Volatile oils: Potential agents for the treatment of respiratory infections

Chapter 16

Volatile oils: Potential agents for the treatment of respiratory infections

A. Pasdaran*,**,

A. Pasdaran

D. Sheikhi
*    Guilan University of Medical Sciences, Department of Pharmacognosy, School of Pharmacy, Research and Development Center of Plants and Medicinal Chemistry, Rasht, Iran
**    Shiraz University of Medical Sciences, Medicinal Plants Processing Research Center, Shiraz, Iran
    Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    Regulations (GCP/ICH), Pharmaceuticals, Denmark


Due to presence of secondary bioactive metabolites, natural compounds are considered a major source of new active molecules that can be developed as new drugs. Infectious diseases, and mainly the common respiratory infections, are major challenges to the current chemotherapy systems and, therefore, there is a requirement to find new compounds with therapeutic potential. The volatile natural compounds and essential oils are the main treasure agents in the natural compounds with antibiotic potential. The present chapter reviews natural traditional remedies used in the treatment of respiratory infections with the emphasis on antibacterial, antiviral, and antiinflammation activities of the volatile natural compounds (essential oils, etc.), and provides a brief view in some of structural activity relationships between antibacterial potencies and chemical structures of the essential oil’s constituents.


natural compounds

volatile oils

antibacterial activity

antiviral activity

antiinflammation activity

1. Introduction

Referring to infectious disease, respiratory tract infections engage with all surfaces in the respiratory tract. Based on the infected zone, respiratory infections can be categorized into upper tract infection (URI or URTI) and lower tract infection (LRI or LRTI). Each involves different parts of the respiratory tract infections, which vary in type and severity of microorganisms. Although there are different types of respiratory tract infections, the acute form in the upper respiratory tract infection predominates and includes several complications, such as sinusitis, pharyngitis, epiglottitis, laryngitis, and tracheitis. On the other hand, lower respiratory tract infection (LRTI) includes both acute and chorionic types, such as pneumonia and bronchitis. Based on pathogenicity, bacterial and viral pathogens are the most common microorganisms in both types (ie, LRTI and URTI). Moreover, infection distribution leads to varieties based on the patient’s age; for example, acute respiratory infections pose severe problem in childhood, which mainly occur in upper respiratory tract. Although the bacterial pathogens play a significant role in intensifying LRTIs, the major acute respiratory infections occur in upper respiratory tract, in these cases viral pathogens are the primary common pathogens, including influenza A and B, parainfluenza (type 1 and 3), adenovirus, and respiratory syncytial virus. Some of the common pathogens of the respiratory tract are listed in Table 16.1. Pathogen biodiversity, complexity, and mixed infections in many cases of respiratory tract infection have generated several problems for the treatment of respiratory infections. For example, various bacterial pathogens are encountered in several cases of viral infections. Therefore, the treatment of respiratory infections is a complex therapy which consists of several chemotherapy strategies.13 Antiviral (the same as antibacterial medication) is used to control the treatment and prevention of respiratory infections.

Table 16.1

Some of the Common Pathogens Involved in Respiratory Tract Infections

Pathogen Name Common Infected Form Category References
Streptococcus pneumoniae Pneumonia/invasive pneumococcal diseases Gram-positive a
Haemophilus influenzae Pneumonia, epiglottitis and sinusitis Gram-negative b
Chlamydophila pneumoniae Atypical pneumonia Obligate intracellular bacterium c
Staphylococcus aureus Sinusitis, pneumonia Gram-positive d
Pseudomonas aeruginosa Sinusitis, pneumonia Gram-negative e
Legionella pneumophila Cough with sputum or bloody sputum/pneumonia, bronchiolitis Gram-negative f
Moraxella catarrhalis Bronchitis, sinusitis, laryngitis and bronchopneumonia Gram-negative g
Rhinoviruses Common cold, sinusitis, pneumonia (in middle-aged adults) Enterovirus h
Coronaviruses Pneumonia Coronavirinae i
Influenza virus Pneumonia Orthomyxovirus j
Respiratory syncytial virus Bronchiolitis, pneumonia Pneumovirus k
Adenovirus Pneumonia, tonsillitis, bronchiolitis Adenoviridae l
Herpes simplex virus Pneumonia, pharyngitis Respirovirus m
Histoplasma capsulatum Pneumonia Histoplasma (dimorphic fungi) n
Cryptococcus neoformans Pneumonia Cryptococcus (yeast) o
Coccidioides immitis Pneumonia Coccidioides (pathogenic fungus) p
Pneumocystis jirovecii Pneumonia Pneumocystis (yeast-like fungus) q

a  Madhi SA, Klugman KP, Group TVT. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004; 10:811–3. Tan TQ, Mason EO, Wald ER, Barson WJ, Schutze GE, Bradley JS, et al. Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae. Pediatrics 2002; 110: 1–6. Lynch JP, Martínez FJ. Clinical relevance of macrolide-resistant Streptococcus pneumoniae for community-acquired pneumonia. Clin Infect Dis 2002; 34: S27–S46.

