J.Mycopathol.Res. 62(2) : 285-291, 2024, ISSN : 0971-3719 (Print), 2583-6315 (Online)© Indian Mycological Society, Department of Botany,
University of Calcutta, Kolkata 700 019, India

10.57023/JMycR.62.2.2024.285

Antioxidant and anticancer potential of endophytic fungus Alternaria
tenuissima PE2 isolated from the leaves of Psidium guajava L.
SOHINI CHATTERJEE1, ANSUMAN CHATTOPADHYAY2 NARAYAN CHANDRA MANDAL1*
1
Mycology and Plant Pathology Laboratory, Department of Botany, Visva-Bharati,
Santiniketan 731235, West Bengal
2
Department of Zoology, Visva-Bharati, Santiniketan 731235, West Bengal
Received : 03.02.2024

Accepted : 24.04.2024

Published : 24.06.2024

For reducing pathological conditions generated by free radicals, it is essential to intake of sufficient amountof antioxidant in the body. Although a large number of plants have been studied for novel source of natural
antioxidants but endophytic microorganisms as antioxidant potential were not studied sufficiently. In thepresent endeavor, potent endophytic fungal strain PE2 was isolated from the healthy and mature leaves of
Psidium guajava L. and was identified as Alternaria tenuissima by 28S rDNA sequence homology. EA
extract of PE2 was subjected for antioxidant studies following different methods. EA extract displayed very
good antioxidant activities through DPPH, ABTS as well as superoxide radical scavenging properties with
IC50 values of 63.01± 2.12 µg/ml, 11.21± 2.12ìg/ml and 138.29 ± 3.10ìg/ml respectively. Apart from this, EA
extract found effective to inhibit the proliferation of breast cancer cell line MDA-MB-231. Survivability of
peripheral blood mononuclear cells in the presence EA extract was also observed. Based on the present
study, PE2 are considered as a probable source of bioactive compounds for the development of new
anticancer drugs.
Keywords: Alternaria tenuissima, antioxidant potential, bioactive compounds, breast cancer cell line,
endophytic microorganisms

INTRODUCTION
In recent years, the free radical chemistry becomes an interested area and achieves more
attention by scientists as well as the relation ofoxidative stress with human disorders is considered as one of important research fields. Free
radicals are molecules or part of molecules withan unpaired electron in their atomic or molecularorbital and are produced naturally by various
physiological activities in the body.
These are reactive oxygen (ROS) or reactive
nitrogen (RNS) species which include superoxideanion (O2•-), hydroxyl (HO•), peroxyl (ROO•)
radicals, nitric oxide (NO•) radical, peroxynitrite
anion (ONOO-) etc. Although free radicals*Correspondence:mandalnc@visva-bharati.ac.inproduced naturally inside the body for performing
important role in a number of cellular functions,
their uncontrolled production stimulates cellularand molecular damages which eventually cause
health disorders. If the body is not able to remove
these excess free radicals efficiently, they cancause a wide array of degenerative humandiseases like cancer, neurodegenerative
disorders, cardiovascular diseases, inflammatory
diseases, Alzheimer’s disease, Parkinson’s
disease and others (Finkel and Holbrook, 2000;
Gülçin, 2007). Antioxidants are those substances
which play important roles to protect the healthby providing an electron to the free radical andstop the chain reaction, therefore slow down
cellular disruption.The human body possess
variety of enzyme systems for scavenging thefree radicals. Besides this, various micronutrientsviz. vitamin C, vitamin E, beta-carotene are also
considered as major antioxidants. These nutrients

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Bioactive potential of an endophyte from guava

