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Harun, Septama, Ahmad, and Suppian: The Potential of Centella asiatica (Linn.) Urban as an Anti-Microbial and Immunomodulator Agent: A Review
Original Article

Natural Product Sciences 2019;25(2):92-102.

Published online: 17 January 2019

DOI: https://doi.org/10.20307/nps.2019.25.2.92

The Potential of Centella asiatica (Linn.) Urban as an Anti-Microbial and Immunomodulator Agent: A Review

Nurul Hikmah Harun1, 2, ∗, Abdi Wira Septama3, Wan Amir Nizam Wan Ahmad1, Rapeah Suppian1

1School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia

2School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, 21300, Kuala Nerus, Terengganu, Malaysia

3Research Center for Chemistry, Indonesian Institute of Sciences, Kawasan Puspitek Serpong, Tangerang Selatan, Banten, 15314 Indonesia

∗Author for correspondence Nurul Hikmah Harun, School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia Tel: +60149137502; E-mail: heekmah85@gmail.com

      Revised 16 April 201917 April 2019       Accepted 17 April 2019

Copyright © 2019 The Korean Society of Pharmacognosy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Centella asiatica (Linn.) Urban (Umbelliferae) which is also known as ‘pegaga’ is highly consumed and eaten raw as ‘ulam’ in Malaysia. C. asiatica is used in traditional medicines to treat various health conditions such as rheumatism, inflammation, syphilis, skin diseases and diarrhoea. Various reports exhibited that the crude extracts and isolated bioactive compounds of C. asiatica possessed a broad range of pharmacological activities such as anti-oxidant, anti-diabetic, anti-tumor, wound healing, anti-microbial, anti-inflammatory, immunomodulatory, hepatoprotective and memory enhancing properties. The pharmacological validation on anti-microbial and immunomodulatory of C. asiatica is very limited and several existence review papers related for this plant had not been focused for both activities. This review therefore attempts to combine the existing literature to offer immense scope for researchers engaged in validation of the traditional claims and bioactivities of this plant related with anti-microbial and immunomodulatory potential.

Keywords: Anti-microbial, Centella asiatica (Linn.) Urban, immunomodulatory, pegaga

