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Scholars Academic Journal of Pharmacy @ OPEN ACCESS

Abbreviated Key Title: Sch Acad J Pharm
ISSN 2347-9531 (Print) | ISSN 2320-4206 (Online) Pha rmacy
Journal homepage: http://saspublishers.com

Review of Phytochemical and Pharmacological Activities of Noni
(Morinda citrifolia L.)

Merisa Norma Ayunda’, Zulharmita', Zikra Azizah', Harrizul Rivai~

‘College of Pharmacy (STIFARM), Jl. Raya Siteba Kurao Pagang, Padang 25147, Indonesia
Faculty of Pharmacy, Andalas University, Limau Manih Campus, Padang 25163, Indonesia

DOI: 10.36347/sajp.2020.v09112.003 | Received: 26.11.2020 | Accepted: 10.12.2020 | Published: 13.12.2020

*Corresponding author: Harrizul Rivai

Abstract Review Article_

Indonesia is a country rich in herbal plants. One of them is noni. Noni (Morinda citrifolia L.) is a plant that has long
been known to have many properties for treatment and disease prevention. This article aims to review the
phytochemical content and pharmacological activity of noni. The way to find information is through Google Scholar
with the keywords "Morinda citrifolia," "phytochemicals," "pharmacological activity." Phytochemically, this plant has

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been reported to contain alkaloids, terpenoids, saponins, carbohydrates, proteins, tannins, flavonoids, steroids,

scopoletin, anthraquinones, and ascorbic acid. Pharmacologically, this plant has been reported to have antioxidant,
antiinflammatory, antifungal, antidiabetic, immunostimulant, anaphylactic, antiulcer, antihypertensive, and
antibacterial properties. The conclusion is that the noni plant contains chemical compounds that are efficacious in
treating various diseases. Because of that, the noni plant can be developed into phytopharmaca.
Keywords: Morinda citrifolia L, noni, phytochemicals, pharmacological activity, phytopharmaca.

License (CC BY-NC 4.0) which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original
author and source are credited.

[1]. Noni (Morinda citrifolia L.) or pace, kudu (Java),
INTRODUCTION cangkudu (Sundanese), koddhu (Madura), tibah (Bali)

originated from Southeast Asia. Other names for this
plant are noni (Betawi, Hawaii), nono (Tahiti), nonu
(Tonga), ungcoikan (Myanmar), and ach (Hindi). Noni
tree reaches 3—8 m high, has white hump flowers. The
fruit is a compound fruit, which is still young, shiny
green, and has spots, and when it is old, it is white with
black spots [2]. The noni fruit is shown in Figure 1, and
the noni plant is shown in Figure-2.

Plants are generally useful as medicine, one of
which is the noni plant. Noni or pace (Morinda citrifolia
L.) is a medicinal plant that has been in demand in
recent years. Noni is a tropical and wild plant. Noni can
grow on the beach to an altitude of 1500 masl (above
sea level), both infertile and marginal lands. Its
distribution is broad, covering the entire South Pacific
archipelago, Malaysia, Indonesia, Taiwan, the
Philippines, Vietnam, India, Africa, and the West Indies

Fig-1: Fruits of Morinda citrifolia L [3]

Scientific classification [1]
Kingdom: Plantae

Subdivision: Angiosperms

Class: eudicots

Clade: Asteridae

Order: Gentianales

Family: Rubiaceae

Genus: Morinda

Species: M. citrifolia

Binomial name: Morinda citrifolia

DATA COLLECTION

In compiling this review article, the technique
used is to use the literature study by finding sources or

Fig-2: Plants of Morinda citrifolia L [4]

Merisa Norma Ayunda et al., Sch Acad J Pharm, Dec, 2020; 9(12): 340-346

literature in primary data or international journals in the
last 20 years (2000-2020). In making this review article,
the search for data used online media with the keywords
Morinda citrifolia, phytochemical and pharmacological
activities. Search for the primary references used in this
review article through trusted websites such as
Mendeley, NCBI, ResearchGate, Google Scholar, and
other published and reliable journals.

