ISSN   0974-3618  (Print)                  www.rjptonline.org

            0974-360X (Online)

 

 

REVIEW ARTICLE

Endophytic Fungi with Antioxidant Activity- A Review

 

Shylaja Gunasekaran , Shoba Sundaramoorthy , Uma Anitha, Mythili Sathiavelu,

Sathiavelu Arunachalam*

School of Bio-Sciences and Technology, VIT University, Vellore-632014, Tamilnadu, India

*Corresponding Author E-mail: asathiavelu@vit.ac.in

 

ABSTRACT:

Plant endophytic fungi have been considered as one of the important and novel resource of natural bioactive compounds, especially in pharmaceutical application. This review mainly deals with the research progression on the production of some of the antioxidant compounds produced by endophytic fungi of various medicinal plants for the last few years. The purpose of this review is to provide integrated information related to antioxidant compounds and fungal endophytes.

 

KEY WORDS: Endophytes; Free radicals; Antioxidant metabolites; Medicinal plants.

 

 


1. INTRODUCTION:

There is increasing evidence indicating that reactive oxygen species (ROS, e.g., 02- and OH-) and free radical-mediated reactions causing oxidative damage to biomolecules (e.g., lipids, proteins, and DNA), which leads to aging, cancer, atherosclerosis, coronary heart ailment, diabetes, Alzheimer's disease, and other neurodegenerative disorders1.

 

Free radicals  also involves in a wide range of toxic oxidative reactions like initiation of the peroxidation of the membrane lipids which eventually leads to the accumulation of lipid peroxides, inhibits mitochondrial respiratory chain enzymes, causes fragmentation or random cross linking of biomolecules which causes cell death. Free radicals also involves in destroying the naturally occurring antioxidant enzymes like superoxide dismutase, catalase and peroxidase; causing destruction and lethal apoptosis through oxidization of membrane lipids, cellular proteins, DNA and enzymes.

 

In a recent research it has been stated that people who consume a wide variety of food which contains phyto-pharmaceutical like carotenoids, fibers, flavonoids, phytoestrogens, vitamins and minerals, shows a reduced occurrence of some diseases and tends to have a better health2.

 

 

Received on 25.03.2015          Modified on 04.04.2015

Accepted on 08.04.2015         © RJPT All right reserved

Research J. Pharm. and Tech. 8(6): June, 2015; Page 731-737

DOI: 10.5958/0974-360X.2015.00116.X

 

Medicinal plants is one of the important source of free radical scavenging molecules, such as phenolic compounds (e.g., phenolic acids, flavonoids, quinones, coumarins, lignans, lignin, stilbenes, and tannins), nitrogen compounds (e.g., alkaloids and amines), vitamins, terpenoids, and other endogenous metabolites. There have been many studies on the antioxidant activities of various medicinal plants 3.

 

However, the resources of medicinal plants are being reduced significantly due to over-harvesting, illegal exploitation and destruction of ecological habitat and thus, there is a need to conserve endangered medicinal plants and to develop new alternative sources for developing antioxidants  from plants. One of the best alternatives is endophytes which are the organisms that inhabit living plants at some stage in their life, without causing apparent harm to the host 4. These endophytes from medicinal plants may be useful as a significant source of antioxidants.

2. Endophytes:

Endophytes involves in the growth of host plant and in the formation of secondary metabolites related to plant defense and it has been found in all parts of plants including xylem and phloem 5. In consideration of host-endophyte interaction, endophytes are not host specific. Single endophytes can have a wide host range and studies suggest that some specific strains of the fungus isolated from different parts of the same host differ in their ability to utilize different substances. So endophytes can be obtained from different plants belonging to different families, classes and can be grown under different ecological and geographical conditions. Host endophyte relationship may be variable from host to host and endophyte6. Endophytes provide a wide variety of structurally unique bioactive natural products, such as alkaloids, benzopyranones, chinones, flavonoids, phenolic acids, quinones, steroids, terpenoids, tetralones, xanthones and others 7.

