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‘AFRICAN POTATO’: A PLANT-MEDICINE FOR MODERN DISEASES? 147
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 23, 147–152 (2009)
DOI: 10.1002/ptr
Copyright © 2008 John Wiley & Sons, Ltd.
PHYTOTHERAPY RESEARCH
Phytother. Res. 23, 147–152 (2009)
Published online 11 August 2008 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/ptr.2595
Received 6 February 2008
Revised 28 April 2008
Accepted 9 May 2008
* Correspondence to: John A. O. Ojewole, Department of Pharmacology,
School of Pharmacy and Pharmacology, Faculty of Health Sciences, Univer-
sity of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
E-mail: Ojewolej@ukzn.ac.za
REVIEW ARTICLE
‘African Potato’ (Hypoxis hemerocallidea
corm): A Plant-Medicine for Modern and 21st
Century Diseases of Mankind? – A Review
Peter M. O. Owira and John A. O. Ojewole*
Department of Pharmacology, School of Pharmacy and Pharmacology, Faculty of Health Sciences, University of KwaZulu-Natal,
Private Bag X54001, Durban 4000, South Africa
The traditional uses, therapeutic attributes, phytochemical and pharmacological profiles of ‘African potato’
(Hypoxis hemerocallidea corm) extracts have been reviewed. Available biomedical evidence suggests that
‘African potato’ is a potential plant-medicine for some modern and 21st century diseases of mankind. Thus far,
biomedical evidence has revealed that ‘African potato’ extracts possess antiinflammatory, antineoplastic, anti-
oxidant, antidiabetic and antiinfective properties in vivo and in vitro. However, more laboratory and clinical
studies are required to clarify these observations, and to isolate, purify and characterize the active chemical
constituents responsible for the herb’s pharmaco-therapeutic effects. Copyright © 2008 John Wiley & Sons, Ltd.
Keywords: traditional herbal medicines; ‘African potato’ extracts; plant-medicine; pharmaco-chemical profiles; therapeutic
attributes.
INTRODUCTION
African Traditional Medicines and ‘African Potato’
It has been estimated that about 80% of the general
population in sub-Saharan Africa use African traditional
medicines (Hostetmann et al., 2000; Puckree et al., 2002)
and that as many as 100 000 traditional healers are in
practice in South Africa alone, with a contingent of
herbal trade industry worth approximately R500 million
per annum (Mander, 1998). It has also been estimated
that the ratio of traditional healers and orthodox medi-
cal doctors to the population in South Africa is 1:500
and 1:40 000, respectively (Abdool-Karim et al., 1994).
Traditional medicine, therefore, plays a critical role in
the healthcare delivery system of South Africa, given
the poor state of healthcare infrastructure, increased
disease burden occasioned by the HIV/AIDS pandemic,
and other chronic ailments that Western medicines
have failed to cure. The importance of herbal medi-
cines (phytomedicines) in this regard is only now being
appropriately recognized. The Ministries of Health of
several African countries have recently formulated
policies that promote the use of African traditional
medicines for the management, control and treatment
of HIV/AIDS-related diseases and other chronic ail-
ments of man (Morris, 2002; Southern Africa Develop-
ment Community, 2002).
The recent renewed interest in African traditional
medicines has attracted the attention of not only
government and private research laboratories and insti-
tutes, but also of pharmaceutical industries, in order
to rationalize the scientific and therapeutic values of
African traditional medicines. One African medicinal
plant that has enjoyed long usage as a traditional herbal
medicine in southern Africa is Hypoxis hemerocallidea
(also known as H. rooperi). This popular ‘miracle’
medicinal plant is widely distributed in the southern
Africa sub-region. The plant is characterized by strap-
like leaves, and bright yellow, star-shaped flowers (Van
Wyk et al., 2002). The tuberous rootstock (i.e. the corm)
of the plant is commonly referred to as ‘African potato’,
because of its potato-like shape. Traditionally, after
washing with clean water, the plant’s corms are chopped
into small pieces, boiled for about 20 min, and then the
decoction is consumed orally. This oral administration
is estimated to correspond to a daily dose of 250 mL,
derived from about 20 g of the corms (Nair et al., 2007a;
Pujol, 1990). ‘African potato’ extracts, powders, infu-
sions and decoctions have been used for centuries by
southern African traditional healers for the treatment,
management and/or control of an array of human ailments,
including cancers, nervous disorders, immune-related
illnesses, heart weaknesses and urinary tract infections
(Singh, 1999). Indeed, among the Swazis of Swaziland,
Hypoxis hemerocallidea is often referred to in siSwati
as ‘zifozonke’, meaning: ‘the plant that can be used to
treat many diseases’ (Amusan et al., 2007). Some of the
outstanding critical questions that still require answers
about ‘African potato’ include: (i) what has made
‘African potato’ so unique in the family of ‘African
herbal medicines’, and (ii) why has it taken researchers
and healthcare providers so long a time to exploit
and maximize the potential therapeutic benefits of this
‘wonder’ plant-medicine?
