023.
Results. From a comprehensive analysis of 13 relevant literature sources, we elucidate the impact of Moringa oleifera leaf extract on
liver histopathology, glucose, and lipid metabolism. Furthermore, we provide insights into its safety prole concerning human
health. Conclusion. e phytochemical content of Moringa oleifera leaf extract had shown a signicant benet in plant medicinal
sector. From the research that had been done, Moringa oleifera leaf extract contributes to give signicant improvement on liver
histopathological features, glucose, and lipid metabolism on animal sample model.
1. Introduction
Moringa leaves (Moringa oleifera), which are members of the
Moringaceae family, are one of the herbal plants that are
widely known in Indonesia [1, 2]. Every part of the moringa
leaf is a storehouse of important nutrients and antinutrients
[3–5]. erefore, moringa leaves are also known as “miracle
trees” or magical plants because of their various benets,
including medicinal plants, cosmetics, and food ingredients
[1]. Phytochemical contents of moringa leaf, such as a-
vonoid, quercetin, and phenolic acid, are believed to have an
eect on improvement of NAFLD [6–8].
Metabolic syndrome encompasses a group of metabolic
irregularities associated with hypertension, central obesity,
insulin resistance, and atherogenic dyslipidemia and is
closely linked to a heightened likelihood of developing
diabetes as well as cardiovascular diseases, both atherogenic
and non-atherogenic in nature [9]. One of the important risk
factors for metabolic syndrome is lack of physical activity
[10]. Several studies have been conducted using accel-
erometric methods to examine the association between
sedentary behaviour and the metabolic syndrome [11]. ese
studies have shown that increasing the duration and per-
centage of time spent in sedentary behaviour is associated
with increased metabolic risk in adults [11]. One of the
concerning manifestations of metabolic syndrome in the
liver is non-alcoholic fatty liver disease [12]. Research in-
dicates a robust connection between NAFLD and the
characteristics of metabolic syndrome. Insulin resistance
serves as a pivotal factor contributing to both NAFLD and
metabolic syndrome [13]. Evidence from clinical trials,
experimental investigations, and population-based studies
Wiley
Journal of Nutrition and Metabolism
Volume 2024, Article ID 6815993, 15 pages
https://doi.org/10.1155/2024/6815993
suggests that NAFLD could potentially manifest in the liver
as a representation of metabolic syndrome [13].
Non-alcoholic fatty liver disease (NAFLD) is identied
by liver fat accumulation, or in medical term called steatosis,
alongside one of the three conditions: excessive weight or
obesity, type 2 diabetes mellitus (T2DM), or being lean or of
average weight with indications of metabolic disruption [14].
Non-alcoholic fatty liver disease (NAFLD) is the liver ex-
pression of a complex disorder that aects multiple systems
[15]. NAFLD as hepatic manifestation of metabolic syn-
drome is also associated with lack of physical activity as one
of the concerning risk factors [16]. Epidemiological studies
reveal that NAFLD global prevalence in 2023 is 30% and still
increasing in upcoming years [17]. It is considerably asso-
ciated to increasing in prevalence of sedentary lifestyle in
human population [18]. is is supported by the results of
a study conducted in South Korea, where there was an
increase in the frequency of NAFLD based on the length of
time a population had been sitting [19].
Lifestyle modication is one of the most recommended
ways for patients with NAFLD or to prevent NAFLD itself.
Available evidence suggests that as little as 3% to 5% weight
loss is needed to improve simple hepatic steatosis [20–23]. In
addition, pharmacological therapy can also be given to in-
dividuals who have NAFLD [24]. e goals for pharma-
cological therapy of NAFLD should target the fat
accumulation that occurs and the injury and brosis that are
consequences of NAFLD [25]. Another way that can be done
as a management or prevention of NAFLD is supplemen-
tation in the form of adjuvants. Many adjuvants are available
in the market, one of which is herbal plants. Herbal plants
that are believed to have an eect on NAFLD are Moringa
oleifera leaves [26].
Until now, research and clinical trials on moringa leaves
have begun to develop and are being intensively carried out.
However, knowledge about the utilization of moringa leaf in
Indonesia is still low [27]. erefore, we are interested in
conducting this review on the eect of giving moringa leaf to
the liver. is study will be conducted on literature review
research design, more specically in the form of a systematic
review. is review was done to see the eect of the nutrient
content and active substances in moringa leaf on tissue
structure and liver function.
2. Research Method
is study is conducted on literature review research design,
more specically in the form of systematic review. is
review identies the eects of Moringa oleifera leaf extract on
liver structure and function in animal sample model. We
used the PICO method approach to generate the clinical
question for designing this study. e population/patient we
use for this study is NAFLD patient. We use Moringa oleifera
leaf extract as the intervention to the population/patient. e
intervention was compared with standard diet control
group. Lastly, we use liver histopathology as the outcome
analysis.
