INTRODUCTION

Bulbine species are geophytic (plants that have a subterranean storage organ known as a corm), aloe-like succulent perennials with rosettes of fleshy leaves. The amount of water stored above ground (succulence) in Bulbine species, however, may be more important for survival than the amount stored in the corm (geophytism).¹ The Bulbine genus includes approximately 78 species² with a highly disjunct distribution,¹ occurring almost entirely in southern Africa,^1,2 but with six species in Australia.³ This article concerns the most widely used African species: B. latifolia (syn. B. natalensis), known as broad-leaved bulbine,⁴ and as rooiwortel (“red root”) in Afrikaans due to its red-orange corm⁵; B. frutescens, known as stalk-bulbine,⁶ burn jelly plant, cat’s tail, and snake flower⁷; and B. narcissifolia, known as strap-leafed bulbine and snake flower.³ While much of the literature and trade refers to B. latifolia and B. natalensis as separate species, version 1.1. of The Plant List (2013) and the updated World Flora Online treat them as synonyms.⁸ In this article, we use the Latin name referred to in the cited references.

Bulbine frutescens, which occurs in South Africa (in the provinces of Free State,⁹ Northern Cape, Eastern Cape, Western Cape, and KwaZulu-Natal), Swaziland,⁶ and Lesotho,⁷ has yellow, sometimes orange, star-shaped flowers.¹⁰ Bulbine latifolia (B. natalensis) is distributed in the fynbos/dry scrub-forest ecotone (transition area between two biomes) region of South Africa⁵ (in Free State,⁹ Mpumalanga, KwaZulu-Natal, and Eastern Cape), as well as in Malawi, Mozambique, and Zimbabwe.⁴ It has yellowish fleshy roots, small yellow flowers with spreading petals, and small blackish, flattened, wind-dispersed seeds.¹⁰ Bulbine narcissifolia, which is gray-green and stemless with yellowish exudate, small bright yellow flowers, and bluish-green, flat twisted leaves,¹⁰ is widely distributed in South Africa (in Western Cape, Eastern Cape, Free State, KwaZulu-Natal, North West, Gauteng, and Limpopo), as well as in Lesotho, Botswana, and Ethiopia.³

Most of the material of commerce is sourced from wild collection and subject to licensing and access and benefit-sharing (ABS) requirements as per the Nagoya Protocol of the Convention on Biological Diversity (CBD).¹¹ Various suppliers of wild-collected B. natalensis plant parts hold the requisite bioprospecting and export permits for legal trade to companies domestically and for the export market.¹² In recent years, a few enterprises began to pioneer commercial cultivation, including the 10-hectare Canterbury Farm of Botanica Natural Products growing B. frutescens in Alldays, Limpopo, South Africa, with US Department of Agriculture (USDA) National Organic Program (NOP) certification,^13,14 and the Edakeni Muthi Futhi Trust growing B. natalensis on a 17-hectare farm in Dakeni, a village in Zululand, KwaZulu-Natal.¹⁵ Cultivated B. natalensis is also subject to South Africa’s Bioprospecting, Access and Benefit-Sharing Regulations. Under this framework, a benefit-sharing agreement was made in 2011 between the Edakeni Muthi Futhi Trust and the Edakeni community in uMlalazi Municipality, KwaZulu-Natal.¹⁶

HISTORY AND CULTURAL SIGNIFICANCE

Preparations of Bulbine plant parts are traditional medicines of the Xhosa and Zulu peoples of southern Africa.^17,18 The genus name Bulbine stems from the Greek bolbine or bolbos, meaning “bulb” or “onion.” In Latin, Bulbine means “little onion” or “bulb.”¹⁰

The genus Bulbine was named by German botanist Nathanael Matthäus von Wolf (1724-1784) in his 1776 publication Genera plantarum vocabulis characteristicis definita, referring to Anthericum as a synonym.¹⁹ In 1781, Anthericum latifolium was described by Swedish naturalist Carl Linnaeus the Younger (1741-1783), stating its habitat as “Caput Bonae Spei” (Cape of Good Hope).²⁰ It was renamed Bulbine latifolia in 1825 by German botanist Kurt Polycarp Joachim Sprengel (1766-1833). The species name latifolia refers to its broad leaves.²¹ In 1809, German botanist and plant taxonomist Karl Ludwig von Willdenow (1765-1812) named the species Bulbine frutescens, listing Anthericum frutescens as a synonym and also naming its habitat as the Cape of Good Hope.²² In 1834, German botanist Joseph zu Salm-Reifferscheidt-Dyck (1773-1861) named the species Bulbine narcissifolia, but added “patria ignota,” meaning native origin unknown.²³ The Latin species name narcissifolia, means “with leaves like a Narcissus” (daffodil).²⁴

