Volume 4, Issue 2, June 2015, Pages 116–123
Medicinal plants used to treat TB in Ghana
- Open Access funded by Asian-African Society for Mycobacteriology
- Under a Creative Commons license
Abstract
Aims
The
current study was designed to document medicinal plant species that are
traditionally used to treat tuberculosis (TB) by Ghanaian communities.
Methods
The
medicinal plants used against TB or its signs and symptoms were
selected using library and online published data searches. A guided
questionnaire interview was also conducted with a botanist involved in
plant collection at the Centre for Scientific Research into Plant
Medicine (CSRPM) at Mampong. Data obtained were entered in Excel and
summarized into means and frequencies using SPSS 12.0.1 for windows, and
expressed as tables and bar graphs.
Results
A
total of 15 medicinal plant species distributed between 13 genera and
13 families were documented. The following medicinal plant species were
found to be used against TB in Greater Accra and Eastern parts of Ghana:
Azadirachta indica A. Juss. Stem bark (Meliaceae), Hygrophila auriculata Heine, whole plant (Acanthaceae), Chenopodium ambrosioides L. leaves (Amaranthaceae), Coix lacryma-jobi L. glumes (Poaceae), Solanum torvum Sw. unripe fruits (Solanaceae), Solanum torvum Sw. leaves (Solanaceae), Bidens pilosa L. whole plant (Asteraceae), Phyllanthus fraternus G.L. Webster leaves (Phyllanthaceae), Dissotis rotundifolia (Sm.) Triana, leaves (Melastomataceae), Cymbopogon giganteus Chiov. Leaves (Poaceae), Cyperus articulatus L. roots (Cyperaceae), Allium sativum L. bulb (Amaryllidaceae), Zingiber officinale Roscoe, rhizomes (Zingiberaceae), Allium cepa L. bulbs (Amaryllidaceae), Allium cepa L. leaves (Amaryllidaceae), Aloe vera var. barbadensis aqueous extract from leaves (Xanthorrhoeaceae), Aloe vera var. barbadensis organic extract from leaves (Xanthorrhoeaceae), Cocos nucifera Linn, water (Arecaceae) and Cocos nucifera Linn. Husk (Arecaceae).
Conclusions
The
collected plant species could be a source of a new class of drugs
against TB. Bioactivity guided fractionation is recommended to identify
lead compounds for antimycobacterial activity. The current paper
documents for the first time medicinal plant species used by Ghanaian
communities to treat TB. These results are a basis for selection of
plants for further pharmacological, toxicological and phytochemical
studies in developing new plant-based antimycobacterial drugs.
Keywords
- Medicinal plants;
- Tuberculosis;
- Ghana
Introduction
Tuberculosis
(TB) is a major public health concern with over 2 billion people
currently infected, 8.6 million new cases per year, and more than
1.3 million deaths annually [1].
The current drug regimen combination for TB consists of isoniazid,
rifampicin, ethambutol and pyrazinamide, administered over six months [2] and [3].
Although this treatment has a high success rate, the utility of this
regimen is limited by compliance issues, which has resulted in the rise
of strains that are resistant to some or all of the first- and
second-line antibiotics [4]. These strains, called multidrug resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains of Mycobacterium tuberculosis (M. tb), have worse disease outcomes [5]. Widespread introduction of antibiotics in the 1940s, beginning with penicillin [6], [7] and [8] and streptomycin [9]
transformed medicine, providing effective cures for the most prevalent
diseases of the time. Resistance development limits the useful lifespan
of antibiotics and results in the requirement of a constant introduction
of new compounds [10]. However, antimicrobial drug discovery is uniquely difficult [11],
primarily due to poor penetration of compounds into bacterial cells.
