Buchu

Buchu (Agathosma betulina and Agathosma crenulata)

1. Identity, Taxonomy, and Natural Source

Buchu refers specifically to two species in the genus Agathosma (meaning "good fragrance") that were used in San-Khoi traditional medicine: Agathosma betulina (round or short leaf buchu) and Agathosma crenulata (oval or long leaf buchu). Agathosma is a genus of 150 species of flowering plants in the family Rutaceae indigenous to South Africa. The two species in commerce are now known as A. betulina (P.J.Bergius) Pillans and A. crenulata (L.) Pillans.

Agathosma betulina (previously Barosma betulina) is a flowering plant in the family Rutaceae, native to the lower elevation mountains of western South Africa, where it occurs near streams in fynbos habitats. It is an evergreen shrub growing to 2 m tall. The leaves are opposite, rounded, about 20 mm long and broad, glossy, and fragrant. The flowers are white or pale pink, with five petals; the fruit is a five-parted capsule which splits open to release the seeds. A. betulina is known by the common name round leaf buchu. The very similar plant Agathosma crenulata (previously Barosma crenulata) is known as the oval leaf buchu, and has been used for the same purposes.

Common names include boegoe, boechoe, boekoe, boggoa, bookoo, bouchou, bugu, buccho, bucchuu, bucco, buchu, bucku and buku. Earlier synonymous genus names for both species were Barosma, and the genus name Diosma was also historically applied to these plants. Taxonomically, the two species A. betulina and A. crenulata can be mainly distinguished by their leaf form. In addition, the cultivation of both species outside their natural habitat has resulted in the formation of hybrid plants.

Wild plants of A. betulina are still plentiful but are being harvested faster than they can reproduce. The threat of their becoming scarce has led to efforts to cultivate them. Rising demand for its essential oils and therapeutic products in the early 2000s led to overharvesting, threatening natural populations.

Common Forms and Preparations

Agathosma betulina is commercially marketed as fresh or dried leaves, tinctures, herbal water and essential oils. The dried leaves are harvested during the flowering season, and the oil can be obtained by steam distillation of the leaves. The essential oils and extracts of the leaves are used as flavoring for teas, candy, and a liquor known as buchu brandy in South Africa. Currently, the aromatic oils of these herbs are used in food preparation as flavoring and in the manufacture of perfumes. Dried buchu leaves have been used for medicinal purposes in tonics and as tablets or powders.

Buchu is an herbal product made from a group of aromatic herbs native to South Africa, the leaves of which were used in traditional Khoisan medicine to treat a variety of conditions and are currently used as buchu tea and as dried extracts.

2. Traditional and Historical Use

Indigenous Khoisan Use

Buchu has been utilised in southern Africa for millennia by the Khoi-San people indigenous to the region for a multitude of daily uses and a plethora of ailments. It is a renowned herb whose traditional benefits have made their way from Africa to the Western world. Traditionally, buchu has been used by the Khoisan for spiritual and medicinal purposes. Initially noted by the early settlers, knowledge and use of buchu spread to Europe and later to the United States.

Before moving on to discuss the records of traditional use of buchu made by early settlers, colonists, and explorers, it must be stressed that the knowledge of buchu and its medicinal properties by the Khoisan precedes written records. True to its description of being a multi-purpose species, Buchu has long been used as an antiseptic, and anti-inflammatory, for urinary problems including maladies such as haematuria, calculi, kidney disease and infections of the bladder, prostate and urethra.

Traditionally, the plant is used to treat cholera, indigestion, constipation, prostatitis, rheumatism, fever, respiratory and urinary tract infections, as well as for disinfecting wounds and relieving menstrual cramps. In South Africa, buchu and other similar plants are additionally used for stomach aches, joint pain, colds, and flu.

Dutch settlers in early times used Agathosma betulina, commonly called buchu, to make a brandy tincture. Buchu is an herb native to the Cape Province of South Africa which was a traditional medicine used by the San (Bushmen) and Khoikhoi (Hottentot) people who introduced the herb to early Dutch settlers, it being subsequently introduced into Europe and used to treat wounds, stomach ailments, arthritis and diseases of the bladder.

