ISSN: 0973-7510

E-ISSN: 2581-690X

Review Article | Open Access
Journey of Limonene as an Antimicrobial Agent
Akshi Gupta , Ebenezer Jeyakumar and Rubina Lawrence
Department of Industrial Microbiology, Jacob Institute of Biotechnology and Bioengineering, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj – 211 007, Uttar Pradesh, India.
J Pure Appl Microbiol. 2021;15(3):1094-1110 | Article Number: 6923
https://doi.org/10.22207/JPAM.15.3.01 | © The Author(s). 2021
Received: 12/03/2021 | Accepted: 02/06/2021 | Published: 22/06/2021
Abstract

Injudicious consumption of antibiotics in the past few decades has arisen the problem of resistance in pathogenic organisms against most antibiotics and antimicrobial agents. Scenarios of treatment failure are becoming more common in hospitals. This situation demands the frequent need for new antimicrobial compounds which may have other mechanisms of action from those which are in current use. Limonene can be utilized as one of the solutions to the problem of antimicrobial resistance. Limonene is a naturally occurring monoterpene with a lemon-like odor, which mainly present in the peels of citrus plants like lemon, orange, grapefruit, etc. The study aimed to enlighten the antimicrobial properties of limonene as per previous literature. Advantageous contributions have been made by various research groups in the study of the antimicrobial properties of limonene. Previous studies have shown that limonene not only inhibits disease-causing pathogenic microbes, however, it also protects various food products from potential contaminants. This review article contains information about the effectiveness of limonene as an antimicrobial agent. Apart from antimicrobial property, some other uses of limonene are also discussed such as its role as fragrance and flavor additive, as in the formation of nonalcoholic beverages, as solvent and cleaner in the petroleum industry, and as a pesticide. Antibacterial, antifungal, antiviral, and anti-biofilm properties of limonene may help it to be used in the future as a potential antimicrobial agent with minimal adverse effects. Some of the recent studies also showed the action of limonene against COVID-19 (Coronavirus). However, additional studies are requisite to scrutinize the possible mechanism of antimicrobial action of limonene.

Keywords

Antibacterial, anti-biofilm, antifungal, antiviral, bioactive compound, limonene, COVID-19

Introduction

Antibiotic resistance is emerging very rapidly because of the inappropriate or misuse of antimicrobials which is facilitated because of their accessibility over the counter, without prescription, and through unregulated delivery chains1. Antimicrobial agents also comprise adverse side effects along with microbial resistance. Hence, the interest of researchers is turned towards ethnopharmacology. Bioactive compounds are natural and ubiquitous in most plants and easily accessible to humans. Plant extracts provide immeasurable occasions for novel drug findings due to the exuberance of multifarious chemicals. Hence, thousands of obtainable medicinal phytochemicals are safe and more effective alternatives, for this reason, coupled with advancing microbial resistance to synthetic drugs; ethnopharmacology is swiftly gaining world acknowledgment2,3. In countries like Japan forest bathing trips are very popular and consider natural chemotherapy. Forest bathing trips include a trip to a forest for recreation and relaxation while breathing in volatile substances which are antimicrobial compounds derived from trees4. One of such components is limonene, which is one of the main constituents present in aromatic plants and the most common terpene present in nature. It is mainly found to be present in essential oils of peels of citrus spp. like lemon, orange, grapefruit, lime, and mandarin, etc. D-limonene is generally recognized as safe (GRAS) to be utilized as a flavoring agent. Due to its citrus fragrance, it is extensively used as a flavor and fragrance additive in soaps, perfumes, and chewing gums5. Limonene is also found to be present in many fruits, vegetables, meats, spices, and other food items6. Limonene is also popular for its various properties like antibacterial, antifungal, antiviral, and anti-biofilm. In the present study, the above-mentioned properties of limonene discussed and proved experimentally in various studies are included and reviewed.

What is Limonene?
Limonene is also known by some other synonyms like D-(+)-limonene, (+)-limonene, (R)-limonene, (R)-(+)-limonene, cajeputene, carvene, cinene, (+)-dipentene, etc. The molecular formula of limonene is C10H16 and molecular weight is 136.24. At room temperature limonene is a colorless liquid having lemon-like odor with a melting point temperature of 74.3°C, boiling point temperature of 175.5-176°C, and density of 0.8411g/ml (at 20°C) and 0.8402g/ml (at 25°C). It is slightly soluble in water (13.8mg/L at 25°C) and easily soluble in acetone, dimethyl sulfoxide, ethanol, benzene, carbon tetrachloride, diethyl ether, and petroleum ether. Limonene also gets oxidized when comes in contact with air and forms various oxidation products like carvone, limonene oxide, carveol, and limonene hydroperoxides hence it should be stored away from light and air. It is found to be present in peels of various citrus fruit species like orange, grape, lemon, and can be produced commercially from alkali treatment and steam distillation of citrus peel and pulp which remain after juice and cold-pressed oil production7-10.

Uses of Limonene
Limonene is used as a flavor and fragrance additive in perfumes (0.005% and 1%), soaps, beverages, food, and household cleaning products for nearly 50 years. It is also used in the formation of nonalcoholic beverages (31ppm), ice creams (68ppm), candy (49ppm), baked goods (120ppm), sweets, gelatin, puddings (48-400ppm), and chewing gums (2300ppm). In the petroleum industry, it has been used as solvent and cleaner, in the transdermal application of medicines it is used as an additive to increase the penetration of active substance, it is also used as a degreasing agent before the lacquering of industrial products (30%), in the electronic industry for cleaning of printed circuits (50-100%) and for cleaning print cylinders in printing work. Pesticide, insect repellent, and dog/cat repellent are also well-known uses of limonene6,7,9,10.

Antimicrobial activities of Limonene
Antiviral
Many viral diseases e.g. caused by Herpes simplex virus (HSV), influenza virus, and HIV are known as life-threatening. However various antiviral drugs against HIV, HSV, influenza, and other pathogenic viruses have been developed but the antecedence of these antiviral drugs is the potential and side effects of these drugs. There is still an urgent need for the development of new anti-viral agents which can fulfill all the drawbacks possessed by different antiviral drugs. Limonene can be used as a suitable anti-viral agent as some of the previous studies have emphasized its anti-viral properties.

Anti-viral properties of limonene were studied against human pathogenic (Herpes simplex and influenza virus) as well as plant pathogenic viruses (tobacco mosaic virus). The anti-viral property of limonene against the Herpes simplex type 1 virus was found as complete inhibition of HSV1 at 25μg/ml concentration of limonene was observed. Limonene inactivated the virus in the early phase of virus multiplication11. Cytotoxic concentration value (CC50) of limonene at 1155μg/ml against HSV1 was also observed in another study12. Inhibition of the herpes simplex virus was observed by the formation of plaque on the kidney Vero cells13. On the other hand, the anti-viral property of Citrus deliciosa14 and Citrus reshni15 essential oils which contain limonene as the major component was also observed against the H5N1 virus. Anti-viral property of limonene against plant pathogenic virus, Tobacco mosaic virus (TMV) was also observed and it was found that TMV was inhibited by more than 45% after limonene treatment16.