Recent efforts in TB drug development have resulted in the discovery of
new therapeutics, including delamanid (previously known as OPC 67683)
and bedaquiline (previously known as TMC 207), which retain activity
against MDR and XDR M. tb strains. However, additional drugs
are urgently needed. Natural products and their plant-derived analogs
are often a source of drugs or drug templates with limited toxicity,
which has the potential to mitigate compliance issues during protracted
administration. Plant-based drugs have been used worldwide in
traditional medicines for the treatment of various diseases and Ghana is
no exception. Approximately 60% of the world’s population still relies
on medicinal plants for their primary healthcare. According to a survey
by the National Cancer Institute (NCI), United States of America (USA),
61% of the 877 small-molecule new chemical entities introduced as drugs
worldwide during the period 1981–2002 were inspired by natural product
research [12].
Plant species still serve as a rich source of many novel biologically
active compounds, yet very few plant species have been thoroughly
investigated for their medicinal properties [13], and thus, there is renewed interest in phytomedicine research.
TB is a huge public health problem in Ghana [14].
It is estimated that approximately 20,000 people contracted TB in Ghana
in 2011, of which around 22% were not detected and/or reported [13] and [14].
According to 2011 data from the World Health Organization (WHO), 14,962
cases of TB were reported, comprising an incidence of 79 cases per
100,000. Of these, 18 cases per 100,000 corresponded to co-infection
with Human Immunodeficiency Virus-Tuberculosis (HIV-TB) co-infection [15].
The Ghanaian population still suffers the problems typical of an
underdeveloped, tropical country, with clear and markedly high death
rates resulting from malnutrition, tropical infectious diseases, and low
vaccine coverage. In Ghana, it is estimated that around 70% of
healthcare is provided by traditional healers using medicinal plants.
There is an estimated one traditional healer for every 400 inhabitants,
and one physician with conventional medical training for every 6200 (in
Accra, the capital city) to 42,200 inhabitants in the rural areas [16].
To achieve global control of this epidemic, there is an urgent need for
new TB drugs which can: (1) shorten treatment duration; (2) target MDR
or XDR strains; (3) simplify treatment by reducing the daily pill
burden; (4) lower dosing frequency (for example, a once-weekly regimen);
and (5) be co-administered with HIV medications [17].
The current study was thus designed to document medicinal plant species
traditionally used by the Greater Accra and Eastern communities of
Ghana to treat TB.
Materials and methods
Library and online published data searches
A
library search was carried out on medicinal plant species used in
traditional medicine to treat TB. In particular, plants cited in the
book “African traditional medicine: a dictionary of plant use and
applications” [18]
and growing in Ghana were selected, verified if they already had been
identified at the Herbarium of the Centre for Scientific Research into
Plant Medicine (CSRPM), Mampong, and assigned a voucher number as a
specimen collection of the CSRPM, with the help of the CSRPM botanist
team, led by Mr. Ofori Lartey. Plant species were collected from the
Greater Accra and Eastern regions of Ghana as shown in Fig. 1.
- Source:www.mapsofworld.com.
Guided questionnaire interview
A
guided questionnaire interview was also administered to the botanist at
CSRPM. The interview elicited information on plant species used in the
traditional treatment of TB. All species obtained from literature and
those mentioned during the interview were collected during July and
December 2014 and are indexed as MN (Mwanzia Nguta). The specimens were
identified by the staff of CSRPM and named according to the Flora of
West Tropical Africa in accordance with the international code for
botanical nomenclature. The specimens were deposited at the CSRPM. Data
obtained were entered in Excel and summarized into means and frequencies
using SPSS 12.0.1 for windows, and expressed as tables and bar graphs.
Ethical approval for this study was granted by the Scientific and
Technical Committee of Noguchi Memorial Institute for Medical Research
(STC-NMIMR), project identification number EC/060/08. Before
interviewing the botanist at CSRPM, the objectives of the study, method
and planned use of the information were explained, and permission to
conduct the interview was sought. Verbal consent was obtained in all
cases before the interview was carried out. Selected plants used against
TB were also checked if they were published elsewhere in Africa, apart
from the work of Neuwinger [18].
Information
on plant extraction procedures utilized by the Greater Accra and
Eastern communities of Ghana was also sought after from the online and
library search. The interview conducted with the botanist at CSRPM also
generated information in regard to the methods used traditionally to
extract the active constituents from the anti-TB medicinal plant
species.