b  Ginsburg CM, Howard JB, Nelson JD. Report of 65 cases of Haemophilus influenzae b pneumonia. Pediatrics 1979; 64: 283–6. Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 2000; 13: 302–17. Cordero E, Pachón J, Rivero A, Girón JA, Gómez-Mateos J, Merino MD, et al. Haemophilus influenzae pneumonia in human immunodeficiency virus-infected patients. Clin Infect Dis 2000; 30: 461–5. Farley MM, Stephens DS, Brachman PS, Harvey RC, Smith JD, Wenger JD. Invasive Haemophilus influenzae disease in adults: a prospective, population-based surveillance. Ann Intern Med 1992; 116: 806–12.

c  Wang X, Li H, Xia Z. Chlamydia pneumoniae Pneumonia. Radiology of Infectious Diseases 2015; 2 : 69–74. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44: S27–S72. Mansel J, Rosenow E, Smith T, Martin J. Mycoplasma pneumoniae pneumonia. CHEST J 1989; 95: 639–46. Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, et al. Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 2004; 113: 701–7.

d  Rubinstein E, Kollef MH, Nathwani D. Pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008; 46: S378–S85. Rello J, Sole-Violan J, Sa-Borges M, Garnacho-Montero J, Muñoz E, Sirgo G, et al. Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides*. Crit Care Med 2005; 33: 1983–7. Jiang R-S, Jang J-W, Hsu C-Y. Post-functional endoscopic sinus surgery methicillin-resistant Staphylococcus aureus sinusitis. Am J Rhinol 1999; 13: 273–7. Solares CA, Batra PS, Hall GS, Citardi MJ. Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant Staphylococcus aureus with mupirocin irrigations. Am J Otolaryngol 2006; 27: 161–5. Brown CA, Paisner HM, Biel MA, Levinson RM, Sigel ME, Garvis GE, et al. Evaluation of the microbiology of chronic maxillary sinusitis. Ann Otol Rhinol Laryngol 1998; 107: 942–5.

e  Ruxana TS, Timothy S B, John WC, Alice SP. Pathogen–Host Interactions in Pseudomonas aeruginosa Pneumonia. Am J Respir Crit Care Med2005; 171: 1209–23. Jordi R, Dolors M, Francesca M, Paola J, Ferran S, Jordi V, Pere C. Recurrent Pseudomonas aeruginosa Pneumonia in Ventilated Patients. Am J Respir Crit Care Med1998;157: 912–6. Zohra B, Jean B, Walid AH, Martin D. Biofilm Formation by Staphylococcus Aureus and Pseudomonas Aeruginosa is Associated with an Unfavorable Evolution after Surgery for Chronic Sinusitis and Nasal Polyposis. Otolaryngol Head Neck Surg 2006; 134: 991–6.

f  Carratala J, Gudiol F, Pallares R, Dorca J, Verdaguer R, Ariza J, et al. Risk factors for nosocomial Legionella pneumophila pneumonia. Am J Respir Crit Care Med 1994; 149: 625–9. Falco V, Fernández dST, Alegre J, Ferrer A, Martínez VJ. Legionella pneumophila. A cause of severe community-acquired pneumonia. Chest 1991; 100: 1007–11. Beigel F, Jürgens M, Filik L, Bader L, Lück C, Göke B, et al. Severe Legionella pneumophila pneumonia following infliximab therapy in a patient with Crohn’s disease. Inflamm Bowel Dis 2009; 15: 1240–4. Sato P, Madtes DK, Thorning D, Albert RK. Bronchiolitis obliterans caused by Legionella pneumophila. CHEST Journal 1985; 87: 840–2.

g  Klugman K. The clinical relevance of in vitro resistance to penicillin, ampicillin, amoxycillin and alternative agents, for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. J Antimicrob Chemother 1996; 38: 133–40. Karalus R, Campagnari A. Moraxella catarrhalis: a review of an important human mucosal pathogen. Microbes Infect 2000; 2: 547–59. DiPersio JR, Jones RN, Barrett T, Doern GV, Pfaller MA. Fluoroquinolone-resistant Moraxella catarrhalis in a patient with pneumonia: report from the SENTRY Antimicrobial Surveillance Program (1998). Diagn Microbiol Infect Dis 1998; 32: 131–5.

h  Winther B. Rhinovirus infections in the upper airway. Proc Am Thorac Soc 2011; 8: 79–89.

i  Peiris J, Lai S, Poon L, Guan Y, Yam L, Lim W, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003; 361: 1319–25. Peiris J, Chu C, Cheng V, Chan K, Hung I, Poon L, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003; 361: 1767–72. Woo PC, Lau SK, Chu C-m, Chan K-h, Tsoi H-w, Huang Y, et al. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol 2005; 79: 884–95. Woo PC, Lau SK, Tsoi H-w, Chan K-h, Wong BH, Che X-y, et al. Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia. Lancet 2004; 363: 841–5. Pene F, Merlat A, Vabret A, Rozenberg F, Buzyn A, Dreyfus F, et al. Coronavirus 229E-related pneumonia in immunocompromised patients. Clin Infect Dis 2003; 37: 929–32.

j  Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis 2006; 42: 518–24.

k  Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986; 140: 543–6. Willson DF, Landrigan CP, Horn SD, Smout RJ. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 2003; 143: 142–9. Falsey AR. Respiratory Syncytial Virus Pneumonia. Community-Acquired Pneumonia: Springer; 2002: 617–28.