Zulu men and adolescents ingest an aqueous decoction of unspecified parts of B. latifolia (known as ibhucu) as an emetic in purification rites for the purpose of preventing antisocial behavior. The Xhosa people prepare a decoction of the subterranean parts to treat convulsions in children.^17,25 Older literature reported that Zulu healers administered an infusion of B. frutescens root and leaf as an emetic “to patients thought to be going mad as a result of being bewitched.”¹⁷ South African Rastafarian bush doctors distinguish two types of B. latifolia roots for different uses: thin red roots are used to treat blood circulation and erectile dysfunction associated with diabetes, and thick yellow roots are used as a blood purifier and to treat kidney and bladder problems.²⁶ The fresh leaf gel of both B. frutescens and B. asphodeloides is applied topically to treat wounds, cuts, grazes, burns, sores, rashes, itches, cracked lips, mosquito bites, ringworm, and herpes.⁷

A survey of local indigenous people, herbalists, and traditional healers in Eastern Cape province found that an aqueous decoction of dried whole plant (including roots, rhizomes, and leaves) of B. latifolia is used to treat stomach ailments and rheumatism.²⁷ A decoction of the ground leaves of B. latifolia also is used in traditional veterinary medicine in Eastern Cape province to control parasites, including ticks and helminths, in goats.²⁸ The leaf sap of B. narcissifolia is used traditionally for burns, wounds, and rashes, and the leaf sap of B. natalensis is used for diarrhea, burns, rashes, sunburn, corns, and warts. Decoctions of both dried whole plant and leaf of B. frutescens are used for treating diarrhea and topically for burns, rashes, blisters, insect bites, cracked lips, and mouth ulcers.²⁷ In western Free State, B. narcissifolia tea is taken orally to treat kidney problems.⁹

In 2004, a monograph for B. frutescens was prepared through the Pharmacopoeia Monograph Project of the South African Traditional Medicines Research Group at the University of the Western Cape’s School of Pharmacy with support from the South African Medical Research Council.²⁹ In 2010, a monograph for this species appeared in the first edition of the African Herbal Pharmacopoeia.⁷

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In the South African market, dry extract of B. natalensis tuber is used as a natural ingredient in non-medicinal food supplement products labeled with the claim “testosterone booster.”³⁰ The leaf juice of B. frutescens is also produced in South Africa for soap and veterinary applications (i.e., to help increase skin hydration and elasticity).¹³

In the European Union (EU), B. frutescens leaf juice is authorized for use as a skin-conditioning component of cosmetic products.³¹ However, for use in oral ingestion products, B. natalensis is presently classified as a Novel Food. A request has been submitted to the European Commission for a determination on whether it will require authorization under the Novel Food Regulation. According to the information available to Member States, B. natalensis was not used as a food or food ingredient before May 15, 1997. Therefore, before it may be placed on the market in the EU as a food or food ingredient, a safety assessment under the Novel Food Regulation is required.³²

In Canada, B. natalensis is regulated as an active ingredient of licensed natural health products (NHPs), which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD).³³ At the time of this writing (February 2020), there were three licensed multi-herb NHPs containing an extract of B. natalensis as one of the active ingredients.³⁴

In the United States, several products labeled as containing an extract of B. natalensis are listed in the National Institutes of Health’s (NIH’s) Dietary Supplement Label Database, mostly with male sexual enhancement-oriented names like “Fornatab,” “Insane Testosterone Booster,” and “Ultra Male RX.”³⁵ No Bulbine species, however, are listed in the American Herbal Products Association’s Herbs of Commerce first edition (1992)³⁶ or second edition (2000).³⁷ Bulbine is also not found in the US Food and Drug Administration’s (FDA’s) inventory of Generally Recognized as Safe (GRAS) notices.³⁸ No public information was found on the status of bulbine extracts either as an old dietary ingredient (ODI) or new dietary ingredient (NDI). It is possible that an independent GRAS conclusion (formerly called GRAS Self-Determination or Self-Affirmed GRAS) has been made or an NDI Notification has been submitted, of which the authors of this article are not aware.

MODERN RESEARCH

Despite Bulbine species’ being well-documented for their traditional uses, modern-day research is still scant. No clinical trials with efficacy endpoints could be found in the literature for preparations of Bulbine species.