PHYTOCHEMICAL REVIEW

The phytochemical content of noni plants is
presented in Table-1 and Table-2 below.

Table-1: The results of the qualitative analysis of phytochemical compounds in noni and their benefits [5]

Plant parts _| Types of compounds

Fruit Alkaloids (xeronin) Increase enzyme activity and protein structure, activate the immune
function.

Polysaccharides (glucuronic acid, | Immunostimulant, anticancer, antibacterial
glycosides)

Scopoletin

Dilates blood vessels, analgesic, antibacterial, antifungal,
antiinflammatory, antihistamine

Antioxidants

Lowering cholesterol, binding fat, regulating blood sugar levels
Deworming, tuberculosis
Anticancer, antibacterial, antiseptic

Table-2: Results of quantitative analysis of the phytochemical content of Morinda citrifolia L

Plant Solvent Compound
parts

Ethanol Alkaloids, flavonoids,
phenols, and terpenoids.
Alkaloids, flavonoids,
phenols, and steroids

Ethyl acetate

Leaf n-hexane,
methanol

Other research discusses the medicinal plant
Morinda citrifolia L containing various phytochemical

Wavelengt Test method

h
Gas
chromatography-
mass spectrometry

17.191 (mg/L) | Folin -Ciocalteu

Alkaloids, flavonoids, Thin-layer
and saponins. chromatography

compounds and their pharmacological activities.
Phytochemical compounds such _ as __ alkaloids,

carbohydrates, proteins, flavonoids, glycosides, fats,
steroids, triterpenoids, and tannins have been identified
from various parts noni plant (Morinda citrifolia L) [9].
Another study showed that flavonoids were present in
the ethanol extract of noni (Morinda citrifolia L) using
thin-layer chromatography (TLC) with a mobile phase

OH
O
flavones flavonols
OT r
[ => oO. - = = 0 _—~
| | |
oe ” i — ™~
O Oo
flavanones flavanonols
[| > cr
T + Y
Oo ‘e)
isoflavones isoflavanones

xanthones chaocones

— OH /_\
(YT rv
OF

fe)

Merisa Norma Ayunda et al., Sch Acad J Pharm, Dec, 2020; 9(12): 340-346

system of butanol-acetic acid glacial-water (3: 1: 1
v/v/v). TLC test results showed the presence of
flavonoids in the extract of noni (Morinda citrifolia L)
[10]. Some of the structures of the noni fruit extract's
flavonoid compounds are shown in Figure-3.

flavanols

anthocy anidins

Oo
om —s o~ O. _CH3
LAS AAS C1 |
o Oo O

furan chromones

aurones

oO” ~~ ~oH
a & 30 7
ge > ocHs
OH O

biflavones

eon”
i ass

a ole 8

dihydrochalcones

Fig-3: Chemical structure and classification of flavonoids contained in noni fruit extract [11]

Phytochemical compounds that have been isolated from noni fruit can be seen in Table 3 below.

Asperuloside

Borreriagenin (previously morindacin)
Deacetylasperuloside

Dehydromethox ygaertneroside

68,7 B -Epoxy-8-epi-splendoside
6a-Hydrox yadoxoside

Table-3: Compounds isolated from the fruit of Morinda citrifolia
Name of the compound
1. Anthraquinones | Anthragallol 1,3-di-O-methyl ether
[12]
Morindone-5-O-methy1 ether
2-Methoxy-1,3,6-trihydrox yanthraquinone [13]
1-n-Butyl-4-(5’-formyl-2'-furanyl) methyl
1-n-Butyl-4-methyl-2-hydroxysuccinate [14]
3. Flavonoids Kaempferol
Quercetin [15]
Nicotifloroside
Rutin [16]
4. Iridoid
[17]
PHARMACOLOGICAL ACTIVITY REVIEW
Diabetes mellitus is a hyperglycemia disease
characterized by absolute insulin deficiency or
decreased cell sensitivity to imsulin [18]. Diabetes is a