Entry into Western Medicine

Buchu, an Agathosma plant native to South Africa, was widely used due to its anti-inflammatory benefits in treating lower urinary tract infections and particularly cystitis. It was introduced to the European medical community in 1822 by London pharmacist Richard Reece (1775–1831) and became extremely popular; Helmbold's Extract Buchu was the bestselling patent medicine on the US market in 1865.

Buchu belongs to a handful of Southern African medicinal plants which reached international markets through colonial interests and entrepreneurship. It has been compendial since 1826 for its diuretic effects and use in the treatment of genito-urinary tract infections, however, became obsolete in the 20th century due to the sparsity of scientific evidence for its efficacy and the advent of antibiotics.

Buchu products quickly gained popularity, however, less so in Central Europe, but rather in the UK and the US. Patients were advised to take the buchu infusion in half pint quantities or a pint as buchu tea diluent. Buchu was also a popular remedy used for its anecdotal diuretic and carminative effects. Its popularity waned after the introduction of sulphonamides, but it is still sold today as a herbal remedy for treating lower urinary tract symptoms and UTI.

At one time, six combination products containing buchu leaf were on the German market. The German Commission E (Kommission E) verdict effectively dealt a "death sentence" to buchu products in Germany, as health claims could no longer be assigned to products and by 1994 medicinal products containing buchu had largely disappeared. The German drug database AMIce lists a total of 129 products containing buchu which are no longer licensed.

Nevertheless, buchu is still found in numerous herbal preparations, sold over-the-counter (OTC) or on the internet, for promoting health and treatment of urinary tract disorders.

3. Key Constituents and Active Compounds

Volatile (Essential Oil) Fraction

Buchu leaves contain from 1.5% to 3.5% volatile oil. Over 100 components exist in the oil, including diosphenol (the main component in distilled oil, also called buchu camphor, barosma camphor or 1-pulegone), limonene, menthone, pulegone, terpinen-4-ol and p-menthan-3-on-8-thiol (responsible for the aroma of the plant).

Apart from the common flavonoids rutin and diosmin, the foliage of A. betulina contains 1.5–2.5% of an essential oil of which the main constituents are menthone/isomenthone (29.83–60.0%), (ψ)-diosphenol/diosphenol (9.46–40.88%), limonene (11.6–17.0%), pulegone/isopulegone (7.0–34.1%) and both cis- and trans-8-mercapto-p-menthane-3-ones (±3%). The latter are said to contribute most to the characteristic odour of the oil, reminiscent of blackcurrants.

Isomenthone, menthone, diosphenol, pulegone, limonene, 4-hydroxydiosphenol, 8-mercapto-p-menthan-3-one, 8-acetylthio-p-menthan-3-one, 8-methylthio-p-menthan-3-one, pseudo-diosphenol, and 1-hydroxydiosphenol are the major marker compounds found in the essential oil profile of A. betulina. Agathosma crenulata was found to contain limonene, menthone, a trace of diosphenol, and large amounts of l-pulegone.

Lamparsky and Schudel isolated 8-mercapto-p-menthan-3-one, a sulphur-containing terpene responsible for the flavour and aroma of the oil. Kaiser et al. identified more than 120 components including the already known pulegone, diosphenol and 8-mercapto-p-menthan-3-one.

Non-Volatile Fraction: Flavonoids and Polyphenols

Flavonoids include diosmetin, quercetin, diosmin, quercetin-3,7-diglucoside and rutin. Chemical profiling of a methanol extract of A. betulina revealed the presence of hesperidin, rutin, and diosmin, all serving as non-volatile marker compounds. Flavonoids such as diosmin, rutin, kaempferol, quercetin, and hesperidin were identified in the methanol extract of buchu.

Other constituents include mucilage, resin, thiamine and sulfur compounds. Coumarins have been reported from other Agathosma species.

Chemical Differences Between Species

The two species are chemically distinct; for example, A. betulina contains quercetin-dimethyl ether-glucoside, while A. crenulata does not. The concentration of pulegone is higher in leaves from Agathosma crenulata than in those of Agathosma betulina. This chemical distinction is significant from both a quality-control and safety perspective (see Safety section below).