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 23, 147–152 (2009)
DOI: 10.1002/ptr
148 P. M. O. OWIRA AND J. A. O. OJEWOLE
BIOLOGICAL ACTIVITY
Therapeutic and pharmacological considerations
In recent years, attempts have been made to investigate
the scientific basis of the therapeutic claims attributed
to ‘African potato’. Evidence-based laboratory investi-
gations indicate that aqueous and alcohol extracts of
‘African potato’ possess many interesting pharmaco-
logical properties, including antinociceptive (in mice),
antiinflammatory and antidiabetic properties (in rats)
in vivo (Ojewole, 2006). ‘Intraperitoneal injections of
50–800 mg/kg body weight of “African potato” extracts
produced significant and dose-dependent anti-nociceptive
effects against chemically- and thermally-induced noci-
ceptive pain in mice’ (Ojewole, 2006). At the same dose
level, oral administrations of H. hemerocallidea corm
extracts also ‘significantly inhibited egg albumin-induced
acute inflammation, and reduced blood glucose levels
in both normal and streptozotocin-induced diabetic rats
in a dose-dependent manner’ (Ojewole, 2006). These
observations, therefore, suggest that extracts of ‘African
potato’ could possess antiinflammatory and antidiabetic
(hypoglycaemic) properties, respectively. As suggested
by Ojewole (2006), the extracts of ‘African potato’ could
inhibit the synthesis, production and/or release of in-
flammatory cytokines and mediators such as prostaglandins.
Recent reports have indicated that lectin-like proteins
purified from aqueous extracts of ‘African potato’ can
inhibit cyclooxygenase (COX) enzyme that mediates
prostaglandin synthesis in vitro (Gaidamashivili and
Van Staden, 2006). However, other studies have shown
that ethanol extracts of H. hemerocallidea have higher
inhibitory effects on COX-1 catalysed prostaglandin
synthesis than aqueous extracts of the plant’s corms
(Steenkamp et al., 2006). Aqueous extracts of H.
hemerocallidea corms have previously been shown
to scavenge free radicals (hydroxyl ions) in vitro
(Mahomed and Ojewole, 2003), and it has been sug-
gested that the ability of the corm’s extracts (both
aqueous and ethanol) to suppress inflammation could
be mediated via its antioxidant activity which, in turn,
inhibits COX enzymes (Feng et al., 1995; Kumagai
et al., 2000; Mahomed and Ojewole, 2003; Steenkamp
et al., 2006). Taken together, these observations appear
to suggest that the reported antiinflammatory activity
of ‘African potato’ extracts could be due to their ability
to inhibit the synthesis of prostaglandins and other in-
flammatory mediators (see Fig. 1).