6-Hydrox yanthragallol-1,3-di-O-methyl ether
Anthragallol 1,3-di-O-methyl ether [12] [13]
2. Esther
1-n-Butyl-4-methyl-3-hydroxysuccinate
Antidiabetic Activity
metabolic disorder due to insulin failure. This study

aimed to observe the antidiabetic effect of Morinda
citrifolia fruit juice. The research was conducted on
Wistar rats consisting of 48 tails from four groups taken
for examination. Three groups of 36 mice induced
diabetes by administering a single 1/ p 5% w/v alloxan
monohydrate in normal saline. One group as a healthy

control (Group-I), and one as a diabetes control (Group-
II), the comparison of the effects of noni juice 2 mg/kg
BW (Group-IV), with the usual standard drug,
metformin 100 mg/kg (Group -III). The drug is given
by oral route. The parameters studied were serum
glucose levels, triglycerides, total cholesterol, HDL,
LDL, and hemoglobin on days 1, 14, 28 after starting
treatment. After the induction of diabetic serum glucose
and elevated triglyceride concentration and _ total
cholesterol, HDL, LDL _ concentration decreased
statistically significantly where there was no statistical
change in the hemoglobin level. The group given noni
juice showed better results, but the best results were
obtained with standard antidiabetic drugs [19].

Other researchers also conducted experiments
by giving noni juice to Sprague-Dawley rats. Twenty
adult male Sprague-Dawley mice weighing from 145 to
230 g were used for the investigation. They were
randomly divided into four groups consisting of five
mice, each mouse. The first group (Group A) served as
control and received standard rat food and water for the
study duration. The second group (Group B) received
pre-treatment with noni juice for four weeks before
introducing diabetes. This group continued treatment
with noni juice for the next four weeks of diabetes
induction. Group C received noni juice treatment after
diabetes induction for four weeks. Group D was given
distilled water at a dose of 1 mL/150 mg body weight
for four weeks before induction of diabetes with alloxan
and distilled water at a quantity of 1 mL/150 mg body
weight for four weeks after induction of diabetes with
alloxan and distilled water at a dose of 1 mL/150 mg
body weight for four weeks afterward induction of
diabetes with alloxan. Animal glycemia levels in all
four groups were monitored and compared. Mice that
received prophylactic noni juice (group B) before
induction of diabetes with alloxan had the best glycemic
control and the best treatment results. However,
discontinuation of treatment with noni juice resulted in
the reversal of hyperglycemia. This study demonstrated
that noni juice had blood-glucose-lowering activity after
trial-induced diabetes in Sprague-Dawley rats [20].

In another study, an evaluation of the effect of
noni (Morinda citrifolia L.) fruit extract in diabetic rats
using glucose tolerance method in rats and alloxan-
induced diabetic mice. Glucose tolerance test in mice
showed a decrease in serum glucose levels 30, 60, and
90 minutes after giving the extract at a dose of 500
mg/kg BW, respectively 37.0 %, 27.4%, and 25.4%;
and at a dose of 1000 mg/kg each of 28.8 %, 19.6 %,
and 21.8 %. This study's results were noni fruit extract
reduced serum glucose levels in rats by glucose
tolerance method, but it was not statistically significant.
In the diabetic mice test with alloxan, noni fruit extract
showed significant antidiabetic activity at 500 and 1000
mg/kg BW [21].