 

Endophytic microbes seems to be a natural ‘warehouse’, approximately 300000 plant species are unexplored on the earth, which are having one or more endophytes. It shows the presence of greatest biodiversity of endophytes considering that only a small amount of endophytes have been studied. Several research groups have been motivated to find the potential of these microorganisms for production of active molecules, since these microbes plays a role in production of pharmacologically active substances with low toxicity toward mammalians. These microbes can produce bioactive compounds themselves similarly as that of plants, or can alter the metabolites produced by the plant. Hence, these microbes can be used as a promising alternative for establishing an inexhaustible, less time consuming, cost-effective renewable resource of high-value natural compound which act as a novel pharmaceutical agents 8. Recent studies have reported most of the natural products from endophytes are antibiotics, anticancer agents, biological control agents and other bioactive compounds and they have not been widely explored for therapeutic properties9. Although studies on endophytes have been developed still there are problems exist in following areas.

 

The natural products obtain from endophytes are usually too low to evaluate and identify.

 

The studies on endophytes have been conducted by culturing. However, the actual diversity of endophyte colonizing plants have been decreased, not all of endophytes can be cultured by this approach, so the chance of obtaining natural products from these uncultured endophytes is limited 10.

 

3. Bioactive Natural Products as an Important Source in the Drug Discovery Process:

There is an increased need for new antibiotics, chemotherapeutic agents and agrochemicals that are highly effective, possessing low toxicity, and should have a less environmental impact. Natural product is one of the best way to meet these criteria. These products are naturally derived metabolites and/or by-products from microorganisms, plants or animals 11 and it has a wide range of applications in pharmaceutical, agriculture and industries.

The discovery of natural products involves isolation from the source, structural elucidation and establishing the bio-synthetic pathway of the secondary metabolites. Due to the wide structural diversity, complexity and various bioactivities of isolated compounds, this area has been more interested to researchers. Crude natural products have been used directly as drugs since it is low cost and one of the important sources of traditional medicines. They also provide the basic chemical architecture for deriving semi-synthetic natural   products 12.

 

The best example of natural product derived drug is paclitaxel (Taxol), from the yew tree which is a most important breakthrough in drug discovery from natural products. Many drug companies have developed interests in making products which are having social benefits, reduced symptoms of allergies and arthritis, or that can soothe the stomach 11.

 

4. Importance of Fungal Endophytes:

Fungi are the most important groups among eukaryotic organisms that are well known for producing many novel metabolites which are directly used as drugs or used as lead structures for synthetic modifications .some examples of medicinal drugs from fungal origin is antibiotic penicillin from Penicillium sp., the immunosuppressant cyclosporine from Tolypocladium inflatum and Cylindrocarpon lucidum, the antifungal agent griseofulvin from Penicillium griseofulvum fungus, the cholesterol biosynthesis inhibitor lovastatin from Aspergillus terreus fungus, and β-lactam antibiotics from various fungal taxa12.

 

Plant endophytic fungi have been considered as an important and novel resource of natural bioactive products, since the most important bioactive compound paclitaxel (taxol) discovered from the endophytic fungus Taxomyces andreanae in 1993, many scientists have been interested in studying fungal endophytes as potential producers of novel bioactive compounds 1.

 

Endophytic fungi residing in the plant host involves continual metabolic interaction with the host 5. There has been increased in the number of US patents filed on endophytic fungi producing important metabolites with different biological activities 8. The interaction between fungal endophyte and host is controlled at the gene level, involving genes of both host and endophyte which are modulated by the environment 13.

 

4.1. Antioxidants from Fungal Endophytes:

Many endophytic fungi have been identified to show antioxidant activity. Pestacin (1,3-dihydroisobenzofuran) and isopestacin (isobenzofuranone)  bioactive compound obtained from an endophytic fungus such as P.microspora from Terminalia morobensis is able to scavenge superoxide and hydroxyl free radicals. The antioxidant activity of isopestacin is due to its structural similarity to flavonoids and activity of pestacin is due to cleavage of an unusually reactive C-H bond and to a lesser extent, though O-H abstraction 13.

 

 

Several efforts have been made to estimate the total number of fungi association with plants. The magnitude of fungal diversity estimated about 1.5 million (more accurately 1.62 million) species, later revised by 2.27 million 14. The research progression on antioxidant compounds produced by endophytic fungi from various medicinal plants is discussed in table 1.