It has been reported that lectin-like proteins derived
from extracts of ‘African potato’ inhibited the growth
of Staphylococcus aureus, in vitro (Gaidamashivili and
Van Staden, 2002). Undoubtedly, agglutinins, found
in the storage parts (corms) of H. hemerocallidea, play
a critical role in the plant’s defensive mechanism against
pathogenic micro-organisms. This observation would,
therefore, support the age-old usage of ‘African potato’
in the treatment of microbial infective disorders (Hutchings
et al., 1996; Van Wyk et al., 2002). Laboratory reports
have further shown that both ethanol and aqueous
extracts of H. hemerocallidea corm inhibit the growth
of Escherichia coli, in vitro (Steenkamp et al., 2006),
an observation quite consistent with the previously
Figure 1. A summary of the putative pharmacological actions of ‘African potato’ extracts (rooperol and stigmasterol) on some cellular
pathways so far investigated. Antiinflammatory activity of ‘African potato’ extracts could be attributed to inhibition of lipoxygenase,
cyclooxygenase (COX) and cytokines production. Antioxidant activity of the extracts could be mediated via reduced reactive oxygen
species (ROS) production, either from diminished activity or expression of drug metabolizing enzymes, or from direct inhibition of
COX. Increased expression of pregnane X receptor (PXR) binds xenobiotics and triggers over-expression of P-glycoproteins and
some drug metabolizing enzymes, thus causing toxicity related to drug resistance or herbal drug reactions. Effects of ‘African potato’
extracts on organic cation transporters (OCT) are not known. = inhibitory effects of ‘African potato’ extracts; = xenobiotics; ↑ =
up-regulation/stimulation; ↓ = down-regulation/inhibition.
‘AFRICAN POTATO’: A PLANT-MEDICINE FOR MODERN DISEASES? 149
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 23, 147–152 (2009)
DOI: 10.1002/ptr
reported antibacterial activity of ‘African potato’
(Gaidamashivili and Van Staden, 2002). Escherichia coli
infection is the most common secondary cause of bac-
terial prostatitis (Steenkamp et al., 2006). This observa-
tion may, therefore, partly also explain the traditional
usage of the extracts of this plant’s corm in the treat-
ment of urinary tract infections (Singh, 1999).
Benign prostate hyperplasia (BPH) can cause blockade
of the urinary tract in men, and this may lead to chronic
bacterial prostatitis. Anecdotal and folkloric reports
have documented that ‘African potato’ extracts have
been used traditionally in the treatment of prostate
hyperplasia (Singh, 1999). The observation that ‘African
potato’ extracts can inhibit the growth of E. coli in vitro,
therefore, seems to support the use of this plant’s corm
in the treatment of prostate hyperplasia. Furthermore,
therapeutically useful steroids are present in Prunus
africanum and H. hemerocallidea. However, more recent
experimental and clinical evidence have suggested that
the effects of H. hemerocallidea corm extracts on BPH
might not only be due to their antibacterial activities,
but could also be due to their antiinflammatory and
antioxidant properties (Ojewole, 2002; Steenkamp
et al., 2006; Nair et al., 2007b). This body of evidence,
therefore, supports the claims that ‘African potato’
extracts may contain chemical compounds that suppress
tumour growth, and hence, its use in the treatment of
cancers.
It has recently been shown that aqueous extracts of
‘African potato’ caused bradycardia and brief hypoten-
sion in guinea-pigs and rats in vitro and in vivo, respec-
tively (Ojewole et al., 2006). Although the investigators
were unable to establish the precise pharmacological
mechanisms underlying their observations, they ruled
out involvement of the cholinergic system, since the
cardio-depressant effects of the extracts were not modi-
fied by atropine pretreatment (Ojewole et al., 2006).
However, in an earlier study using Chacma baboons,
Coetzee et al. (1996) reported that a purified extract of
H. hemerocallidea corm (rooperol) increased myocardial
contractility in vivo. Recently, a case study was pub-
lished where it was reported that chronic ingestion
of aqueous extract of ‘African potato’ (as tea) caused
ventricular tachycardia in a 25-year-old male subject
(Ker, 2005). The above conflicting cardiovascular ob-
servations tend to suggest that extracts of H. hemerocallidea
corm contain some bioactive chemical compounds with
cardiovascular activities. These findings may also lend
pharmacological credence to the age-old usage of this
plant in the treatment and/or management of heart
ailments and hypertension in some rural communities
of southern African.