Merisa Norma Ayunda et al., Sch Acad J Pharm, Dec, 2020; 9(12): 340-346

Antiinflammatory Activity

Utilization of the fruit of the noni (Morinda
citrifolia L.) plant to treat inflammatory diseases such
as arthritis was common in the ancient South Pacific
[22]. Another study was also conducted by someone
with noni juice experiments on people with gingivitis.
This inflammatory process is caused by several species
of bacteria in the dental plaque. In vivo and in vitro
experiments were prepared. Patients from the in vivo
group were divided into noni and control groups. Both
groups consisted of patients suffering from
gingivitis/periodontitis who were introduced _ to
excellent and standardized oral hygiene practices.
Patients in the noni group also used noni juice to wash
their mouths with their mouths twice a day. The
Papillae-Bleeding-Index (PBI) was evaluated by
comparing the inflammation status in the two groups.
Bacterial probes were isolated from the patient's
gingival pouch for species identification and performed
in vitro experiments for possible antimicrobial effects
of noni juice. Papillae-Bleeding-Index (PBI) noni group
experienced a very significant increase from a mean of
2.25 at the start of the observation period (to) to 1.01
after four weeks of noni treatment (t1), compared with a
change of 2.11 at tg to 1.95 m tl in the control group.
Comparing the difference in PBI values (t0-t1) between
the noni group and the control group was very
significant using the t-test at the level of p = 0.01. Only
small zones of inhibition were observed in agar
diffusion tests on agar plates coated with aerobic,
anaerobic, and Candida cultures isolated from the
patient's gingival pouch after treatment with real or
neutralized noni juice in different concentrations. The
weak bacteriostatic effect occurred in the agar dilution
experiment with noni juice in higher concentrations
(original and balanced noni juice). This study has
shown that a combination of good oral hygiene and
noni juice administration is a promising treatment for
gingivitis and periodontitis. Additional therapy with
noni juice significantly reduced gingival inflammation
[23].

Antifungal Activity

Morinda citrifolia juice extract was used in the
antifungal test. The antifungal properties of Morinda
citrifolia fruit extract against Candida albicans were
tested in vitro at various concentrations and at different
times. The inhibitory effect of Morinda citrifolia extract
on Candida albicans was determined by culture and
broth dilution test. Using culture was that the growth of
Candida albicans was not detected with 50 mg/mL
extract at 30 minutes contact time or with 60 mg/mL
extract at 15 minutes contact time. With the broth
dilution test, the minimum fungicide concentration of
the extract against Candida albicans was 40 mg/mL at a
contact time of 90 minutes or with 50 mg/mL at 15
minutes. This study indicated that the Morinda citrifolia
fruit extract had an antifungal effect against Candida
albicans and the inhibitory effect varied in
concentration and contact time [24].

Antioxidant Activity

One of the antioxidant activity of noni fruit
ethanol extract is the presence of flavonoids and
phenolic compounds. Antioxidants are electron-giving
compounds (electron donors) that play a role in
inhibiting oxygen-mediated oxidation. Antioxidant
compounds can prevent the harmful effects caused by
free radical compounds, so they play an essential role in
the body's defense against disease. In this experiment,
the antiradical activity test used the DPPH (1,1-
diphenyl-2- picrylhydrazyl) method. The DPPH method
is an effective and fast colorimetric method for
estimating antiradical activity. Antioxidant activity is
expressed by IC50, which is the concentration required
to produce a 50% decrease in DPPH activity. The
smaller the [Cs , the stronger the antioxidant activity.
From the calculation, it was obtained that the [C59 value
for comparison was 10.56 + 0.42 ug/mL and the [Cs
for the ethanol extract of noni fruit was 104.73 + 4.56
ug/mL. Based on the level of antioxidant strength,
Rutin has extreme antioxidant activity (ICso < 50
ug/mL), while the ethanol extract of noni fruit has
moderate antioxidant activity (ICs) 101 - 250 ug/mL).
One of the antioxidant activity of noni fruit ethanol
extract is the presence of flavonoids and phenolic
compounds. As an antioxidant, these compounds can
stabilize free radicals by complementing the lack of
electrons that free radicals have, and inhibiting chain
reactions from forming free radicals [25].