Results
Medicinal plant species used by the Greater Accra and Eastern communities to treat TB
The
global problem presented by the rise in multidrug-resistant strains of
TB has necessitated research for new sources of lead antimycobacterial
compounds. The current study was designed to document antimycobacterial
plants traditionally used by Ghanaian communities to treat TB. A total
of 15 plant species distributed between 13 genera and 13 families were
documented as illustrated in Table 1. The documented medicinal plants were: Azadirachta indica A. Juss. Stem bark (Meliaceae); Hygrophila auriculata Heine. whole plant (Acanthaceae); Chenopodium ambrosioides L. leaves (Amaranthaceae); Coix lacryma-jobi L. glumes (Poaceae); Solanum torvum Sw. unripe fruits (Solanaceae); S. torvum Sw. leaves (Solanaceae); Bidens pilosa L. whole plant (Asteraceae); Phyllanthus fraternus G.L. Webster leaves (Phyllanthaceae); Dissotis rotundifolia (Sm.) Triana leaves (Melastomataceae); Cymbopogon giganteus Chiov. Leaves (Poaceae); Cyperus articulatus L. roots (Cyperaceae); Allium sativum L. bulb (Amaryllidaceae); Zingiber officinale Roscoe rhizomes (Zingiberaceae); Allium cepa L. bulbs (Amaryllidaceae); A. cepa L. leaves (Amaryllidaceae); Aloe vera var. barbadensis leaves (Xanthorrhoeaceae); Cocos nucifera Linn. Water (Arecaceae) and C. nucifera Linn. husk (Arecaceae).
Plant species Voucher specimen Number Family Plant part Azadirachta indica A. Juss. MND14/7 Meliaceae Stem bark Hygrophila auriculata Heine. MNS14/7 Acanthaceae Whole plant Chenopodium ambrosioides L. MNA14/7 Amaranthaceae Leaves Coix lacryma-jobi L. MNO-K24/7 Poaceae Glumes Solanum torvum Sw. MNB-N(A)24/7 Solanaceae Unripe fruits Solanum torvum Sw. MNBL-N(A)24/7 Solanaceae Leaves Bidens pilosa L. MNM24/7 Asteraceae Whole plant Phyllanthus fraternus G.L. Webster MNM20/7 Phyllanthaceae Leaves Dissotis rotundifolia (Sm.) Triana MNM22/7 Melastomataceae Leaves Cymbopogon giganteus Chiov. MNM21/7 Poaceae Leaves Cyperus articulatus L. MNB31/7 Cyperaceae Roots Allium sativum L. MNK31/7 Amaryllidaceae Bulbs Zingiber officinale Roscoe MNK24/7 Zingiberaceae Rhizomes Allium cepa L. MNKB14/7 Amaryllidaceae Bulbs Allium cepa L. MNKL14/7 Amaryllidaceae Leaves Aloe vera var. barbadensis MNMA26/11 Xanthorrhoeaceae Leaves (aqueous extract) Aloe vera var. barbadensis MNM026/11 Xanthorrhoeaceae Leaves (Organic extract) Cocos nucifera Linn. MNKW14/12 Arecaceae Coconut water Cocos nucifera Linn. MNKH14/12 Arecaceae Husk
Different
families produced varying numbers of anti-TB plant species, with the
highest number of medicinal plants documented belonging to the
Amaryllidaceae family as demonstrated in Fig. 2.
Leaves were reported to be the most commonly used plant to treat TB as shown in Fig. 3 below.
The
local Ghanaian communities use water mainly to prepare anti-TB
treatments from the listed plant parts as decoctions or infusions. These
extraction methods have been utilized since time immemorial, and to the
best of their knowledge, they yield active principles required to treat
TB. The studied plant species have been shown to possess activity
against the slow growing pathogenic strain of M. tb as shown in Table 2
below. This observation further validates the ethnomedical use of the
studied ethnobotanicals in traditional medicine to treat conditions with
signs and symptoms that closely resemble TB. These reports clearly
indicate that Ghanaian communities can be trusted with their knowledge,
and the documented medicinal plants are a potential source of a new
class of drugs against TB.