However, what has recently stimulated the greatest
interest, not only among traditional healers and their
patients, but also in scientific communities, the phar-
maceutical industries, as well as in government circles,
is the claim that H. hemerocallidea corm can boost human
immune system. Some healthcare providers in South
Africa are currently using extracts of H. hemerocallidea
corms as immunostimulant preparations for patients
living with HIV/AIDS, on the strength of the recom-
mendation of South Africa’s national Department of
Health (Southern Africa Development Community,
2002; Mills et al., 2005a). In this regard, the use of this
plant’s corms has been extended to immune-related
illnesses, such as common cold, flu and arthritis (Mills
et al., 2005a). Unfortunately, despite the popular belief
in the immune-boosting properties of this plant’s corms,
there is absolutely no laboratory or clinical evidence
yet to support this immunostimulant claim, which at
present still remains speculative. Many clinical and labo-
ratory studies are, however, currently under way to
substantiate or refute the immunostimulant property
attributed to ‘African potato’ extracts.
PHYTOCHEMISTRY
Chemical constituents
Hypoxis hemerocallidea corm has a catalogue of anecdotal,
folkloric and therapeutic uses. Undoubtedly, ‘African
potato’ is one of the most popular and ethnobotanically
acknowledged medicinal plants in southern Africa
(Drewes and Khan, 2004). Attempts have been made
in some laboratories to isolate, purify and characterize
the chemical constituents of this plant’s corm that could
be responsible for its medicinal properties. One of the
most important chemical constituents of the herb which
has been confirmed to be abundantly present in extracts
of ‘African potato’ is a norlignan diglucoside, hypoxoside,
a biologically inactive pro-drug (Marini-Bettolo et al.,
1982), with an uncommon aglycone structure, consisting
of diphenyl-1-en-4-yne-pentane skeleton (Nair and Kanfer,
2006a; Nair et al., 2007a). Hypoxoside is reported to
have low toxicity, hence, the traditional consumption
of ‘African potato’ as a food (Drewes et al., 1984; Smit
et al., 1995). In the human gut, hypoxoside is converted
to rooperol, a biologically active compound, by beta-
glucosidase enzyme, which is abundantly present in the
human gut and rapidly dividing cancer cells (Mills et al.
2005a) – see Fig. 2.
Both rooperol and its pro-drug, hypoxoside, have been
shown to undergo phase I hepatic metabolism by cyto-
chrome P450 (probably CYP 3A4) enzyme, while their
phase II metabolic products, consisting of diglucuronide,
disulphate and mixed glucuronide-sulphates, are elimi-
nated by first-order kinetics (Albrecht et al., 1995a; Mills
et al., 2005b). Rooperol can be recovered from these
metabolites by deconjugation reactions (Albrecht et al.,
1995b). Most of the therapeutic properties of ‘African
potato’ extracts observed clinically in man and in labo-
ratory animals to date, have been attributed to rooperol
(Albrecht et al., 1995a; Albrecht et al., 1995b; Vinesi
et al., 1990). Rooperol has been shown to be antineoplas-
tic, bacteriostatic and bactericidal (Drewes et al., 1984;
Drewes and Khan, 2004; Albrecht et al., 1995a). It
has been suggested that the antimetastatic activity of
rooperol could be mediated through its ability to stimu-
late the synthesis of collagen type I that could impede
cell invasions (Dietzsch et al., 1999). However, hypoxo-
side as an oral pro-drug, has failed to exhibit any toxi-
city in phase I clinical trials for cancer therapy (Smit
et al., 1995; Albrecht et al., 1995a; Albrecht et al., 1995b).
Recent laboratory investigations have shown that rooperol
has a strong antioxidant activity, a strong affinity for
phospholipid membranes, and that it inhibits free
radical-induced membrane lipo-oxidation (Laporta et al.,
2007) – see Fig. 1. These findings seem to suggest that
rooperol is important in the maintenance of cell mem-
brane stability (Hostetmann et al., 2000), a phenomenon
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 23, 147–152 (2009)
DOI: 10.1002/ptr
150 P. M. O. OWIRA AND J. A. O. OJEWOLE
Figure 2. Structures of hypoxoside, rooperol and
β
-sitosterol. The biologically inactive norlignan diglucoside, hypoxoside, is
deconjugated and converted by
β
-glucosidase enzyme to form the biologically active aglucone, rooperol.
which may partially explain its activity against neoplastic
cells.
