IngredientsBotanical name: Buxus sempervirens L. Common names include box, boxtree, buksbom (Danish), buis (French), Buchsbaum (German), and boj (Spanish). In English the plant is known as common box, European box, or boxwood; Buxus colchica of western Caucasus and B. hyrcana of northern Iran and eastern Caucasus are commonly treated as synonyms of B. sempervirens.
The scientific name Buxus sempervirens originates from the Latin buxus, derived from the ancient Greek pyxos (πύξος), the name the Greeks gave to boxwood. The specific epithet sempervirens alludes to its evergreen nature.
Boxwood is an evergreen shrub or small tree belonging to the family Buxaceae. The genus Buxus is composed of various species including B. sempervirens, B. papillosa, B. microphylla, B. hildebrandtii, and B. hyrcana.
Buxus sempervirens is native to western and southern Europe, northwest Africa, and southwest Asia, from southern England south to northern Morocco, and east through the northern Mediterranean region to Turkey. The plant is now cultivated worldwide. In the wild, boxwoods grow in open, rocky areas and can grow as large as small trees; they are characteristic shrubs of sub-Mediterranean Europe.
Common boxwood is a woody evergreen shrub growing to a height of 5 meters, densely branching, with a trunk up to 20 centimeters in diameter. The twigs or branches are densely leafed and the leaves are dark green, ovate, smooth, thick and leathery. The plant blooms in April and May with yellow-green, tiny flowers. The fruit is a three-lobed capsule containing 3 to 6 seeds. The plant has a dense root system, which forms a mesh of thin, yellow roots. In ideal conditions, boxwoods can live anywhere from 70–150 years.
The leaves, bark, and wood have been used as medicine. The leaves are collected before flowering in early spring and dried for use in extracts; they have an unpleasant odor and a bitter, astringent taste. The bark is shredded and dried for use in decoction.
Boxwood is a shrub; people use chemicals (extracts) from the leaf of boxwood to make medicine, though the leaf itself should not be used directly as medicine. The principal standardized preparation used in clinical research is SPV30, an ethanolic extract of B. sempervirens. The study preparation SPV30 was tested at doses of 990 mg/d and 1,980 mg/d. In the context of gemmotherapy — a phytotherapeutic approach using embryonic plant tissues — this type of phytotherapy is called gemmotherapy, and the corresponding plant-derived products are named gemmotherapy extracts (GTEs). Few studies address extracts from meristematic tissues such as buds, young shoots, and root tips, despite their potentially superior bioactive composition.
The common boxwood has a long historical and cultural trajectory. Since classical antiquity, Greeks and Romans used it to delineate gardens and decorate public spaces. The common box was first utilized for its aesthetic values by the Egyptians in 4000 B.C.
B. sempervirens was not known for its medical use until the beginning of the 1600s. After this it was found that the leaves (containing alkaloids, oils and tannin), the bark (containing chlorophyll, wax, resin, lignin and minerals) and the oil from the wood had a medical effect.
After it entered medical use, boxwood was employed to treat gout, urinary tract infections, intestinal worms, chronic skin problems, syphilis, hemorrhoids, epilepsy, headache, and piles, and also had a reputation for curing leprosy, rheumatism, HIV, fever, and malaria. Historically, boxwood has been used as a sedative and as a treatment for syphilis, rheumatism, epilepsy, and malaria.
In the medicinal field, the species was once used as an alternative to quinine in the treatment of malaria between the 17th and 19th centuries. The leaves were formerly used in place of quinine as a fever reducer. Among its attributed effects, boxwood was considered sudorific, antirheumatic, antiseptic, antimalarial, and cholagogue; these alkaloids were responsible for the sudorific properties of the plant, formerly used against malarial fever.
Buxus sempervirens is known in the Mediterranean area as a plant with antimalarial activity. Ethnomedicinal studies show that populations from geographically isolated areas have independently acquired knowledge about the therapeutic use of box plants against malaria. The form of application reported in independent studies is a decoction of the leaves.
In folk medicine, Buxus sempervirens is used to treat rheumatism, arthritis, bile duct infections, diarrhea, fever, and skin ulceration. The crude extracts of various Buxus species have been reported to have applications in traditional medicine to cure fatigue, rheumatism, malaria, depression, and skin infections. For the liver, boxwood was considered a bitter tonic liver and cholagogue remedy, believed to benefit the operation of the gallbladder and favor bile expulsion; these properties were considered useful against biliary dyskinesia and heavy digestion, but the plant was not recommended in people with gallstones.
Because of the many adverse side effects of the plant and the availability of more appropriate herbs to treat the same ailments, the medical use of boxwood has almost ceased.
Phytochemical studies on various plants of the genus Buxus have resulted in the isolation of over 200 new steroidal alkaloids. A few of these alkaloids have shown interesting biological activities, including antibacterial, antimycobacterial, and other properties.
Cyclobuxine is an alkaloid found in Buxus sempervirens and is derived from the cholesterol skeleton. Alkaloids can be found in the whole plant, but the largest amounts of alkaloids (up to 3%) including cyclobuxine are found in the leaves and bark.
