Anti-Mycobacterium tuberculosis Effects of Folk Medicinal Plants in Iran: A Mini-Systematic Review

Ramazanzadeh, Rashid; Marzban, Abdorazagh; Khalili Fard Ardali, Javad; Saki, Reza; Esmaeil Lashgarian, Hamed; Shakib, Pegah

doi:10.30699/ijmm.17.1.1

year 17, Issue 1 (January - February 2023) Iran J Med Microbiol 2023, 17(1): 1-6 | Back to browse issues page

‎ 10.30699/ijmm.17.1.1

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Ramazanzadeh R, Marzban A, Khalili Fard Ardali J, Saki R, Esmaeil Lashgarian H, Shakib P. Anti-Mycobacterium tuberculosis Effects of Folk Medicinal Plants in Iran: A Mini-Systematic Review. Iran J Med Microbiol 2023; 17 (1) :1-6
URL: http://ijmm.ir/article-1-1715-en.html

Anti-Mycobacterium tuberculosis Effects of Folk Medicinal Plants in Iran: A Mini-Systematic Review

Rashid Ramazanzadeh¹

, Abdorazagh Marzban²

, Javad Khalili Fard Ardali³

, Reza Saki⁴

, Hamed Esmaeil Lashgarian⁵

, Pegah Shakib

⁶

1- Department of Microbiology, Ardabil University of Medical Sciences, Ardabil, Iran
2- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
3- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4- Department of Microbiology, Kermanshah University of Medical Sciences, Kermanshah, Iran
5- Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
6- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran , shakib.pegah@yahoo.com

Keywords: Folk medicinal plants, Mycobacterium Tuberculosis, Native medicinal plants, Systematic review

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Introduction

Mycobacterium tuberculosis (M. tuberculosis, Mtb) lives inside human cells and invades them, thereby causing tuberculosis (1). This disease is an ancient illness that is spread in communities by droplets. Tuberculosis has been controlled after discovering antituberculosis drugs such as ethambutol, isoniazid, streptomycin, and rifampin (2, 3). However, with the evolution of drug resistance via diverse mechanisms, such as the development of drug-inactivating enzymes, changes in drug target sites, and the emergence of isolates with multiple resistance, there has been an upsurge in new cases reported (4, 5). Thus, healthcare systems worldwide confront many challenges in managing and treating these infections. According to statistics from 2010, 650000 instances of multidrug-resistant TB (MDR) were documented as attributable to M. tuberculosis (6).
Many plants are used in traditional medicine worldwide to treat bacterial infections (7). Recent research has aimed to identify herbal medicines that are simpler to obtain, have fewer adverse effects, and are less expensive to be used in conjunction with synthetic pharmaceuticals. Because of their secondary components, herbal medicines have proved to be an effective source of therapy for controlling and treating bacterial infections (8, 9). In Iran, the use of traditional medicinal remedies for the treatment of infections has been widespread since ancient times. Our objective in this review is to summarize the research being done on Iranian medicinal plants as a way to tackle TB infection.

Materials and Methods

According to the Preferred Systematic Review Reporting (PRISMA) guidelines, relevant data were retrieved from papers in October 2021 by two authors. This systematic review was conducted by evaluating papers published in both English and Persian. Several databases, including Science Direct, Scopus, PubMed, Ovid, Cochrane, Scientific Information Database (SID), Iran Medex, Iran Doc, and Magiran, were searched using relevant keywords for papers published between 2000 and 2020. The following keywords were used to describe the study: medicinal plants, M. tuberculosis infection, tuberculosis, MTB, essential oils, and extracts. Two authors read the literature and then combined their findings in consultation and collaboration.

Criteria Consideration

Inclusion Criteria

The following criteria were used to select the published articles for inclusion in the discussion: studies describing the effect of Iranian native medicinal plants on M. tuberculosis in their entirety, including the full text of the studies written in Persian and English, studies published in reputable journals, studies with clear information, and those that only demonstrated the effect of Iranian native medicinal plants on M. tuberculosis.

