Ifora et al Asian Journal of Pharmaceutical Research and Development.

2021; 9(2): 47:52

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Open Access Review Article

Potential anti-inflammatory effects of Psidium guajava L.: A review
M. Sofyan souri, Sri Oktavia, Ifora Ifora*
Department of Pharmacology and Clinical Pharmacy, School of Pharmaceutical Science Padang (STIFARM Padang), West
Sumatera, Indonesia, 25147

ABSTRACT

Inflammation is a defence mechanism of a body against foreign substances. However, Inflammation also plays a key role in
diseases such as diabetes, asthma, cardiovascular diseases, and cancer. Increasing scientific evidence has shown that fruits,
vegetables, and legumes can have anti-inflammatory properties. This paper aims to provide recent studies on the anti-
inflammatory properties of Psidium guajava L. A review was conducted on the studies of Psidium guajava L. anti-inflammatory
properties performed during the past 10 years with the literature databases such as Pub Med, Science Direct, Google Scholar.
Based on our eligibility criteria, a total of ten studies were included in this paper. The studies suggest that the anti-
inflammatory activity of Psidium guajava occurs mainly through inhibition of PGE2, COX-2, NO, iNOS, ERK1/2, leukocyte cell
migration, and suppression of edema, paw withdrawal latency as well as exhibited a membrane stabilization effect. This review
has demonstrated the importance of Psidium guajava L. as a natural anti-inflammatory potential.
Keywords: Anti-inflammatory, Inflammation, Psidium guajava L.

A R T I C L E I N F O: Received 16 Jan. 2021; Review Complete 21 Feb. 2021; Accepted 25 March 2021; Available online 15 April. 2021
Cite this article as:
M. Sofyan souri, Sri Oktavia, Ifora ifora, Potential anti-inflammatory effects of Psidium guajava L. : A review. Asian Journal of
Pharmaceutical Research and Development. 2021; 9(2):47-52. DOI: http://dx.doi.org/10.22270/ajprd.v9i2.941

*Address for Correspondence:

Ifora ifora, Departement of Pharmacology and Clinical Pharmacy, School of Pharmaceutical Science Padang (STIFARM
Padang), West Sumatera, Indonesia, 25147

INTRODUCTION (CV) and gastrointestinal (GI) events, high blood pressure,

renal toxicity, and worsening of ongestive heart failure 4–7.

I nflammation is an organism's defense mechanism

against foreign substances. Systemic and local
inflammatory responses aim to remove the
triggering stimulus, facilitate tissue repair and healing, and
develop immune memory in the case of infection so that in
Natural medicines have become increasingly used in recent
years as alternative treatments for inflammation because of
their relatively mild side effects 8–11. There is a strong
interest in natural products that have few side effects. The
the future, the host mounts a more rapid and targeted previous research found that the various plants have distinct
response 1,2. However, in some cases, Excessive and/or therapeutic activities, including anti-inflammatory
chronic inflammation may result in severe tissue damage, behaviors 12–14. Scientific increasing evidence indicates that
organ dysfunction, and death. The importance of fruits, legumes, and vegetables can have anti-inflammatory
inflammation in diseases as varied as cancer, properties 15–17.
atherosclerosis, reperfusion injury, diabetes and
Psidium guajava L. is the most important fruit of the genus
Alzheimer's disease has prompted a major research effort
Psidium, which consists of around 150 species. Many parts
into the processes that activate and control the
of the plant, including the fruits, leaves, and bark, have
inflammatory response 3.
long been used as herbal medicines for a range of ailments,
Nowadays, NSAIDs are some of the most widely including inflammation 18. The vitamins C, which are
prescribed medications in the world, and their analgesic, relatively abundant in guava berries, which have high
anti-inflammatory, and anti-pyretic properties are widely antioxidant ability, are even more essential. The presence
acknowledged. Like many other drugs, however, NSAIDs of polyphenols such as flavonoids, phenolics, and tannins
have a wide range of side effects, including cardiovascular enhances this ability even more 18–21. Carotenoids, such as
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 Ifora et al Asian Journal of Pharmaceutical Research and Development. 2021; 9(2): 47:52