l  Siegal FP, Dikman SH, Arayata RB, Bottone EJ. Fatal disseminated adenovirus 11 pneumonia in an agammaglobulinemic patient. Am J Med 1981; 71: 1062–7. Castro-Rodriguez JA, Daszenies C, Garcia M, Meyer R, Gonzales R. Adenovirus pneumonia in infants and factors for developing bronchiolitis obliterans: A 5-year follow-up. Pediatr Pulmonol 2006; 41: 947–53. Pichler M, Reichenbach J, Schmidt H, Herrmann G, Zielen S. Severe adenovirus bronchiolitis in children. Acta Paediatr 2000; 89: 1387–92. Murtagh P, Giubergia V, Viale D, Bauer G, Pena HG. Lower respiratory infections by adenovirus in children. Clinical features and risk factors for bronchiolitis obliterans and mortality. Pediatr Pulmonol 2009; 44: 450–6.

m  Luyt C-E, Combes A, Deback C, Aubriot-Lorton M-H, Nieszkowska A, Trouillet J-L, et al. Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am J Respir Crit Care Med 2007; 175: 935–42. Ljungman P, Ellis MN, Hackman RC, Shepp DH, Meyers JD. Acyclovir-resistant herpes simplex virus causing pneumonia after marrow transplantation. J Infect Dis 1990; 162: 244–8. Ramsey PG, Fife KH, HACKMAN RC, Meyers JD, Corey L. Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med 1982; 97: 813–20. Mcmillan JA, Weiner LB, Higgins AM, Lamparella VJ. Pharyngitis associated with herpes simplex virus in college students. Pediatr Infect Dis J 1993; 12: 280–3.

n  Tinelli M, Michelone G, Cavanna C. Recurrent Histoplasma capsulatum pneumonia: a case report. Microbiologica 1992; 15: 89–93.

o  Shrestha RK, Stoller JK, Honari G, Procop GW, Gordon SM. Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab: possible zoonotic transmission from a pet cockatiel. Respir Care 2004; 49: 606–8. Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis 1991; 13: 1163–9. Subramanian S, Kherdekar S, Babu P, Christianson C. Lipoid pneumonia with Cryptococcus neoformans colonisation. Thorax 1982; 37: 319. Jensen WA, Rose RM, Hammer SM, Karchmer AW. Serologic Diagnosis of Focal Pneumonia Caused by Cryptococcus neoformans 1, 2. Am Rev Respir Dis 1985; 132: 189–91.

p  Swartz J, Stoller JK. Acute eosinophilic pneumonia complicating Coccidioides immitis pneumonia: a case report and literature review. Respiration 2009; 77: 102–6. Standaert SM, Schaffner W, Galgiani JN, Pinner RW, Kaufman L, Durry E, et al. Coccidioidomycosis among visitors to a Coccidioides immitis-endemic area: an outbreak in a military reserve unit. J Infect Dis 1995; 171: 1672–5. Lopez AM, Williams PL, Ampel NM. Acute pulmonary coccidioidomycosis mimicking bacterial pneumonia and septic shock: a report of two cases. Am J Med 1993; 95: 236–9.

q  Kanemoto H, Morikawa R, Chambers JK, Kasahara K, Hanafusa Y, Uchida K, et al. Common variable immune deficiency in a Pomeranian with Pneumocystis carinii pneumonia. J Vet Med 2015. Tasci S, Ewig S, Burghard A, Lüderitz B. Pneumocystis carinii pneumonia. Lancet 2003; 362: 124. Helweg-Larsen J, Lundgren JD, Benfield T. Pneumocystis carinii pneumonia. Curr Treat Options Infect Dis 2002; 4: 363–75. Mayer KH, Fisk DT, Meshnick S, Kazanjian PH. Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome. Clin Infect Dis 2003; 36: 70–8.

Besides the antimicrobial activity of the essential oils in natural products, other characteristics such as high vapor pressure, low toxicity, and antiinflammatory potential create a worthwhile theme for using of these natural compounds for new drug development in respiratory infections. Parallel to the roles of the microorganisms in the pathology of respiratory infections diseases, inflammatory process also have a considerable role in the persistence and recurrence of respiratory infectious diseases.

This chapter reviews the antibacterial, antiviral, and antiinflammation effects of essential oils as effective natural compounds. It will also discuss the use of these natural compounds as traditional remedies in treatment of respiratory infections.

2. Traditional remedies in respiratory infections

Traditional medicines utilize natural sources for the treatment of the many diseases.1113 Historically, infectious diseases have been the major human ailment. Natural sources are used in a variety of forms, including water extracts, tincture or alcoholic extract and incense.14 Based on the historical uses and effective treatments that have been based on many of these traditional remedies, extensive pharmacological research of their antibacterial, antiviral, and antiinflammation activity have been performed.1517 Abundant information about plants and active compounds in infectious diseases and inflammation related process is available.1821 Aromatic and fragrant plants are a major part of traditional therapeutic remedies, and they have shown remarkable antibacterial and antiviral activity. Furthermore, many of them also have a significant antiinflammatory activity and are used as adjuvant remedies in the treatment of infection (Table 16.2 and Fig. 16.1). Some of the most active extracts of traditional herbs which have been used as antibacterial and antiviral in the treatment of respiratory infections are summarized in Table 16.3.