Plant species Family Pharmacological activity reported Reported phytochemical constituents Azadirachta indica A. Juss. Meliaceae Activity against S. aureus; E. coli and K. pneumoniae [22], M. smegmatis and M. aurum [23] Flavonoids, tannins [22] Hygrophila auriculata Heine. Acanthaceae No reports Saponins, alkaloids, steroids, tannins, flavonoids and triterpenoids [23] and [31] Chenopodium ambrosioides L. Amaranthaceae Activity against MDR strains of M. tb [32] Phenolics, flavonoids, saponins, ecdysteroids and triterpenoids [32] Coix lacryma-jobi L. Poaceae Antimutagenic activity [34] p-Hydroxybenzaldehyde, vanillin, syringaldehyde, trans-coniferylaldehyde, sinapaldehyde, and coixol [34] Solanum torvum Sw. (unripe fruits) Solanaceae Activity against M. tb H37Rv [26] Sterols, tannins, saponins, flavonoids, glycosides [33] Solanum torvum Sw. (leaves) Solanaceae Activity against M. tb H37Rv [26] Sterols, tannins, saponins, flavonoids, glycosides [33] Bidens pilosa L. Asteraceae Activity against drug sensitive M. tb [27] Chalcone glucosides [35] Phyllanthus fraternus G.L. Webster Phyllanthaceae No reported activity Alkaloids, tannins, saponins, terpenoids and steroids [36] Dissotis rotundifolia (Sm.) Triana Melastomataceae No reported activity C-glycosyl-flavones, orientin, vitexin, isovitexin [37] Cymbopogon giganteus Chiov. Poaceae No reported activity Acyclic alcohol (1-hentriacontanol), three triterpenes (sistosterol, stigmasterol and methoxyparkeol) and a dipeptide (N-benzoylphenylalanine-Nbenzoylphenylalanilate) [38] Cyperus articulatus L. Cyperaceae Anti-Onchocerca activity [39] Terpenoids, hydrocarbons and fatty acids [39] Allium sativum L. Amaryllidaceae Active against M. tb MDR strains and H37Rv [21] Alkaloids, flavonoids, cardiac glycosides, terpenes, resin [40] Zingiber officinale Roscoe Zingiberaceae Antimicrobial activity [29] Monoterpenoids, sesquiterpenoids, phenols [29] Allium cepa L. (bulb) Amaryllidaceae Active against M. tb MDR strains and H37Rv [21] Alkaloids, flavonoids, cardiac glycosides, terpenes, resin [40] Allium cepa L. (leaves) Amaryllidaceae Active against M. tb MDR strains and H37Rv [21] Alkaloids, flavonoids, cardiac glycosides, terpenes, resin [40]. Aloe vera var. barbadensis (organic extract) Xanthorrhoeaceae Active against M. tb MDR strains and H37Rv [21]; Active against S. pyogenes and P. aeroginosa [42] Tannins, saponins, flavonoids, terpenoids [42] Aloe vera var. barbadensis (aqueous extract) Xanthorrhoeaceae Active against M. tb MDR strains and H37Rv [21]; S. pyogenes and P. aeroginosa [42] Tannins, saponins, flavonoids, terpenoids [42] Cocos nucifera Linn. (water) Arecaceae Anticancer activity [41] Phytohormones (cytokinins, auxin, gibberellins, abscisic acid, salicylic acid) [41] Cocos nucifera Linn. (husk) Arecaceae Selective activity against S. aureus [30] Catechin, epicatechin, tannins [30]
Discussion
TB remains a major global health problem [19].
It causes ill-health among millions of people each year and ranks as
the second leading cause of death from an infectious disease worldwide,
after HIV [20].
