Honeybush (Cyclopia spp.): A Comprehensive Reference
1. Identity, Taxonomy, and Botanical Characteristics
Botanical Classification
Honeybush (genus Cyclopia) is a flowering plant in the legume family named for the honey-like aroma of its flowers. The genus Cyclopia (Fabaceae family) includes a number of shrubs endemic to the Cape Fynbos region of South Africa. There are 24 Cyclopia species used to brew honeybush tea, a unique South African herbal beverage with a pleasant taste and flavor.
The honeybush plant is unique to South Africa; exemplary species include Cyclopia genistoides, Cyclopia longifolia, Cyclopia maculata, Cyclopia subternata, and Cyclopia intermedia. The most common of these plants is Cyclopia intermedia E. Mey., used together with other Cyclopia species (mainly C. subternata and C. sessiliflora) to manufacture the honeybush herbal tea, which has been produced in South Africa roughly since the beginning of the 19th century.
The term "honeybush" applies to several different species of Cyclopia. These plants are all woody, fynbos shrubs with golden yellow stems and hairless, stalkless leaves. One key species, Cyclopia subternata Vogel (Family: Fabaceae; Tribe: Podalyrieae), is an endemic South African fynbos plant that traditionally has been used as a herbal tea called honeybush after "fermentation," a high-temperature oxidative process required to produce its characteristic sweet aroma and flavor.
Honeybush was first documented in the 1700s and used for medicinal purposes by the early settlers in the Cape Colony. It was later named by Swedish botanist Carl Peter Thunberg, when he discovered it while on a field trip in the Cape in the 1770s.
Common Names
Honeybush (Cyclopia species) is a fragrant fynbos shrub known for its sweet, honey-like scent and delightful flavour when brewed into tea. The Khoekhoen and Bushman people recognised its value long before it gained global recognition. It is known colloquially as "heuningtee," meaning "honey tea," aptly capturing its natural sweetness.
Forms and Preparations
The shoots (leaves and twigs) of the honeybush plant are typically harvested and chopped or shredded. Thereafter, the plant material can be used as-is in "green" form, which is lighter in color and less sweet, or subjected to a fermenting process to produce "red" honeybush, which enhances the sweetness and produces a rich amber color. The main topics of product development have included the preparation of phenolic-rich extracts from green honeybush, as well as spray-dried extract powder as a food ingredient, and "instant" powders and ready-to-drink beverages as final consumer products. Honeybush products range from loose teas and iced teas to honeybush gin and cosmetics.
Fermentation leads to quantitative changes in the phenolic composition of the soluble solids, with the total polyphenol content reduced from 32.4 to 17.5%. Consequently, unfermented plant material should preferentially be used for preparation of extracts, as fermentation significantly lowered antioxidant activity of all species, except in the case of C. genistoides, where the ability to inhibit lipid peroxidation was not affected. Unfermented plant material also retained the highest concentration of mangiferin.
2. Traditional and Historical Use
Indigenous Khoisan Use
The First Nations, Khoekhoen and Bushman (San) people, indigenous to the arid landscapes of Southern Africa, have a rich history intertwined with the natural world. Among the treasures of their traditional knowledge is their use of honeybush, a plant native to their ancestral lands. For generations, these indigenous communities have harnessed the medicinal and culinary properties of honeybush tea, passing down their wisdom through oral traditions.
The Khoisan of the South African Cape were also using the tea for treatment of coughs and other upper respiratory symptoms associated with infections. As traditional medicine, honeybush was utilized to treat digestive problems, promote lactation, and cure skin rashes. In addition, it functioned as a restorative and an expectorant in chronic catarrh and pulmonary tuberculosis, but was later also known for its anti-inflammatory, antioxidant, antimutagenic, phytoestrogenic, and antimicrobial effects with relative low toxicity.