γ-carotene, β-carotene, β-cryptoxanthin, rubixanthin, update, the search terms were “Anti-inflammatory”,
cryptoflavin, lycopene, lutein, and neochrome, play an “Inflammatory”, “Psidium guajava L.” using the
important role in the fruits' health benefits, including its publication from 2010 to 2020. Only accessible online
superfood status. The fruits' high polyphenolic content, articles in English or Indonesian were reviewed. All
with about 40 mg gallic acid equivalent per gram, is a abstracts, and full-text articles were collected, examined,
significant benefit that contributes to their antioxidant and summarized, and conclusions made accordingly. The
pharmacological properties 22–24. taxonomy of plants has been verified from the database
“The Plant List” (www.theplantlist.org).
Currently, there is increasing interest in studying plants
regarding their effects on several diseases, and for human RESULTS AND DISCUSSION
health, it may be used as functional foods and/or
nutraceuticals. 25. Thus, this paper aims to provide the Psidium guajava L. has anti-inflammatory activities,
current studies on the anti-inflammatory of Psidium according to in vitro and in vivo studies. Based on our
guajava L. eligibility requirements, a total of 10 studies were included
in this article. The anti-inflammatory properties of Psidium
METHODS guajva L. are summarized in Table I.
The present review was performed using the databases,
including Google Scholar, Science Direct, PubMed. In this

Table: 1. Summary of anti-inflammatory properties of Psidium guajava L. (In vivo and In vitro studies)

Plant part
Animal or disease
Type of extract or and source Dose/
Experimental Model models or Reported activity Region Ref.
Formulation used for concentration
Cell/specimen
studies
The extracts
Ethyl acetate and Carrageenan-induced paw exhibited significant 26
Leaves 200 mg/kg bw The wistar albino rat India
methanol extract edema (In vivo) anti-inflammatory
activity
The aqueous extract
exhibited anti-
125, 250, and Carrageenan-induced paw Male Sprague-Dawley 27
Aqueous extract Leaves inflammatory Indonesia
500 mg/kg BW edema ( In vivo ) rats
properties through
decreasing edema
The crude extract of
Psidium guajava
Carrageenan-induced paw 28
Methanolic extract Leaves 300 and 500 mg/ml Swiss albino mice leaves significantly Ethiopia
edema ( In vivo )
decreased paw
edema
Mixture of solvents The mixture extract
(Chloroform, Carrageenan-induced paw showed a significant 29
Leaves 200 and 400 mg/kg Wistar albino rats India
Methanol, Pet. edema ( In vivo ) anti-inflammatory
ether) extract activity
- 10% : 8% The extract showed
Decoction and Carrageenan-induced paw 30
Leaves - 5% : 5% Wistar Rat an anti-inflammatory Indonesia
infusion edema ( In vivo )
- 8% : 10% effect
The essential oils
Lipoposaccharide-induced showed anti- 31
Essential oil Leaves 100 mg/kg Male Swiss mice Brazil
pleurisy (In vivo) inflammatory
activity
32
Ethanolic extract Leaves 100, 200, and 1. Male Sprague- The ethanolic extract Korea
400 mg/kg Freund’s complete adjuvant Dawley rats exhibited significant
5, 10, 30, or 50 μg induced arthritis (In vivo) 2. RAW264.7 anti-inflammatory
/mL LPS-stimulated RAW264.7 macrophage cells activity
macrophage model (In vitro)

The methanol and

ethanol extracts
Hypotonicity induced human showed membrane
Methanol and red blood cell (HRBC) Human Red Blood stabilization effect 33
Leaves 10,000 µg/ml India
ethanol extract membrane stabilization (In Cell (HRBC) by inhibiting
Vitro) hypotonicity-induced
lysis of erythrocyte
membrane.
34
Ethanol extract Leaves 10, 25, 50, and 100 LPS-stimulated RAW264.7 RAW 264.7 The ethanolic extract Korea
µg/mL macrophage model (In vitro) macrophage cells showed an anti-
inflammatory effect
through inhibiting
NO production.
Acetone–water The extract exhibited
50, 100 and 200 Carrageenan-induced peritonitis 35
extract and aqueous Leaves Female Swiss mice anti-inflammatory Brazil
mg/kg (In vivo)
extract effect

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 Ifora et al Asian Journal of Pharmaceutical Research and Development. 2021; 9(2): 47:52