must be supplied in the body through regular dietas our body is unable to produce these(Ramassamy, 2006). Although medicinal plants,
fresh vegetables and fruits are the main sourcesof natural antioxidants, several bioactive
compounds obtained from endophytic fungi arealso found to have antioxidant properties (Zhaoet al. 2012; Khiralla et al. 2015).
On the other hand, different types of cancers are
the leading cause of death worldwide. About 7.6
millions death happened in over the world due tocancer and it is predicted that this number will
increase to 13.1 millions in 2030 (WHO, 2013).
The majority of the existing anticancer drugs are
toxic to normal cells; therefore exhibiting adverse
side effects as well as they are less effective
against several kinds of cancer (Remesh, 2017).
To overcome these, there is a basic need forsearching of bioactive metabolites from natural
sources. The medicinal plants therefore
considered as an alternative source of anticancer
drugs due to their intrinsic potential without side
effects, as well as low levels of cytotoxicity(Mbavenget al. 2011; Debbie et al. 2012). Several
plant derived compounds, for example, taxol,
vinblastine, vincristine, camptothecin ,podophyllotoxins played an important role in thedevelopment of potent anticancer drugs (Cragg
and Newman, 2004; Srivastava et al. 2005). It was
already reported that some of the endophytic fungi
have the ability to produce similar or identicalsecondary metabolites as their host plants which
revealed promising biological potential (Tan andZou, 2001; Zhao et al. 2011;Jia et al. 2016).
Therefore, they have been considered asprobable source of novel anticancer drugs(Kharwaret al.2011; Schulz et al.2002; Newman
and Cragg, 2007). The world’s first billion dollar
anticancer drug taxol was initially discovered fromthe gymnosperm Taxus brevifolia. Later on the
taxol producing endophytic fungi Taxomyces
andreanae was isolated from the plant Taxus
brevifolia (Strobel, 2003), which significantly
reduced the destruction of Taxus plant.
Psidium guajava L. (Family Myrtaceae),
commonly known as ‘guava’ is a popular fruit plant
as well as a very common home garden tree in
India. Different parts of this plant, including leaves,[J.Mycopathol.Res :barks, roots and fruits have several medicinal
importance likeanti-microbial, anti-oxidant, antiinflammatory, anti-cancer, analgesic,anti-malarial,anti-diabetic and others (Guti´errezet al. 2008).In
traditional medicines,it is widely used for anumber of illnesses. From various parts ofP.guajava,numbers of chemical constituents havebeen reported which includedphenolic
compounds,isoflavonoids, carotenoids, catechin,epicathechin, gallic acid, rutin, kaempferol,
ascorbic acid, naringenin etc. (Barbalho et al.
2012).
In our previous study, we have isolated an
endophytic fungus Alternaria tenuissima PE2 withbioactive potential from the leaves of Psidium
guajava L. grown in the lateritic belt ofSantiniketan, West Bengal, India. (Chatterjee etal. 2022). The EA extract of PE2 was found very
effectivefor controlling the growth of pathogenic
as well as spoilage bacterial and fungal strains.
Apart from this, it was also exhibited anticandidal
activity against human pathogenic yeast Candida
albicans (Chatterjee et al. 2022).
The present study was aimed to evaluate theantioxidant activity of the ethyl acetate (EA) extractof potent endophytic isolate Alternaria tenuissima
PE2 by DPPH, ABTS and superoxide free radical
scavenging assays. Besides this, anticancer
properties of PE2 were also determined byevaluating its effects on human breast cancer cellline MDA-MB-231. The survivability of normal cells
in the present of EA extract were also checkedusing human peripheral blood mononuclear cells(HPBMCs).
MATERIALS AND METHODS
Collection of plant materials and identificationof PE2The endophytic fungus PE2 was isolated from
fresh and mature leaves of Psidium guajava L.
were collected randomly from plants grown in
Santiniketan (23.6816660 °N, 87.6714825 °E),
W est Bengal, India, during the month of
September. (Chatterjee et al. 2022).The leaves
were collected when the plants were blossomed.
The plant was identified by Professor Subrata
Mondal, Plant Biosystematics Laboratory,

62(2) June, 2024]

Sohini Chatterjee and others

287

Department of Botany, Visva-Bharati,
Santiniketan.
The potent isolate PE2 was identified based on
the morphological characters as well as byamplification followed by sequencing of D1/D2
region of large sub unit 28S rDNA (Chatterjee etal. 2022)

A blank: absorbance of control, A sample:
absorbance of methanolic solution and DPPH.
IC50 value was calculated by plotting straight line
equation. The well known antioxidant ascorbic
acid was considered as positive control during
this assay and its free radical scavenging potential
also determined following the same process.