Table 16.2

Some Famous Traditional Plants That Are Used as Treatment Remedies for Respiratory Diseases

Plant Species (Family) Plant Parts Used Indications References
Acacia polyacantha Willd. (Forssk.) Willd. (Mimosaceae) Stem bark Cough a
Andira inermis (Wright) DC. (Fabaceae) Leaves Cough, respiratory diseases a
Asparagus africanus Lam. (Asparagaceae) Whole plant Respiratory diseases a
Cussonia arborea Hochst. ex A. Rich. (Araliaceae) Leaves Cough, respiratory diseases a
Entada africana Guill. and Perr. (Mimosaceae) Roots Respiratory diseases a
Euphorbia hirta L. (Euphorbiaceae) Whole plant Sore throat a
Keetia hispida (Benth.) Bridson (Rubiaceae) Leaves Respiratory diseases a
Phyllanthus muellerianus (O. Ktze) Exell (Euphorbiaceae) Leaves Respiratory diseases a
Terminalia schimperiana Hochst. (Combretaceae) Leaves Cough, respiratory diseases a
Sophora flaescens Ait. (Fabaceae) Roots Respiratory diseases b
Scutellaria baicalensis Georgi (Lamiaceae) Root Respiratory diseases b
Artemisia afra (Asteraceae) Leaves and bark Colds, coughs, and influenza c
Sambucus nigra L. (Caprifoliaceae) Leaves and bark Bronchitis d
Anchusa italica Retz. (Boraginaceae) Flowers Common colds e
Cynodon dactylon (L.) Pers. (Gramineae) Whole plant Coughs e
Thymus kotschyanus Boiss. et Hoh. (Lamiaceae) Leaves, flowers Common colds, bronchitis e
Glycyrrhiza echinata L. (Leguminosae) Roots, stolons Coughs, bronchitis e
Trigonella foenum-graecum L. (Leguminosae) Seeds, leaves Cure of inflamed throat e
Althaea officinalis L. (Malvaceae) Flowers, leaves, roots Coughs, bronchitis e
Malva sylvestris L. (Malvaceae) Whole plant Coughs, respiratory inflammation e
Prunus mahaleb L. (Rosaceae) Fruits Emollient for upper respiratory organs f
Adiantum capillus-veneris L. (Adiantaceae) Leaves Respiratory ailments, cough g
Ferula oopoda (Boiss. & Buhse.) Boiss. (Apiaceae) Seed, latex Cough, asthma, respiratory disorders g
Stachys turcomica Trautv (Lamiaceae) Whole plant Bronchitis, influenza g
Acacia kempeana F. Muell. (Mimosaceae) Bark, leaves, root bark Chest infection, severe cold h
Acacia ligulata Cunn. ex Benth. (Mimosaceae) Bark, leaves Cough, cold, chest infection i
Eremophila alternifolia R. Br. (Myoporaceae) Seed, leaves Respiratory tract infection j
Cymbopogon ambiguus (Steudel) A. Camus (Poaceae) Leaves Respiratory tract infection k

a  Kone W, Atindehou KK, Terreaux C, Hostettmann K, Traore D, Dosso M. Traditional medicine in North Côte-d’Ivoire: screening of 50 medicinal plants for antibacterial activity. J Ethnopharmacol 2004; 93: 43–9.

b  Ma S-C, Du J, But PP-H, Deng X-L, Zhang Y-W, Ooi VE-C, et al. Antiviral Chinese medicinal herbs against respiratory syncytial virus. J Ethnopharmacol 2002; 79: 205–11.

c  Rood B. Uit die veldapteek (Out of the field-pharmacy) Tafelberg. Cape Town 1994.

d  Miraldi E, Ferri S, Mostaghimi V. Botanical drugs and preparations in the traditional medicine of West Azerbaijan (Iran). JEthnopharmacol 2001; 75: 77–87.

e  Amin GR. Popular medicinal plants of Iran: Iranian Research Institute of Medicinal Plants Tehran; 1991.

f  Mir-Heidari H. Encyclopedia of Medicinal Plants of Iran. Islamic Culture Press, Tehran, Iran; 1993.

g  Ghorbani A. Studies on pharmaceutical ethnobotany in the region of Turkmen Sahra, north of Iran: (Part 1): General results. J Ethnopharmacol 2005; 102: 58–68.

h  O’Connell JF, Latz PK, Barnett P. Traditional and modern plant use among the Alyawara of central Australia. Econ Bot 1983; 37: 80–109.

i  Latz PK. Bushfires & bushtucker: Iad Press; 1995.

j  Territory CCotN. Traditional aboriginal medicines in the Northern Territory of Australia: Conservation Commission of the Northern Territory of Australia; 1993.

k  Smith NM. Ethnobotanical field notes from the Northern Territory, Australia. J Adelaide Bot Gard 1991; 1–65.


Figure 16.1 Some of the Famous Edible Plants That Are Used as Traditional Antibacterial and Antiinflammations Remedies
(a) Citrus paradise (grapefruit), (b) Perilla frutescens (perilla), (c) Cymbopogon citratus (lemmon grass), (d) Origanum vulgare (oregano), (e) Salvia officinalis (sage), (f) Thymus vulgaris (thyme), (g) Satureja hortensis (savory).