Five major web electronic databases, including PubMed,
Scopus, Google Scholar, Cochrane, and ScienceDirect, were
used for identifying the literature that provides explanation
on eects of Moringa oleifera leaf extract on liver histopa-
thology. Search of the literature was conducted through
a thorough searching process by using some concepts as
Moringa oleifera, leaf extract, liver histopathology, rat, mice,
and guinea pigs. Every concept was searched and combined
using Boolean Operators “AND.” Other similar terms of the
concepts also were searched and combined using Boolean
Operators “OR.” Research conducted from 2014 to 2023 was
encompassed in the analysis. e pertinent research papers
were gathered and will be selected through thorough se-
lection process. Before the identied research papers were
selected, the research articles identied as duplicates were
eliminated.
e selection process is conducted in two steps. e
initial step involved screening the titles and abstracts of the
articles and studies identied from the search results. e
title and abstract were screened by matching the criteria of
the inclusion. Inclusion criteria used in the selection process
were papers that explained the eects of Moringa oleifera on
liver histopathology. Also, we only included experimental
studies that used rat, mice, or guinea pig as the animal
sample model. Other research designs, such as review,
comment, and letter, were excluded. Experimental studies
that used animal sample model besides rat, mice, or guinea
pig were also excluded. We also veried that the chosen
articles and studies were indexed in the Scimago Journal and
Country Rank (SJR) and Science and Technology Index
(SINTA) for journal publications. Two reviewers (MFR and
TN) independently screened the titles and abstracts in
duplicate with >80% agreement. In cases where screening
results were conicting, a third reviewer (PT) was involved
to resolve the discrepancies.
e next selection steps were to screen the full text of the
articles that passed the rst selection process. In the full-text
screening, we carefully reviewed the articles to meet the right
criteria and outcome related to the eects of Moringa oleifera
leaf extract on liver histopathology. e same two reviewers
(MFR and TH) did the full-text screening independently and
in duplicate with >80% agreement. e same third reviewer
(PT) also did take part to resolve some conicts.
To assess the quality of the literature that included, we
used Joanna Briggs Institute (JBI) Critical Appraisal
Checklist [28]. e quasi-experimental checklist type was
used to evaluate the quality of the literature [28]. e studies
were considered of good quality if they obtained a minimum
of 60% “YES” responses across all questions and of lower
quality if they did not meet this threshold. e critical
appraisal was done by the same two reviewers (MFR and
TH) independently and in duplicate.
Two reviewers (MFR and TH) extracted data in-
dependently and in duplicate using a standardized form
designed for this study. Several data provided by the articles
that were eligible were collected. We retrieved the following
data: research objective, study design, target groups, and
major ndings. e data were compiled using Microsoft
Excel and arranged in the form of table.
Various varieties of Moringa oleifera leaf extracts, model
experiments, phytochemical content, and outcomes were
2Journal of Nutrition and Metabolism
explained and compared. Besides liver histopathology, we
also explain the eects of Moringa oleifera leaf extract on
glucose and lipid metabolism. In addition, we also provide
explanation on safety of Moringa oleifera leaf extract usage,
including lethal dosage and toxicological properties.
3. Result
3.1. Studies Included in the Review. Six hundred twenty-
seven studies were identied through literature search in
5 databases. We found 0 studies on PubMed, 0 studies on
Cochrane Library, 70 studies on Scopus, 26 studies on
ScienceDirect, and 531 studies on Google Scholar. Before
screening, we deleted 129 studies identied as duplicate.
After removal of duplicate studies, we screened the title and
abstract of 498 studies by matching the inclusion and ex-
clusion criteria that we used. en, 435 studies were ex-
cluded and 63 studies remained. Studies that passed the rst
selection then went through the full-text screening. After
that, 50 studies were excluded and 13 studies remained.
ese 13 studies have met our inclusion criteria, so we used
these included studies for this literature review research.
3.2. Data Collected from the Included Studies. All included
studies are experimental studies, specically the included
literatures are a randomized control trial in animal sample
model. All studies explained the eects of Moringa oleifera
leaf extract on liver histopathology. e principle ndings
and all collected data from the included literature were
summarized in Table 1.
e included studies were conducted by experts from
Indonesia, Mexico, Egypt, Nigeria, Iran, Saudi Arabia, South
Korea, Pakistan, and Libya.
In addition, some references, besides included literature,
were chosen to provide the eects of Moringa oleifera leaf
extract on glucose and lipid metabolism. Glucose and lipid
metabolism were also illustrated due to their involvement in
the pathogenesis and pathophysiology of liver disease,
specically non-alcoholic fatty liver disease. e phyto-
chemical contents of Moringa oleifera are provided in the
form of Table 2. In addition, we also provide the safety of
Moringa oleifera leaf extract usage by explaining its lethal
dosage. Figure 1 shows the ow diagram of literature se-
lection process from the electronic databases.
4. Discussion
4.1. Phytochemical Content of Moringa oleifera Leaf Extract.
e phytochemical composition of Moringa oleifera leaf
primarily comprises phenolic compounds, which are es-
sential plant-derived micronutrients [1]. Phenolic com-
pounds are a group of compounds characterized by hydroxyl
groups directly attached to aromatic structures, encom-
passing phenolic acids, avonoids, xanthones, quinones,
coumarins, tannins, and lignans [2]. Phenolic compounds
play signicant roles in safeguarding plants against physical
damage, ultraviolet radiation, oxidative stress, and similar
factors. Currently, there is growing interest in uncovering,
extracting, and enhancing phytochemicals due to their
potential to serve as alternatives to synthetic drugs with
fewer side eects. Unquestionably, dried Moringa oleifera
leaves serve as signicant natural reservoirs of phenolic
compounds [3].
is nding conrmed the phenolic compound stated in
the included literature. Some of the included literature also
conducted an analysis on phytochemical component in the
Moringa oleifera. e analysis was conducted to reassuring
the presence of the phytochemical compound in the Mor-
inga oleifera leaf extract. Most of the articles that conducted
analysis on phytochemical content stated that they identied
phenolic acid and quercetin as the key ndings for the
phytochemical content of Moringa oleifera leaf extract
[29–41].