Apart from influenza and other viruses limonene also identified as the inhibitor of the SARS corona virus as described in many studies. The SARS corona virus has protein S a specific binding site for the angiotensin-converting enzyme 2 (ACE2) which serves as an entry point into the host cell. Limonene can act as the inhibitor for ACE2 target which is verified by performing docking studies17. Mechanism of action of herbal essential oils against viruses is either they coat the glycol proteins (potent of viral sites) of viruses or they bind with the human cell receptors (respiratory cells ACE- 2) which lead to the nonspecific and nonproductive binding of the virus particle to host cells which hinder the virus from infection. Some of the herbal essential oils which have antiviral or virucidal properties such as lavender oil, peppermint oil, and eucalyptus oil have limonene as the component18. ACE-2 inhibition property of limonene as a receptor for SARS-CoV-2 can prevent the invasion of SARS-CoV-2/COVID-19 into the human body19,20. Immunomodulatory, anti-inflammatory, and anti-viral properties of limonene can help limonene to limit the severity and succession of the COVID-19. Hence, limonene can act as a possible candidate against infection, immunity, and inflammation in COVID-1921. An oil blend was synthesized for the investigation of the effectiveness of the oil for the treatment in patients having COVID-19 like symptoms. The oil consisted of limonene as one of the chief components which provided anti-viral property to the oil. Limonene is known to restrain exclusively the viral DNA polymerase during the reproduction cycle when new viral DNA is synthesized. Hence, the oil was found as an effective remedial measure for COVID-1922. Limonene was also used for the quantitative evaluation of olfactory dysfunction in asymptomatic COVID-19 carriers23.

Antibacterial
Antibacterial properties of limonene are well known and discussed in several reports against various bacterial species. Limonene is known to be active against many pathogenic bacteria involved in different diseases such as respiratory or skin diseases whereas some are known as contaminants causing contamination in the food industry. Synergistic activity of the combination of limonene enantiomers (D and R) and with other compounds has also been very well documented in many studies. Some of the studies have also highlighted the evaluation of chemical compositions of various essential oils from different plant materials and observed limonene as a major constituent and the reason for antibacterial activity shown by that essential oil. On the other hand, several methods were also reported in various studies to design nano-emulsions of limonene to be utilized in drug delivery, etc. Antibacterial actions of limonene against various bacterial species in various studies are summed up in Table 1.

Table (1):
Antibacterial activity of Limonene.

S. No. Study Concentration Effective against References
Antibacterial activity of Limonene used in pure form
1 Action of oxidized d-limonene on microorganisms Pure S. elipsoideus, W. hansenula and O. lactis [33]
2 Antibacterial activity of limonene against food borne bacteria 98% E. coli, S. aureus, S. senftenberg and Pseudomonas spp. [34]
3 Antibacterial action of limonene from Douglas Fir against Bacillus thuringiensis. Pure Bacillus thuringiensis [35]
4 Antibacterial action of limonene against 16 bacterial isolates Pure Nine gram positive and 16 gram negative bacteria [36]
5 Antibacterial action of limonene against respiratory tract pathogens Pure S. pyogenes, S. aureus, S. pneumoniae, H. influenzae and E. coli [37]
6 Antibacterial action of two enantiomers of limonene Pure E. coli, E. faecalis, S. typhi, S. aureus, M. smegmatis, S. mutans, B. subtilis and E. aerogenes [38]
7 Anti-listerial action of limonene as essential oil component of Conifers Pure (98%) L. monocytogenes [39]
8 Antibacterial action of limonene as component of Juniper berry oil Pure S. marcescens, E. cloace, K. pneumoniae, A. baumani and S. aureus [40]
9 Antimicrobial activity of limonene Pure E. coli, S. typhi, S. enteritidis, M. luteus, S. aureus, S. epidermidis, P. tolaasii [41]
10 Antibacterial action of limonene against E. coli Pure E. coli [42]
11 Antibacterial action of limonene against fruit juice spoiling bacteria Pure Lactobacillus plantarum, Lactobacillus brevis, and Bacillus coagulans [43]
12 Antibacterial action of limonene from commonly consumed medicinal herbs against human pathogenic bacteria Pure M. flavus, B. subtilis, S. epidemidis, S. aureus, S. enteritidis, S. typhimurium, E. coli, E. cloacae and L. monocytogenes [44]
13 Antibacterial action of limonene isolated from Umbelliferae and Labiatae plants Pure P. aeruginosa, P. mirabilis, K.pneumoniae, A. baumannii, S. aureus, E. faecalis and B. subtilis [45]
14 Antimicrobial property of limonene Pure Unknown organisms [46]
15 Antibacterial action of limonene from Wedelia prostrata plant Pure P. aeruginosa, E. coli, B. subtilis, S. aureus [47]
16 Antibacterial action of limonene against food related microorganisms Pure B. cereus, E. coli, P. anomala and P. putida [48]
17 Antibacterial action of limonene from indigenous plants against some clinical isolates Pure (98%) S. aureus, S. pneumoniae, S. typhi, E. coli, P. aeruginosa,
S. dysenteriae, and P. mirabilis		 [49]
18 Antibacterial action of limonene against E. coli Pure (97%) E. coli [25]
19 Use of limonene as a biocidal agent Pure S. aureus [50]
20 Antibacterial action of limonene from Monarda punctata essential oil against respiratory tract pathogen Pure S. pyogenes, S. aureus, S. pneumoniae, H. influenzae and E. coli [51]
21 Antibacterial action of limonene against food-borne pathogens Pure (95%) Y. enterocolitica, S. aureus and L. monocytogenes [52]
22 Antibacterial activity of limonene from
Artemisia capillaris essential oil against respiratory tract infection-causing pathogens		 Pure S. pyogenes, S. aureus, S. pneumoniae, K. pneumoniae, E. coli and H. influenzae [53]
23 Antibacterial activity of limonene against Streptococcus uberis Pure S. uberis [54]
24 Inhibition of P. aeruginosa involved in biofilm formation by limonene from Citrus species Pure P. aeruginosa [55]
25 Antibacterial action of Fish Gelatin-Chitosan edible films supplemented with D-Limonene Pure (≥ 95%) E. coli [56]
26 Antibacterial action of limonene against fish pathogenic bacteria Pure >99%
concentrated		 Seven gram negative and nine gram positive bacteria [57]
Synergistic activity of Limonene
27 Antimicrobial action of limonene ennatiomers and 1,8-cineol alone and in combination Pure (97%) S. aureus, B. cereus, E. faecalis, E. coli, P. aeruginosa, K. pneumoniae and
M. catarrhalis		 [58]
28 Synergistic combination of limonene with high hydrostatic pressure for preservation of fruit juices 97% (Pure) E. coli and L. monocytogenes [59]
29 Synergistic antibacterial property of limonene in combination with heat treatment and its use in food preservation 97% (Pure) E. coli [24]
30 Antibacterial action of terpenes in combination with antibiotics against M. tuberculosis Pure (98%) M. tuberculosis [60]
Nanoemulsion Of Limonene
31 Antibacterial action of limonene used in nanoemulsion Pure E. coli and L. delbrueckii [61]
32 Effects of nisin on the antimicrobial activity of D-limonene
and its nanoemulsion		 Pure E. coli, S. aureus and B. subtilis [26]
33 Antibacterial action of nisin and D-limonene containing organogel-nanoemulsion Pure E. coli, S. aureus and B. subtilis [27]
34 Combined anti-listerial action of nanoemulsion of d-limonene and nisin Pure L. monocytogenes [62]
35 Improving antimicrobial action of D-limonene by using novel
organogel-based nanoemulsion		 Pure E. coli, S. aureus and B. subtilis [28]
36 Antibacterial Cyclodextrin/
Limonene-Inclusion Complex Nanofibrous Webs		 Pure (97%) E. coli and S. aureus [63]
Antibacterial activity of essential oils containing Limonene
37 Antibacterial action of C. carvi essential oil containing limonene 18.2% (second highest) 14 gram negative and 4 gram positive bacteria [64]
38 Antibacterial action of essential oils  from Korean citrus species 55.4 to 91.7% (Major) P. acnes and S. epidemidis [65]
39 Antibacterial action of Pimpinella puberula (DC.) Boiss. aerial parts
essential oil		 21.7-82.4% (Major) Pseudomonas, Y. enterocolitica, B. cereus, M. luteus, B. subtilis and S. aureus [66]
40 Antibacterial
activity of essential oil of Lantana camara aerial parts		 16.9% (second highest) E. coli, P. aeruginosa, S. aureus, S. faecium, M. leutus and L. monocytogenes [67]
41 Antibacterial action of Crassocephalum rubens leaf extract 48.8% (Major) S.  aureus, Streptococcus faecalis Escherichia coli and Salmonella typhi [68]
42 Activity of Citronella oil against spoilage bacteria of semi dried round scad 86% (Major) Pseudomonas spp., S. aureus and Klebsiella spp. [69]
43 Antibacterial action of limonene present in aerial parts of
Nepeta pungens Benth essential oil		 12% (second highest) S. aureus [70]
44 Antibacterial action of limonene as a component of essential oil of Aloysia polystachya leaves 20.22-14.65% (second highest) E. coli and S. aureus [71]
45 Antibacterial action of Makrut lime essential oil against respiratory tract pathogens 40.65% (Major) A. baumannii, Streptococci, H. influenzae, M. catarrhalis, S. aureus and S. pneumoniae [72]
46 Antibacterial action of sweet oranges peel essential oil 95.62% (Major) S. typhi, S. aureus, B. cereus, P. aeruginosa and Shigella spp. [73]
47 Antibacterial action of essential oil of Sweet lime 95.98% (Major) S. aureus, B. subtilis, B. cereus and L. acidophilus [74]
48 Antibacterial action of Ammodaucus leucotrichus Coss. and Dur. seeds essential oil 23.89% B. subtilis and E. coli [75]
49 Antibacterial action of leaves and fruit peel essential oil of Citrus sinensis Linn. 30.1% (second highest) S. aureus  and E. coli [76]
50 Antibacterial action of essential oil of Citrus paradisi and Citrus grandis 96.06% and 55.74% P. aeruginosa, E. coli, S. enterica, S. aureus and S. faecalis [77]
51 Antibacterial activity of Citrus paradise essential oil 92.6% L. plantarum, L. mesenteroides, L. lactis, S. aureus and E. coli. [78]
52 Antibacterial action of essential oil components of orange peel 73.9-97% (Major) S. aureus, L. monocytogenes and P. aeruginosa [79]
53 Antibacterial action of essential oils from Melissa officinalis leaves 60.70% (Major) B. cereus, S. aureus, E. coli and S. enterica [80]
54 Antibacterial activity of Pistacia terebinthus
essential oils		 13.95-46.29% (second highest) S. aureus [81]
55 Antimicrobial action of black pepper, cardamom, cumin and coriander essential oil. 16.924%, 0.07%, 0.565% and 2.526% S. aureus, P. vulgaris,
Salmonella sp. and E. coli		 [82]
56 Antibacterial action of Citrus medica L. var proper leaf essential oil 11.54% (third highest) S. aureus and P. acne [83]
57 Antibacterial action of essential oils from Citrus species 66-93% E. coli, B. cereus, S. aureus, S. typhimurium, L. monocytogenes and E. faecalis [84]
58 Antibacterial action of essential oil of lemon peel 46.93% (Major) S. aureus [85]
59 Antibacterial
action of the essential oil of Citrusaurantifolia L. leaves		 63.35% (Major) E. coli and S. aureus [86]
60 Antibacterial action of essential oils from Lamiaceae Family Plants 0.17-13.5% S. lutea, E. coli and S. saproph. [87]