Other studies were also conducted to evaluate
noni (Morinda citrifolia L.) fruit extracts’ antioxidant
activity, including leaves, fruits, and roots. The solvents
used were methanol and ethyl acetate, and the
antioxidant effect was measured by the Ferric
thiocyanate method (FTC) and thiobarbituric acid test
(TBA). The methanol extract of noni root showed high
antioxidant activity, which was not significantly
different (P < 0.05) with a-tocopherol or butylated
hydroxyl toluene (BHT). In contrast, the methanol
extract of fruit and leaves showed negligible activity.
On the other hand, the ethyl acetate extract from all
noni parts showed significant antioxidant activity,
comparable to a-tocopherol and BHT. Antioxidant
activity was observed using the FTC or TBA method.
The highest antioxidant activity is found in the roots.
The results showed that several compounds contributed
to the antioxidant activity in various parts of noni.
Training in the seeds may be due to polar and non-polar
compounds but, in leaves and fruit, only to non-polar
compounds [26].

Immunostimulant Activity

The alkaloid fraction from the dried noni fruit
was known to have immunostimulant activity at all test
concentrations [27]. Another study was designed to
verify the stimulating effect of the Morinda citrifolia
fruit extract and fraction on the adaptive immune
system's important components such as T lymphocytes
and B lymphocytes. The effect of plant extracts on

Merisa Norma Ayunda et al., Sch Acad J Pharm, Dec, 2020; 9(12): 340-346

lymphocytes was tested using in vitro (MTT test) and in
vivo (cell response) methods. The results of the MTT
study showed that hydroalcoholic extracts (0.5 and 1.0
mg/mL) and water extracts (0.5 and 1.0 mg/mL)
significantly (p < 0.05) increased the extent of
splenocyte proliferation in vitro 43.6, 54.5, 32.7, and
36.4 % respectively. In addition, hydroalcoholic extract
(200 mg / kg) and aqueous extract (200 mg/kg)
significantly (p < 0.05) enhanced cell-mediated immune
response to levels of 33.52 and 18.56 %, respectively.
Fraction I, Fraction II, and Fraction III failed to obtain
lymphocyte stimulating effect in vitro and in vivo
studies. The effect of Morinda citrifolia fruit extraction
on B cells was measured by the delayed-type
hypersensitivity method. Thus, this study shows that
Morinda citrifolia L. fruit stimulates the adaptive
immune system's main components, namely T cells, and
B cells [28].

Anaphylactic Activity

This study aims to prove that the n-hexane
extract of noni fruit can inhibit anaphylactic reactions in
male Wistar rats induced by the hepatitis B vaccine.
This study used an active cutaneous anaphylaxis
method, followed by histopathological observations. A
functional cutaneous anaphylaxis test was performed
for two weeks. The test animals were divided into five
groups, namely the control group without treatment,
treatment with n-hexane extract of noni fruit at a dose
of 50 mg, 100 mg, and 200 mg/kg BW rats. The group
was given chromolin at a dose of 2.16 mg/kg BW rats
as control positive. The test animals were sensitized
twice (once per week) with hepatitis B vaccine (dose
145 ug/kg BW rats) subcutaneously on the back. In the
second week, four animals were taken randomly from
each group to be sacrificed, and their skin tissue and
liver tissue were taken. The tissue was made as a
histopathological preparation with hematoxylin-eosin
staming. The results showed that administering n-
hexane extract of noni fruit at a dose of 50 mg, 100 mg,
and 200 mg/kg BW to Wistar male rats induced by the
hepatitis B vaccine could inhibit active cutaneous
anaphylactic reactions [29].