Table 16.3

Some Active Traditional Plants Remedies Extracts With Antibacterial and Antiviral Effects

Plant Species (Family) Antiinfection Activity Indications Using Form of Plants Extracts References
Polygonum punctatum (Polygonaceae; aerial parts) RSV ED50 = 120 (mg/μL) against RSV of the assayed extracts in HEp-2 cells Aqueous extracts a
Lithraea molleoides (Anacardiaceae; aerial parts) RSV ED50 = 87 (mg/μL) against RSV of the assayed extracts in HEp-2 cells Aqueous extracts a
Myrcianthes cisplatensis (Myrtaceae; aerial parts) RSV ED50 = 78 (mg/μL) against RSV of the assayed extracts in HEp-2 cells Aqueous extracts a
Azadirachta indica (Meliaceae; stem bark) S.a, P.a

MIC 90% = 1, MBC 90% = 1 (mg/mL) for S.a

MIC 90% = 1, MBC 90% = 2 (mg/mL) for P.a

Methanolic extracts b
Entada abyssinica (Leguminosae; stem bark) S.a, P.a

MIC 90% = 0.5, MBC 90% = 2 (mg/mL) for S.a

MIC 90% = 0.5, MBC 90% = 2 (mg/mL) for P.a

Methanolic extracts b
Eremophila duttonii (Myoporaceae; leaves) S.a Diameters of the zones of growth inhibition in plate-hole diffusion assays (12 mm) with 0.77 mg/mL of extract Ethanolic extracts c
Artemisia capillaries Thunb. (Asteraceae; aerial parts) RSV IC50 = 13 (μg/mL) concentration of the sample required to inhibit virus-induced Aqueous extracts d
Arctium lappa L. (Asteraceae; aerial parts) RSV IC50 = 6.3 (μg/mL) concentration of the sample required to inhibit virus-induced Aqueous extracts d
Prunella vulgaris L. (Lamiaceae; fruit spike) RSV IC50= 10.4 (μg/mL) concentration of the sample required to inhibit virus-induced Aqueous extracts d
Anemone obtusiloba (Ranunculaceae; aerial parts) HSV Lowest concentration of extract able to partially inhibit the virus (100 μg/mL) Methanolic extracts e
Centipeda minima (Asteraceae; aerial parts) HSV Lowest concentration of extract able to partially inhibit the virus(13 μg/mL) Methanolic extracts e
Byrsonima verbascifolia (Malphigiaceae; aerial parts) HSV Minimum concentration causing complete inhibition (MIC) of viral (2.5 μg/mL) Methanolic extracts f
Symphonia globulifera (Clusiaceae; aerial parts) HSV Minimum concentration causing complete inhibition (MIC) of viral (2.5 μg/mL) Methanolic extracts f
Dracaena cinnabari (Agavaceae; aerial parts) I.A IC50 = 1.5 (μg/mL) concentration of the sample required to inhibit virus-induced Methanol extracts g
Exacum affine (Gentianaceae; aerial parts) I.A IC50 = 0.7 (μg/mL) concentration of the sample required to inhibit virus-induced Methanol extracts g
Scrophularia amplexicaulis Benth. (Scrophulariaceae; aerial parts) S.a Diameters of the zones of growth inhibition in well-diffusion method (13 mm) with 100 mg/mL of essential oil Essential oil h
Cinnamomum zeylanicum (Lauraceae; bark) H.i, S.p, S.a The lowest concentration of oil inhibiting the growth of each organism (MIC = 0.00625, 0.00625, 0.0125 mL/mL) Essential oil i
Cupressus sempervirens (Cupressaceae; aerial parts) H.i, S.p, S.a MIC = 0.00625, 0.00625, 0.0125 mL/mL Essential oil i

RSV, respiratory syncytial virus; ADV, adenovirus; HSV, herpes simplex virus 1; I.A, influenza virus-A; S.a, Staphylococcus aureus; P.a, Pseudomonas aeruginosa; S.p, Streptococcus pneumonia; H.i, Haemophilus influenza.

a  Smith NM. Ethnobotanical field notes from the Northern Territory, Australia. J Adelaide Bot Gard 1991; 1–65.

b  Fabry W, Okemo PO, Ansorg R. Antibacterial activity of East African medicinal plants. J Ethnopharmacol 1998; 60: 79–84.

c  Palombo EA, Semple SJ. Antibacterial activity of traditional Australian medicinal plants. J Ethnopharmacol 2001; 77: 151–7.

d  Ma S-C, Du J, But PP-H, Deng X-L, Zhang Y-W, Ooi VE-C, et al. Antiviral Chinese medicinal herbs against respiratory syncytial virus. J Ethnopharmacol 2002; 79: 205–11.

e  Taylor R, Manandhar N, Hudson J, Towers G. Antiviral activities of Nepalese medicinal plants. J Ethnopharmacol 1996; 52: 157–63.

f  Lopez A, Hudson J, Towers G. Antiviral and antimicrobial activities of Colombian medicinal plants. J Ethnopharmacol 2001; 77: 189–96.

g  Mothana RA, Mentel R, Reiss C, Lindequist U. Phytochemical screening and antiviral activity of some medicinal plants from the island Soqotra. Phytother Res 2006; 20: 298–302.

h  Pasdaran A, Delazar A, Nazemiyeh H, Nahar L, Sarker SD. Chemical composition, and antibacterial (against Staphylococcus aureus) and free-radical-scavenging activities of the essential oils of Scrophularia amplexicaulis Benth. Rec Nat Prod 2012; 6: 350–5.

i  Fabio A, Cermelli C, Fabio G, Nicoletti P, Quaglio P. Screening of the antibacterial effects of a variety of essential oils on micro-organisms responsible for respiratory infections. Phytother Res 2007; 21: 374–7.