Apart from the study on the antibacterial action of limonene, the mechanism of antibacterial action of limonene was also explained in some of the studies. A β-barrel protein (LptD) is an essential protein of the outer membrane present in lipopolysaccharide (LPS) assembly, depletion of this protein leads to the increase in membrane permeability of the bacterial cell. Attenuated total reflectance infrared microspectroscopy results after the treatment of E. coli cells with limonene showed the damage of LPS and altered outer membrane permeability was also observed in the study. It was concluded that the damage of LPS is the mechanism of inactivation by (+)-limonene and cell envelopes are the important target of limonene24. It was also explained that the mechanism of inactivation of E. coli cells by the treatment of limonene depends on the physiological state of the cell and the concentration of limonene. Exponentially growing E. coli cells were inactivated by limonene at the concentration of 2,000μL/L and the mechanism of bacterial inactivation was observed to be the Fenton-mediated hydroxyl radical formation which leads to the oxidative DNA damage of the bacterial cell. On the other hand, 4,000μL/L concentration of limonene caused a change in the membrane permeability of the cells and it was observed that at higher concentrations, inactivation of the bacterial cell is related to the altered membrane permeability25. Treatment of limonene nano-emulsion also showed the complete collapse of the cell structure which leads to the cell lysis and release of intracellular material from inside of the cell. The effect of limonene nano-emulsion was not only restricted to Gram-negative bacteria (E. coli) but a similar effect was also observed with Gram-positive isolates (B. subtilis and S. aureus)26. A similar effect of limonene nano-emulsion was also observed as limonene nano-emulsion altered the cell membranes of E. coli, S. aureus, and B. subtilis which lead to the outflow of intracellular substances from the treated bacterial cells of all three isolates27. Moreover, deformed and incomplete shapes of the bacterial cells (E. coli, S. aureus, and B. subtilis) were also scrutinized by scanning electron microscopy due to an increase in the permeabilization of the cells which leads to disruption of membrane integrity by the treatment of limonene nano-emulsion28.

It is evident by above-mentioned studies that limonene causes damage to the cell membrane of Gram-positive as well as Gram-negative bacterial cells which initiates the leakage of intracellular materials and ultimately leads to cell death. However, the efficacy of limonene or any other antibacterial agent may differ in Gram-positive and Gram-negative cells. The cytoplasmic membrane is known as the primary target in Gram-positive bacterial cells while in Gram-negative bacteria outer membrane is known as the primary target for antibacterial agents29. Gram-negative cells are more efficient than Gram-positive bacterial cells in maintaining their membrane homeostasis, which is why there is a difference between antimicrobial agents towards the bactericidal activity30. It was also explained that the outer membrane of Gram-negative bacteria, which is composed of lipopolysaccharide molecules establishs a hydrophilic permeability barrier that protects against the effect of highly hydrophobic drugs31. This also explains the reason for the low sensitivity of Gram-negative bacterial cells to the lethal effects of lipophilic monoterpenes like limonene.

Most of the studies mentioned above-observed cell membrane damage and alteration in the membrane permeability as the mechanism of action of limonene. However, the precise mechanism of limonene as an antibacterial drug is largely unknown as the series of events which leads to the cell death by the action of limonene are not studied. In a recent study, the effects of limonene on protein expressions related to respiratory chain complex in L. monocytogenes were studied. Limonene treatment to bacterial cells was observed to down-regulate different respiratory chain-related complexes32. Moreover, additional studies are required to decipher the exact molecular mechanisms of limonene against various other pathogenic Gram-positive or Gram-negative bacteria.

Antifungal
Limonene is also known for its antifungal properties. It has been observed that limonene is effective against various yeasts and molds which are known as the major contaminant of food products (pudding), dairy (yogurt, cheese, and dairy caramels), fruits (Wine grapes, satsumas, apples, strawberries), grains (wheat flour, corn, peanuts, coffee, cocoa powder, cereal), flavored water and chocolate88. Some of the yeasts are known to cause contamination in other food products such as meat, vegetables, nonalcoholic beverages, alcoholic beverages, and bakery products89. While some of the fungal species are known to be pathogenic to humans. Antifungal properties of limonene have been explored against various fungal species. Various antifungal properties of limonene are summarized in Table 2.

Table (2):
Antifungal Activity of Limonene.