Antiulcer Activity

This study aims to analyze ethyl acetate
extract's antiulcer activity from the fruit extract of
Morinda citrifolia Linn (Rubiaceae) using different
gastric and duodenal ulceration models in rats. The
work was carried out by inducing gastric ulcers with
oral administration of ethanol, aspirin by pyloric
ligation, and duodenal ulcers caused by oral cysteine
HCl. The extract was administered at 200 and 400
mg/kg orally 30 minutes before ulcer induction. The
reference standard used is ranitidine (50 mg/kg). The
antiulcer activity was tested by determining and
comparing the test group's ulcer index with the standard
drug treatment group. Gastric volume, total acid, and
free acid were estimated in pylorus-bound mice.
Morinda citrifolia (400 mg/kg) showed maximum

inhibition of gastric acid, free acid, and total acid to
53.54 %, 52.55 %, and 30.30 %, respectively. The ulcer
index in the animals treated with Morinda citrifolia was
much less than the standard cases treated with the drug.
The results showed that Morinda citrifolia has
significant antiulcer properties, which could be due to
the drug's cytoprotective action or strengthening of the
gastric and duodenal mucosa by increasing mucosal
defences [30].

Antihypertensive activity

This study aims to examine the effect of
Morinda citrifolia on hypertension in the elderly group.
The noni fruit from generation to generation has been
known as a traditional medicine to treat hypertension.
This research is an experimental study with a pretest-
posttest randomized control group design. The research
subjects were 30 people. The statistical analysis test for
systolic blood pressure is that there is a decrease in
systolic blood pressure before and after drinking
Morinda citrifolia extract capsules. Likewise, with
diastolic blood pressure, there was decreased diastolic
blood pressure before and after drinking Morinda
citrifolia extract capsules. The results showed a
decrease in systolic and diastolic blood pressure in the
elderly who routinely took Morinda citrifolia extract
capsules regularly [31].

Other researchers also revealed a decrease in
blood pressure by consuming processed noni fruit and
the effect of back massage in patients with hypertension
aged 60-74 years. The average reduction in systolic area
was 10.46 mmHg with p-value = 0.001, diastolic 3.23
mmHg with p-value = 0.003. Both treatments are
known to have the same effect as vasodilation of blood
vessels [32].

Antibacterial Activity

This study studied the antibacterial activity of
noni leaf, fruit, and seed extracts in vitro using the
diffusion disc method. Five different accessions of the
Morinda citrifolia plant were randomly selected and
screened for antibacterial activity against five other
bacterial pathogens. The overall analysis of the various
extracts' antibacterial activity revealed that the best
inhibitory activity was produced by seed extracts (12.23
mm) compared to leaf and fruit extracts. All extracts
inhibited E. coli and Pseudomonas. However,
Salmonella, Staphylococcus aureus, and Klebsiella
were not deterred by all extracts. The antibacterial
activity analysis in all accessions showed the best
antibacterial activity was produced by acquisitions 5,
followed by accessions 1, 2, 3, and 4, respectively [33].

Other studies have also revealed that noni leaf
processing has antibacterial effects. Noni leaf
processing is carried out using flour, blending, juicing,
and decoction. However, it did not show any inhibition
against Escherichia coli and Salmonella typhimurium
using the diffusion well test (negative). Liquid extract

Merisa Norma Ayunda et al., Sch Acad J Pharm, Dec, 2020; 9(12): 340-346

of noni leaf flour is obtained by extracting flour using
different solvents, namely water, ethanol, ethyl acetate,
and hexane, then macerated for 24 hours, used for well
testing. The liquid extract of noni leaf meal, which was
macerated for 24 hours, was unable to inhibit the
pathogenic bacteria Escherichia coli and Salmonella
typhimurium but macerated using ethanol and ethyl
acetate for 48 hours. There was an inhibitory power
against the growth of Salmonella typhimurium bacteria
[34].

CONCLUSION

Noni (Morinda citrifolia L.) has _ several
bioactive components related to health benefits such as
alkaloids, saponins, carbohydrates, proteins, tannins,
flavonoids, steroids, and glycosides. Therefore, noni has
biological activities such as analgesic, antipyretic,
antiinflammatory, antioxidant, antifungal,
antimicrobial, antiulcer, anaphylaxis, immunostimulant,
and antidiabetic. Noni (Morinda citrifolia L.) has also
been shown to have vigorous antihypertensive activity
and may help develop new antihypertensive therapies.
Because of that, the noni plant can be grown into
phytopharmaca.

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