Effect of Psidium guajava L. on inhibition of carrageenan- Effect of Psidium guajava L. on alterations in MAPK
induced edema signalling pathways and regulation of inflammatory
mediators
The carrageenan-induced oedema assay was used to search
for possible activity against pro-inflammatory mediators. Macrophages, which release pro-inflammatory mediators
This model also has two phases: an early phase that starts 6 and proteins such as cyclooxygenase-2 (COX-2),
hours after carrageenan injection and lasts 72 hours, and a interleukin-6 (IL-6),inducible nitric oxide synthase (iNOS),
later phase that starts 6 hours after carrageenan injection and and tumour necrosis factor- α (TNF- α) are important
lasts 72 hours. Inflammation reaches its highest between 48 players in inflammatory diseases and the immune response
and 72 hours 36. In the early stages of this experiment, 39
. When activated by lipopolysaccharide (LPS), the RAW
histamine, serotonin, and increased prostaglandin synthesis 264.7 mouse macrophage cell line produces
were identified (between 1 h and 2 h after injection). Direct proinflammatory cytokines and other inflammatory
prostaglandins released by damaged tissue, as well as mediators, such as a prostaglandin E2 (PGE2) and nitric
bradykinin, leukotrienes, polymorphonuclear cells, and oxide (NO), which are produced by COX-2 and iNOS,
macrophage-produced prostaglandins, trigger the later stage respectively 40. COX-2 is a prostaglandin-producing enzyme
of oedema 37,38 . There are several previous studies that have that is stimulated by proinflammatory cytokines and other
shown anti-inflammatory activity of Psidium guajava L. activators including LPS, resulting in a significant amount
through reducing edema, as the following research : of PGE2 being released at inflammation sites. As a result,
discovering COX-2 inhibitors is thought to be a promising
A study conducted by Bera et al. reported that the ethyl
strategy for preventing inflammation and tumorigenesis 41,42.
acetate and methanol extracts of Psidium guajava L. leaf
NO, a well-known pro-inflammatory mediator developed by
exhibited significantly reduced carrageenan-induced rat paw
iNOS, is involved in a number of physiological and
oedema after a period of 4 h. The two Psidium guajava
pathological processes. Suppression of NO output has
extracts tested were effective in both the early and late
recently been promoted as a novel pharmacological
phases. It was discovered that the methanol extract was
technique for treating inflammation-related diseases. The
significantly more active than the ethyl acetate extract 26.
inhibition of iNOS activity is a promising therapeutic target
Aqueous leaves extract of Psidium guajava L. at doses of
for a number of pathological conditions 41. Recent studies
125, 250, and 500 mg/kg was observed to show potent anti-
have discovered that MAPK signalling pathways are
inflammatory activity. The extract at a dose of 250 mg/kg
important in the regulation of the inflammatory response
gives the best effect among the three doses tested. The
and in the coordination of the induction of many genes that
impact is better than Indomethacin beginning at the 4th hour
code for inflammatory mediators. The three main MAPK
in reducing edema 27. In another study revealed that the 80
pathways are composed of a family of highly conserved
percent methanolic extract inhibited oedema for 5 hours
protein kinases called ERK, JNK, and p38. Immune
period, which is possibly due to inhibition of various
responses also including pro-inflammatory cytokine
chemical mediators of inflammation. The 80 percent
production, mitosis, differentiation, and cell
methanol extract of Psidium guajava leaves at doses of 300
survival/apoptosis are all regulated by these kinases. For
and 500 mg/ml significantly reduced carrageenan-induced
LPS-treated RAW264.7 cells and peritoneal macrophages,
paw oedema at all time points assessed after administration
ERK is important for COX-2 expression. LPS-induced NO
(p<0.001). At both test doses of 300 and 500 mg/kg, the
synthesis was suppressed by the ERK1/2 inhibitor, PD98059
extract had the greatest anti-inflammatory activity at the
and the p38 inhibitor, SB203580, according to the study
third hour after administration. Carrageenan-induced edema 43,44
. There are several previous studies that have shown
was decreased by 51% and 57%, respectively, while the
anti-inflammatory activity of Psidium guajava L. through
standard medication at a dosage of 20 mg/kg prevented
inhibition of PGE2, COX-2, NO, iNOS, ERK1/2, as the
edema by 58.5 percent as compared to the control group. It
following reported:
was discovered that the plant extract's anti-inflammatory
activity was largely due to the inhibition of second-phase The anti-inflammatory activities of Psidium guajava
chemical mediators such as prostaglandins 28. Similarly, at ethanolic leaf extract were observed in vitro and in vivo.
doses of 200 mg/kg and 400 mg/kg, a mixture of solvent The results show that guava leaf extract (GLE) significantly
extract of Psidium guajava leaf demonstrated important decreased the production of inflammatory mediators
anti-inflammatory activity using the Carrageenan mediated including nitric oxide and prostaglandin E2 induced by
rat paw edema method using the Plethysmometer. The 400 lipopolysaccharide (LPS). GLE also inhibited the expression
mg/kg dose demonstrated strong activity as compared to the and activity of inducible nitric oxide synthase (iNOS) and
normal dose and the 200 mg/kg dose. When compared with cyclooxygenase-2 (COX-2) in RAW264.7 macrophages by
control, the anti-inflammatory activity had a significant inhibiting ERK1/2 activation 32.
effect 29. Marsh fleabane roots (Pluchea indica L.) and
Freund's complete adjuvant is widely used to cause arthritis
guava leaves (Psidium guajava L.) were combined at a
in animal models by causing inflammation in the hind paw
concentration of 5% : 5% and showed anti-inflammatory
of rats. The FCA-induced inflammatory hyperalgesia rat
effects through edema suppression. It's a better mix than the
model is a well-known model for testing drug analgesic
others, and it's equivalent to the positive control 30.
efficacy. During the first week following the intervention,
FCA-injected rats have elevated serum IL-6, extreme
hyperalgesia, and oedema 45,46. Jang et al. reported that