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Table 1.
Taxonomy of Centella asiatica
Classification Name
Kingdom Eukaryota/Plantae
Subkingdom Embryophyta
Division Spermatophyta
Subdivision Angiospermae
Class Dicotyledoneae
Subclass Rosidae
Superorder Aralianae
Order Apiales/Umbelliflorae
Family Apiaceae/Umbelliferae
Subfamily Mackinlayoideae/Hydrocotyle
Genus Centella
Species Asiatica
Table 2.
Vernacular (Dialect) names of Centella asiatica
Language/region Vernacular (Dialect) name
Bengali Thankuni
China Fo-ti-tieng, Chi-hsueuh-ts'ao
Hawaii Pohe Kula
Hindi Mandookaparni
Malay/Malaysia Pegaga
Malayalam Kodagam
Nepal Ghodtapre
Urdu Brahmi
USA Indian Pennywort, Marsh Pennywort
Table 3.
Anti-microbial activities of Centella asiatica
No. Tested substances Anti microbial properties Method Tested microorganisms Results References
1. Ethanol extract Anti-bacterial Disc diffusion P. vulgaris, S.aureus, B.subtilis and E.coli. Range of inhibition zone were 16-19 mm 29
2. Ethanol extract Anti-bacterial Agar dilution Shigella sp., V. cholera and S.aureus 400 mg/mL of agar 30
3. Ethanol extract Anti-bacterial Disc diffusion P. aeruginosa Average inhibition zone was 6 mm 31
4. Ethanol extract Anti-bacterial Resazurin microtiter plate S. aureus MIC and MBC values of 8 and 16 mg/mL 32
5. Ethanol extract Anti-bacterial Broth microdilution B. cereus and L.monocytogenes MIC values of 16 and 8 µg/mL, and MBC values of 16 and >32 µg/mL 33
6. Methanol extract Anti-bacterial Disc diffusion S. aureus and MRSA 1 000 μg/disc of methanol extract of C. asiatica was effective to inhibit the growth of tested bacteria 34
7. Rich flavonoid extract Quorum sensing and virulence factors inhibiton Violacein, pyoyanin production, swarming motility, and antibiofilm production C. violaceum and P. aeruginosa The extract at 300 µg/disc completely inhibited violacein production. The extract at 400 µg/mL completely inhibited pyocyanin production, biofilm production as well as elastolytic and proteolytic activity in P. aeruginosa PAO1 35
8. Methanol extract Anti-fungal Spore germination assay F. udum, D. monoceras The result showed that the extract at 5000 µg/mL completely inhibited the spore germination of F. udum, D. monoceras 36
9. Ethanol extract Anti-fungal Disc diffusion A. niger and C. albicans Inhibiton zone was 16 mm against A.niger and 15 mm agaisnt C. albicans 29
10. Aquoes extract Anti-fungal Microdilution method C. cladosporidies, A. flavus, and F. oxysporum Aqueous extract of C. asiatica had satisfied activity in inhibiting those that of fungi with MICs in the range of 80 to 90%. 37
11. Silver nanoparticle synthesised using C. asiatica Anti-bacterial Disc diffusion S. aureus, B. subtilis, E. coli and P. aeruginosa AgNPs has strong anti-bacterial activity against S. aureus, B. subtilis, E. coli and P. aeruginosa with inhibition zone of 21.3, 19.4, 16.2 and 18.8 mm, respectively 40
12. Asiatic acid Anti-bacterial Broth microdilution E. faecalis and E. coli Against E. faecalis, MIC and MBC values of 20 and 32 µg/mL and against E. coli, MIC and MBC value of 24 and 36 µg/mL. 42
13. Ursolic acid Quorum sensing and virulence factors inhibiton Virulence factor inhibiiton methods E. coli Ursolic acid at 50 µg/mL completely inhibited virulence factors of E. coli, including P-fimbriae, curli fibres and alpha-hemolysin 43
14. Volatile oil Anti-bacterial Microplate dilution method B. subtilis, S. aureus, E. coli, P. aeruginosa and S. sonnei MIC values of in the range of 0.039 to 1.29 µg/mL against tested bacteria 44
Table 4.
Immunomodulatory activities of crude extracts, bioactive fractions and compounds derived from Centella asiatica
No. Tested substances Model used Tested dose Results References
1. Ethanol extract of leaves Human neutrophil cells 25, 50 and 100 mg/mL The concentration of extract 25 to 100 mg/mL increase chemotactic, phagocytic and intracellular killing potency of human neutrophil 46
2. Methanol extract of whole plant Immunized Swiss albino mice with sheep red blood cell suspension 100 to 500 mg/kg BW All concentration of extracts increased the phagocytic index in dose-dependent manner and only 500 mg/kg BW concentration of extract enhanced total white blood cells count 47
3. Aqueous extract of whole plants Human peripheral blood mononuclear cells and BALB/C mice 10, 100, 200 μg/mL (in-vitro),10, 100, 300 mg/kg BW (in-vivo) Increased lymphocytes proliferation in a dose- dependent manner and IgM and IgG antibodies production in100 mg/kg BW-treated mice 48
4. Aqueous extract of whole plants Rabbit erythrocyte suspension 15.625 to 1000 μg/mL (in-vitro) The extract showed concentration dependent increase in alternate pathway activity of erythrocytes with AP 50 is 617.02 ± 16.4 μg/mL 3
5. Ethanol extract of leaves Balb/C mice (6-8 weeks old and 25-30 g weight) infected by Listeria monocytogenes 50, 150 and 450 mg/kg BW The extract at 50 and 150 mg/kg BW dose showedsignificantly higher IFN-γ secretion compared to untreated group at day-2 and 4 after infection 49
6. Methanol extract of leaves Mice (2 weeks old) infected by Salmonella typhi 125, 250 and 500 mg/kg BW The extract at 500 mg/kg BW dose showed increase pH phagocytosis activity of macrophage cells. 50
7 Ethanol extract of aerial parts Immunized Swiss albino mice (20-25 g) with sheep red blood cells 100 mg/kg BW Extract induced haemagglutination titre values after 14 days treatment 52
8. Pulverization of aerialparts Crossbred pigs (8 weeks old) Conventional diet supplemented with 0.5%, 1%and 2% Pigs fed with 1% and 2 % pulverized C. asiatica demostrated significantly reduced IL-10 levels afterthree-month feeding 51
9. Titrated extract In-vivo:phthalic anhydride-induced atopic dermatitis animal model 0.2% and 0.4% of extract (40 µg or 80 µg/cm2) Inhibited mast cells and infiltration of inflammatory cells and expression of iNOS and COX-2, and NF-κB and secretion of TNF-α, IL-1, IL-6, and IgE. 58
In- vitro: LPS stimulated murine macrophage cell line RAW264.7 1, 2, 5 µg/mL Inhibit nitrite oxide production and expression of iNOS and COX-2, and NF-κB DNA binding activities
10. Triterpenoid saponin fraction Wistar female rats (120-180g) induced wound infliction 25 mg/rat Treatment decreased the IL-1β and NF-κB 54
11. Asiatic acid LPS-induced RAW 264.7 macrophage cells 40, 80 µM Both concentration 40 and 80 µM reduced NO in dose-dependant manner 54
12. Medacassic acid CT26 cells-bearing mouse model 50 mg/kg BW Induced CD4+ and CD8+ T- lymphocytes subpopulations and proinflammatory cytokines IFN-γ and IL-4 53
13. Asiatic acid LPS stimulated murine macrophage cell lineRAW264.7 30, 60, 120 μM Reduced the production of NO, IL-6, IL-1β, TNF-αand protein and gene expression of iNOS in dose-dependent manner 57
14. Asiatic acid In-vivo: Male Sprague-Dawley rats (7 weeksold) induced periodontitis 100 mg/kg BW IL-6 and IL 8 expression levels significantly inhibited in LPS-stimulated gingival tissues 59
In-vitro: LPS stimulated murine macrophagecell line RAW264.7 or human gingival fibroblast (HGF) 25, 50, 100 µM IL-6, and IL-8 productions were significantly reduced by asiatic acid in both LPS-stimulated murine macrophage cell line RAW264.7 and HGF meanwhile PGE2 and NO secretion, p65 NF-κB phosphorylation were inhibited in LPS-stimulated HGF
15. Ethanolic, methanolic and aqueous extract ofwhole plant, asiaticosi-de and madecassoside TPA-stimulated fibroblast cells Extracts (30 g/mL), compounds (5 µg/mL) Suppressed the TPA-induced production of PGE2 and inhibited both COX-1 and COX-2. 61
16. Asiatic acid LPS-induced inflammatory response in human corneal epithelial cells (HCECs). 20 μmol/L IL-8 and IL-6, IL-1β, TNF-α and TGF-β mRNA expression levels were significantly reduced in inflammatory model. Content of reactive oxygen species also decreased. 60
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