Investigation of the composition of Bulbine species started in the 1990s, when van Staden and Drewes (1994) isolated the anthraquinone knipholone from B. latifolia and B. frutescens.³⁹ It took almost 10 years until these findings were affirmed and other phenylanthraquinones (4'-O-demethylknipholone-4'-O-β-D-glucopyranoside and gaboroquinones A and B) were isolated from B. frutescens.⁴⁰ Mutanyatta et al. (2005) elucidated four novel O-sulfated phenylanthraquinones, along with their non-sulfated parent compounds from the root of B. frutescens.⁴¹ The first chemical investigation of B. natalensis was reported by Bae et al. (2016),⁴² who isolated chrysophanol, 10,7'-bichrysophanol, knipholone, and isoknipholone. An additional six anthraquinones, one naphthalene derivative, bulbnatalonosides A-E, bulbnatalone, and bulbnatalol were isolated from the stem of B. natalensis by the same group.^43,44 These authors subsequently published their development and validation of a method for identification and quantification of anthraquinone-type compounds in B. natalensis samples and dietary supplements.⁴⁵

A number of experimental studies have attempted to substantiate traditional uses of Bulbine species. Widgerow et al. (2000) predicted hydration and antibacterial properties for an extract of B. frutescens in scar management.⁴⁶ Mocktar (2000) confirmed antimicrobial activities of methanolic extracts of B. frutescens, B. narcissifolia, and B. abyssinica in a battery of tests against Klebsiella pneumoniae, Staphylococcus aureus, Salmonella typhi, and Shigella flexneri and demonstrated that a B. frutescens root extract inhibited Candida albicans.⁴⁷ Brine shrimp assay was used to assess toxicity. Most extracts proved toxic at high concentrations, with the exception of root extracts of B. frutescens, B. narcissifolia, and B. abyssinica.

Antimicrobial, anti-inflammatory, antioxidant, wound-healing, and other activities affecting skin parameters received renewed attention in the 2010s and have since remained the focus of investigations.^{27,43,44,48-58} Coopoosamy (2011) showed moderate activity against gram-positive bacteria with acetone and ethyl acetate extracts of Bulbine species but low to no activity with water extracts,²⁷ implying polarity of the active compounds, which was confirmed in experiments conducted by Mzindle (2017).⁵³ Bulbine anthraquinones were tested for antimicrobial activity, and bulbnatalonoside A showed a moderate inhibitory effect against methicillin-resistant Staphylococcus aureus (MRSA).^43,44 In an experimental setting, Pather et al. (2011 and 2012) demonstrated a wound-healing effect of B. natalensis and B. frutescens leaf gels (specifically, an increase in tensile strength by increasing fibroplasia, collagen deposition, and maturation).^48,49

Other effects investigated include antidiabetic,^59-63 androgenic,^64,65 antiproliferative,^66,67 and anti-HIV.⁶⁸ An aqueous extract of B. frutescens whole plant was shown to increase glucose utilization significantly more than insulin in C2C12 cells, and to promote glucose uptake in Chang liver cells (HeLa).⁶⁰ Kibiti (2016) demonstrated antidiabetic effects — presumably through affecting carbohydrate metabolism, oxidative stress, and opportunistic infections — with aqueous and acetone extracts of Bulbine species and the essential oil of B. abyssinica.⁶¹ Odeyemi and Afolayan (2018) investigated polyphenolic fractions of a methanolic extract of B. abyssinica leaves and found them to be amylase and glucosidase inhibitors, active against free radicals, as well as showing ferric ion-reducing capacity.⁶² Yakubu and Afolayan (2009 and 2010) showed a prosexual stimulatory potential, as well as anabolic and androgenic activities with an aqueous extract of B. natalensis stem in male rats.^65,69

Crude aqueous and ethanolic extracts of B. natalensis and B. frutescens leaf, bulb, and root were investigated for cytotoxicity in a human laryngeal carcinoma cell line (HEp-2).⁶⁶ While all Bulbine species fractions showed the ability to induce HEp-2 cell death, likely through apoptosis (caspase-3 induction), no clear link could be established between apoptosis and cytotoxicity. Isofuranonaphthoquinone isolated from B. frutescens showed significant antiproliferative effects on Jurkat T-cells by producing reactive oxygen species resulting in apoptosis and inhibiting glutathione transferase and drug efflux pumping activities.⁶⁷ Shikalepo et al. (2018) demonstrated moderate inhibitory activity with an extract of B. frutescens aerial parts on HIV-1 protease, reverse transcriptase, and integrase enzymes in vitro.⁶⁸