It is still unclear at the moment, whether the ability
of rooperol to inhibit inflammatory processes in vitro
and in vivo, is as a consequence of its direct ability to
inhibit the production of pro-inflammatory cytokines,
tumour necrosis factor (TNF)-
α
, and interleukins; or
due to its inhibitory effects on enzymes involved in
the synthesis of pro-inflammatory mediators, such as
leukotrienes and prostaglandins. In an earlier study,
Van der Merwe et al. (1993) showed that rooperol is
a potent inhibitor of lipo-oxygenase (an enzyme that
catalyses the first-step in the conversion of arachidonic
acid to leukotrienes), but not cyclooxygenase (COX),
which catalyses the rate-limiting step in the conversion
of arachidonic acid to prostaglandins (Fig. 1). Subse-
quent study by Guzek et al. (1996), in an investigation
which attempted to highlight the potential therapeutic
benefit of ‘African potato’ extracts in the treatment of
airways inflammatory diseases, showed that rooperol
and its derivatives inhibit the production of TNF-
α
,
interleukin1-
β
and interleukin-6, and also suppress the
production of nitric oxide in vitro. However, direct
inhibitions of COX-1 (constitutive) and COX-2 (induc-
ible) isoforms of the COX enzymes by extracts of H.
hemerocallidea corm, have also recently been reported
(Gaidamashivili and Van Staden, 2006; Steenkamp
et al., 2006). Despite the prevailing uncertainties about
the precise mechanism/s by which rooperol exerts its
antiinflammatory effects, it is important to recognize
that rooperol shares intimate structural similarity with
a well-known, strong antioxidant, nordihydroguairectic
acid (Nair et al., 2007b), and comparably inhibits leuko-
triene and prostaglandins synthesis in polymorpho-
nuclear leukocyte and platelet microsomes, respectively
(Van der Merwe et al., 1993; Coetzee et al., 1996). On
the strength of the available scientific, pharmacological
and clinical evidence, several patents have been registered
on rooperol, and the extract has also been registered
under the trade name of ‘Harzol™’ in Germany for the
treatment of prostate cancer (Pegel, 1979; Tyler, 1986;
Drewes and Lieberg, 1987; Albrecht et al., 1995a; Nair
et al., 2007a). At present, there are numerous commercial
herbal preparations which contain rooperol or extracts
of ‘African potato’ in the market for the treatment,
management and/or control of many modern and 21st
century diseases of man (Nair et al., 2007a).
Among the chemical constituents of ‘African potato’,
phytosterols have been suggested to be partly responsi-
ble for some of the observed therapeutic and pharma-
cological properties of the corm’s extracts. Mohamed
and Ojewole (2003) attributed the hypoglycaemic effect
of ‘African potato’ extracts observed in streptozotocin-
induced diabetic rats to phytosterols and sterolins in
the extracts of ‘African potato’. Phytosterols are known
to stabilize plant cell membranes (Nair and Kanfer,
2006b), and are also known to have many therapeutic
benefits, including enhancement of immune system
in immunocompromised individuals (Bouic et al., 2001;
Van Wyk et al., 2002; Nair and Kanfer, 2006b). The
antiprostatic adenoma activity attributed to extracts of
‘African potato’, has also been ascribed to phytosterol
glycosides, mainly
β
-sitosterol glycosides (Hostetmann
et al., 2000). These claims, however, remain speculative
in view of the fact that daily intake of the same amounts
of phytosterols and their glycosides from other plant
sources have not produced the same magnitude of thera-
peutic effects (Hostetmann et al., 2000).
TOXICITY
A recent laboratory report has indicated that chronic
infusion of ‘African potato’ extracts may cause a decrease
in glomerular filtration rate, and can elevate plasma
creatinine concentrations in rats, suggesting an impair-
ment of kidney function (Musabayane et al., 2005). No
‘AFRICAN POTATO’: A PLANT-MEDICINE FOR MODERN DISEASES? 151
Copyright © 2008 John Wiley & Sons, Ltd. Phytother. Res. 23, 147–152 (2009)
DOI: 10.1002/ptr
further reports are available in the biomedical litera-
ture to corroborate or dispute this observation. Studies
based on experimental animal models have also shown
that aqueous extracts of ‘African potato’ may cause
bradycardia and brief hypotension (Ojewole et al., 2006)
in guinea-pigs and rats in vitro and in vivo, respectively;
while rooperol has been reported to increase myocardial
contractility in vivo in baboons, possibly due to its catechol
structure (Coetzee et al., 1996). It has been suggested,
however, that these cardiovascular effects of ‘African
potato’ extracts may be clinically benign (Albrecht et al.,
1995a). The case report of a patient with a known his-
tory of ischaemic heart disease who presented with
ventricular tachycardia after chronic ingestion of aque-
ous extract of ‘African potato’ may be a strong evidence
for cardio-toxicity associated with cardio-active chemi-
cal compounds present in ‘African potato’ extracts (Ker,
2005). In South Africa, the national Department of Health
(DoH) recently prematurely terminated a clinical study
on ‘African potato’ extracts in HIV-positive patients due
to a controversial report of ‘bone marrow suppression’
in some of the patients (Mills et al., 2005a). At present,
it is difficult to clarify these claims, given the charged
atmosphere of HIV/AIDS politics in South Africa.