4. Proposed Mechanisms of Action

Buchu contains bioactive compounds such as diosphenol, menthone, and pulegone, which have demonstrated antibacterial, anti-inflammatory, and antioxidant properties in preclinical studies. No scientific evidence is available to justify buchu's herbal uses, but its diuretic and anti-inflammatory effects may be attributed to the volatile oil and flavonoids' irritant nature. Diosphenol, the flavonoids and terpinen-4-ol may contribute to the plant's diuretic activity, but this action of buchu teas is probably no greater than that of the xanthine alkaloids in coffee or tea.

With respect to anti-inflammatory pathways, in the 5-lipoxygenase (5-LO) assay the essential oil of both species revealed IC₅₀ values of 50.37 ± 1.87 μg/ml and 59.15 ± 7.44 μg/ml, respectively. In another study, 98% inhibitory activity was determined for 250 μg/ml of an ethanolic extract of A. betulina on cyclooxygenase (COX)-1 and a 25% inhibitory activity on COX-2.

Regarding antioxidant mechanisms, these flavonoids have antioxidant properties and guard the cells against the harmful unstable oxygen molecules. Recent in vitro studies with a commercial aqueous extract of buchu revealed significant inhibition of the respiratory burst of neutrophils and monocytes, reduction in the expression of adhesion molecules and inhibition of the release of IL-6 and TNF-α.

In the context of potential antidiabetic mechanisms, a computational study bioprospected the antidiabetic potential of metabolites in Agathosma betulina essential oil through analysis of their ability to inhibit protein tyrosine phosphatase 1B (PTP1B), a therapeutic diabetes target. Molecular dynamic simulation revealed that compounds linalylanthranilate (−20.18 kcal/mol) and γ-diosphenol (−16.49 kcal/mol) found in the oil exhibited stronger PTP1B inhibition than the reference compound ursolic acid (−15.98 kcal/mol). This study provides the first evidence that these Buchu oil compounds could potentially serve as PTP1B inhibitors to enhance insulin receptor sensitivity, showing promise for T2DM treatment. These findings are in silico only and have not been validated in living systems.

5. Scientific Evidence by Area of Use

5.1 Urinary Tract Infections and Urinary Health

Buchu leaf preparations have a long history of use in traditional herbal medicine as a urinary tract disinfectant and diuretic. Buchu was used by herbalists to treat urinary tract infections and inflammation, as well as inflammation of the prostate.

Evidence strength: No human clinical evidence. No meaningful scientific documentation of this or any other medicinal effect of buchu exists. Only double-blind, placebo-controlled studies can confirm efficacy, and buchu has only been studied through in vitro and animal studies. Recent pharmacological studies unfortunately could not alleviate the justified doubts regarding the traditional use of buchu for the treatment of urinary tract infection.

A review of the scarce pharmacological research revealed moderate antimicrobial activity for a leaf extract but not the essential oil of both species in the MIC assay. The results of the antimicrobial tests remain inconclusive because the tentative active coumarins and flavonoids inherent in the different extracts have not been identified, preventing a direct comparison. Surprisingly, the monoterpenes in the essential oils also failed to exert any antimicrobial effects they are known for. This was explained by the insolubility or reciprocal inactivation of the inherent ingredients in buchu by the ingredients in the growth medium. However, no further investigations were carried out to verify or deny these hypotheses.

Despite the lack of evidence, buchu is still used today in western herbal medicine for urinary tract ailments, cystitis or urethritis prophylaxis and prostatitis. Buchu is listed in the German Commission E Monographs to treat inflammation, kidney and urinary tract infections, and also is used as a diuretic, but the monograph explains that the plant's activity in these claimed uses has not been substantiated.

5.2 Anti-Inflammatory and Analgesic Effects

In a preclinical study, 98% inhibitory activity was determined for 250 μg/ml of an ethanolic extract of A. betulina on COX-1 and 25% on COX-2. Analgesic activity of an ethanolic extract of A. betulina was shown in mice. In vitro studies with a commercial aqueous extract of buchu also revealed significant inhibition of the respiratory burst of neutrophils and monocytes, reduction in the expression of adhesion molecules and inhibition of the release of IL-6 and TNF-α.