Yakubu and Afolayan (2009) demonstrated localized systemic toxicity with a B. natalensis stem extract in male Wistar rats; specifically, an increase in platelets and monocytes and a decrease in neutrophils, eosinophils, basophils, and lymphocytes. They also reported an increase in atherogenic index and of serum concentrations of cholesterol and triacylglycerols, and a decrease in high-density lipoprotein, pointing toward an increased risk of atherosclerosis with long-term consumption.⁶⁴

On the other hand, Hofheins et al. (2012) performed a placebo-controlled, double-blind clinical trial to assess the short-term safety of supplementation with an undefined extract of B. natalensis (ProLensis™; Sports Nutrition Research, Ltd.; Franklin Square, New York) in 32 healthy male adults by assessing changes in heart rate, blood pressure, and renal, hepatic, and hematological biomarkers.⁷⁰ Supplementation was found to be safe at 650 mg/day (28 days) of B. natalensis as no significant differences occurred between groups in 27 of the 29 markers. The only changes were a marginal increase in alkaline phosphatase compared to a parallel decrease in the placebo group and a decrease in creatinine compared to no change in the placebo group; however, these changes were within normative clinical limits.

ADULTERATION

Because of the wide use of Bulbine genus plant parts within South Africa, it is possible that materials of different related species of the same genus could be substituted.³ According to the African Herbal Pharmacopoeia, Bulbine frutescens gel can be intentionally adulterated or confused with the gel of the leaves of various Aloe species, and gel powder can be adulterated with various undeclared substances such as malic acid or lactic acid.⁷ A recent study quantifying levels of heavy metals in frequently used South African medicinal plants found very high levels, especially of aluminum and iron, in samples of B. natalensis obtained from open street markets.⁷¹

SUSTAINABILITY AND FUTURE OUTLOOK

The conservation status of the Bulbine species discussed in this article has not yet been assessed using the International Union for Conservation of Nature’s (IUCN’s) Red List Categories and Criteria. An early 1970s vegetation and botanical exploration of the Addo Elephant National Park (AENP) in Eastern Cape, South Africa, ranked B. frutescens as very common, B. natalensis as rare, and B. narcissifolia as present (but without an occurrence ranking).⁷² The current manual used by nature and field guides operating in AENP lists only B. abyssinica and B. frutescens, noting that roots of the latter are eaten by porcupines.⁷³ A survey conducted in 1999-2000 in the communities of Tsehlanyane and Bokong, Lesotho, found that wild populations of some commercialized plant species, including B. narcissifolia, were decreasing in the area due to overharvesting.⁷⁴

Already in the 1980s, B. latifolia was reported among plant species most frequently demanded by consumers in KwaZulu-Natal and with large quantities in regional trade.⁷⁵ In the early 2000s, it was reported that increased demand for B. latifolia corm in the Rastafarian community led to cases of illegal and destructive wild-harvesting practices.⁵ One study reported that B. latifolia was among the 10 most frequently sold plant species in Eastern Cape and observed to be unsustainably harvested at the study sites.⁷⁶ A 2009 dissertation on the use and conservation status of medicinal plants in Western Cape found B. frutescens to be the fifth most frequently used medicinal plant out of 112 plants in the survey.¹⁸ Although B. latifolia ranked 55th in that survey, a 2010 dissertation listed it among the most culturally important medicinal plants used by Rastafarian bush doctors of Western Cape. Wild harvesting of this species in the area of Knysna, Western Cape, and Eastern Cape was described in the 2010 dissertation as destructive, unsustainable,²⁶ and of conservation concern. A more recent study ranked B. latifolia among three medicinal substances that are important to trade in both Eastern Cape and Western Cape.⁷⁷

The market for ingredients and products made from South African species of Bulbine is growing beyond the region and entering Europe and the Americas in the form of cosmetics, personal care products, dietary supplements, natural health products, novel foods, and veterinary products. A recent use is topical application of B. frutescens leaf gel to soothe new tattoos, applying the anti-inflammatory and wound-healing properties of the gel. New global demand may not be satisfied by sustainably sourcing solely from wild populations. Bulbine species are relatively easy to cultivate, and innovative companies in South Africa are actively developing raw material production bases where voluntary standards for sustainable agriculture (e.g., organic) are being implemented. Furthermore, some sustainable wild-collection operations have entered into ABS agreements with indigenous communities. If the global market for southern African Bulbine species products continues to grow, it should be possible to scale up production through both sustainable agriculture and sustainable wild collection, in both cases within a context of ABS.

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