S. No. Study Concentration Effective against References
Antifungal activity of Limonene used in pure form
1 Antifungal action of two enantiomers of limonene Pure M. gypseum, A. niger, A. flavus, T. rubrum, S. schenckii, C. albicans AI and C. albicans [38]
2 Antifungal action of limonene against clinical isolates Pure C. albicans [40]
3 Antifungal action of limonene against some fungal isolates and dermatomycetes Pure C. albicans, A. niger, A. ochraceus, A. versicolor, A. flavus, A. terreus, A. alternate, P. ochrochloron, P. funiculosum, C. cladosporioides, T. viride, F. tricinctum, P. helianthi, M. canis, E. floccosum, T. rubrum, T. mentagrophytes and T. tonsurans [41]

 
4 Antifungal action of limonene and 1,8-cineol alone and in combination Pure (97%) Cryptococcus neoformans [58]
5 Inhibitory effect of cyclic terpenes
on Fusarium verticillioides		 Pure Fusarium verticillioides [94]
6 Antifungal action of Limonene against Trichophyton rubrum Pure Trichophyton rubrum [95]
7 Antifungal action of limonene against some clinical isolates and dermatomycetes Pure C. albicans, C. parapsilosis, R. rubra, A. niger, P. tardum, C. krusei, E. floccosum, A. fumigatus and P. chrysogenum [96]
8 Antimicrobial action of limonene against fruit juice spoiling micro flora Pure S. bayanus,
P. membranifaciens, and R. bacarum		 [43]
9 Antifungal action of d-limonene on toxigenic strains of Aspergillus Pure A. flavus [97]
10 Antifungal action of limonene used as nanoemulsion Pure Saccharomyces cerevisiae [61]
11 The Effects of limonene on Some Spoilage Fungi Pure C. albicans, Penicillium sp., Aspergillus sp. and A. niger [98]
12 Structure alteration of A. flavus and A. parasiticus by limonene Pure A. flavus and A. parasiticus [99]
13 Anti yeast activities of limonene in growth medium, fruit juices and milk Pure Saccharomyces cerevisiae [100]
14 Antifungal action of limonene Pure C. albicans and C. parapsilosis [45]
15 Antifungal action of limonene against dermatomycetes Pure T. mentagrophytes, T. rubrum and T. tonsurans [101]
16 Antifungal and inhibitory effects of DL-limonene on some yeasts Pure 14 yeast strains [102]
17 Effect of limonene on Saccharomyces cerevisiae 93% Saccharomyces cerevisiae [90]
18 Antimicrobial action of limonene from Wedelia prostrata Pure H. anomala, S. cerevisiae, A. niger,
C. globosum, M. racemosus and M. anka		 [47]
19 Response of Saccharomyces cerevisiae to D-limonene-induced
oxidative stress		 Pure Saccharomyces cerevisiae [91]
20 Antifungal action of limonene from genus Citrus Pure Aspergillus niger, A. flavus and A. carbonarius [50]
21 Effects of nisin on the antimicrobial activity of D-limonene
and its nanoemulsion		 Pure Saccharomyces cerevisiae [26]
22 Antifungal action of limonene from Mentha L. essential oils Pure A. alternate, A. solani, A. flavus, A. niger, F. solani and R. solani [103]
23 Improving antimicrobial action of D-limonene using a novel organogel-based nanoemulsion Pure Saccharomyces cerevisiae [28]
24 Antifungal action of limonene against biofilm forming pathogenic fungi Pure C. albicans, C. parapsilosis, A. fumigatus, A. terreus and S. apiospermum [55]
25 Antimicrobial action of limonene Pure (97%) C. albicans  and A. niger [104]
Antibacterial activity of essential oils containing Limonene
26 Antifungal action of
the essential oils of Cotinus coggygria		 39.2 and 47% (Major) A. niger, A. ochraceus, A. versicolor, A. flavus, A. fumigatus, P. ochrochloron , P. funiculosum, T. viride, C. Albicans and T. mentagrophytes. [105]
27 Antimicrobial action of the essential oil of Pimpinella puberula (DC.) Boiss. 21.7-82.4% (Major) C. albicans [66]
28 Antifungal action of Citrus reticulata Blanco essential oil 46.7% (Major) Alternaria alternata, Rhizoctonia solani, Curvularia lunata, Fusarium oxysporum and Helminthosporium oryzae [106]
29 Biological activities of two Citrus species 75.56 and 92.48% (Major) S. cerevisiae and C. albicans [107]
30 Antimicrobial action of Turkish citrus peel oils 36.8 to 94.1% (Major) C. albicans, K. fragilis , R. rubra , D. hansenii and H. guilliermondii [108]
31 Antifungal action of plant essential oils
against Malassezia furfur		 51.07% (Major) Malassezia furfur [109]
32 Antimicrobial action of essential oils of Aloysia triphylla Major C. albicans Hansenula sp and Rhodotorula sp [110]
33 Antifungal activities of volatile extracts from fresh leaves of Crassocephalumrubens against food borne pathogens 48.8% (Major) C. albicans [68]
34 Antimicrobial action of essential oil of Citrus limetta var 95.98% (Major) A. niger, A. flavus, A. fumigatus, A. ficuum, F. oxysporum, P. digitatum, F. saloni and C. utilis. [74]
35 Antifungal action of essential oils in the control of food-borne fungi growth Major A. flavus, A. ochraceus,  A. parasiticus, F. verticillioides, E. repens  P. corylophilum [111]
36 Antimicrobial action of essential oils of Tunisian Citrus aurantium L. 87.02% C. albicans [112]
37 Antifungal efficacy of essential oil from the Egyptian sweet orange peel 86.75% (Major) A. flavus, and A. paraciticus [113]
38 Antimicrobial action of Bergamot Oil 40% (Major) Trichophytonverrucosum [114]
39 Antimicrobial action of essential oil of Ammodaucus leucotrichus Coss. & Dur. seeds 23.89% (second highest) C. albicans,S. cerevisiae, A. flavus and P. escpansum [75]
40 Antimicrobial activities of leaves and fruit peels of Citrus sinensis Linn. 30.1% (second highest) C. albicans and A. niger [76]
41 Antimicrobial action of Leaf, Ripe and Unripe Peel of Bitter Orange (Citrus aurantium) Essential Oils Major Saccharomyces cerevisiae [115]
42 Antifungal action of essential oils from Protium heptaphyllum against Candida spp. 36.01 (Major) 16 species of Candida [116]
43 Antimicrobial action of Citrus reticulata Blanco Cultivar Murcott 13.9 to 93.71% (Major) A. fumigates, C. albicans and S. cerevisiae [117]
44 Antimicrobial action of Citrus medica L. var proper leaf essential oil against skin pathogens 11.54% (third highest) C. albicans [83]

 
45 Antimicrobial action of Citrus lemon essential oil 39.4% (Major) A. niger, A. flavus, A. nidulans, A. fumigates, F. graminearum, F.oxysporum, F. culmorum and A. alternata [118]

The antifungal mechanism of action of limonene was also studied against few fungal isolates. Treatment of limonene to yeast cells arise a compensatory response in the form of over-expression of various genes (i.e., ROM1, RLM1, PIR3, CTT1, YGP1, MLP1, PST1, CWP1) which are involved in cell wall integrity signaling pathway. It was concluded that limonene treatment leads to cell wall deterioration in the yeast cells. The fact of alteration in structure and function of yeast which further affects the cytokinesis due to limonene was established90. Limonene was also observed to induce the accumulation of reactive oxygen species (ROS) in fungal isolates and leads to cell death91. Scanning electron microscopic analysis of fungal isolates after the treatment of limonene showed the deformation and distortion of the fungal cells which further leads to the leakage of intracellular material due to damaged cell membrane26,28. Mechanism of antifungal action of limonene was also studied against Candida albicans in which treatment of limonene cause alteration in membrane permeabilization of up to 82-88% of the cells55. Mechanism of action of limonene against Candida sp. involved in intra-vaginal infections was also examined. Results of the study showed the protective role of limonene against Vulvovaginal candidiasis causing fungal isolates, as a low fungal burden in mice was observed after the treatment with limonene in comparison to untreated mice. Electron microscopy also revealed that limonene treatment caused dramatic structural changes in fungal cells including cell wall rupture92. Limonene is also found to inhibit the intracellular and extracellular enzymes such as cellulase and pectin methyl esterase present in some fungal isolates such as A. niger, P. digitatum, F. oxysporium and R. solani93.