‘AFRICAN POTATO’ EXTRACTS–DRUG
INTERACTIONS
Potential drug interactions between extracts of ‘African
potato’ and antiretroviral drugs have been reported
(Mills et al., 2005b). ‘African potato’ extracts have been
reported to inhibit CYP3A4 isoform of cytochrome P450
and drug transporter protein (P-glycoprotein). Further-
more, ‘African potato’ extracts have been claimed
to activate drug nuclear receptor pregnane X (PXR)
which modulates expressions of both CYP3A4 and
P-glycoprotein (Mills et al., 2005b) – see Fig. 1. Many
antiretroviral drugs are substrates of CYP3A4, and some
herbal preparations are known to alter blood levels
of these drugs through their effects on CYP3A4 and
P-glycoprotein (Mills et al., 2005c). ‘African potato’
extracts, therefore, could potentially interact with HIV
drug-metabolizing enzymes (Mills et al., 2005a). A re-
cent study (Nair et al., 2007a) which compared various
extracts and commercial formulations of ‘African potato’
extracts interestingly showed that only stigmasterol and
rooperol had inhibitory effects on CYP3A4, CYP3A5
and CYP19-mediated drug metabolism. In addition,
the study showed that hypoxoside significantly induced
P-glycoprotein, compared with ritinovir®. Fairly recent
studies (Kuehl et al., 2001; Williams et al., 2002) have
also shown that CYP3A5 may represent more than 50%
of the total CYP3A isoforms of cytochrome P450 in some
individuals, and that CYP3A5 has a higher incidence
among southern African populations (Williams et al.,
2002). CYP19, also known as aromatase, has been
implicated in the development of truncal obesity and
increased adiposity (due to inhibition of oestrogen
synthesis) in patients taking antiretroviral drugs (Toda
et al., 1996). No studies have yet been reported about
the effect of ‘African potato’ extracts on organic cation
transporters (OCT). It is not unreasonable to specu-
late, however, that since up-regulation of pregnane
X nuclear receptor has been reported, it is likely that
‘African potato’ extracts would have an effect on
cellular drug transport systems (Fig. 1). Taken together,
these observations, even though largely in vitro, seem
to suggest possible in vivo interactions between
‘African potato’ extracts and antiretroviral drugs.
Patients taking ‘African potato’ extracts concurrently
with antiretroviral drugs may, therefore, be at risk of
developing adverse events which may lead to treatment
failure, viral resistance and/or drug toxicity.
CONCLUSION
The therapeutic attributes and pharmaco-chemical
profiles of ‘African potato’ (H. hemerocallidea corm)
extracts have been reviewed. From available folkloric,
anecdotal and laboratory evidence, ‘African potato’
extracts contain some chemical compounds with anti-
inflammatory, antidiabetic, antineoplastic, antiinfective
and antioxidant activities. It is highly unlikely that all
these potential medicinal properties of ‘African potato’
extracts could be attributed solely to rooperol and
stigmasterol, which are the two main biologically active
chemical constituents of the herb so far identified. It is
possible that these chemical compounds act in concert
together with other compound/s yet to be identified.
Certainly, more laboratory and clinical studies are re-
quired to clarify this situation. However, the tendency
to irrationally commercialize these findings by way of
seeking patents, or packaging of the known chemical
constituents, may negate genuine efforts to unravel the
potential therapeutic mystery of this ‘miracle’ medicinal
plant.
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