The use of aromatic extracts or burning plants is a common process in traditional medicine. The resultant smoke or fragrance is inhaled to treat respiratory complaints, including cough, cold, infections, and asthma.22,23 Inhalation administration goes back to the ancient cultures and its techniques may be considered as a progressive point in respiratory complaints treatment. The direct effect of such fragrance on the respiratory tract is an advantage of this form of treatment.

Inhalation therapy often involves the aromatic extracts or burning of plant material, and the volatile fraction liberated during the process is inhaled to aid in the healing process. Inhalation of the volatile fraction from aromatic extracts or burning plant matter is a unique method of administration and has been used traditionally to treat respiratory conditions, such as, asthma, bronchitis, and other respiratory infections including the common cold.24 In addition, aerosol delivery of such remedies is well practiced in allopathic medicine and has the advantage of being site specific, thus enhancing the therapeutic ratio for respiratory ailments.25

Table 16.4 and Fig. 16.2 describe several essential oils from Achilla species (Asteraceae family) that have demonstrated appropriate effects on some of the major respiratory infections caused by microorganisms.

Table 16.4

Achilla Species Essential Oils, Their Major Chemical Compositions and Their Effects on Some of the Microorganisms That Cause Major Respiratory Infections

Plant Name Tested Microorganisms Major Compounds References
Achillea clavennae L. K. pneumonia, penicillin-susceptible and penicillinresistant S. pneumonia, H. influenza and P. aeruginosa Camphor, 1,8-cineole a
A. fragrantissima (Forssk) Sch. Bip. K. pneumonia, P. aeruginosa, S. faecalis, S. aureus and C. albicans Terpinen-4-ol b
A. sintenisii Hub. Mor. K. pneumonia, P. aeruginosa and S. aureus Camphor, 1,8-cineole c
A. biebersteinii Afan. S. pneumonia and S. aureus Piperitone, 1,8-cineole, camphor d
A. taygetea Boiss & Heldr. K. pneumonia, P. aeruginosa and S. aureus Borneol, 1,8-cineole e
A. frasii Schultz Bip. K. pneumonia, P.aeruginosa and S. aureus 1,8-cineole, α-pinene (4), β-pinene (5) e
A. holosericea Sibth. & Sm. K. pneumonia, P. aeruginosa and S. aureus Borneol, camphor f

a  Bezić N, Skočibušić M, Dunkić V, Radonić A. Composition and antimicrobial activity of Achillea clavennae L. essential oil. Phytother Res 2003; 17: 1037–40.

b  Barel S, Segal R, Yashphe J. The antimicrobial activity of the essential oil from Achillea fragrantissima. J Ethnopharmacol 1991; 33: 187–91.

c  Sökmen A, Vardar-Ünlü G, Polissiou M, Daferera D, Sökmen M, Dönmez E. Antimicrobial activity of essential oil and methanol extracts of Achillea sintenisii Hub. Mor. (Asteraceae). Phytother Res 2003; 17: 1005–10.

d  Sökmen A, Sökmen M, Daferera D, Polissiou M, Candan F, Ünlü M, et al. The in vitro antioxidant and antimicrobial activities of the essential oil and methanol extracts of Achillea biebersteini Afan. (Asteraceae). Phytother Res 2004; 18: 451–6.

e  Magiatis P, Skaltsounis A-L, Chinou I, Haroutounian SA. Chemical composition and in vitro antimicrobial activity of the essential oils of three Greek Achillea species. Z Naturforsch C 2002; 57: 287–90.

f  Stojanović G, Asakawa Y, Palić R, Radulović N. Composition and antimicrobial activity of Achillea clavennae and Achillea holosericea essential oils. Flavour Fragr J 2005; 20: 86–8.


Figure 16.2 Some Plants of Achillea Species Whose Essential Oils Are Used in the Treatment of Respiratory Infections
(a) Achillea fragrantissima, (b) A. sintenisii, (c) A. clavennae, (d) A. taygetea, (e) A. biebersteinii.

3. Screening of the antibacterial effects of essential oils

The antimicrobial effects of plants and their extracts have been recognized for a long time. Essential oil is one of the most important and wide spread secondary metabolite in plants and this class of phytochemical compounds and their activities needs attention. These phytochemicals are generally isolated from plant material by distillation methods, such as, hydrodistillation and steam distillation. They contain variable mixtures of several chemical classes, such as terpenoids, specifically monoterpenes and simple phenolic compounds. Some of the higher molecular structures with high molecular weight, such as sesquiterpenes and diterpenes, may be present. A variety of low molecular weight aliphatic hydrocarbons, acids, alcohols, esters or lactones, sulfur-containing compounds and other chemical groups may also be observed. Among the phytochemical compounds, terpenes are responsible for many therapeutic effects in medicinal plants.2630 Most terpenes are derived from the condensation of isoprene units and are categorized according to the number of these units present in the carbon skeleton. These compounds are responsible for aromaticity and fragrance in many of the plants. The antibacterial activity of volatile oils has been assessed by many researchers.3134 This potential of essential oils has been used in many pharmaceutical, cosmeceutical, and nutraceutical applications and industrials. There are many differences between the antimicrobial effects of different essential oils. Essential oils and their constituents are an attractive source in new antimicrobial compounds evaluation.35,36