All the above-mentioned studies explained a few of the antifungal mechanisms of action of limonene against various fungal isolates. However, exact mechanisms of the anti-fungal actions of limonene are not yet unrevealed hence; further studies are required to explore the antifungal mechanisms of limonene.

Anti-biofilm production property of Limonene
Resistance in microorganisms against various antimicrobial agents has become the main concern in the medical industry nowadays. The formation of biofilm by microorganisms is one of the mechanisms to acquire resistance against antimicrobial agents. Hence, it is important to find alternative therapeutic agents with anti-biofilm properties. Many plant-based compounds are being examined for their therapeutic properties of which only a few are reported to exhibit anti-biofilm activity119. Limonene is one the plant-based compounds which possess anti-biofilm property. The anti-biofilm property of limonene is also investigated and proved in various studies by many researchers. The anti-biofilm property of limonene was examined against B. cereus, E. coli, P. anomala and P. putida and significant inhibition of biofilm of B. cereus, E. coli, and P. anomala by limonene was observed48. About 75-95% biofilm inhibition was observed against S. pyogenes, S. mutans, and S. mitis at 400μg/ml concentration of limonene120. Limonene was also found to reduce the biofilm mass production up to 90% after 8h of incubation at the concentration of 2000μl/L in different strains of S. aureus121. In another study, effective biofilm inhibition by limonene against P. aeruginosa, C. albicans, and C. parapsilosis was also observed55. In silico determination of anti-biofilm property of limonene against S. mutans showed that limonene can act as a good candidate for the inhibition of development in biofilm formation122.

Concluding Remarks and Future Perspectives
As discussed above, limonene possesses antimicrobial properties such as antibacterial, antifungal, and antiviral. Limonene was also found to hinder biofilm formation and most importantly limonene also shows the inhibitory action against COVID-19. Limonene is suggested to be safe as it is derived from natural sources e.g. citrus plants. Hence, the use of limonene in the future for therapeutic purposes in clinical settings may be considered. Moreover, researches on combinatorial studies of limonene with other drugs are also inevitable to achieve better outcomes in breaking the therapeutic resistance of microbes. Delineation of the mechanistic approach of limonene towards antimicrobial activities is also desirable. Therefore, it may be suggested that there is still a wide lacuna of knowledge to be acquired to venture limonene as a future potential drug molecule.

Declarations

ACKNOWLEDGMENTS
The authors gratefully acknowledge the support extended by Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, towards this piece of work.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.

AUTHORS’ CONTRIBUTION
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

FUNDING
None.

ETHICS STATEMENT
Not applicable.