The plant contains numerous steroidal alkaloids: buxine, parabuxine, parabuxinina, cloprotobuxine, buixidine, buxenone, buxandrine, buxinamine, bebeerine, bebbuxine, buxalphine, buxamine, buxaminol, buxanine, buxatine, cyclovirobuxine-D, and related derivatives. The main toxins in boxwood are various steroidal alkaloids, with buxine identified as the primary alkaloid; other alkaloids such as buxinidine, cyclobuxine, and cycloprotobuxine are also found.
Buxus alkaloids are a unique steroid-triterpenoid class of alkaloids having a pregnane-type basic skeleton with a 4-dimethyl-9β,10β-cycloartenol system and a C-20 degraded side chain; this type of alkaloid has shown interesting pharmacological activities such as antimalarial, antituberculosis, and anti-HIV effects.
The cyclobuxine molecule has a substitution pattern at C-4 and C-14 which is intermediate in the biogenetic scheme between lanosterol- and cholesterol-type steroids. The biosynthetic precursor of cyclobuxine is cycloartenol, synthesized by a side chain degradation of the 17β-side chain.
The leaves of boxwood contain essential oil, tannins, and the alkaloids buxine (chiefly responsible for the bitter taste), parabuxine, and parabuxonidine. The bark contains chlorophyll, wax, resin, lignin, and minerals such as potassium, magnesium, phosphorus, iron, and silicium. B. sempervirens contains steroidal alkaloids such as cyclobuxine, and also flavonoids.
B. sempervirens has been used ethnopharmacologically against a wide variety of diseases due to it containing nor-triterpene alkaloids of the nor-cycloartane type; over a period of one year (February 2019–January 2020), shoot tips of a box hedge were harvested every month to create a seasonal alkaloid profile. Such data underscore that the pharmacological potency of boxwood preparations can vary depending on harvest timing and plant part selected.
Alzheimer's disease is a progressive neurodegenerative disease wherein a progressive loss of cholinergic synapses occurs in the hippocampus and neocortex. Decreased concentration of the neurotransmitter acetylcholine (ACh) appears to be a critical element in the development of dementia, and the most appropriate therapeutic approach is to restore acetylcholine levels by inhibiting both major forms of cholinesterase: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Buxus alkaloids have shown significant potential in the area of enzyme inhibition activities; steroidal bases isolated from B. hyrcana exhibit enzyme inhibitory activities including GST, AChE, and BChE inhibition.
As cyclobuxine is presumed to interfere in the pathway resulting in HIV/AIDS, it is the most understood pharmacological mechanism. The antiretroviral effect of SPV-30 was first identified by Durant — it is an herbal extract containing cyclobuxine from B. sempervirens. The nucleic interactions of cyclobuxine have been studied; it was found that cyclobuxine has a biphasic effect on the stability of nucleic acids: at low concentrations, cyclobuxine has a favorable stabilizing effect on the original conformation of DNA and other polydeoxynucleotides, while at higher concentrations it has an adverse destabilizing effect.
Extracts of Buxus sempervirens displayed high antimalarial and anti-BChE effects as well as quite high iron-chelation capacity; it was suggested that active antimalarial extracts may show their effects through the mechanism of BChE inhibition combined with iron-chelation ability. The cycloartane alkaloid O-tigloylcyclovirobuxeine-B was isolated and evaluated for antiplasmodial activity, yielding an IC50 of 0.455 µg/mL against Plasmodium falciparum; this compound is thus most significantly responsible for the high potency of the crude extract.
Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a, and BT-20 breast cancer cell lines, concomitant with cyclin D1 downregulation. Results showed that the Buxus extract has specific cytotoxic effects toward cancer cell lines by mainly inducing a decrease in cyclin D1; the extract induced autophagic cell death and apoptosis in breast cancer cells tested, and a caspase-3-independent apoptosis in the aggressive MCF10CA1a cells.
The antiproliferative effects of a hydroalcoholic extract of B. sempervirens (BSHE) involved cell cycle regulators such as p21 and cyclin B1, and among apoptosis markers, BSHE decreased (30–40% at 48 h) the expression of the antiapoptotic protein survivin. It was concluded that BSHE impairs autophagic flow with arrest of proliferation and death in both fibroblasts and cancer cells, the latter being much more sensitive to these effects.
The alkaloids of boxwood have cardiotoxic effects at toxic doses by impairing cardiac conduction and contractility; it is suspected that they affect sodium and potassium channels in heart muscle cells, which can lead to arrhythmias. At the pharmacological level, however, earlier isolated studies reported a different dimension: cyclobuxine was reported to protect the isolated rat heart from myocardial injuries produced by ischemia and reperfusion (Planta Med., 1993). This apparent paradox — cardioprotection at sub-toxic doses versus cardiotoxicity at higher doses — reflects the narrow therapeutic window that characterizes this class of alkaloids.