Evidence strength: Preclinical only (in vitro and animal studies). Other pharmacological assays devoted to the study of anti-inflammatory, analgesic and antioxidant effects must be considered to be of limited scientific value, which is attributed to the very small number of potential pharmacological targets that have been tested. No human clinical trials have been conducted on buchu's anti-inflammatory or analgesic effects.

5.3 Antioxidant Properties

Moderate antioxidant activity was determined for methanol:dichlormethane extracts of A. betulina and A. crenulata, and an aqueous extract of A. betulina showed a Trolox equivalent antioxidant capacity (TEAC) of 11.8 µM Trolox.

Evidence strength: Preclinical (in vitro) only. These findings have not been translated into human clinical research, and their biological relevance in humans is unknown.

5.4 Metabolic Effects: Antidiabetic, Anti-Obesity, and Antihypertensive

Recent in vitro studies with a commercial aqueous extract of buchu revealed increased uptake of glucose in a 3T3-L1 cell line. In diabetic rats, ingestion of aqueous buchu extract completely normalized the glucose level, and in rats receiving a high fat diet, consumption of aqueous buchu extract resulted in less weight gain and less intraperitoneal fat gain as well as reduction of elevated blood pressure to normal, associated with cardioprotective effects.

Evidence strength: Preclinical only (in vitro and animal studies); results inconclusive. Limitations in the hitherto conducted research lie in the undisclosed composition of the buchu extracts used and the difficulty in extrapolating data from animal studies to humans. Unless clinical trials are conducted, the reported positive anti-diabetic, anti-obesity, and anti-hypertensive effects of buchu water in rats remain questionable in humans. Even in rats the described effects remain inconclusive because of the missing information on extract composition. They also remain questionable as long as they are not further verified by independent research studies.

5.5 Other Traditional Uses Investigated Preclinically

Dried buchu leaves have been used for medicinal purposes in tonics and as tablets or powders to treat musculoskeletal pain, chronic arthritis, dyspepsia, edema, fever, the common cold, ulcers, irritable bowel syndrome, gout, prostatitis, prostatic hypertrophy, and sexually transmitted diseases. However, the efficacy of buchu has not been proven in prospective clinical trials for any of these conditions.

5.6 Overall Assessment of the Clinical Evidence Base

Despite preliminary research suggesting pharmacological potential regarding its antimicrobial, anti-inflammatory, and antioxidant properties, buchu has not retained its place in the mainstream market. This is unsurprising as many of the effects have only been observed at exorbitantly high doses in the respective animal models. Effects reported for aqueous buchu extracts from animal studies cannot be related to putative active ingredients either, as doses were too low for explaining any direct actions on pharmacological targets. At the same time, urgently needed clinical trials have not been conducted.

Health claims for buchu products need to be substantiated by randomized, double-blind and placebo-controlled studies. Only then can they be promoted for their true therapeutic potential.

6. Body Systems and Health Areas Associated with Buchu

• Urinary system: Buchu is a natural plant product often used as a dietary supplement, primarily associated with promoting urinary health. Traditionally used in South Africa, buchu is believed to treat various ailments, including urinary tract infections, inflammation, and digestive issues.
• Musculoskeletal system: Dried buchu leaves have been used to treat musculoskeletal pain and chronic arthritis.
• Gastrointestinal system: Buchu has been used as a stomach tonic, with carminative action for dyspepsia and digestive complaints.
• Metabolic/endocrine system: Principal proposed uses include anti-inflammatory activity, digestive health, antibacterial and antifungal action, gout, and high blood pressure.
• Reproductive/genitourinary system: Other uses include treatment of cystitis, urethritis, prostatitis, gout, leukorrhea and yeast infections.
• Cardiovascular system: Based on animal studies only, buchu has been investigated for potential antihypertensive and cardioprotective effects, as described above.
• Flavor/fragrance industry: Buchu is currently primarily used in the fragrance and flavour industry due to its sulphur-containing compounds and sensory properties.

7. Dosage Forms and Reported Dosages

There is no recent clinical evidence to guide dosage of buchu. Classical doses were from 1 to 2 g of the leaves daily. Dosage typically involves 1 to 2 grams of dried leaves taken three times a day, although safety concerns arise due to the presence of the liver toxin pulegone.