4.2. Eects of Moringa oleifera Leaf Extract on Glucose
Metabolism. As previously noted, a variety of polyphenols
are present in Moringa oleifera. Many compounds contained
in moringa leaf are proven to have involvement in the
metabolism of glucose homeostasis [46]. Among the most
noteworthy are avonoids like quercetin and kaempferol, as
well as phenolic acids such as chlorogenic acid and caf-
feoylquinic acid [51]. ese compounds appear to possess
antihyperglycemic attributes, acting as competitive in-
hibitors of sodium-glucose linked transporter type 1
(SGLT1) in the mucosa of the small intestine (specically,
the duodenum and jejunum). is action leads to a re-
duction in the absorption of glucose in the intestines [52].
However, it is important to note that glucose absorption
involves other mechanisms, including the involvement of
glucose transporter 2 (GLUT2), which can be inuenced by
the presence of circulating glucose, directing it towards the
basolateral membrane of the small intestine [53].
Moringa oleifera has been investigated for its potential in
managing glucose metabolism by contributing to the re-
duction of glucose levels. One suggested mechanism in-
volves quercetin, which can function as an inhibitor of
GLUT2 at the apical surface [54]. It is important to note that
this inuence is specic to GLUT2 and does not aect
GLUT5 or SGLT1 [55]. Moreover, quercetin has demon-
strated the ability to activate adenosine monophosphate-
activated protein kinase (AMPK), thereby enhancing glu-
cose uptake through the stimulation of GLUT4 in skeletal
muscle. Additionally, it plays a role in diminishing glucose
production by suppressing the activity of phosphoenol-
pyruvate carboxykinase (PEPCK) and glucose-6-phospha-
tase (G6Pase) in the liver [56].
e aqueous leaf extract of Moringa oleifera has dem-
onstrated the ability to hinder the activity of α-glucosidase,
pancreatic α-amylase, and intestinal sucrose, contributing to
its antihyperglycemic eects [57]. ese inhibitory outcomes
are attributed to the presence of phenols, avonoids, and
tannins in Moringa oleifera. By delaying the digestion of
carbohydrates through enzyme inhibition, there is a conse-
quent reduction in post-meal hyperglycemia and levels of
hemoglobin A1C (HbA1C). e inhibitory impact of a-
vonoids like quercetin and kaempferol can be explained
biochemically by their increased number of hydroxyl groups
Journal of Nutrition and Metabolism 3
Table 1: Studies dealing with the eects of Moringa oleifera leaf extract on liver histopathology [29–41].
Research objective Study
design Target groups Major ndings Other ndings References
To investigate how a water-based
extract derived from Moringa oleifera
aects liver microRNAs, gene and
protein expression, and histological
and biochemical factors, within an
experimental NASH model, with
a focus on its potential
hepatoprotective properties
RCT
Classication of C57BL/6J strain mice:
(a) Signicant diminution and
reduction of inammatory nodules,
extracellular matrix quantication,
collagens, presence of αSMA, and
activation of hepatic stellate cells
measured by histological analysis of
liver in MO treated group
(a) Signicant weight reduction of animal
body weight, liver weight, and epididymal
fat pad weight in MO treated group
[29]
(1) Standard diet control group (n�5)
(b) Signicant reduction of serum glucose
level due to preserved insulin sensitivity in
MO treated group
(2) High-fat diet group (n�10)
(a) High-fat diet group without
treatment (n�5)
(b) High-fat diet group supplied by
150 L aqueous Moringa oleifera extract
(62.5 mg/mL) (n�5)
(c) Showed reduction of AST, ALT,
cholesterol, insulin, resistin, leptin, and
PAI-1 levels in MO treated group
(d) Signicant reduction of lipid
peroxidation due to lower MDA levels in
MO treated group
To investigate the impacts of
a nanoplatform containing Moringa
oleifera extract, along with vitamin C
and selenium (MO/asc.-Se-NPs), on
the prevention and treatment of
hepatocellular carcinoma (HCC)
RCT
Classication of male Wistar albino rats:
(a) Signicant reduction of
perivascular inltration with
broblast, vessel congestion, and
lymphocyte cell inltration
measured by histological analysis of
liver in MO prevention and MO
treated groups
(a) Showed reduction of AST, ALT, and
albumin in MO prevention and MO
treatment groups
[30]
(1) Control normal group (n�5)
(b) Signicant reduction of lipid
peroxidation due to lower MDA level in
MO prevention and MO treated groups
(2) MO/asc.-Se-NPs supplement group
(1 mL/kg weekly) (n�5)
(3) HCC induction group
(4) HCC induction + MO/asc.-Se-NPs
(1 mL/kg weekly) (n�5)
(5) MO/asc.-Se-NPs treatment (1 mL/kg
weekly) after HCC induction (n�5)
To investigate the potential
hepatoprotective and antioxidant
eects of an ethanol extract of Moringa
oleifera (EEMO) against hepatocellular
injury and oxidative stress induced by
potassium dichromate (K2Cr2O7) in
male Wistar rats
RCT
Classication of male Swiss albino rat:
(a) Showed amelioration of
hepatocellular degeneration and
severe necrosis measured by
histological analysis of liver in
EEMO treated group
(a) Signicant reduction of nal body
weight, liver weight, percentage body
weight change, and relative liver weight in
EEMO treated group
(b) Signicant reduction of AST and ALT
in EEMO treated group
(c) Signicant improvement of MDA level,
SOD activity, and GST activity in EEMO
treated group
[34]
(1) Negative control group (n�5)
(2) Positive control group fed by
K2Cr2O712 mg/kg body weight weekly
(n�5)
(3) Rats fed by EEMO 3.5 mg/kg body
weight weekly (n�5)
(4) Rats fed by EEMO 7 mg/kg body
weight weekly (n�5)
(5) Rats fed by K2Cr2O712 mg/kg body
weight + EEMO 3.5 mg/kg body weight
weekly (n�5)
(6) Rats fed by K2Cr2O7 12mg/kg body
weight + EEMO 7 mg/kg body weight
weekly (n�5)
4Journal of Nutrition and Metabolism
Table 1: Continued.