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 Ifora et al Asian Journal of Pharmaceutical Research and Development. 2021; 9(2): 47:52

administration of Psidium guajava leaf extract exhibited neutrophil and mononuclear cell migration inhibition 31. In
inhibitory activity in FCA-induced paw withdrawal latency addition, in another study by De Araújo et al., the aqueous
32
and acetone-aqueous extracts of Psidium guajava showed
anti-inflammatory activity, these extracts significantly
In addition, the ethanolic extract demonstrated an anti-
reduced the migration of leukocytes 35.
inflammatory effect through inhibiting NO production and
exhibited a concentration-dependent inhibitory effect on NO CONCLUSIONS AND FUTURE PROSPECTS
production when treated with guava leaf extract. This study
Herbal remedies provide significant guidance for the
showed a significant NO inhibitory effect of 50.4% at 100
development of drugs, such as anti-inflammatory
μg/mL 34.
medications. The importance of Psidium guajva L. as an
Effect of Psidium guajava L. on lysosomal membrane anti-inflammatory agent has been demonstrated in this
stabilization study. Several molecular pathways have been used to
evaluate the anti-inflammatory properties of Psidium
Acute and chronic inflammatory disorders are regulated by
guajava L. in vitro and in vivo. Psidium guajava L. has been
lysosomal enzymes. Inflammatory mediators such as oxygen
reported to significantly reduce TNF- α and IL-6 levels, as
radicals and prostaglandins are activated when lysosomal
well as inhibit COX-2, PGE2, NO, iNOS, ERK1/2,
enzymes are released into the cytoplasm. By preventing the
leukocyte cell migration, and suppression of edema. In
release of lysosome constituents, lysosomal membrane
addition, the Psidium guajava L. also showed a significantly
stabilization is essential in reducing the inflammatory
reduce paw withdrawal latency as well as exhibited a
response 47. Membrane stabilizers inhibit the release of lytic
membrane stabilization effect by inhibiting hypotonicity-
enzymes and active mediators of inflammation, which
induced lysis of erythrocyte membrane. However, more
prevent serum protein and fluid leakage through the cell
research is needed to better understand metabolism in the
membrane 48.
body and the role of metabolites in anti-inflammatory
A study with a different method on membrane stabilization action, which may contribute to the production of new anti-
effect conducted by Hotta et al., the study reported that inflammatory drugs in the future. Furthermore, Future
methanol and ethanol leaf extracts of Psidium guajava L. research on the anti-inflammatory activity of Psidium
were found to have a membrane-stabilizing effect by guajava L. should include clear sources and specifications
inhibiting hypotonicity-induced erythrocyte membrane lysis, for the ingredients used, particularly when plant extracts are
according to the report. The methanol leaf extract of used. To ensure the anti-inflammatory activity of Psidium
Psidium guajava had the strongest anti-inflammatory guajava L., the methods and conditions used in vitro and in
function, while the ethanol leaf extract had the weakest 33. vivo must be validated.
Effect of Psidium guajava L. on inhibition of leukocyte ACKNOWLEDGMENTS
migration
The authors are grateful to all colleagues at The
Exogenous and endogenous agents lead to pulmonary Departement of Pharmacology and Clinical Pharmacy,
damage, with the involvement of several inflammatory School of Pharmaceutical Science Padang (STIFARM
mediators and enzymes. Inflammation, in particular, plays Padang), for helpful discussions.
an important role in lung damage. During the early phase of
CONFLICT OF INTEREST
lung injury, an increase in the percentage of leukocytes,
eosinophils, neutrophils, lymphocytes, and macrophages in The authors declare that they have no conflicts of interest.
bronchoalveolar lavage fluid (BALF), and there was an
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