Exclusion Criteria

Exclusion criteria included studies with no available full text, case report studies, case series, systematic reviews, abstracts of papers presented at seminars and conferences, and studies with insufficient evidence for analysis (Figure 1).

Figure 1. PRISMA graph of data retrieved from various databases based on inclusion and exclusion criteria

Data Extraction

The required information was extracted from articles, including plant name and its family, concentration, positive control dose, and treatment period by two researchers and then merged with consultation as well as consensus.

Results

Selected studies

Data details, including their herbal family, used organs of the plants, and place of occurrence, are reported in Table 1. According to these results, 13 medicinal plants were detected with anti-M. tuberculosis effects in Iran include Peganum harmala, Humulus lupulus, Capparis spinosa, Thymus vulgaris, Pulicaria gnaphalodes, Perovskia abrotanoides, Peganum harmala, Punica granatum, Digitalis sp., Citrus lemon, Rosa canina, Berberis vulgaris, Aloe vera, mint, Hypericum perforatum, Humulus lupulus, Trachyspermum copticum, Pelargonium graveolens, and Levisticum officinale Dracocephalum kotschyi.

Table1. List of medicinal plants affecting Mycobacterium tuberculosis

Ref	MIC	Zone(mm)	Native	Organ	Herbal family	Scientific name
(10)	-	18.7±3.5	North of Iran	Root and seed	Nitrariaceae	Peganum harmala
(11)	4 and 8 mg/mL	-	Iran	stems, leaves and roots	Cannabaceae	Humulus lupulus
(12)	25 mg/mL	-	Iran	fruit	Caper bush	Capparis spinosa
(13)	0.5-40 μg/mL	-	Tehran, Iran	oil	Lamiaceae	Thymus vulgaris
(14)	640 μg/mL	-	Iran	oil	sunflower	Pulicaria gnaphalodes
(14)	640 μg/mL	-	Iran	oil	Salvia	Perovskia abrotanoides
(15)	50 mg/mL	18.7	North of Iran	seed	Nitrariaceae	Peganum harmala
(15)	25 mg/mL	18.8	North of Iran	peel	Lythraceae	Punica granatum
(15)	100mg/mL	12.5	North of Iran	leaf	Plantaginaceae	Digitalis sp.
(15)	200mg/mL	12.5	North of Iran	fruit	Rutaceae	Citrus lemon
(15)	0	0	North of Iran	fruit	Rosaceae	Rosa canina
(15)	0	0	North of Iran	fruit	Berberidaceae	Berberis vulgaris
(16)	-	60	Iran	leaves,	Asphodelaceae	Aloe vera
(16)	-	0	Iran	leaves	Lamiaceae	mint
(16)	-	41	Iran	leaves	Hypericaceae	Hypericum perforatum
(17)	15.7 μg/mL(Aqueous) 31.2 μg/mL(ethanol)	-	Iran	Petals	Cannabaceae	Humulus lupulus
(18)	19.5 μg/mL	-	Iran	oils	Apiaceae	Trachyspermum copticum
(18)	78 μg/mL	-	Iran	oils	Pelargonium graveolens	Pelargonium graveolens
(19)	32 and 64 μg/mL	-	Iran	roots	Apiaceae	Levisticum officinale
(20)	640 μg/mL	-	Iran	leaves	Lamiaceae	Dracocephalum kotschyi