Research objective Study
design Target groups Major ndings Other ndings References
To investigate the eects of medicinal
properties like quercetin, gallic acid,
and caeic acid of stem and leaf extract
of Moringa oleifera in protecting liver
steatosis in high-fat diet fed rats
RCT
Classication of male Wistar rat:
(a) Signicant reduction of macro-
and microvesicular fat, hepatocyte
swelling measured by histological
analysis of liver in MO treated
group
(a) Showed reduction of body weight and
visceral fat weight in MO treated group
(b) Signicant reduction of AST and ALT
level in MO treated group
(c) Signicant reduction of TG, TC,
LDL-C, and VLDL-C in MO treated group
[35]
(1) Standard diet control group (n�5)
(2) High-fat diet group (n�5)
(3) High-fat diet + MO leaf powder 2%
(n�5)
(4) High-fat diet + MO leaf powder 4%
(n�5)
(5) High-fat diet + MO stem powder 2%
(n�5)
(6) High-fat diet + MO stem powder 4%
(n�5)
To investigate the eects of Moringa
oleifera leaf extract on lead acetate
poisoning
RCT
Classication of mice:
(a) Signicant reduction of
cytoplasmic vacuolation,
granulation in some cells, pyknosis
of the nuclei, inammatory cell
inltration, vessel congestion, and
hepatocyte necrosis measured by
histological analysis of liver in MO
treated group
(a) Signicant improvement of AST, ALT,
and ALP in MO treated group
(b) Signicant improvement of cholesterol,
HDL-C, LDL-C, and TG in MO treated
group
(c) Signicant reduction of serum glucose
level in MO treated group
[36]
(1) Normal control group (n�15)
(2) Mice fed by MO leaf extract 300 mg/
kg body weight weekly (n�15)
(3) Mice fed by 1/10LD50 of Pb
(C2H3O2)2 (60 mg/kg body weight) for
45 days (n�15)
(4) Mice fed by 1/10 LD50 of Pb
(C2H3O2)2 (60 mg/kg body
weight) + by MO leaf extract 300 mg/kg
body weight for 45 days (n�15)
To study the eectiveness of fermented
extract from Moringa oleifera (FM) in
addressing glucose intolerance and the
buildup of liver fats induced by
a high-fat diet (HFD)
RCT
Classication of C57BL/6J rat:
(a) Signicant reduction of hepatic
lipid accumulation in MO treated
group measured by histological
analysis of liver
(a) Signicant better glucose tolerance in
MO treated group [37]
(1) Normal control group
(2) Rat fed by high-fat diet group
(3) Rat fed by high-fat diet + fermented
MO extract 250 mg/kg body weight daily
(4) Rat fed by high-fat
diet + non-fermented MO extract
250 mg/kg body weight daily
Journal of Nutrition and Metabolism 5
Table 1: Continued.