Today, many of the drugs currently used are derived from natural
products or have depended upon a natural product for their development,
and the recent discoveries of the antimalarial artemisinin and the
anticancer agent taxol indicate the continuing importance of plant
species in drug discovery. However, only a small proportion of plant
species have been thoroughly investigated for their medicinal properties
[19]
and undoubtedly there are many novel biologically active compounds yet
to be discovered. The current study was designed to document
antimycobacterial plant species used by the Greater Accra and Eastern
communities of Ghana. A database of medicinal plants used to treat TB by
Ghanaian communities was generated. To the best of the present
research’s knowledge, the current paper reports for the first time
medicinal plant species used in Ghana to treat TB. This repository of
selected anti-TB plants can be used in future studies aimed at high
throughput screening for antimycobacterial activity using fast-growing
laboratory strains of Mycobacterium smegmatis. Such studies may lead to the isolation of active ligands against sensitive, latent and drug-resistant strains of M. tb. A total of 15 plant species belonging to 13 genera and distributed in 13 families as summarized in Table 1
were documented. The majority of these species belonged to the families
Amaryllidaceae (3), Xanthorrhoeaceae (2), Arecaceae (2), Poaceae (2)
and Solanaceae (2) as indicated in Table 1.
A diverse group of phytochemical compounds and pharmacological
activities have been associated with the documented plant species as
reported in Table 2, supporting their ethnopharmacological use against TB by the Ghanaian communities.
The use of some of the documented antituberculous plants is supported by earlier observations of antimycobacterial activity [21] against MDR strains and laboratory reference strain H37Rv while screening aqueous extracts of A. sativum, A. cepa and Aloe vera
using Lowenstein–Jensen medium and Middlebroook 7H9 broth. The observed
antimycobacterial activity validates the ethnopharmacological
utilization of the medicinal species to treat TB, and calls upon further
investigation to isolate the phytochemical compounds responsible for
the reported activity. Methanolic and ethanolic crude extracts obtained
from A. indica have been reported to possess potent activity against Escherichia coli, K. pneumonia and methicillin resistant S. aureus [22], while moderate activity from methanolic leaf extracts against M. smegmatis and M. aurum has been reported [23].
The observed biological activities, especially those against
mycobacterial species, adds more weight to the ethnobotanical reports in
regard to the use of A. indica crude extracts against TB,
justifying why more studies are required to isolate and purify the
active constituents responsible for the reported activity. This
observation further validates the ethnobotanical usage of the documented
plants against TB by Ghanaian communities. The utilization of leaves
from H. auriculata as antituberculous agents has been reported in Uganda, East Africa [24].
This cross-cultural acceptance and use of the same plant species in
different geographical zones is an indication of the potential of the
plant species as a future source of a new class of drugs against TB. The
documentation of the plant species in Uganda supports the Ghanaian
traditional claims in regard to the antituberculous activity of H. auriculata,
calling for more studies aimed at isolating and characterizing the
phytochemicals responsible for the reported anecdotal efficacy of the
said plant. Antimicrobial activity from the acetonic leaf extracts
obtained from Chenopodium ambrosoides against MDR strains of M. tb has been reported [25],
validating the ethnopharmacological use of the plant among Ghanaian
communities and the inclusion of the plant in Ghanaian pharmacopoeia as a
potential source of anti-TB drugs. This observation adds more weight to
the documentation of the said plant in regard to its traditional use
against TB. Moderate inhibition of the pathogenic laboratory reference
strain H37Rv by hydromethanolic fruit extracts from S. torvum has been observed [26]
in Malaysia, validating the ethnopharmacological use of the unripe
fruits against TB by the Ghanaian communities. This observation is in
agreement with this documented report and supports further studies in
search for anti-TB drugs from Ghanaian pharmacopoeia. The use of the
plant in different continents throws more weight into the
antimycobacterial potential of the documented plant, calling for more
resources to disclose the active ligands behind the reported
observation. The leaves of B. pilosa from Rwanda have been reported to possess activity against M. tb [27]
further validating the use of this plant in Ghanaian ethnotherapy and
this subsequent documentation of the said plant for further
investigations in search of an agent against TB. Scientists from Kwazulu
Natal have reported C. articulatus to be used traditionally against cough and related upper respiratory tract conditions [28],
supporting the traditional use of the plant against TB in Ghana. The
use of the plant for related illnesses in different countries further
validates its ethnopharmacological utilization and positions it as a
possible source of future agents against TB. Ginger (Z. officinale) extract (10 mg/kg) administered intraperitoneally has been shown to possess a dose-dependent antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, E. coli and Candida albicans.