Solvent extraction of PE2

Determination of antioxidant activity by ABTS
free radical scavenging assay

Initially different solvents were used but basedon ability of the ethyl acetate (EA) for extracting
the bioactive compounds was chosen as themost suitable one. PE2 was grown in 1 l of ME
broth at 28 ºC for 21 days. The cell freesupernatant (CFS) was collected by filtration withmuslin cloth followed by centrifugation at 10,000rpm for 20 min. Each 100 ml of CFS was mixed
with 40 ml of EA, shaken vigorously and the upper
EA fraction was collected by separating funnel.
The EA portion was evaporated to dryness using
rotary vacuum evaporator at room temperature(26 ± 2 °C) and stored at 4 °C for future
experimentations.
Study of Antioxidant activity of EA extract ofPE2
To evaluate the antioxidant potential of EA extractof PE2, 2, 2-Diphenyl-1-picrylhydrazyl (DPPH),
2, 2' – azino- bis (3- ethylbenzothiazoline-6sulphonic acid) (ABTS) free radicals andsuperoxide radical assay were performed.
Determination of antioxidant activity by DPPH
free radical scavenging assay
DPPH free radical scavenging assay was carriedout following the method described by Lee et al.
(1998). The dried EA extract was dissolved inmethanol at a concentration of 10 mg/ml. 100 ìlof methanolic solutions containing different
concentrations of extract of PE2 were mixed with
2900 ìl of DPPH solution and incubated for 30
minutes at room temperature in dark condition.
In control set, only 100 ìl of methanol was added
to the DPPH solution. The absorbance wasrecorded at 517 nm after the incubation period
and the percentage of inhibition (%I) of free
radicals was calculated as: %I = [(A blank-A
sample)/A blank]×100, where,

Free radical scavenging activities of EA extractof PE2 was also checked using 2, 2'– azino- bis(3- ethylbenzothiazoline- 6- sulphonic acid)(ABTS) radical cation decolorization assay (Reet al. 1999). The reaction between 7 mM ABTS inwater and 2.45 mM potassium persulfate (1:1)
produced ABTS·+ cation radical. After 12-16 hours
incubation at room temperature in the dark,
ABTS·+ solution was diluted with methanol for
getting an absorbance of 0.700 ± 0.002 at 734
nm. 5 ìl of sample solutions containing different
concentrations of EA extracts were added to3.995 ml of diluted ABTS·+ solution. After 30
minutes of the initial mixing, the absorbance wasmeasured at 734 nm. Percentage of inhibition was
calculated using the formulaABTS·+ scavenging effect (%) = [(AB–AA)/AB)]×100 , where,
AB is absorbance of ABTS radical + methanol;
AA is absorbance of ABTS radical + sample
extract or standard. Trolox was used as astandard in this assay.
Determination of antioxidant activity bysuperoxide radical scavenging assay
Superoxide radical scavenging activities of the EA
extract was determined by using phenazine
methosulfate-nicotinamide adenine dinucleotide(PMS/NADH) system (Fontana et al., 2001). One
ml of reaction mixture was prepared by adding
sodium phosphate buffer (20 mM, pH 7.4), NADH
(73 ìM), nitro blue tetrazolium or NBT (50 ìM), PMS(15 ìM) and EA extract of PE2 (0-250 ìg/ml).
Absorbance was recorded at 562 nm in thepresence of appropriate blank after five minutesof incubation at room temperature. Quercetin was
taken as positive control during this study.

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Bioactive potential of an endophyte from guava

Percentage of inhibition (%I) of each radical was
calculated as: %I = [(A blank-A sample)/ A blank]
×100, where, A blank: Absorbance of control(without EA extract of PE2), A sample: Absorbanceof sample (with EA extract of PE2). IC50 value
was calculated from straight line equation.
Study of anticancer activity by MTT assay
Anticancer study was carried out using humanbreast cancer cell line MDA-MB-231 after treatingthem with different concentrations (20- 300 µg/ml) of EA extract of PE2. Cell culture plates wereincubated at 37°C in a 5% CO 2 incubator(Thermo Scientific, USA). After 48 hours, cellproliferations were estimated by MTT assay(Mosmann, 1983) where absorbance was taken
at 595 nm. Cell survival percentages were
calculated considering 100% survival in control
set where only equal amount of DMSO was added
without any EA extract. 50 mM mitomycin C wasused as positive control. Survivability of normal
cells in the presence of EA extract were also
checked using human peripheral bloodmononuclear cells (HPBMCs) using the sameprocess.