Research objective Study
design Target groups Major ndings Other ndings References
To investigate the protective eect of
Moringa oleifera leaf extract on liver
and kidney damage induced by
gentamicin in rats
RCT
Classication of rat:
(a) Signicant reduction of
hepatocyte degeneration, sinusoid
dilatation, and hepatic cell necrosis
in MO treated group measured by
histological analysis of liver
(a) Signicant reduction of lipid
peroxidation characterized by lowered
MDA level in MO treated group
[38]
(1) Normal control group (n�5)
(2) Rat fed by gentamicin 80 mg/kg body
weight (n�5)
(3) Rat fed by gentamicin 80 mg/kg body
weight + MO leaf extract 150 mg/kg
body weight (n�5)
(4) Rat fed by gentamicin 80 mg/kg body
weight + MO leaf extract 300 mg/kg
body weight (n�5)
(5) Rat fed by gentamicin 80 mg/kg body
weight + MO leaf extract 300 mg/kg
body weight (n�5)
To investigate the eects of multilevel
doses of Moringa oleifera leaf extract
on the microscopic appearance of the
livers of formalin-induced Wistar rats
RCT
Classication of male Wistar rat:
(a) Signicant reduction of
hepatocyte degeneration and
necrosis measured by histological
analysis of liver tissue using Manja
Roenigk scoring in MO treated
group
— [39]
(1) Negative control group (n�5)
(2) formalin 100 mg/kg body weight
daily (n�5)
(3) Rat fed by normal diet + MO leaf
extract 200 mg/kg body weight
daily + formalin 100 mg/kg body weight
daily
(4) Rat fed by normal diet + MO leaf
extract 400 mg/kg body weight
daily + formalin 100 mg/kg body weight
daily
(5) Rat fed by normal diet + MO leaf
extract 800 mg/kg body weight
daily + formalin 100 mg/kg body weight
daily
To investigate the eect and eective
dose of the ethyl acetate fraction of
moringa leaf on histopathological
features of the liver and SGPT and
SGOT levels in monosodium
glutamate-induced rats
RCT
Classication for rat:
(a) Signicant reduction of
hepatocyte degeneration and lipid
accumulation between hepatic cells
in MO treated group measured by
histological analysis of liver
(a) Signicant reduction of SGOT and
SGPT levels in MO treated group [40]
(1) Normal control group (n�5)
(2) Rat fed by MSG 3.6 mg/g body
weight (n�5)
(3) Rat fed by MSG 3.6 mg/g body
weight + MO ethyl acetate fraction
20.17 mg/g body weight (n�5)
(4) Rat fed by MSG 3.6 mg/g body
weight + MO ethyl acetate fraction
30.26 mg/g body weight (n�5)
(5) Rat fed by MSG 3.6 mg/g body
weight + MO ethyl acetate fraction
45.39 mg/g body weight (n�5)
6Journal of Nutrition and Metabolism
Table 1: Continued.
Research objective Study
design Target groups Major ndings Other ndings References
To investigate the healing capabilities
of Moringa oleifera in the context of
fatty liver induced by ethanol
consumption
RCT
Classication of male mice:
(a) Signicant reduction of hepatic
steatosis, lobular inammation, and
hepatic ballooning in MO treated
group measured by histological
analysis of liver
(a) Signicant reduction of ALT, AST, and
TG in MO treated group
(b) Signicant reduction of TNF-αin MO
treated group measured by
immunohistochemistry analysis of liver
[41]
(1) Normal control group (n�8)
(2) Mice fed by 30% ethanol 100 l
(n�8) daily
(3) Mice fed by 30% ethanol 100 l + MO
extract 100 mg/kg body weight (n�8)
(4) Mice fed by 30% ethanol 100 l + MO
extract 200 mg/kg body weight (n�8)
(5) Mice fed by 30% ethanol 100 l + MO
extract 400 mg/kg body weight (n�8)
To investigate the phytochemical
capacity of Moringa oleifera in
countering oxidative stress induced by
acetaminophen and its role in
inuencing liver biomarkers, liver
tissue structure, and the JNK pathway
within the MAPK signaling cascade
RCT
Classication of Wistar rat:
(a) Signicant improvement of
hepatocyte degeneration, hepatic
cell necrosis, inammation, and
vascular injury in MO treated group
measured by histological analysis of
liver
(a) Signicant reduction of ALT, ALP,
AST, bilirubin, and GGT levels in MO
treated group
[31]
(1) Normal control group (n�10)
(2) Rat fed by acetaminophen 200 mg/kg
body weight (n�10)
(3) Rat fed by acetaminophen 200 mg/kg
body weight + silymarin 200 mg/kg body
weight (n�10)
Rat fed by acetaminophen 200 mg/kg
body weight MO extract (200 mg/kg
body weight) (n�10)
Journal of Nutrition and Metabolism 7
Table 1: Continued.