Colonial-Era Documentation
In 1814, the British purchased the Cape Colony from the Dutch, and English became the official language a few years later, helping to spread knowledge of South Africa to England and America. In King's American Dispensatory of 1898, under the heading of tea, honeybush is already listed as a substitute, with reference to a report from 1881 indicating use of honeybush as a tea in the Cape Colony of South Africa.
Honeybush infusions have been noted historically as a tonic for colds and influenza, catarrh, and pulmonic tuberculosis, and became well-known for its purported effectiveness in alleviating menopausal symptoms in women. The plant is also used to manufacture a sweet herbal infusion used for restorative properties such as soothing coughs and alleviating bronchial complaints including tuberculosis, pneumonia, and catarrh.
Industrialization
Honeybush tea, one of the traditional South African herbal teas with a long history of regional use, remained a cottage industry until the mid-1990s when researchers were instrumental in the development of a formal agricultural and agro-processing industry. It is one of the few indigenous South African plants that made the transition from the wild to a commercial product during the past 100 years. Research activities during the past 20 years included propagation, production, genetic improvement, processing, composition, and the potential for value-adding.
3. Phytochemistry: Key Constituents and Active Compounds
Overview of Phenolic Profile
The phenolic profile of honeybush varies qualitatively and quantitatively depending on the Cyclopia species. Major phenolic constituents belong to xanthone, benzophenone, flavanone, flavone, and dihydrochalcone subclasses. Extracts from different honeybush species vary in chemical composition; however, the main active constituents of honeybush have been reported to be mangiferin and hesperidin, and there are some data available with regard to their bioavailability and their ability to cross the blood-brain barrier.
Xanthones
Mangiferin (C-glucosyl xanthone) and its isomer isomangiferin are among the most extensively studied phenolics in honeybush. Three major constituents of the leaves were identified as mangiferin (a xanthone) and glycosides of the flavanones hesperetin and isosakuranetin. Mangiferin, isomangiferin, hesperidin and vicenin-2 — the main honeybush constituents — are highly pharmacologically active polyphenols, known also for their antioxidant and protective effects on cells. Foremost is the potential of Cyclopia spp., especially C. genistoides, for the production of an antioxidant product high in mangiferin content. The latter and its sustainability make C. genistoides an attractive source of mangiferin.
Flavanones, Flavones, and Isoflavones
The processed leaves and stems of Cyclopia intermedia contain 4-hydroxycinnamic acid, the isoflavones formononetin, afrormosin, calycosin, pseudobaptigen, and fujikinetin, the flavanones naringenin, eriodictyol, hesperitin, and hesperidin, the coumestans medicagol, flemichapparin, and sophoracoumestan B, the xanthones mangiferin and isomangiferin, the flavone luteolin, and the inositol (+)-pinitol.
Unfermented leaves of C. subternata contain pinitol, shikimic acid, p-coumaric acid, 4-glucosyltyrosol, epigallocatechin gallate, the isoflavone orobol, the flavanones hesperedin, narirutin, and eriocitrin, a glycosylated flavan, the flavones luteolin, 5-deoxyluteolin, and scolymoside, the xanthone mangiferin, and the flavonol C-6-glucosylkaempferol.
Continued investigations into the phenolic content of the leaves and stems of C. intermedia yielded tyrosol and a methoxy analogue, along with five glycosylated flavonols, two isoflavones, four flavanones, two additional isoflavones, and two flavones.
Benzophenones and Dihydrochalcones
Apigenin-6,8-di-C-glucoside (vicenin-2) and diosmetin-7-O-rutinoside (diosmin) have been identified in C. genistoides and other Cyclopia species, with vicenin-2 confirmed using an authentic reference standard. Diosmin has been identified for the first time in Cyclopia spp. Tentatively identified dihydrochalcones include 3-hydroxyphloretin-3',5'-di-C-hexoside and phloretin-3',5'-di-C-glucoside.
Pinitol
Pinitol ((+)-3-O-methyl-D-chiro-inositol) is a cyclitol present in significant quantities in honeybush. Pinitol exerts an insulin-like effect, as published in the British Journal of Pharmacology (2000; 130(8):1944–1948). The presence of pinitol has been connected to honeybush's traditional use as a remedy for respiratory ailments, as pinitol is recognized as a potential expectorant compound.