Many of the essential oils have been tested for bactericidal and bacteriostatic effects against a wide range of microorganisms including food spoiling organisms, pathogenic bacteria, yeasts, fungi, and many others. The major differences in antimicrobial activity have been yielded of several distinctive parameters which identify antibacterial characters of the essential oils, some of the major parameters include: (1) bacterial membrane permeability, (2) the hydrophobicity/hydrophilicity of the bacterial membrane, (3) the metabolic characteristics of the microorganism, and (4) their Gram-positive or negative pattern. Although susceptibility of the bacteria to the essential oils is not exactly predictable, many researchers have tried to determine the relationship between the origin of the essential oils and their compounds with their antimicrobial activity. Furthermore, the delivery of medications to the respiratory tract has become an increasingly important method for respiratory disease treatment. The use of inhaler medications has become an invaluable therapeutic in the treatment of different pulmonary disorders, including bronchitis, pneumonia, and others complications.37 Several studies have reported the clinical efficacy of inhalation therapy for the treatment of lung disorders.38,39 Through the effective delivery of medication to the action site, the active compounds are delivered directly into the lungs and this can result in respiratory tract local treatment. This method achieves maximum therapeutic effect, small dose usage, and has fewer side-effect risks compared with those associated with larger doses. Inhalation is a unique treatment with direct effects on respiratory disorder site and is based on the volatility potential of essential oils. Furthermore, there is a need to develop new therapeutic agents for respiratory infections.4042

Research has been carried out on the wide spectrum of edible plants essential oils to determine the antibacterial potential of their essential oils. The role of these plants as therapeutic agents is remarkable in many cultures. Investigations have reported that thyme and oregano essential oils, based on the phenolic components [such as carvacrol (1) and thymol (2) (Fig. 16.3)] have shown a strong correlation with the inhibition of some of the pathogenic bacterial strains (eg, in Escherichia coli). The correlation between the antibacterial effect of the volatile oils and their chemical compounds, including high amount of the phenolic components such as carvacrol (1) or eugenol (3), has also been confirmed.43 Other essential oils such as oregano, savory, clove, and nutmeg with high concentrations of volatile phenolic compounds inhibit Gram-positive more than Gram-negative pathogenic bacteria.44 However, in some essential oils such as Achillea spp. (Yarrow) strong antibacterial activity was observed against the Gram-negative respiratory pathogens (Haemophilus influenzae, Pseudomonas aeruginosa) while Streptococcus pyogenes was the most resistant to the this oil.45 The other essential oils such as peppermint and spearmint inhibit the methicillin-resistant type of Staphylococcus aureus. Previous reports have clarified that the essential oils containing aldehyde or phenol as a major component represent the highest antibacterial activity. These antibacterial potencies are lower in the essential oils that contain high amounts of terpene alcohols compared to the essential oils containing aldehyde or phenol as a major component.


Figure 16.3 Structures of the Major Bioactive Chemical Compounds Isolated From Essential Oils

Other essential oils containing terpene ketone, or ether showed much weaker activity, and oil containing terpene hydrocarbon was relatively inactive. Based on these findings, essential oils such as thyme, cinnamon, lemongrass, perilla, and peppermint have demonstrated suitable effects on respiratory tract infection.46 The tolerance of Gram-negative bacteria to essential oils has been attributed to the presence of a hydrophilic outer membrane that blocked the penetration of hydrophobic essential oils to the target cell membrane because the Gram-positive bacteria were more exposed to the essential oils than Gram-negative bacteria, which has been reported several times.4750

Lipids are one of the principal constituents for normal cell membrane function and these compounds supply many operations, such as barrier function in the bacterial cell membrane. The external capsule of some Gram-negative bacteria limits or prevents the penetration of the essential oils into the microbial cell. One of the pronounced examples of the hydrophobicity/hydrophilicity role in bacterial sensitivity to antibacterial compound is H. influenzae. It should be pointed out that the outer membrane of H. influenzae (which forms rough colonies) was more hydrophobic. Hydrophobic antibiotics, such as macrolides, are more active against H. influenzae than E. coli through their shorter oligosaccharide chains than those in E. coli. The effects of the cytoplasmic membrane and/or the embedded enzymes in it have demonstrated lipophilic biocide actions.51 It is generally recognized that the antimicrobial action of essential oils depends on their hydrophilic or lipophilic character. Based on these observations, investigators are trying to indicate the relationship between structural activity of the essential oils compounds and their antibacterial activity.

Certain components of the essential oils can act as uncouplers, which interfere with proton translocation over a membrane vesicle and subsequently interrupt ADP phosphorylation pathways (primary energy metabolism). As a member of the phytochemicals, terpenoids have been observed as a model of lipid soluble agents, which have an impact on the activities of membrane catalyzed enzymes; for example, enzymes involved in respiratory pathways. Particular terpenoids with functional groups, such as phenolic alcohols or aldehydes, also interfere with membrane-integrated or associated enzyme proteins, inhibiting their production or activity. A good deal of antimicrobial compounds which act on the bacterial cytoplasmic membrane cause the loss of 260 nm absorbing material. This causes an increased susceptibility to NaCl, the lysosomes formation and loss of potassium ions, which results in inhibiting respiration and the loss of cytoplasmic material.