Research objective Study
design Target groups Major ndings Other ndings References
To investigate the impacts of Moringa
oleifera leaf extract on alterations
caused by bisphenol-A (changes in
hepatocyte diameter and
vacuolization) in the livers of rats
RCT
Classication of albino rat:
(a) Signicant reduction of
hepatocyte diameter and hepatic
vacuolization in MO treated group
measured by histological analysis of
liver
[32]
(1) Normal control group (n�8)
(2) Rat fed by BPA 50 mg/kg body
weight (n�8)
(3) Rat fed by BPA 50 mg/kg body
weight + MO leaf extract 250 mg/kg
body weight (n�8)
(4) Rat fed by BPA 50 mg/kg body
weight + MO leaf extract 500 mg/kg
body weight (n�8)
To investigate the potential of
antidiabetic impact of methanolic
extracts from Moringa oleifera leaf,
seeds, and a combination of both,
administered at a dosage of 500 mg/kg
of body weight per day
RCT
Classication of mice:
(a) Showed reduction of
accumulation of fat vacuoles in
hepatocytes, inammatory cell
inltration, vascular dilatation and
congestion, and brosis at the
pericellular and perisinusoidal level
in MO treated group measured by
histological analysis of liver
(a) Signicant reduction of blood glucose
level in MO treated group
(b) Signicant reduction of ALT, AST, and
ALP activity in MO treated group
(c) Signicant reduction of total
cholesterol and triglycerides in MO treated
group
[33]
(1) Normal control group (n�3)
(2) Alloxan induced diabetic mice group
(n�3)
(3) Diabetic mice + insulin
administration 0.7 mg/kg body weight
daily for 1 month (n�3)
(4) Diabetic mice + MO leaf extract
500 mg/kg body weight daily for
1 month (n�3)
(5) Diabetic mice + MO seed extract
500 mg/kg body weight daily for
1 month (n�3)
(6) Diabetic mice + MO combination
extract 500 mg/kg body weight daily for
1 month (n�3)
(7) Diabetic mice + MO leaf extract
500 mg/kg body weight daily for
3 months (n�3)
(8) Diabetic mice + MO seed extract
500 mg/kg body weight daily for
3 months (n�3)
(9) Diabetic mice + MO combination
extract 500 mg/kg body weight daily for
3 month (n�3)
RCT: randomized control trial; microRNA: microribonucleic acid; NASH: non-alcoholic steatohepatitis; MO: Moringa oleifera; AST: aspartate aminotransferase; ALT: alanine transaminase; PAI-1: plasminogen
activator inhibitor-1; αSMA: alpha-smooth muscle actin; MDA: malondialdehyde; ASC: ascorbic acid; -Se-: selenium; NPs: nanoplatform; mL: milliliter; mg: milligram; n: natural number; L: microliter; kg:
kilogram; HCC: hepatocellular carcinoma; EEMO: ethanol extract of Moringa oleifera; K2Cr2O7: potassium dichromate; SOD: superoxide dismutase; GST: glutathione S-transferase; TG: triglyceride; TC: total
cholesterol; LDL-C: low density lipoprotein-cholesterol; VLDL-C: very low density lipoprotein-cholesterol; LD50: lethal dose, 50%; Pb (C2H3O2)2: lead (II) acetate; HDL-C: high density lipoprotein-cholesterol;
HFD: high-fat diet; FM: fermented extract of Moringa oleifera; SGPT: serum glutamic pyruvic transaminase; SGOT: serum glutamic oxaloacetic transaminase; MSG: monosodium glutamate; TNF-α: tumor
necrosis factor-α; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinases; GGT: gamma-glutamyltransferase; BPA: bisphenol-A; ALP: alkaline phosphatase.
8Journal of Nutrition and Metabolism
on the B ring and the presence of a 2,3-double bond [58].
Moreover, these compounds have undergone scrutiny for
their protective and regenerative eects on pancreatic beta-
cells, leading to enhanced insulin production and release
[59]. Quercetin, for instance, stimulates insulin secretion by
activating the extracellular signal-regulated kinase 1/2
(ERK1/2) pathway and simultaneously shields pancreatic
beta-cells against oxidative harm [5].
is mechanism of action of polyphenols contained in
Moringa oleifera leaf extract is in parallel with the ndings of
the included literature. Some studies showed that there is
signicant reduction of blood glucose level and improve-
ment of insulin sensitivity measured in group of animals
treated by Moringa oleifera leaf extract [29, 33, 36, 37, 49].
From the studies included, we conclude that dosage of
Moringa oleifera leaf extract of more than 200 mg/kg body
weight showed more signicant result of glucose and insulin
prole than the lower dosage [29, 33, 36, 37, 49].
4.3. Eects of Moringa oleifera Leaf Extract on Lipid
Metabolism. Phenolic compounds, as well as avonoids,
have an important role in lipid regulation [49, 60].
erefore, Moringa oleifera has also been considered as
a potential hypolipidemic agent. An aqueous extract derived
from Moringa oleifera leaf has been reported to possess lipid-
lowering attributes by diminishing the creation of choles-
terol micelles and inhibiting enzymes like pancreatic lipase
and pancreatic cholesterol esterase, as well as impeding bile
acid binding [57]. Furthermore, an increase in the expres-
sion of peroxisome proliferator-activated receptors (PPARs)
α1 (PPARα1) and c(PPARc) has been observed in rats
administered Moringa oleifera seed powder [61]. PPARs play
a pivotal role in lipid metabolism, ketogenesis, and cellular
energy balance, and they are present in various organs,
including the liver, brain, muscles, and heart, among others.
Additionally, PPARs are implicated in processes such as
inammation, immunity, and glucose regulation [62]. An-
other research demonstrated that administering Moringa
oleifera leaf extract during the process of adipogenic dif-
ferentiation leads to a decrease in inammation and lipid
buildup, while also triggering thermogenesis through the
activation of key proteins such as uncoupling protein 1
(UCP1), sirtuin 1 (SIRT1), peroxisome proliferator-activated
receptor alpha (PPARα), and coactivator 1 alpha (PGC1α).
Furthermore, Moringa oleifera Lam. induces the expression
Table 2: Phenolic compounds of Moringa oleifera leaf extract [42–49].