Effect of Processing on Composition
Polyphenolic contents in honeybush extracts differ depending on the season, the plant material used (fermented or nonfermented), as well as the kind of extraction solution employed. HPLC-DAD analysis indicates the highest mangiferin contents in ethanol, acetone, and n-butanol extracts, while in water extracts hesperidin is the dominant compound.
4. Established Mechanisms of Action
Antioxidant Activity
Due to their phenolic composition, honeybush extracts have been shown to possess antioxidant activities which are of great importance and interest in the research of oxidative stress-related diseases. The antioxidant properties of honeybush extracts, estimated with FRAP and DPPH tests, indicate strong antioxidant activity, similar to ascorbic acid for the acetone extract in both tests.
Anti-Inflammatory Mechanisms
Mangiferin and hesperidin, major polyphenolic constituents of honeybush, were shown to inhibit the inflammatory response by suppressing cytokines as well as other pro-inflammatory mediators such as adhesion molecules and prostaglandins in vitro and in vivo. Naturally occurring plant polyphenols can modulate UVB-induced inflammatory and apoptotic signalling pathways associated with oxidative stress and DNA damage in skin.
Apoptotic and Cancer-Related Mechanisms
Mangiferin has been shown to exhibit anti-diabetic, antiviral, immunomodulatory, radioprotective, hepatoprotective, anti-inflammatory, vasodilatory, and antiplatelet activities under different experimental conditions. Mangiferin also has effects on metalloproteinase-7 (MMP-7) and -9, the epithelial-mesenchymal transition (EMT), the β-catenin pathway, and inhibits proliferation and suppresses the migration and invasion of breast cancer cells. Studies in the human acute myeloid leukemia cell line HL-60 showed that mangiferin induces apoptosis by suppressing entry of nuclear NF-κB.
Higher hesperidin content in non-fermented "green" extracts correlates with their higher cytotoxicity in HeLa cell assays compared to fermented extracts. Mangiferin had a modulatory effect on the apoptotic effects of hesperidin. Quantitative PCR analysis of hesperidin-induced changes in apoptotic gene expression indicated that two death receptor pathway members, TRADD and TRAMP, were upregulated. The results suggest that hesperidin mediates apoptosis in HeLa cells through the extrinsic pathway for programmed cell death.
Phytoestrogenic Mechanisms
The genus Cyclopia contains phytoestrogenic compounds. An extract from C. subternata, SM6Met, displays three desirable estrogenic attributes for future development of a phytoestrogenic nutraceutical, namely, ERα antagonism, ERβ agonism, and antagonism of E2-induced breast cancer cell proliferation.
Metabolic and Mitochondrial Mechanisms
A crude polyphenol-enriched fraction of Cyclopia intermedia (CPEF) induced uncoupling protein 1 (UCP1, 3.4-fold) and peroxisome proliferator-activated receptor alpha (PPARα, 2.6-fold) expression in brown adipose tissue of db/db mice. In the liver, CPEF induced PPARα expression (2.2-fold), accompanied by a 31.9% decrease in fat droplets. Molecular docking analysis revealed that hesperidin and neoponcirin had the highest binding affinities for UCP1 and PPARα, respectively.
Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts at a concentration range of 0.1–1 ng/ml had a beneficial effect on bioenergetics, increasing ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides showed a protective effect by rescuing bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H₂O₂ for 3 hours).
Skin-Related Enzymatic Inhibition
Significant hyaluronidase inhibition was observed for ethanol, acetone and water extracts (IC₅₀ values of 10.99, 13.21, and 14.62 μg/mL, respectively). Collagenase activity was inhibited effectively by honeybush acetone extract (IC₅₀ 42.5 ± 1.05 μg/mL). The wound healing properties of the honeybush extracts, estimated in vitro in human keratinocytes (HaCaTs), were indicated for water and ethanol extracts.