Peganum harmala: Based on the results of the antimicrobial and antioxidant properties of Davoodi et al. and Jahanpour et al. studies, it was found that Peganum harmala leaves and seeds have potential as complementary medicine for the treatment of M. tuberculosis, even against resistant strains (10, 15).
Humulus lupulus: Serkani et al. described the antimicrobial effect of stems, leaves, and roots of Humulus lupulus on rifampin-sensitive and resistant isolates of M. tuberculosis in different concentrations of hop ethanol extract (4 and 8 mg/mL) (11). In Rafiee et al. study, the MIC levels of aqueous and ethanol extracts of Humulus lupulus were reported as 7.8 μg/mL and 15.7 μg/mL, respectively. The amount of MBC was 15.7 μg/mL and 31.2 μg/mL, respectively. Therefore, the results indicated strong antimicrobial activity of aqueous and ethanolic extracts of Humulus lupulus against M. tuberculosis (17).
Capparis spinosa: In the study of Ehsanifar et al., the antimycobacterial effect of the methanolic extract of the Capparis spinosa at a concentration of 25 mg/mL was reported in clinical isolates sensitive to rifampin (12).
Thymus vulgaris: Pourazar Dizaji reported the MIC values of isoniazid, ethambutol, streptomycin, and cycloserine less than 10 μg/mL and MIC values for rifampicin and kanamycin 40 μg/mL. In addition, they reported MIC of Thymus vulgaris essential oil between 0.5 and 40 µg/mL (P<0.05). Therefore, they showed that thyme essential oil has antibacterial activity against M. tuberculosis (13).
Pulicaria gnaphalodes: The results of Hozoorbakhsh et al. showed that the essential oil extract of P. gnaphalodes has strong inhibitory effects on MTB up to about (70.9%) (14). In Jahanpour et al. study, the ethanol extract of Punica granatum bark showed an average inhibition zone of 18.8 mm at a concentration of 200 mg/mL against M. tuberculosis isolates, while the average inhibition zone around isoniazid and rifampin was 19.2 and 18.8 mm. The results indicated a potential activity against M. tuberculosis isolates (15).
Perovskia abrotanoides: The results of Hozoorbakhsh et al. showed that the essential oil extract of Perovskia abrotanoides has strong inhibitory effects on M. tuberculosis up to about (86%) (14).
Digitalis sp: In Jahanpour et al. study, the Ethanol extract of Digitalis sp. has a mild antimycobacterial effect at concentrations of 200 and 100 mg/mL showed that in this study, isoniazid and rifampin antibiotics inhibited non-MDR M. tuberculosis isolates, so the results indicate the potential efficacy of Digitalis sp ethanolic extract against M. tuberculosis (15).
Citrus lemon: The results of the Jahanpour et al. study showed that the ethanolic extract of Citrus lemon could prevent the growth of non-MDR M. tuberculosis in concentrations of 200 and 25 mg/mL (15).
Rosa canina and Berberis vulgaris: In investigating the antimicrobial activity of Berberis vulgaris and Rosa canina fruit extracts, it was found that the extracts of these fruits do not have antimicrobial activity against M. tuberculosis isolates (15).
Aloe vera: In investigating the antimicrobial properties of A. vera against M. tuberculosis isolates by disc diffusion method, the inhibition zones of A. vera extract of 60 mm were reported. Also, based on the results, 50% of the cells were killed in 24 hours and 20% in 10 minutes when exposed to Aqueous A. vera extract (16).
Mint: Antimicrobial effects of mint on M. tuberculosis isolates showed that the zone of inhibition of mint extract was 0 mm, also, the time to kill 95% of cells in contact with the aqueous extract of mint was reported for a week (16).
Hypericum perforatum: In a study, the inhibition zones of the aqueous extract of Hypericum perforatum against M. tuberculosis were reported 41 mm. 50% of the cells were killed in 24 hours and 20% in 10 minutes when exposed to Aqueous Hypericum perforatum (16).
Trachyspermum copticum: In Kardan et al., study the MIC values for Trachyspermum copticum against M. tuberculosis isolates were from 19.5 µg/mL to 78 µg/mL (18). Therefore, the antimicrobial properties of Trachyspermum copticum against M. tuberculosis were reported.
Pelargonium graveolens: In Kardan et al. study, the MIC values for Pelargonium graveolens against M. tuberculosis isolates was 78 µg/mL (18). As a result, this essential oil was effective against M. tuberculosis isolates.
Levisticum officinale: Monsefesfahani et al.’s study of phytochemical isolation of Levisticum officinale extract and investigation of their antimicrobial properties showed that Falcarindiol and oxypeucedanin have moderate antimicrobial activity against MDR M. tuberculosis with MIC values = 32 and 64 μg/mL (19).
Dracocephalum kotschyi: In the study, it was found that the methanolic extract of Dracocephalum kotschyi at a concentration of 640 μg/mL was significantly effective against M. tuberculosis sensitive and resistant to isoniazid (20).