Constituent Content
in leaf (mg/g) Extraction method
Phenolic acid
Caeic acid 6.28 Distilled water
Chlorogenic acid 50.69 Distilled water
79.31 Distilled water
Ellagic acid 33.15 Distilled water
52.95 Distilled water
Gallic acid
32.45 Distilled water
105.67 Distilled water
1.03 Distilled water
Salicylic acid 0.24 Ethanol extract
Ferulic acid 0.128 Distilled water
Flavonoid
Isoquercitrin 64.53 Distilled water
75.65 Distilled water
Quercitrin 29.74 Distilled water
74.90 Distilled water
Epicatechin 10.03 Distilled water
29.73 Distilled water
Catechin 15.27 Distilled water
20.19 Distilled water
Rutin 15.27 Distilled water
60.38 Distilled water
Quercetin
137.81 Methanol 70%
10.7 Distilled water
47.91 Pressurized hot
water extraction
38.2 Distilled water
Kaempferol
18.23 Distilled water
106.75 Distilled water
47.4 Pressurized hot
water extraction
2.8 Methanol 70%
Myricetin 1.53 Methanol 80%
Vanillin 0.137 Distilled water
Journal of Nutrition and Metabolism 9
of heme oxygenase-1 (HO-1), a well-recognized protective
and antioxidant enzyme [63].
ose ndings on hypolipidemic eects of Moringa
oleifera are in parallel with the outcomes of the included
literature. Most of the studies provide explanation of the
resulting eects of Moringa oleifera leaf extract on lipid
prole. e collected data of included literatureexplained
that Moringa oleifera leaf extract provided signicant re-
duction of triglyceride, LDL-C, VLDL-C, and cholesterol in
group fed by Moringa oleifera leaf extract [29, 33, 35, 36, 49].
Besides that, included literature also stated that there is an
improvement of HDL-C in lipid prole of group fed by
Moringa oleifera leaf extract [36].
By now, it is recognized that the consumption of a high-
fat diet stimulates the generation of proinammatory cy-
tokines like IL1B and TNFA, which are activated via the
NFkB pathway [64, 65]. is dietary pattern also results in
an elevation of mitochondrial ROS production. ese free
radicals contribute to the peroxidation of lipids on cellular
and organelle membranes, leading to the formation of
malondialdehyde (MDA), which serves as an indicative
marker of oxidative stress [66]. Choi and Das illustrated an
increase in lipid peroxidation products such as MDA and
4HNE in a model of NAFLD, attributable to the generation
of reactive oxygen species [67, 68]. Some studies revealed
that the application of moringa results in a decline in the
generation of MDA, attributed to a reduction in ROS
production [49]. is nding is in parallel with some in-
cluded studies that also show signicant reduction of lipid
peroxidation in liver characterized by reduction of MDA
level in group fed by Moringa oleifera leaf extract
[29, 30, 34, 38].
Identified literature from:
Pubmed (n = 0)
Cochrane Library (n = 0)
Google Scholar (n = 531)
Scopus (n = 70)
Science Direct (n = 26)
Literature deleted before
screening:
Deleted duplicate (n = 129)
Non-eligible literature (n = 0)
Literature deleted due to other
reason (n = 0)
Literature screening
(Title and abstract)
(n = 198)
Literature excluded (n = 435)
Reason:
Not Moringa oleifera (n = 306)
Not liver histopathology (n = 44)
Wrong sample (n = 42)
Wrong study design (n = 31)
Wrong outcome (n = 6)
Foreign language (n = 6)
Literature screening (full-text)
(n = 63)
Literature excluded (n =50)
Reason:
Article not indexed (n =25)
Article not published (n = 7)
Review article (n = 4)
Wrong outcome (n = 3)
More than 10 years (n = 2)
Not liver histopathology (n = 2)
Full-text not found (n =7)
Literature included (n = 13)
Literature identication from electronic databases
Identification
Screening
Included
Figure 1: Flow diagram of literature selection process from the electronic databases [50].
10 Journal of Nutrition and Metabolism
From the studies included, we conclude that dosage of
Moringa oleifera leaf extract of more than 200 mg/kg body
weight showed more signicant result on lipid prole and
MDA level than the lower dosage [29, 30, 34, 38].
4.4. Eects of Moringa oleifera Leaf Extract on Liver
Histopathology. Several hypotheses have been proposed to
explain the mechanisms of liver injury leading to liver
steatosis. ese include liver injury caused by hepatotoxins,
damage from a diet high in fat, and liver injury related to
metabolic disorders [69–71]. All those etiologies may trigger
liver damage by means of oxidative stress, inammation,
brogenesis, and liver necrosis. Sudden damage to liver cells
disrupts their transport function and the permeability of
their membranes, causing the release of marker enzymes
[72]. e internal processes of damage within hepatocytes
involve the creation of reactive metabolites, reduction of
glutathione levels, and protein alkylation, particularly af-
fecting mitochondrial proteins [73]. ese initial actions
prompt the opening of the mitochondrial membrane,
resulting in permeability transition. e deterioration of the
mitochondrial membrane permeability transition occurs
prior to the failure of the cell’s outer membrane, leading to
cell swelling and the release of cellular contents. is ulti-
mately culminates in cell death through a process known as
oncotic necrosis [74].
e evaluation of liver damage was gauged through the
measurement of serum levels of ALT and AST, which are
widely recognized as prevalent indicators of liver harm. When
the integrity of the liver cell membrane is compromised, several
enzymes that typically reside within the cell’s cytosol are
discharged into the bloodstream. e concentration of these
enzymes in the serum provides a valuable quantitative gauge of
the magnitude and nature of hepatocellular injury [71].