 


 

 

Table 1: Endophytic fungi producing metabolites with anti oxidant

S.

no

Endophyte

Host plant

(Locality)

Extract

Metabolite compound

Type of assay

Reference

1

Pestalotiopsis microspora

Terminalia morobensis

(China)

Crude

Pestacin and Isopestacin

Hydroxyl radical scavenging assay,

Superoxide anion scavenging assay

Gary Strobel,

et al.,2002

2

Cephalosporium

sp.

 

Trachelospermum jasminoides

(China)

Methanol

Graphislactone A

DPPH radical scavenging assay,

Hydroxyl radical scavenging assay

Yong Chun song,

et al.,2005

 

3

Xylaria sp.

Ginkgo biloba

(China)

Methanol

Unknown

DPPH Radical

Scavenging assay,

β- carotene/linoleic acid assay

Xiaoli Liu,

et al.,2007

4

Chaetomium sp.

Nerium oleander

(HongKong)

Crude

Unknown

Total antioxidant capacity assay,

Xanthine oxidase inhibition assay,

Determination of TPC

Wu-Yang Huang,

et al.,2007

5

Aspergillus aculeatus,

Muscodor sp.,

Pestalotiopsis sp.,

Phomopsis sp.

Garcinia sp.

(Southern Thailand)

Methanol, Hexane, and Ethyl acetate

Unknown

DPPH  radical scavenging assay,

Hydroxyl radical scavenging assay,

Superoxide anion scavenging assay

S. Phongpaichit,

et al.,2007

6

Neotyphodium lolii

Lolium perenne

(Australia)

Crude

Chlorogenic acid

DPPH radical scavenging assay

Abdelqader Qawasmeh,

et al., 2007

7

Aspergillus sp.,

Paecilomyces sp.

Withania somnifera

(Belgaum, Karnataka)

Ethyl acetate,

Acetone

Unknown

DPPH radical Scavenging Assay,

Nitric Oxide Radical scavenging Assay

M. A. Madki,

et al., 2010

8

 Phomopsis sp.

Mesua ferrea

(Coimbatore district, Tamil Nadu)

Ethyl acetate

Unknown

DPPH radicals scavenging assay

Jayanthi, et al.,

2011

9

Tsc 24 Fungi

Taxus sumatrana

(Indonesia)

Ethyl acetate

Unknown

DPPH radical  scavenging assay,

β carotene bleaching assay

N Artani, et al.,

2011

10

Aspergillus niger, Alternaria alternate

Tabebuia argentea

(Tumkur, Karnataka)

Ethyl acetate

 

Lapachol

FRAP assay,

DPPH radical  scavenging assay

 

Sadananda,

et al., 2011

11

Fusarium sp., Aspergillus sp., Penicillium sp., Mucor sp.

Lobelia

Nicotianifolia

(Karnataka)

Methanol

Unknown

DPPH radical scavenging assay,

Phosphomolybic acid method,

Folin’s Ciocaltue method

Nitya. K. Murthy,

et al., 2011

12

 

 Phomopsis amygdale

Mangrove sp.

(Karankadu, Tamil nadu)

Ethanol

Unknown

ABTS assay,

DPPH radicals scavenging assay

Bharathidasan and Panneerselvam,

2012

13

Aspergillus sp.,

Penicillium chrysogenum,

Phoma sp.

Salvadora oleoides

(Haryana, India)

Acetone

Methanol

Water

Unknown

Reducing Power Assay,

Metal Chelating Activity,

Superoxide Radical Scavenging Assay,

Hydroxyl Radical scavenging  assay,

Nitric Oxide Radical Scavenging Assay,

β-Carotene -linoleic acid assay

Yadav,

et al., 2012

14

Acremonium sp.

Garcinia griffithii

(West

Sumatra)

Ethyl acetate

 

3,5-dihydroxy-2,5-dimetiltrideka-2,9,11-triene-4,8-

dione

DPPH Radical Scavenging Assay

 

Elfita,

et al., 2012

 

15

Fusarium solani,

Fusarium proliferatum

Cajanus cajan

(China)

 

Crude

Cajaninstilbene Acid

 

DPPH radical scavenging assay

Jin tong zhao,

 et al., 2012

16

Paraconiothyrium

sp.