Investigations about the cytoplasmic membrane effects of α-pinene (4), β-pinene (5), 1,8-cineole (6), and electron microscopy studies have shown that the essential oils containing these compounds triggered such cytoplasmic material with losing in treated bacterial cells.31,32 The perturbation of the lipid fraction in the plasma membrane causes antimicrobial activity of some of the phytochemicals such as α,β-unsaturated aldehydes and some of monoterpenes. Although these aldehyde compounds can elicit antibacterial effects by acting on membrane functional proteins, such antibacterial effect would be achieved with modifications of membrane permeability and intracellular materials leakage.5254 The membrane damage leading to whole-cell lysis has been reported by oregano and rosewood essential oils which contains major components as: carvacrol (1), citronellol (7), and geraniol (8).26,55 Phenols such as carvacrol (1), thymol (2), eugenol (3), and other oxygenated aromatic essential oil compounds including phenol ethers [trans-anethole (9), methyl chavicol (10)] and aromatic aldehydes [cinnamaldehyde (11), cuminaldehyde (12)] have been reported to exert both antibacterial and antifungal activity. However, this chemical class—based on the concentration used—are known as either bactericidal or bacteriostatic agents,56 but the phenolic component’s high activity may be further explained in terms of the alkyl substitution into the phenol nucleus, which is known to increase the antimicrobial activity of phenols. The alkylation has been known to change the distribution ratio between the hydrophilic and the hydrophobic phases (including bacterial phases) by the surface tension reduction or the species selectivity mutate based on the bacteria cell wall characters.57 This does not happen with etherified or esterified isomeric molecules, it is possible by describing their relative lack of activity.58 As a member of these compounds carvacrol (1) is one of the few components that has a break apart from effect on the outer membrane of Gram-negative bacteria and causes release of lipopolysaccharide and alters cytoplasmic membrane ions transportation, Similar to carvacrol (1), thymol (2) antimicrobial activity results in structural and functional alterations in the cytoplasmic membrane.59 Interestingly, eugenol (3) and isoeugenol (13) exhibit higher activity against Gram-negative bacteria than Gram-positive bacteria, and when cinnamaldehyde (11) is used against E. coli, its activity is similar to carvacrol (1) and thymol (2) (Fig. 16.3). These compounds alter the membrane, affect the transport of ions and ATP, and change the fatty acid profile of different bacteria.60

Although in some cases alcoholic form shows better potencies compared to acetate form, the presence of an acetate moiety in the structure appeared to increase the activity of the parent compound. In the case of geraniol (8), the geranyl acetate (14) demonstrated an increase in activity against the test microorganisms.48,61,62 A similar effect was also observed in the case of borneol (15), bornyl acetate (16), linalool (17), and linalyl acetate (18) (Fig. 16.3). In addition, the effectiveness of alcoholic compounds very closely depended on the bacterial cell wall, which showed different permeability to alcohol based on chain length.44,63 It has been suggested that an aldehyde group conjugated to a carbon double bond such as citral (19) is an extremely electronegative order, which may explain their activity, and an increase in electronegativity can raise up the antibacterial activity.64 In addition, the under research of aldehydes potency seems to depend not only on the existence of the α,β-double bond but also on the chain length from the renal group and on microorganism tested. It seems that some electronegative compounds, mainly from the cell surface, are responsible for the inhibited growth of the microorganisms, which may interfere in biological processes involving electron transfer and respond with vital nitrogen components and alteration in the operation of membrane-associated proteins. Actually, a greater electronegativity of the molecule would cause a greater encounter of intermolecular hydrogen bond formation with membrane nucleophilic groups and thus a significant irregularity in the lipidic bilayer. Some studies have recommend that carbon tail length also affects the electronegativity of the aldehyde oxygen atom and thus its interaction with the nucleophilic groups of the cell membrane.65 Comparably, the similar antimicrobial activity was detected in the series of the long-chain alcohols which is demonstrated to be resulted from the alkyl chain length.66,67 This structural activity relationship is notable between farnesol (20), nerolidol (21), plaunotol (22), geranylgeraniol (23), phytol (24), geraniol (8), and linalool (17) which act on S. aureus with damages of the cell membranes and losing of K+ ions, while similar mode of actions can be detected by the aminoglycosides such as kanamycin and streptomycin. Farnesol (20) was able to damage cell membranes most effectively than other terpene alcohols. The activities of farnesol (20), nerolidol (21) (sesquiterpenes compounds) on S. aureus were higher than that of plaunotol (22) (diterpene). The effectiveness against S. aureus are in order as follows: farnesol (19) > nerolidol (20)> plaunotol (22) > geranylgeraniol (23), phytol (24) > geraniol (8) and linalool (17) (Fig. 16.3). It has been suggested that maximum activity against S. aureus might depend on the number of carbon atoms in the hydrophobic chain from hydrophilic hydroxyl group, which should be less than 12 but as close to 12 as possible. Neither a shorter nor a longer aliphatic carbon chain, could increase such activity.68,69 The increased effectiveness of sesquiterpenes as enhancers of membrane permeability may stem from their structural resemblance to membrane lipids (eg, linear molecules with internal lipophilic character and a more polar terminus).70 The bacteriostatic potential of the terpenoids was also increased when the carbonyl groups increased in structure.63

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Dec 14, 2017 | Posted by in MICROBIOLOGY | Comments Off on Volatile oils: Potential agents for the treatment of respiratory infections
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