In addition, out of 29 plant extracts screened, ginger extract was
found to have the broadest range of anti-fungal activity measured either
by the fungi inhibited or as the average diameter of the zones of
inhibition and was the only crude extract that was active against Rhizopus
sp., an organism that was not inhibited by any of the other plant
extracts tested or by the anti-fungal agent ketoconazole or berberine [29]. Based on these findings, it is plausible to argue out that the crude extract could be efficacious against M. tb,
underpinning its traditional use by the Ghanaian communities to treat
TB. This calls for evaluation of the antimycobacterial activity of Z. officinale crude extracts using M. tb specific assays. Selective antimicrobial activity against S. aureus has been observed while evaluating C. nucifera for antimicrobial activity [30]. Since this plant enjoys diverse medicinal uses [30], other activities, including antimycobacterial activity, may be identified using different biological assays. C. nucifera may be important in the identification of some novel agents against drug-resistant strains of M. tb.
The majority of the plants documented in this study were collected from
community land, which is facing great pressure due to overutilization
of indigenous trees and hence medicinal plants may disappear before
their uses are documented. Most of the inhabitants of Greater Accra and
Eastern regions of Ghana are in the low social-economic bracket and very
often the medicinal plant use is the only affordable treatment option.
Medicinal plant use will therefore remain an integral part of the health
care system to the community for a long time to come. Consequently,
ethnobotanical exploration should not only be a cost-effective means of
locating new and useful tropical plant compounds against TB, but also be
linked to the urgent need for sustainable conservation strategies for
medicinal plants, since human expansionist demands can be expected to
cause environmental deterioration and biotic destruction well into the
next century.
Conclusions
The
documented medicinal plant species used by the Ghanaian communities are
a potential source of a new class of antituberculous drugs. The current
study recommends bioactivity guided isolation and purification of lead
compounds for antimycobacterial activity from the selected plant
species. Many plant species reported in this study have been
investigated for their phytoconstituents and pharmacological activities,
the latter being in agreement with ethnomedical uses associated with
the documented species in Ghana. Nine plant species documented in the
current study have not been investigated for their antimycobacterial
activity. In Ghana, traditional methods of treatments based on medicinal
plants are still an important part of social life and culture, and the
acceptability of these plants as claimed effective remedies is quite
high among the population of this area. The claimed therapeutic value of
the reported species call for modern scientific studies to establish
their safety and efficacy and to preserve and document this flora which
may otherwise be lost due to erosion of age-old traditional methods of
biodiversity conservation and medicinal knowledge [43].
There is a general consensus that traditional knowledge on the use of
medicinal plants must be conserved because of its vital role for human
well-being. It is often argued that if traditional knowledge which has
been generated over a long period of time is lost, exploitation of
plants among other things will become difficult, if not impossible.
Among the reasons traditional knowledge is considered reliable for the
exploitation of herbal remedies is that indigenous communities through a
period of long experimentation with herbal medicines are likely to have
retained those that are effective and tolerably safe while discarding
preparations with low efficacy or acute toxicity [44].
Conflict of interest
We have no conflict of interest to declare.
Acknowledgements
The
Bill and Melinda Gates Foundation is gratefully acknowledged for
supporting this study through the postdoctoral training fellowship in
infectious disease program at Noguchi Memorial Institute for Medical
Research (NMIMR), project identification number [STC] 3(1)2014-15. The
herbarium staff at the Centre for Scientific Research into Plant
Medicine (CSRPM), Mampong is acknowledged for identification, collection
and voucher specimen preparation of the selected plant species.