[J.Mycopathol.Res :2015). By considering EA as most suitable
solvent for extracting bioactive compounds fromendophytic fungi, EA extract of PE2 was subjected
for antioxidant studies following different methods.
During DPPH free radical scavenging assay inthe presence of different concentrations of EA
extract of PE2, the pink color DPPH solution
turned into yellow along with increased
concentration of the extracts which suggested its
strong antioxidant property. In the presence of 150
ìg/ml concentration of EA extract of PE2, 91.38%
inhibitions of free radicals were recorded. Fromthe standard curve of percentages of inhibition,
IC50 value revealed as 63.01 g/ml for EA extractof (Table 1). On the other hand, ascorbic acid,
which was used as positive control in this study,
exhibited an IC50 value of 20.23 g/ml (Table1).
Endophytic fungi Chaetomium sp. and Aspergillus
sp. isolated from Eugenia jambolana Lam. also
exhibited 80% inhibition of free radicals during
DPPH free-radical scavenging assay (Yadav etal. 2014).

Statistical analysis
All the data represented the means of at least
three replicates. Means and standard deviation
were calculated with the help of Microsoft Excel
program version 2007.
RESULTS AND DISCUSSION
Isolation and identification of PE2

Fig. 1: Survival percentage of Cancer cell lines against different
concentrations of EA extracts of endophyte strain PE2

The potent strain PE2 with antioxidant andanticancer potential which was isolated from freshand mature leaves of Psidium guajava, wereidentified as Alternaria tenuissima on the basisof its morphological characteristics as observed
under light microscope as well as based on D1/
D2 region of LSU (Large subunit 28S rDNA) genesequences (Chatterjee et al. 2022).
Antioxidant activities of EA extract of PE2
DPPH free radical scavenging potential
Antioxidants are obtained naturally from different
plants, fruits and vegetables, few reportssuggested that endophytic organisms also havevery good antioxidant potential (Khiralla et al.

Fig. 2: Survivability of cells us ing human peripheral bloodmononuclear cells (HPBMCs) in the presence of EA extract ofPE2

Sohini Chatterjee and others

62(2) June, 2024]

289

Table 1: DPPH free radical scavenging activities of EA extract of PE2

Percentage (%) of inhibition
Concentration (µg/ml)

Ethyl acetate extract of PE2

Ascorbic acid (positive control)

55.94 ± 1.88

23.76 ± 1.67

10

11.18 ± 1.93

31.72 ± 2.88

20

20.82 ± 1.87

49.43 ± 2.2230

24.0 ± 1.93

79.23 ± 3.12

40

35.07 ± 1.95

88.98 ± 2.82

50

43.38 ± 2.11

97.27 ± 1.70

60

48.61 ± 2.26

97.77 ± 1.51

80

67.07 ± 2.82

98.25 ± 1.20

100

75.38 ± 2.54

98.42 ± 0.41

150

91.38 ± 2.11

98.51± 0.22

IC50

63.01 ± 2.12

20.23 ± 1.83

Table 2 : ABTS free radical scavenging activities of EA extract of PE2.

Percentage (%) of inhibition
Concentration (µg/ml)

Ethyl acetate extract of PE2

Trolox (positive control)

525.37 ± 1.87

9.95 ± 1.26

10

44.60 ± 2.23

19.84 ± 2.12

20

76..81 ± 1.85

42.18 ± 2.67

30

90.79 ± 1.32

65.63 ± 1.68

40

96.10 ± 1.89

72.42 ± 2.41

50

97.52 ± 1.10

87.54 ± 1.82

100

98.05 ± 1.04

96.23 ± 1.54

IC50

11.21 ± 2.12

23.21 ± 1.32

Table 3: Superoxide radical scavenging activities of EA extract of PE2.