Preparations described in the historical and ethnobotanical literature include:

• Herbal infusion (tea): Patients were historically advised to take the buchu infusion in half pint quantities or a pint as buchu tea diluent.
• Tincture/brandy infusion: Dutch settlers commonly used A. betulina to make a brandy tincture.
• Vinegar preparation: In the early 1860s, infusions of Agathosma leaves were sold in bottles. Buchu vinegar was made by placing leaves and stalks in vinegar.
• Commercial forms: Agathosma betulina is commercially marketed as fresh or dried leaves, tinctures, herbal water and essential oils.

At this time there is not enough scientific information to determine an appropriate range of doses for buchu.

8. Safety Considerations

8.1 Pulegone: The Principal Toxicological Concern

Buchu contains the hepatotoxin pulegone, also known to be present in pennyroyal. Essential oils at high doses were found to be hepatotoxic in rats, affecting liver and uterine functions. This was attributed to R-(+)-pulegone which is known to be a hepatotoxic compound causing depletion of glutathione at high doses. Large oral doses have been found to deplete glutathione, which may be the mechanism of its toxic effects.

This depletion along with excess pulegone leads to centrilobular hepatocellular necrosis. Caution should be exercised with essential oil from A. crenulata that contains higher amounts of pulegone. Pulegone is not water soluble, thus this caution does not apply to water extracts.

The European Medicines Agency (EMA)'s public statement on the use of herbal medicinal products containing pulegone recommends an acceptable intake level of 0.75 mg/kg body weight/day based on data from a 2011 National Toxicology Program (NTP) study (three-month repeat-dose toxicity study).

Pulegone is classified as possibly carcinogenic to humans (Group 2B) by the WHO International Agency for Research on Cancer (IARC). In vitro genotoxicity studies were generally negative, with few (weak) positive findings in the Ames test. IARC regarded pulegone as non-genotoxic in vitro.

Pulegone has been approved by the US FDA for use in the food industry (with a FEMA GRAS status) and is listed among the authorized synthetic flavouring substances (CFR 21–172.515).

8.2 Gastrointestinal and Renal Irritation

Essential oil components diosmin and pulegone can cause gastrointestinal and renal irritation. Buchu can cause stomach and kidney irritation and can be an abortifacient. It can also induce increased menstrual flow. Buchu is not recommended during pregnancy.

8.3 Uterine and Reproductive Effects

Documented adverse effects include uterine stimulant effects. Pulegone is known to be hepatotoxic (depletes glutathione and leads to hepatocellular necrosis), an abortifacient, and to increase menstrual flow; therefore, use is not recommended during pregnancy.

8.4 Hepatotoxicity in Humans

Buchu preparations have not been linked to instances of serum enzyme elevations or clinically apparent liver injury with jaundice. Hepatotoxicity from buchu must be quite rare if it occurs at all. In the presence of liver injury, stopping use of buchu promptly, even when used as an herbal tea, is warranted. A single published case report exists: a 52-year-old man developed jaundice one month after starting buchu and rooibos herbal tea.

8.5 Cytotoxicity Data

In an MTT cellular viability assay, several dilutions of methanol-dichloromethane extracts displayed different degrees of cellular inhibition, but extracts of A. betulina and A. crenulata were not toxic at concentrations up to 100 μg/ml. The essential oils of both species proved to exhibit higher toxicity at the concentrations tested, both having IC₅₀ values of <0.0001 μg/ml.

8.6 Drug Interactions

Formal contraindications have not yet been identified. Documented adverse effects include uterine stimulant effects. No well-documented drug–drug interactions have been reported in the peer-reviewed literature for buchu preparations. The diuretic potential of buchu, if confirmed, could theoretically potentiate the effects of antihypertensive or diuretic drugs, but this has not been studied in humans.

8.7 Regulatory Status

The German Commission E published a "negative" monograph for buchu: "Since the claimed effectiveness has not been documented, the application of buchu leaf cannot be recommended. The use of buchu leaf as an aroma or flavor corrigent in tea mixture is acceptable," based on the absence of toxicological and clinical data. It has been compendial since 1826 for its diuretic effects and use in the treatment of genito-urinary tract infections, however, became obsolete in the 20th century due to the sparsity of scientific evidence for its efficacy and the advent of antibiotics.

References

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