5. Scientific Evidence by Area of Health Application
5.1 Antioxidant and Oxidative Stress Protection
Evidence level: Predominantly in vitro and animal; limited clinical human data.
Antioxidant activity of honeybush extracts has been confirmed by in vitro and in vivo tests. Extracts obtained from Cyclopia plants are rich in polyphenols, including xanthones (mangiferin and isomangiferin), flavanones (hesperidin), flavones and isoflavones, and as such exhibit substantial antioxidative and antimutagenic activity. The majority of published antioxidant studies use cell-free or cell-based models; robust randomized controlled trials (RCTs) in humans measuring honeybush-specific antioxidant outcomes are lacking.
5.2 Antimutagenicity and Chemoprotection
Evidence level: In vitro and animal studies; no human RCTs.
Antimutagenic activity of aqueous extracts of the South African herbal teas, Aspalathus linearis (rooibos) and Cyclopia spp. (honeybush), was compared with that of Camellia sinensis (black, oolong and green) teas in the Salmonella mutagenicity assay using aflatoxin B₁ (AFB₁) and 2-acetylaminofluorene (2-AAF) as mutagens. The herbal teas demonstrated protection against both mutagens in the presence of metabolic activation, with the exception of "unfermented" C. genistoides against 2-AAF, which either protected or enhanced mutagenesis depending on the concentration. Aqueous extracts of honeybush have been reported to have antimutagenic activities against 2-acetylaminofluorene- and aflatoxin B1-induced mutagenesis and chemoprotective properties against cancer. Cyclopia intermedia, used in a skin cancer study, showed promise for inhibition of tumour development. These findings are derived from laboratory models; no human clinical trials on cancer prevention with honeybush have been published.
5.3 Breast Cancer and Estrogen Receptor Biology
Evidence level: In vitro and in vivo (animal); no human clinical trials.
Extracts of Cyclopia species have been shown to possess phenolic compounds that exhibit phytoestrogenic and chemopreventive activities against breast cancer development and progression. Several in vitro and in vivo studies have already shown that several Cyclopia species have antimutagenic, antioxidant, anticancer, and also phytoestrogenic properties. Women undergoing the menopausal transition have shown great interest in phytoestrogenic nutraceuticals as an alternative to conventional hormone replacement therapy (HRT) due to the disquieting side-effect profile of HRT, with breast cancer as a primary adverse outcome. Studies have shown that phytoestrogen consumption cannot only alleviate menopausal symptoms, but may also lower the incidence of osteoporosis, cardiovascular disease, and hormone-dependent cancers, such as breast cancer. No human RCTs specifically testing honeybush extract for breast cancer outcomes have been published at the time of this writing.
5.4 Menopausal Symptoms
Evidence level: Mechanistic and preclinical; no published human RCTs specifically for honeybush and menopausal symptoms.
Other potential applications for honeybush include the alleviation of menopausal symptoms and lowering of blood glucose levels. Extracts of unfermented and fermented plant material of a number of species were initially screened for phytoestrogenic activity. The isoflavone content of honeybush (including formononetin and calycosin) alongside demonstrated ERα antagonism and ERβ agonism in cell-line models lends biological plausibility to menopausal applications. However, the evidence remains at the preclinical stage and lacks confirmation from well-designed human trials.
5.5 Metabolic Syndrome, Obesity, and Diabetes
Evidence level: Animal and in vitro studies; no human clinical trials specifically for honeybush.
A crude polyphenol-enriched fraction of Cyclopia intermedia (CPEF) reduced lipid content in 3T3-L1 adipocytes and inhibited body weight gain in obese, diabetic female leptin receptor-deficient (db/db) mice. The antidiabetic and anti-obesogenic potentials of different extracts (dichloromethane, ethyl acetate, ethanol, and aqueous) of the red honeybush (Cyclopia genistoides) tea were investigated in vitro and ex vivo. Other biological activities proven by a number of in vitro studies include: antimutagenic, anti-inflammatory, anti-angiogenic, and hypoglycemic effects. These findings remain preclinical; there are no published human trials on honeybush for diabetes or obesity management.