 

Rheedia brasiliensis

(Brazil)

Ethyl acetate

Butanodioic,

Butanoic acid,

Benzoic acid,

Benzenepropanoic

acid

DPPH radical scavenging assay

Patrícia Lunardelli Negreiros de Carvalho, et al.,

2012

17

Aspergillus flavus

 

Mangrove plants

Avicennia officinalis,  Kandelia candel, Excoecaria agallocha,  Rhizophora mucronata

( Goa, India)

Methanol

Unknown

Determination of TPC,

Determination of TFC,

DPPH radical Scavenging Assay,

Hydrogen peroxide

Scavenging Assay,

Hydroxyl Radical

Scavenging Assay, 

Reducing power determination,

Β-carotene /linoleic acid assay

Chinnarajan Ravindran,

et al., 2012

18

Aspergillus flavus, A. niger, Fusarium oxysporum,

F. solani

Crotalaria pallida

(Karnataka, India)

 

Methanol

Coumarin and Ortho-coumaric acid

DPPH radical scavenging assay,

FRAP assay, ABTS assay

 

T Umashankar, et al., 2012

19

 Aspergillus. niger, Penicillium sp., Trichoderma sp.

 Tabebuia argentea

(Karnataka)

 Methanol

 Unknown

DPPH radical scavenging assay, FRAP assay,  Superoxide Radical Scavenging Assay, TBA test, FTC assay, Iron methods

 

 M.Govindappa,

et al., 2013

20

Acremonium sp.,

Aspergillus fumigatus ,

Fusarium verticillioides ,

Botryodiplodea theobromae

 

Garcinia gummigutta,

G. indica,

G. morella and

G. xanthochymus

 (Western Ghats, India)

Ethyl acetate

 

 Phloroglucinol

DPPH radical scavenging assay,

ABTS Radical Cation Decolorization Assay

Determination of TPC

Prakash,

et al., 2013

21

TRF-3 and TRF-6

Ocimum sanctum

(Karnataka, India)

Crude

Unknown

DPPH assay,

hydroxyl radical assay

Determination of reducing power

Smita Madagundi,

et al., 2013

22

Penicillium sp.

Ocimum sanctum

(Tamil Nadu, India)

Ethyl acetate

 

Unknown

DPPH photometric assay

S. Gurupavithra and A. Jayachitra, 2013

23

Aspergillus sp.,

A. terreus,

A. versicolor,

Mycelia sterilia

Ocimum sanctum

(Andhra pradesh, India)

Ethyl acetate

 

Unknown

DPPH radical scavenging assay, Reducing power assay, FRAP assay,

Determination of TPC and TFC

Robin Sharma an B.S. Vijaya Kumar, 2013

24

Aspergillus glaucus

Ipomoea batatas

Ethyl acetate

2,14-dihydrox-7-drimen-12,11-olide

DPPH radical scavenging assay

Asker MMS,

 et al, 2013

25

 Mycelia sterilia,

Aspergillus sp.

Gymnema sylvestre

(Belgaum, Karnataka)

Ethyl acetate

Unknown

ABTS Assay,

DPPH radicals scavenging assay

Nithyananda,

 et al., 2013

26

 Aspergillus sp.,

Penicillium sp.

 

Triticum durum

(Algeria)

Crude

Unknown

β-carotene/linoleic acid test

 Nouari Sadrati, et al., 2013

27

Aspergillus sp.

Emericella bicolor

 

Datura stramonium,

Moringa oleifera

Ethyl acetate

 

Unknown

DPPH Radical

Scavenging assay

Tawasol

Mahdi, et al., 2014

28

Cochliobolus

geniculatus, Cochliobolus spicifer,  Myrothecium roridum,

Cochliobolus lunatus, Chaetomium globosum and Myrothecium roridum

Cynodon dactylon and Dactyloctenium

(Western Ghats region, Karnataka)

Ethyl acetate

 

 

Methanol

4- [3, 4,

diethoxy phenyl-]-1-butanol.

 

Tridecan-3-yl 2-

methoxyacetate

DPPH Radical

Scavenging assay

D.Rekha and M.B.Shivanna,

2014

29

Chaetomium sp.,

Aspergillus sp.