AVAILABILITY OF DATA
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References
  1. Ayukekbong JA, Ntemgwa M, Atabe AN. The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 2017;6:47.
    Crossref
  2. Sasidharan S, Chen Y, Saravanan D, Sundram KM, Latha LY. Extraction, isolation and characterization of bioactive compounds from plant extracts. Afr J Tradit Complement Altern Med. 2011;8(1):1-10.
    Crossref
  3. Achilonu MC, Umesiobi DO. Bioactive phytochemicals: bioactivity, sources, preparations, and/or modifications via silver tetrafluoroborate mediation. J Chem. 2015;2015:629085.
    Crossref
  4. Li Q. Effect of forest bathing trips on human immune function. Environ Health Prev Med. 2010;15(1):9-17.
    Crossref
  5. Sun J. D-limonene: safety and clinical applications. Altern Med Rev. 2007;12(3):259-264.
  6. United States Environmental Protection Agency. Prevention pesticides and toxic substances (7508W). Reregistration Eligibility Decision (RED). EPA 738-R-94-034, September, 1994.
  7. IARC monograph. Some naturally occurring substances: Food items and constituents, heterocyclic aromatic amines and mycotoxins. D-limonene. 1993;56.
  8. IARC monograph. Some chemicals that cause tumours of the kidney or urinary bladder in rodents and some other substances. D-limonene. 1999;73.
  9. Danish ministry of the environment, Environmental protection agency. Evaluation of health hazards by exposure to d-limonene and proposal of a health based quality criterion for ambient air. 2013.
  10. National toxicological program technical report series No. 347. Toxicology and carcinogenesis studies of d-limonene in F344/N rats and B6C3F1 mice. U.S. department of health and human services. Public health service. National institutes of health. January 1990.
  11. Astani A, Schnitzler P. Antiviral activity of monoterpenes beta-pinene and limonene against herpes simplex virus in vitro. Iran J Microbiol. 2014;6(3):149-155.
  12. Vogt MV, Sutil SB, Escobar FM, et al. Minthostachys verticillata essentials oil and its major components: anti herpetic selective action in HEp-2 cells. Mol Med Chem. 2010;21:117-120.
  13. Franchomme P. Pharmacology of R (+)-Limonene and some citrus peel essences. Proceedings of the 4th Aromatherapy Conference on the therapeutic uses of essential oils. San Francisco, 2000.
  14. El-hawary SS, Taha KF, Abdel-Monem AR, Kirillos FN, Mohamed AA. Chemical composition and biological activities of peels and leaves essential oils of four cultivars of Citrus deliciosa Var. tangarina. Am J Essent Oil Nat Prod. 2013;1(2):1-6.
  15. Nagy MM, Al-Mahdy DA, Aziz OMAE, Kandil AM, Tantawy MA, Alfy TSME. Chemical composition and antiviral activity of essential oils from Citrus reshni hort. Ex Tanaka (Cleopatra mandarin) cultivated in Egypt. J Essent Oil Bear Plants. 2018;21(1):264-272.
    Crossref
  16. Min L, Han Z, Xu Y, Yao L. In vitro and In vivo anti Tobacco mosaic virus activities of essential oils and individual compounds. J Microbiol Biotechnol. 2013;23(6):771-778.
    Crossref
  17. Abdelli I, Hassani F, Brikci SB, Ghalem S. In silico study the inhibition of angiotensin converting enzyme 2 receptor of COVID-19 by Ammoides verticillata components harvested from Western Algeria. J Biomol Struct Dyn. 2021;39(9):3263-3276.
    Crossref
  18. Al-garawyi AMA, Hussein TA, Jassim MMA. Inhibition of viral infection by using of natural herbal remedies as alternative treatment. Sys Rev Pharm. 2020;11(6):416-419.
    Crossref
  19. Khan ZA. Preventive role of mouthwashes in COVID-19 disease transmission: An overview. Asian J Oral Health Allied Sci. 2020;10(9):1-5.
    Crossref
  20. Kumar KJS, Vani MG, Wang CS, et al. Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain, in epithelial cells. Plants. 2020;9(6):770.
    Crossref
  21. Meeran MFN, Seenipandi A, Javed H, et al. Can limonene be a possible candidate for evaluation as an agent or adjuvant against infection, immunity, and inflammation in COVID-19? Heliyon. 2020;7(1):e05703.
    Crossref
  22. Bahl AS. Effectiveness of polyherbal topical oil treatment for patients either with ‘COVID-19 like symptoms or ‘COVID-19 Positive’: A prospective study. Insights In Biomed. 2020;5(4):1-10.
    Crossref
  23. Bhattacharjee AS, Joshi SV, Naik S, Sangle S, Abraham NM. Quantitative assessment of olfactory dysfunction accurately detects asymptomatic COVID-19 carriers. E. Clinical Medicine. 2020;28:100575.
    Crossref
  24. Espina L, Gelaw TK, Castellvi SDL, Pagan R, Gonzalo DG. Mechanism of bacterial inactivation by (+)-Limonene and its potential use in food preservation combined processes. PLoS One. 2013;8(2):e56769.
    Crossref
  25. Chueca B, Pagan R, Gonzalo DG. Differential mechanism of Escherichia coli inactivation by (+) Limonene as a function of cell physiological state and drug’s concentration. PLoS One. 2014;9(4):e94072.
    Crossref
  26. Zhang Z, Vriesekoop F, Yuan Q, Liang H. Effects of nisin on the antimicrobial activity of D-limonene and its nanoemulsion. Food Chem. 2014;150:307-312.
    Crossref
  27. Bei W, Zhou Y, Xing X, et al. Organogel-nanoemulsion containing nisin and D-limonene and its antimicrobial activity. Front Microbiol. 2015;6:1010.
    Crossref
  28. Zahi MR, Liang H, Yuan Q. Improving the antimicrobial activity of D-limonene using a novel organogel based nanoemulsion. Food Control. 2015;50:554-559.
    Crossref
  29. Li J, Ahn J, Liu D, Chen S, Ye X, Ding T. Evaluation of ultrasound-induced damage to Escherichia coli and Staphylococcus aureus by flow cytometry and transmission electron microscopy. Appl Env Microbio. 2016;82(6):1828-1837.
    Crossref
  30. Sani MA, Henriques ST, Weber D, Separovic. Bacteria may cope differently from similar membrane damage caused by the Australian tree frog antimicrobial peptide maculatin 1.1. J Biol Chem. 2015;290(32):19853-19862.
    Crossref
  31. Trombetta D, Casteelli F, Sarpietro MG, et al. Mechanisms of antibacterial action of three monoterpenes. Antimicrob Agents Chemother. 2005;49(6):2474-2478.
    Crossref
  32. Han Y, Sun Z, Chen W. Antimicrobial susceptibility and antibacterial mechanism of limonene against Listeria monocytogenes. Molecules. 2019;25(1):33.
    Crossref
  33. Zukerman I. Effect of oxidized d-limonene on microorganisms. Nature. 1951;168:517.
    Crossref
  34. Dabbah R, Edwards VM, Moats WA. Antimicrobial action of some citrus fruit oils on selected food borne bacteria. Appl Microbiol. 1970;19(1):27-31.
    Crossref
  35. Andrews RE, Parks LW, Spence KD. Some effects of Douglas Fir terpenes on certain microorganisms. Appl Environ Microbiol. 1980;40(2):301-304.
    Crossref
  36. Dorman HJD, Deans SG. Antimicrobial agents from plants: antibacterial activity of plant volatile oils. J Appl Microbiol. 2000;88(2):308-316.
    Crossref
  37. Inouye S, Takizawa T, Yamaguchi. Antibacterial activity of essential oils and their major constituents against respiratory tract pathogens by gaseous contact. J Antimicrob Chemother. 2001;47(5):565-573.
    Crossref
  38. Aggarwal KK, Khanuja SPS, Ahmad A, Kumar TRS, Gupta VK, Kumar S. Antimicrobial activity profiles of the two enantiomers of limonene and carvone isolated from the oils of Mentha spicata and Anethum sowa. Flavour Fragr J. 2002;17(1):59-63.
    Crossref
  39. Mourey A, Canillac N. Anti-Listeria monocytogenes activity of essential oils components of Conifers. Food Control. 2002;13(4-5):289-292.
    Crossref
  40. Filipowicz N, Kaminski M, Kurlenda J, Asztemborska M, Ochocka JR. Antibacterial and antifungal activity of Juniper berry oil and its selected components. Phytother Res. 2003;17(3):227-231.
    Crossref
  41. Rancic A, Sokovic M, Griensven LV, Vukojevic J, Brkic D, Ristic MS. Antimicrobial activity of limonene. Zb Rad. 2003;23(23):83-88.
  42. Nannapaneni R, Muthaiyan A, Crandall PG, et al. Antimicrobial activity of commercial citrus-based natural extracts against Escherichia coli 0157:H7 isolates and mutant strains. Food borne Pathog Dis. 2008;5(5):695-699.
    Crossref
  43. Bevilacqua A, Corbo MR, Sinigaglia M. In vitro evaluation of the antimicrobial activity of eugenol, limonene, and citrus extract against bacteria and yeasts, representative of the spoiling micro flora of fruit juices. J Food Prot. 2010;73(5):888-894.
    Crossref
  44. Sokovic M, Glamoclija J, Marin PD, Brkic D, Van Griensven LJLD. Antibacterial effects of the essential oils of commonly consumed medicinal herbs using an in vitro model. Molecules. 2010;15(11):7532-7546.
    Crossref