5.6 Skin Health, Photoprotection, and Anti-Aging
Evidence level: In vitro and animal studies, with one small randomized controlled clinical trial.
Rooibos and honeybush possess antioxidant and anti-inflammatory properties that have been implicated in the photoprotective and anti-carcinogenic mechanisms in skin. Honeybush polyphenolic compounds work as a shield against skin degradation caused by UV radiation. In addition, the plant is effective in the inhibition of wrinkle formation and the skin aging process.
A human clinical study was reported in the literature: A randomized, double-blinded, placebo-controlled study evaluated the efficacy and safety of fermented honeybush (Cyclopia intermedia) extract (HU-018) for skin rejuvenation. One hundred and twenty Korean subjects with crow's feet wrinkles were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo for 12 weeks. Wrinkles were evaluated using JANUS® and PRIMO pico®. Skin elasticity, hydration, and transepidermal water loss were measured. Global skin wrinkle grade was significantly improved in both low-dose and high-dose groups compared to the placebo group, as well as for skin hydration and elasticity. This single RCT provides preliminary positive evidence for oral honeybush extract supplementation on skin parameters; independent replication is needed before definitive conclusions can be drawn.
Semi-solid formulations containing either Cyclopia maculata (2%) or Cyclopia genistoides (2%) underwent accelerated stability studies. Membrane release studies, Franz cell skin diffusion and tape stripping studies were performed. Antioxidant potential was determined with the 2-thiobarbituric acid assay and clinical efficacy studies were performed to determine the formulations' effect on skin hydration, scaliness, and smoothness after 2 weeks of treatment on the volar forearm. The formulations were unstable over 3 months. These topical formulation studies produced inconclusive permeation data, limiting conclusions about topical efficacy.
5.7 Neuroprotection and Mitochondrial Function
Evidence level: In vitro only.
Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress- or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts at a concentration range of 0.1–1 ng/ml had a beneficial effect on bioenergetics, increasing ATP production, respiration, and mitochondrial membrane potential. The aqueous extracts of C. subternata and C. genistoides showed a protective effect under oxidative stress conditions. These findings are limited to cell culture and cannot be extrapolated to human neurological outcomes without further research.
5.8 Respiratory Health
Evidence level: Traditional use documentation only; no clinical trials.
Honeybush infusions have been noted as a tonic for colds and influenza, catarrh, and pulmonic tuberculosis. The traditional use of the tea for treating cough may be explained, in part, by its content of pinitol. There are no published clinical trials evaluating honeybush for respiratory conditions.
6. Body Systems Associated with Honeybush
- Integumentary system: Photoprotection, anti-aging, wound healing, inhibition of skin-degrading enzymes (collagenase, elastase, hyaluronidase, tyrosinase).
- Endocrine/reproductive system: Phytoestrogenic activity; ERα antagonism and ERβ agonism; potential for menopausal symptom support.
- Metabolic/endocrine system: Preclinical antidiabetic effects; pinitol-mediated insulin-like activity; anti-obesogenic effects in animal models.
- Immune/inflammatory system: Suppression of pro-inflammatory cytokines, adhesion molecules, and prostaglandins; antimutagenic effects against dietary mutagens.
- Neurological system: In vitro mitochondria-protective effects in neuroblastoma cell models.
- Respiratory system: Traditional use for coughs, catarrh, and pulmonary conditions; potential expectorant activity attributed to pinitol.
- Digestive system: Traditional use for digestive complaints; antimicrobial properties relevant to gut pathogens documented in vitro.
7. Dosage Forms and Reported Dosages
Honeybush is available in several dosage forms, and the dosages reported in studies vary by application:
- Herbal tea infusion (oral beverage): Honeybush infusions are characterized by a honey-like flavour, low tannin content, and absence of caffeine. No standard therapeutic dose has been established in clinical trials for the infusion form.