Eugenia jambolana

(Haryana, India)

Ethyl acetate

Crude

Unknown

Hydrogen peroxide scavenging (H2O2) assay,

DPPH Radical

Scavenging assay,

Reducing power assay

 

Manila Yadav, et al., 2014

30

Aspergillus flavus,

Fusarium oxysporum, Fusarium moniliforme, Trichothecium sp.

Viscum album

(Tumkur, Karnataka)

Crude

Lectin

DPPH-radical scavenging assay,

phosphomolybdic acid method,

FRAP assay,

(Fe3+) reducing power assay,

Hydrogen peroxide scavenging activity.

T. S. Sadananda,

et al., 2014

31

Phomopsis sp., Cochliobolus sp., Sordariomycetes sp.

Costus spiralis

(Brazil)

Ethanol

Unknown

DPPH radical scavenging assay,

FRAP assay

Poliana Guerino Marson Ascêncio, et al., 2014

32

Tricoderma sp.

Mangrove leaves

(Andaman and Nicobar islands)

Crude

Pregnane-3,20β-diol, 14α,18α-[4-methyl-3-oxo-(1-oxa-4-azabutane-1,4-diyl)],

diacetate; 4-piperidineacetic acid,1- acetyl-5-ethyl-2-[3-

(2-hydroxyethyl)-1-H-indol-2-yl]-a- methyl, methyl ester;

Corynan-17-ol, 18,19-didehydro-10-methoxy and oleic acids

DPPH  radical scavenging assay,

NO2 radical scavenging activity,

H2O2 radical scavenging activity,

Determination of TPC

Saravanakumar Kandasamy, Kathiresan Kandasamy, 2014

33

Colletotrichum gloeosporioides

Phlogacanthus thyrsiflorus Nees

( Manipur)

Ethyl acetate

Unknown

DPPH radical scavenging assay,

Determination of TPC

Nameirakpam Nirjanta Devi and Mutum Shyamkeso Singh, 2014

34

Alternaria sp.

Tabebuia argentea

(Tumkur, Karnataka)

 Methanol

Phenyl methyl ester phenol, 2,4 bis(1,1 dimethylethyl)

diethyl Phthalate, dodecanoic acid, 1-methylethyl ester,2-pentadecanone, 6,10,14 trimethyl,

1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester, Pentadecanoic acid, 14-methyl-, methyl ester, 2-benzenedicarboxylic acid

butyl 2-methylpropyl ester,

10,13-octadecadienoic acid, methyl ester

 9-octadecenoic acid (Z)-, methyl ester

 and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester

DPPH radical  Scavenging assay,

Superoxide Radical Scavenging Assay

Govindappa,

 et al., 2014

35

Aspergillus

oryzae and

Colletotrichum gloeosporioides

 

Centella asiatica

and

Murraya koengii

(India)

 

Ethanol

Unknown

DPPH radical scavenging assay,

Determination of TPC

Nath, et al., 2014

 

36

Colletotrichum sp.

Polygala elongate

(Western Ghats)

Ethyl acetate

Crude

Unknown

ABTS assay,

DPPH radicals scavenging assay, Phosphomolybdenum assay

Gauri Pawle and Sanjay K Singh,

2014

DPPH- Diphenylpicrylhydrazyl

FRAP- Ferric ion reducing antioxidant power assay

ABTS- 2, 2’-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid)

FTC- Ferric thiocyanate assay

TPC- Total phenolic content

TFC- Total flavonoid content

 


5. CONCLUSION AND PERSPECTIVES:

The special ability of plant endophytic fungi, to produce the same or similar compounds as from their host plants, and also other bioactive compounds, have increased the interest to many researchers to carry out the research in this area. This review has highlighted importance of fungal endophytes and some of the antioxidant compounds produced from endophytic fungi.

 

In the future, studies on the isolation and identification of new endophytic fungi strains which produce antioxidant compounds will be of great interest to the researchers since the new source of antioxidant compounds will provide a promising chance to decrease the risk of diseases due to oxidative damage.

 

6. ACKNOWLEDGMENTS:

The authors of this paper would like to thank the Management of VIT University for supporting.

 

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