  45. Orhan IE, Ozcelik B, Kartal M, Kan Y. Antimicrobial and antiviral effects of essential oils from selected umbelliferae and Labiattae plants and individual essential oil components. Turk J Biol. 2012;36(3):239-246.
    Crossref
  46. Azarakhsh N, Osman A, Ghazali HM, Tan CP, Adzahan NM. Effect of limonene incorporation into Gellan based edible coating on the changes in microbiological and sensory characteristics of fresh cut pineapple during cold storage. Acta Hortic. 2013;1012:999-1004.
    Crossref
  47. Dai J, Zhu L, Yang L, Qui J. Chemical composition, antioxidant and antimicrobial activities of essential oil from Wedelia prostrata. Excli Journal. 2013;12:479-490.
    Crossref
  48. Kerekes EB, Deak E, Tako M, et al. Anti-biofilm forming and anti-quorum sensing activity of selected essential oils and their main components on food related microorganisms. J Appl Microbiol. 2013;115(4):933-942.
    Crossref
  49. Vimal M, Vijaya PP, Mumtaj P, Farhath MSS. Antibacterial activity of selected compounds of essential oils from indigenous plants. J Chem Pharm Res. 2013;5(1):248-253.
  50. Gomes MS, Cardoso MDG, Soares MJ, et al. Use of essential oils of the Genus Citrus as biocidal agent. Am J Plant Sci. 2014;5(3):299-305.
    Crossref
  51. Li H, Yang T, Li FY, Yao Y, Sun ZM. Antibacterial activity and mechanism of action of Monarda punctata essential oil and its main components against common bacterial pathogens in respiratory tract. Int J Clin Exp Pathol. 2014;7(11):7389-7398.
  52. Haiyan LU, Chongxin XU, Xiao Z, Ying L, Xianjin LIU. Antibacterial effect of limonene on food-borne pathogens. J Zhejiang Univ. 2016;42(3):306-312.
    Crossref
  53. Yang C, Hu DH, Feng Y. Antibacterial activity and mode of action of the Artemisia capillaris essential oil and its constituents against respiratory tract infection-causing pathogens. Mol Med Rep. 2015;11(4):2852-2860.
    Crossref
  54. Montironi ID, Cariddi LN, Reinoso EB. Evaluation of the antimicrobial efficacy of Minthostachys verticillata essential oil and limonene against Streptococcus uberis strains isolated from bovine mastitis. Rev Argent Microbiol. 2016;48(3):210-216.
    Crossref
  55. Pekmezovic M, Aleksic I, Barac A, et al. Prevention of poly microbial biofilms composed of Pseudomonas aeruginosa and pathogenic fungi by essential oils from selected Citrus species. Pathog Dis. 2016;74(8):1-10.
    Crossref
  56. Yao Y, Ding D, Shao H, Peng Q, Huang Y. Antibacterial activity and physical properties of fish gelatin-chitosan edible films supplemented with D-limonene. Int J Polym Sci. 2017;1837171.
    Crossref
  57. Pathirana HNKS, Wimalasena SHMP, Silva BCJD, Hossain S, Heo GJ. Antibacterial activity of lime (Citrus aurantifolia) essential oil and limonene against fish pathogenic bacteria isolated from cultured olive flounder (Paralichthys olivaceus). Fish Aquat Life. 2018;26(2):131-139.
    Crossref
  58. Vuuren SF, Viljoen AM. Antimicrobial activity of limonene enantiomers and 1,8-cineole alone and in combination. Flavour Fragr J. 2007;22(6):540-544.
    Crossref
  59. Espina L, Garcia-Gonzalo D, Laglaoui A, Mackey BM, Pagan R. Synergistic combinations of high hydrostatic pressure and essential oils or their constituents and their use in preservation of fruit juices. Int J Food Microbiol. 2013;161(1):23-30.
    Crossref
  60. Sieniawska E, Ossor MS, Sawicki R, Wozniak KS, Ginalska G. Natural terpenes influence the activity of antibiotics against isolated Mycobacterium tuberculosis. Med Princ Pract. 2017;26(2):108-112.
    Crossref
  61. Donsi F, Annunziata M, Sessa M, Ferrari G. Nano encapsulation of essential oils to enhance their antimicrobial activity in foods. LWT- Food Sci Technol. 2011;44(9):1908-1914.
    Crossref
  62. Mate J, Periago PM, Palop A. Combined effect of a nanoemulsion of D-limonene and nisin on Listeria monocytogenes growth and viability in culture media and foods. Food Sci Technol Int. 2015;22(2):146-152.
    Crossref
  63. Aytac Z, Yildiz ZI, Senirmak FK, et al. Fast-Dissolving, prolonged release and antibacterial cyclodextrin/ limonene-inclusion complex nanofibrous webs via polymer free electrospinning. J Agric Food Chem. 2016;64(39):7325-7334.
    Crossref
  64. Iacobellis NS, Cantore PL, Capasso F, Senatore F. Antibacterial activity of Cuminum cyminum L. and Carum carvi L. essential oils. J Agric Food Chem. 2005;53(1):57-61.
    Crossref
  65. Baik JS, Kim SS, Lee JA, et al. Chemical compositions and biological activities of essential oils extracted from Korean endemic Citrus species. J Microbiol Biotechnol. 2008;18(1):74-79.
  66. Askari F, Sefidkon F, Teimouri M, Nanaei SY. Chemical composition and antimicrobial activity of the essential oil of Pimpinella puberula (DC.) Boiss. J Agric Sci Technol. 2009;11(4):431-438.
  67. Benites J, Moiteiro C, Miguel G, et al. Composition and biological activity of the essential oil of Peruvian Lantana camara. J Chil Chem Soc. 2009;54(4):379-384.
    Crossref
  68. Yehouenou B, Wotto V, Bankole H, Sessou P, Noudogbessi JP, Sohounhloue D. Chemical study and antimicrobial activities of volatile extracts from fresh leaves of Crassocephalum rubens (Juss and Jack) S. moore against food borne pathogens. Scientific Study and Research: Chemistry and Chemical Engineering, Biotechnology, Food Industry. 2010;11(3):343-351.
  69. Jaroenkit P, Matan N, Nisoa M. In vitro and in vivo activity of Citronella oil for control of spoilage bacteria of semi dried round scad (Decapterus maruadsi). Int J Med Aromatic Plants. 2011;1(3):234-239.
  70. Farjam MH. Antibacterial activity and composition of essential oil of Nepeta pungens Benth Iran. J Appl Pharm Sci. 2012;2(4):103-105.
    Crossref
  71. Pina ES, Coppede JDS, Sartoratto A, et al. Antimicrobial activity and chemical composition of essential oils from Aloysia polystachya (Griseb.) Moldenke grown in Brazil. J Med Plants Res. 2012;6(41):5412-5416.
    Crossref
  72. Srisukh V, Tribuddharat C, Nukoolkarn V, et al. Antibacterial activity of essential oils from Citrus hystrix (makrut lime) against respiratory tract pathogens. Sci Asia. 2012;38(2):212.
    Crossref
  73. Ullah N, Amin M, Ali J, et al. Chemical composition and antimicrobial activity evaluation of Sweet Oranges (Citrus cinenses) peels essential oil. J Pharm Res. 2012;5(3):1698-1700.
  74. Javed S, Ahmad R, Shahzad K, Nawaz S, Saeed S, Saleem Y. Chemical constituents, antimicrobial and antioxidant activity of essential oil of Citrus limetta var. Mitha (Sweet lime) peel in Pakistan. Afr J Microbiol Res. 2013;7(24):3071-3077.
    Crossref
  75. Louail Z, Kameli A, Benabdelkader T, Bouti K, Hamza K, Krimat S. Antimicrobial and antioxidant activity of essential oil of Ammodaucus leucotrichus Coss. and Dur. seeds. J Mater Environ Sci. 2018;7(7):2328-2334.
  76. Singh V, Katiyar D, Ali M. Comparative study of volatile constituents and antimicrobial activities of leaves and fruit peels of Citrus sinensis Linn. J Pytopharmacol. 2015;4(2):102-105.
  77. Ou MC, Liu YH, Sun YW, Chan CF. The composition, antioxidant and antibacterial activities of cold-pressed and distilled essential oils of Citrus paradisi and Citrus grandis L. Osbeck. Evid Based Complement Alternat Med. 2015;2015:804091.
    Crossref
  78. Vasek OM, Caceres LM, Chamorro ER, Velasco GA. Antibacterial activity of Citrus paradisi essential oil. J Nat Prod. 2015;8:16-26.
  79. Geraci A, Stefano VD, Martino ED, Schillaci D, Schicchi R. Essential oil components of orange peels and antimicrobial activity. Nat Prod Res. 2017;31(6):653-659.
    Crossref
  80. Jafari NK, Sani AM. Chemical composition and antibacterial activity of essential oil from Melissa officinalis leaves. J Agric Biol Sci. 2016;11(9):367-372.
  81. Pulaj B, Mustafa B, Nelson K, Quave CL, Hajdari A. Chemical composition and in vitro antibacterial activity of Pistacia terebinthus essential oils derived from wild populations in Kosovo. BMC Complement Altern Med. 2016;16:147.
    Crossref
  82. Teneva D, Denkova Z, Goranov B, et al. Chemical composition and antimicrobial activity of essential oils from black pepper, cumin, coriander and cardamom against some pathogenic microorganisms. Acta Universitatis Cibiniensis Series. E: Food Technol. 2016;20(2): 39-52.
    Crossref
  83. Aliyah, Himawan A, Rante H, Mufidah Ningish DR. GC-MS analysis and antimicrobial activity determination of Citrus medica L. var proper leaf essential oil from South Sulawesi against skin pathogen microorganism. IOP Conf Ser Mater Sci Eng. 2017;259:012001.