Percentage (%) of inhibition
Concentration (µg/ml)

Ethyl acetate extract of PE2

Quercetin (positive control)

1014.93 ± 1.41

35.92 ± 1.78

20

29.87 ± 1.76

41.63 ± 2.1130

31.65 ± 1.14

59.18 ± 2.34

40

38.15 ± 2.34

93.22 ± 2.72

50

54.23 ± 3.12

98.65 ± 1.02

100

69.25 ± 3.00

98.88 ± 1.08

IC 50

138.29 ± 3.10

42.31 ± 1.80

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Bioactive potential of an endophyte from guava

ABTS free radical scavenging potential
A prominent decoloration of ABTS solution fromgreenish blue color was noticed along withincreased concentrations of the EA extract of
PE2. ABTS is most commonly used substanceby the various food industry and researchers for
estimating the antioxidant properties of different
foods or other natural products. EA extract wasable to inhibit more than 90% free radicals at aconcentration of 30 g/ml. IC50 value of EA extractof PE2 was calculated as 11.21g/ml (Table 2),
which was much lower than the IC50 value(23.21g/ml) of the standard substance trolox.
The EA extract of Cytospora rhizophorae andSeiridium ceratosporum isolated from
Rhizophora stylosa, found most effective
scavengers of ABTS radicals with IC50 values of
0.50 mg/mL and 0.37 mg/ml respectively (Zhouet al. 2018).
Superoxide radical scavenging assay
It has been reported previously that the presenceof flavonoids in the plant or their endophytic
extracts is responsible for scavenging thesuperoxide free radicals which are highly reactive
molecules. In addition to DPPH and ABTS free
radical scavenging properties, the EA extract of
PE2 also exhibited substantial superoxide free
radical scavenging potential. Along with increased
concentration of EA extract, prominent reductionof the purple color solution was noticed. EA extractof PE2 showed an IC50 value of 138.29 ìg/ml. In
comparison, the IC50 value of the well-known
standard quercetin (positive control) was
calculated as 42.31µg/ml (Table 3). EA fractionof Alternaria alternata AE1 exhibited superoxide
free radical scavenging activity with IC50 valueof 11.38 ìg/ml (Chatterjee et al.2019).

[J.Mycopathol.Res :presence of 200 g/ml EA extract (Fig. 1). On theother hand, in the presence of 50 mM mitomycin
C which was used as positive control, 54.56 %cell survivals was recorded during MTT assay.
On the other hand, when the survivability ofnormal cells were checked using humanperipheral blood mononuclear cells (HPBMCs) inthe presence of EA extract, 63.21 % cells remain
survived in the presence of 100 g/ml of EA
extract PE2 (Fig. 2). The inhibition of proliferationof human breast cancer cell line suggested
strong anticancer potentiality of the EA extract of
PE2. Anticancer properties of bioactive
compounds derived from endophytic fungi havealso been reported earlier (Fernandes et al. 2009;
Arivudainambi et al. 2014).
CONCLUSION.
From the above study, DPPH and ABTS free
radical as well as superoxide scavenging assays
suggested very good antioxidant activity of EA
extract of endophytic isolate PE2. In addition, EA
extract also found effective to inhibit the
proliferation of breast cancer cell line MDA-MB231. Therefore it was considered as a mostpromising source of bioactive compounds for thedevelopment of new anticancer drugs.Survivabilityof peripheral blood mononuclear cells in thepresence EA extract also suggested its specificactivities to cancer cells and may open new
window for cancer chemotherapy.
ACKNOWLEDGEMENTSC sincerely acknowledge UGC for providing
UGC-BSR fellowship [No.F.25-1/2013-14(BSR)/
7-220/2009(BSR)] as financial support. Authors
are also thankf ul to Arindam Chatterjee,
Department of Zoology, Visva-Bharati for
anticancer study.

Anticancer activity of EA extract of PE2
DECLARATIONS
Now a day, searching of novel anticancer drug
from natural sources becomes one of theimportant fields of research. EA extract of PE2
was also found effective to inhibit the proliferationof breast cancer cell line MDA-MB-231 whentested at different concentrations (20- 300 µg/ml).
45.70 % cell survival was found in the presenceof 100 ìg/ml which decreased to 15.72 % in the

Conflict of Interest. Authors declare no conflict ofinterest.
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