- Standardized oral extract capsule/tablet (skin aging study): 120 Korean subjects were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo for 12 weeks.
- Polyphenol-enriched extract (rat safety study): Polyphenol-enriched extracts (PEEs) of Cyclopia subternata and Cyclopia genistoides were fed at 2.5 g/kg feed to male Fischer rats for 28 days, while PECsub was also fed for 90 days.
- Topical semi-solid formulation (skin study): Semi-solid formulations containing either Cyclopia maculata (2%) or Cyclopia genistoides (2%) were tested for skin hydrating effects.
- Cell-culture studies: The most beneficial concentrations of honeybush extracts in neuroblastoma bioenergetics studies were found to be as low as 0.1 and 1 ng/ml.
No universally accepted therapeutic dose for any health indication has been established in human clinical medicine. The oral supplemental doses evaluated in clinical research to date range from 400 mg/day to 800 mg/day of a standardized extract.
8. Safety, Toxicology, and Drug Interactions
General Safety Profile
Honeybush infusions are gaining popularity due to their characteristic honey-like flavour, low tannin content, absence of caffeine, and potential health effects. Honeybush contains various antioxidants and very low tannin content, and no caffeine. The absence of caffeine and low tannin content are consistent with a favorable tolerability profile for habitual tea consumption.
Preclinical Toxicology Studies
Interest in Cyclopia spp. as a source material for production of polyphenol-enriched extracts (PEEs) for the food ingredient and nutraceutical markets requires investigation of their safety. PEEs of Cyclopia subternata and Cyclopia genistoides were fed (2.5 g/kg feed) to male Fischer rats for 28 days, while PECsub, having the highest total polyphenol content and antioxidant activity, was also fed for 90 days. Their dietary intake did not significantly affect body weight gain or relative liver and kidney weight.
Polyphenol interactions reduced serum iron levels after chronic feeding of 90 days. This finding is noteworthy as it suggests that long-term consumption of concentrated honeybush polyphenol extracts may have an impact on iron bioavailability, though this was observed in animal models and has not been confirmed in human studies.
Phytoestrogenic Considerations
Honeybush contains several classes of phytoestrogens, including isoflavones (formononetin, calycosin) and coumestans. An extract from C. subternata demonstrates ERα antagonism, ERβ agonism, and antagonism of E2-induced breast cancer cell proliferation. The estrogenic activity of honeybush extracts, while potentially beneficial in certain contexts, has not been studied in populations for whom estrogen-modulating substances may carry risk (e.g., individuals with hormone-sensitive conditions), and relevant human safety data are absent.
Bioavailability Limitations
Despite high polyphenolic contents in extracts, low intestinal absorption is a limiting factor. The compounds may be used as antioxidants in dermatology and in topical ways of drug administration, especially due to the limited oral absorption of both polyphenols. This pharmacokinetic limitation is relevant to interpreting the clinical significance of in vitro findings.
Compositional Variability
A major disadvantage of using plant material is the high variability in chemical composition and antioxidant properties, which depends not only on the changing environmental conditions, but also on the time of harvest, as well as storage and transport conditions. This variability makes dose standardization challenging and complicates assessment of consistent pharmacological effects across commercial products.
Summary of Evidence Gaps
The overall body of human clinical evidence for honeybush is very limited. Most published research consists of in vitro cell studies and animal models. Increased consumption and popularity of honeybush has come along with increasing research interest in order to reveal new bioactivities and to examine its potential use as a nutraceutical and functional food. Several in vitro and in vivo studies have shown that several Cyclopia species have antimutagenic, antioxidant, anticancer, and phytoestrogenic properties. However, with the exception of one randomized placebo-controlled trial in skin rejuvenation, no large-scale human clinical trials have confirmed any of these effects in human populations. Claims about efficacy for any specific health condition therefore remain preliminary.
References
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