    Crossref
  84. Bozkurt T, Gulnaz O, Kacar YA. Chemical composition of the essential oils from some citrus species and evaluation of the antimicrobial activity. IOSR J Environ Sci Toxicol Food Technol. 2017;11(10):29-33.
    Crossref
  85. Moosavy MH, Hassanzadeh P, Mohammadzadeh E, Mahmoudi R, Khatibi SA, Mardani K. Antioxidant and antimicrobial activities of essential oil of Lemon (Citrus limon) peel in vitro and in a food model. J Food Qual Hazards Control. 2017;4:42-48.
  86. Al-Aamri MS, Al-Abousi NM, Al-Jabri SS, Alam T, Khan SA. Chemical composition and in-vitro antioxidant and antimicrobial activity of the essential oil of Citrus aurantifolia L. leaves grown in Eastern Oman. J Taibah Univ Med Sci. 2018;13(2):108-112.
    Crossref
  87. Shutava HG, Shutava TG, Kavalenka NA, Supichenka HN. Antiradical and Antibacterial activity of essential oils from the Lamiaceae family plants in connection with their composition and optical activity of components. Int J Second Metab. 2018;5(2):109-122.
    Crossref
  88. Dagnas S, Membre JM. Predicting and preventing mold spoilage of food products. J Food Prot. 2013;76(3):538-551.
    Crossref
  89. Kurtzman CP, Fell JW, Boekhout T. The Yeasts, a taxonomic study, 5th Ed.Elsevier. 2011.
  90. Brennan TCR, Kromer JO, Nielsen LK. Physiological and transcriptional response to d-limonene in Saccharomyces cerevisiae shows changes to the cell wall, not the plasma membrane. Appl Environ Microbiol. 2013;79(12):3590-3600.
    Crossref
  91. Liu J, Zhu Y, Du G, Zhou J, Chen J. Response of Saccharomyces cerevisiae to D-limonene-induced oxidative stress. Appl Microbiol Biotechnol. 2013;97(14):6467-6475.
    Crossref
  92. Munoz JE, Rossi DCP, Jabes DL, et al. In vitro and In vivo inhibitory activity of limonene against different isolates of Candida sp. J Fungi. 2020;6(3):183.
    Crossref
  93. Marei GIKh, Rasoul MAA, Abdelgaleil SAM. Comparative antifungal activities and biochemical effects of monoterpenes on plant pathogenic fungi. Pestic Biochem Phys. 2012;103:56-61.
    Crossref
  94. Dambolena JS, Lopez AG, Canepa MC, Theumer MG, Zygadlo JA, Rubinstein HR. Inhibitory effect of cyclic terpenes (limonene, menthol, menthone and thymol) on Fusarium verticillioides MRC 826 growth and fumonisin B1 biosynthesis. Toxicon. 2008;51(1):37-44.
    Crossref
  95. Chee HY, Kim H, Lee MH. In vitro antifungal activity of limonene against Trchophyton rubrum. Mycobiology. 2009;37(3):243-246.
    Crossref
  96. Startseva VA, Nikitina LE, Sirazieva EV, et al. Synthesis and biological activity of monoterpenoids belonging to menthane series. Chem Sustain Dev. 2009;17:533-539.
  97. Singh P, Shukla R, Prakash B, et al. Chemical profile, antifungal, antiaflatoxigenic and antioxidant activity of Citrus maxima Burm. and Citrus Sinensis (L.) osbeck essential oils and their cyclic monoterpene, DL- limonene. Food Chem Toxicol. 2010;48(6):1734-1740.
    Crossref
  98. Omran SM, Moodi MA, Amiri SMBN, et al. The effects of limonene and Orange peel extracts on some spoilage Fungi. Int J Mol Clin Microbiol. 2011;1:82-86.
  99. Rammanee K, Hongpattarakere T. Effects of tropical citrus essential oils on growth, aflatoxin production, and ultra structure alterations of Aspergillus flavus and Aspergillus parasiticus. Food Bioproc Tech. 2011;4:1050-1059.
    Crossref
  100. Tserennadmid R, Tako M, Galgoczy L, et al. Anti yeast activities of some essential oils in growth medium, fruit juices and milk. Int J Food Microbiol. 2011;144(3):480-486.
    Crossref
  101. Sokovic M, Glamoclija J, Ciric A, et al. Antifungal activity of the essential oils and components in vitro and in vivo on experimentally induced Dermatomycosis Rats. Dig J Nanomater Bio Structures. 2012;7(3):959-966.
  102. Unal MU, Ucan F, Sener A, Dicner S. Research on antifungal and inhibitory effects of DL-limonene on some yeasts. Turk J Agric For. 2012;36(5):576-582.
    Crossref
  103. Kostik V, Gjorgeska B, Petkovska S. Mentha L. essential oils composition and in vitro antifungal activity. IOSR J Pharm. 2015;5(7):1-7.
  104. Antosik AK, Wilpiszewska K, Wroblewska A, Szczupak AM, Malko MW. Fragrant starch based films with limonene. Curr Chem Lett. 2017;6:41-48.
    Crossref
  105. Novakovic M, Vuckovic I, Janackovic P, et al. Chemical composition, antibacterial and antifungal activity of the essential oils of Cotinus coggygria from Serbia. J Serbian Chem Soc. 2007;72(11):1045-1051.
    Crossref
  106. Chutia M, Bhuyan PD, Pathak MG, Sarma TC, Boruah P. Antifungal activity and chemical composition of Citrus reticulata Blanco essential oil against phyto pathogens from North East India. LWT-Food Sci Technol. 2009;42(3):777-780.
    Crossref
  107. Hamdan D, El-Readi MZ, Nibret E, et al. Chemical composition of the essential oils of two Citrus species and their biological activities. Pharmazie. 2010;65(2):141-147.
    Crossref
  108. Kirbaslar FG, Tavman A, Dulger B, Turker G. Antimicrobial activity of Turkish citrus peel oil. Pak J Bot. 2009;41(6):3207-3212.
  109. Hyun LJ, Lee JS. Chemical composition and antifungal activity of plant essential oils against Malassezia furfur. Korean J Microbiol Biotechnol. 2010;38(3):315-321.
  110. Oliva MM, Beltramino E, Gallucci N, Casero C, Zygadlo J, Demo M. Antimicrobial activity of essential oils of Aloysia triphylla (L’Her.) Britton from different regions of Argentina. Bol Latinoam Caribe Plantas Med Aromat. 2010;9(1):29-37.
  111. Tanackov SDK, Dimic GR. Antifungal activity of essential oils in the control of food-borne fungi growth and mycotoxin biosynthesis in food. Microbial pathogens and strategies for combating them: science, technology and education. 2013;838-849.
  112. Trabelsi D, Ammar AH, Bouabdallah F, Zagrouba F. Antioxidant and antimicrobial activities of essential oils and methanolic extracts of Tunisian Citrus aurantium L. J Environ Sci Toxicol Food Technol. 2014;8(5):18-27.
    Crossref
  113. Fattah A, Yehia HA, Fouzy ASM, Ramadan MM, Nooh A. Antifungal efficacy and chemical composition of essential oil from the Egyptian sweet orange peel (Citrus sinensis, L). Int J Adv Res. 2015;3(10):1257-1269.
  114. Hafez EA. Antimicrobial activity of Bergamot oil against Trichophyton verrucosum isolated from local cows. J Biochem Microbiol Biotechnol. 2015;3(1):7-9.
  115. Azhdarzadeh F, Hojjati M. Chemical composition and antimicrobial activity of leaf, ripe and unripe peel of Bitter orange (Citrus aurantium) essential oils. Nutr Food Sci Res. 2016;3(1):43-50.
    Crossref
  116. Mobin M, De Lima SG, Almeida LTG, et al. MD/GC-MS analysis of essential oils from Protium heptaphyllum (Aubl.) and their antifungal activity against Candida specie. Braz J Med Plants. 2016;18(2):531-538.
    Crossref
  117. Al-Gendy AA, El-Sayed MA, Hamdan DI, El-Shazly AM. Volatile constituents, antimicrobial and cytotoxic activities of Citrus reticulata Blanco Cultivar Murcott. Int J Pharmacogn Phytochem Res. 2017;9(3):376-386.
    Crossref
  118. Hsouna AB, Hamila NB, Smaoui S, Hamdi N. Citrus lemon essential oil: chemical composition, antioxidant and antimicrobial activities with its preservative effect against Listeria monocytogenes inoculated in minced beef meat. Lipids Health Dis. 2017;16:146.
    Crossref
  119. Alasil SM, Omar R, Ismail S, Yusof MY. Anti-biofilm activity, compound characterization, and acute toxicity of extract from a novel bacterial species of Paenibacillus. Int J Microbiol. 2014;2014:649420.
    Crossref
  120. Subramenium GA, Vijayakumar K, Pandian SK. Limonene inhibits streptococcal biofilm formation by targeting surface-associated virulence factors. J Med Microbiol. 2015;64(8):879-890.
    Crossref
  121. Espina L, Pagan R, Lopez D, Gonzalo DG. Individual constituents from essential oils inhibit biofilm mass production by multi-drug resistant Staphylococcus aureus. Molecules. 2015;20(6):11357-11372.
    Crossref
  122. Nosrati M, Behbahani M, Mohabatkar H, Shakeran Z. Antibacterial and anti biofilm activities of Prangos acaulis Bornm. extract against Streptococcus mutans: an in silico and in vitro study. J Herb med Pharmacol. 2018;7(3):176-184.
    Crossref
Cite This Article

Article Metrics

Article View: 7174
JPAM.15.3.01 (1736 downloads)

Share This Article

© The Author(s) 2021. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License which permits unrestricted use, sharing, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Copyright © 2024 Journal of Pure and Applied Microbiology. All Rights Reserved.