Liver injury, in the term of NAFLD, is often charac-
terized by macrovesicular steatosis, ballooning degeneration
of hepatocytes, scattered (mainly lobular) inammation and
apoptotic bodies, and Mallory-Denk bodies (MDBs). Fi-
brosis also often presents alongside the other histological
features [75].
e included literature had revealed that there is sig-
nicant improvement in the histopathological analysis of the
liver tissue conducted on animal sample treated by Moringa
oleifera leaf extract. All studies included explained that after
administration of Moringa oleifera leaf extract, there is
signicant reduction of brosis, hepatic cells necrosis, lipid
accumulation, inammatory cells inltration, hepatocellular
degeneration, vesicular congestion, and sinusoidal di-
latation. Various dosages of Moringa oleifera leaf extract had
been analyzed. Higher dosage of Moringa oleifera extract
showed more reduction on the histopathological feature of
the liver tissue, while lower dosage did not give any notable
improvement on the histopathological feature of the liver
tissue [29–41, 49]. Some studies included also measured liver
injury biomarkers as other ndings besides liver histo-
pathological features. ese studies stated that there is
signicant reduction on the AST, ALT, ALP, SGOT, and
SGPT in the group of animals treated by Moringa oleifera leaf
extract [29–31, 33–36, 40, 41, 49].
From the studies included, we conclude that dosage of
Moringa oleifera leaf extract of more than 200 mg/kg body
weight showed more signicant result on liver histopath-
ological feature and liver biomarkers than the lower dosage
[29–41].
4.5. Safety of Moringa oleifera Leaf Extract. Earlier in-
vestigations were carried out on animal models to analyze
the oral toxicity (LD50) of Moringa oleifera leaf extract [76].
e ndings indicated that the aqueous leaf extract of
Moringa oleifera did not result in any fatalities even at the
highest administered dose of 6400 mg/kg body weight [77].
A study conducted by Fouad et al. [78] on acute oral toxicity
reported that Moringa oleifera leaf extract demonstrated
non-lethal eects on animals at a dose of 2000 mg/kg body
weight and mentioned that animals may display some ad-
verse changes at doses beyond this level. Moreover, Diallo
et al. [79] documented that the aqueous leaf extract of
Moringa oleifera was safe even at dosages as high as 5000 mg/
kg body weight.
ese ndings suggest that the aqueous leaf extract of
Moringa oleifera is safe for oral consumption, displaying no
lethal eects during acute administration. It is noteworthy that
a dose of 2 g/kg body weight was identied as the threshold for
medicinal plant toxicity in acute oral toxicity studies [80].
However, this safety assertion might not hold true for medicinal
plants consumed over an extended period. Slight lethargy was
observed in animals receiving doses above 1600 mg/kg body
weight during acute administration, which aligns with the
observations of Adedapo et al., who noted toxic changes in
animals above 2000 mg/kg body weight. e LD50 from an
acute oral intraperitoneal toxicity study for Moringa oleifera leaf
extract was determined to be 1585 mg/kg body weight.
Previous study conducted by Kushwaha et al. [81] docu-
mented the adverse outcomes of Moringa oleifera leaf extract in
studies involving human subjects. In this research, a group of
30 post-menopausal women was provided a daily supple-
mentation of 7 g of Moringa oleifera leaf powder for a duration
of 12 weeks, and their results were compared with those of
a control group. e study revealed a rise in antioxidant
biomarkers that contributed to hypoglycemic and hypolipi-
demic eects, all without inducing any harmful eects.
5. Conclusion
e phytochemical content of Moringa oleifera leaf extract
had shown a signicant benet in plant medicinal sector.
From the research that had been done, Moringa oleifera leaf
extract contributes to give signicant improvement on liver
histopathological features, glucose, and lipid metabolism on
animal sample model. In the coming times, further in-
vestigation into this medicinal plant could oer promising
prospects regarding its eectiveness and safety as a thera-
peutic solution for NAFLD.
Journal of Nutrition and Metabolism 11
5.1. Limitation. Due to the various types of extracts
employed in studies, it becomes imperative to determine if
specic phytochemicals within Moringa oleifera leaf extract
are present in each variant. Consequently, additional in-
vestigations are warranted to discern the most potent type of
Moringa oleifera leaf extract and its optimal bioavailability.
Data Availability
All relevant data are included within the article and the
attached supplementary information le.
Conflicts of Interest
e authors declare that they have no conicts of interest.
Authors’ Contributions
All authors conceived and designed the study.
Acknowledgments
e authors were funded by external nancial support from
2203/UN6.3.1/PT.00/2022 Riset Disertasi Dosen Universitas
Padjadjaran to Vita Murniati Tarawan. is research was
supported by Medical Faculty of Universitas Padjadjaran,
Bandung.
Supplementary Materials
Table presenting the results of the quality assessment,
providing detailed information on the quality indicators of
the included literature using JBI quasi-experimental critical
appraisal tools [28]. (Supplementary Materials)
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