Discussion

The emergence of multidrug-resistant M. tuberculosis (MDR) and extended drug-resistant M. tuberculosis (XDR) are the most important challenges in TB control. The mechanisms of drug resistance are attributed to the inappropriate use of anti-TB drugs. Thus, the long-standing prevalence of TB in various communities and the lack of novel drugs that may be used to treat it has exacerbated concerns. In this regard, scientists worldwide attempt to create new treatments that might eliminate TB. According to the findings, herbal medicines are sought for development as alternative pharmaceuticals to manage TB cases since they are less costly and have fewer adverse effects than chemical drugs. Peganum harmala, Humulus lupulus, Capparis spinosa, Thymus vulgaris, Pulicaria gnaphalodes, Perovskia abrotanoides, Peganum harmala, Punica granatum, Digitalis sp., Citrus lemon, Rosa canina, Berberis vulgaris, Aloe vera, Mentha spp., Hypericum perforatum, Humulus lupulus, Trachyspermum copticum, Pelargonium graveolens, and Levisticum officinale Dracocephalum kotschyi have been reported as Iranian native plants affecting tuberculosis infection. Humulus lupulus was effective against susceptible and resistant Mycobacterium isolates, with Humulus lupulus also exhibiting antibacterial efficacy against rifampin-resistant Mycobacterium isolates at a MIC value of 8 mg/mL (11). Also, Thymus vulgaris showed effects on M. tuberculosis. It was observed that T. Vulgaris essential oil had a substantially lower MIC value than typical medications, including ethambutol, isoniazid, streptomycin, and cycloserine, which are often used for the treatment of infections (13). Another study evaluated the inhibitory effect of alcoholic extracts of Berberis vulgaris, Rosa canina, Peganum harmala, Punica granatum, Digitalis sp, and Citrus lemon on Mycobacterium isolates. The findings indicated that extracts of Peganum harmala, Punica granatum, Digitalis sp, and Citrus lemon exhibited inhibitory effects against non-MDR bacteria at various doses, with Punica granatum showing the maximum inhibition zone (19.5 mm) against isoniazid and rifampin-resistant isolates. On the other hand, neither Berberis vulgaris nor Rosa canina inhibited M. tuberculosis isolates (18).
These findings revealed that various natural Iranian plants might effectively inhibit Mycobacterium isolates. However, in vitro and in vivo experiments are required to obtain further insight into antimycobacterial mechanisms.

Conclusion

There are promising results regarding the antibacterial efficacy of Iranian medicinal plants that have been studied recently. However, further investigation into their metabolites will be required to corroborate these claims. Additionally, a combination treatment, including using these herbs in conjunction with one another or with standard antibiotics, may effectively reduce antibiotic resistance in M. tuberculosis.

Acknowledgment

The authors appreciate the Vice Chancellor for Research and Technology of Lorestan University of Medical Sciences and state that this review article did not receive any financial support.

Funding

None.

Author s Contributions

Conceptualization, Shakib. P; methodology, Marzban. A & Lashgarian. H.E; investigation, Saki. R; writing—original draft preparation, Ramazanzadeh. R; writing—review and editing, Khalili Fard Ardali. J; supervision, Shakib. P.

Conflicts of Interest

The authors declared no conflicts of interest.

Type of Study: Review Article | Subject: Medical Bacteriology
Received: 2022/04/5 | Accepted: 2022/08/3 | ePublished: 2023/01/20

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