Human Clinical Evidence (Level: Single Randomized Controlled Trial — Moderate)
The objective of the key clinical study was to compare the efficacy and safety of two doses of SPV30 in HIV-asymptomatic patients. The study was designed as a randomized, double-blind, multicentre trial of two doses of SPV30 (990 mg/d and 1,980 mg/d) versus placebo, with 145 previously untreated subjects with asymptomatic HIV infection (CDC group IV) and CD4 cell counts between 250 and 500 × 10⁶/L recruited.
There was a statistically significant difference in therapeutic failures between groups in favor of SPV30 990 mg/d, including decreases of CD4 cell count below 200 × 10⁶/L and/or number of clinical aggravations (progression to AIDS or AIDS-related complex). The treatment groups differed statistically in the rate of disease progression, also in favor of SPV30 990 mg/d. Fewer patients receiving SPV30 990 mg/d had at the end an increase of viral load greater than 0.5 log (P = 0.029). No severe side effects were reported in any of the three groups. The authors concluded that SPV30 990 mg/d has beneficial effects in HIV-asymptomatic patients and appears to delay the progression of HIV disease.
A higher dose of 1,980 mg per day had no effect, possibly due to the oxidative stress induced by flavonoids in the extract.
Limitations: People use boxwood extract for conditions such as HIV/AIDS, malaria, and arthritis, but there is no good scientific evidence to support these uses from multiple high-quality trials. The Durant et al. (1998) trial predates modern antiretroviral combination therapy and was conducted in pre-HAART patients, limiting the applicability of findings to contemporary clinical contexts. No subsequent large-scale human trials have been published to replicate or extend these findings.
Scientific Evidence (Level: Preclinical — In Vitro Only)
In a prior study, O-tigloylcyclovirobuxeine-B was recovered from a B. sempervirens leaf extract by bioactivity-guided isolation; this nor-cycloartane alkaloid was identified as possessing strong and selective in vitro activity against the causative agent of malaria tropica, Plasmodium falciparum.
Several of the isolated compounds from B. sempervirens displayed promising in vitro activity against pathogens in a sub-micromolar range with concurrent high selectivity indices; consequently, various alkaloids from B. sempervirens have the potential to serve as novel antiprotozoal lead structures.
Antiprotozoal activity of extracts was tested against the parasites Plasmodium falciparum (malaria) and Trypanosoma brucei rhodesiense (human African trypanosomiasis) at 0.81 and 4.85 µg/mL concentrations.
Limitations: All evidence for antimalarial activity is currently preclinical (in vitro and activity-guided fractionation). No human clinical trials have evaluated B. sempervirens extracts specifically for malaria treatment.
Scientific Evidence (Level: Preclinical — In Vitro / Biochemical Only)
Two alkaloids, (+)-buxabenzamidienine and (+)-buxamidine, were isolated from Buxus sempervirens using bioassay-guided fractionation; their AChE and BChE inhibitory activities were studied and the compounds were found to be quite selective inhibitors of AChE. IC50 values of compound 1 (buxabenzamidienine) for electric eel AChE and horse BChE were 0.787 and 7.68 mM, respectively; while the corresponding IC50 of compound 2 (buxamidine) were 1.70 and 549.98 mM, respectively.
A comprehensive review of advances in the field of cholinesterase inhibitors isolated from the Buxaceae family found that naturally occurring anticholinesterases derived from plants are considered a potential source of new drug candidates for treating Alzheimer's disease. Steroidal and terpenoidal alkaloids isolated from plants of the Buxaceae family have been reviewed for their anticholinesterase activity; most of them have shown in vitro inhibition of horse serum butyrylcholinesterase and electric eel acetylcholinesterase.
Currently, boxwood is being studied as a treatment for Alzheimer's. The general consensus is that cholinesterase inhibitors may alleviate AD symptoms but cannot cure the disease; steroidal and terpenoidal anticholinesterase alkaloids can prove to be a promising group of AChE inhibitors.
Limitations: All cholinesterase-inhibition data from B. sempervirens are in vitro and biochemical assay-based. No human clinical trials examining cognitive outcomes in Alzheimer's patients have been conducted using boxwood extracts. The pathway from in vitro AChE inhibition to clinical benefit in humans remains undemonstrated for this plant.
Scientific Evidence (Level: Preclinical — In Vitro Only)
The cytotoxic activity of the acetonic extract of Buxus sempervirens was investigated on five breast cancer cell lines (MCF7, MCF10CA1a, T47D, BT-20, and MDA-MB-435), using MCF10A as a non-tumoral control. The acetonic extract showed cytotoxic activity towards all five breast cancer cell lines with an IC50 ranging from 7.74 µg/mL to 12.5 µg/mL, while it was less toxic towards MCF10A with an IC50 of 19.24 µg/mL.
A study of a hydroalcoholic extract from dried leaves of B. sempervirens (BSHE) investigated its effect on four human cell lines (BMel melanoma cells, HCT116 colorectal carcinoma cells, PC3 prostate cancer cells, and HS27 skin fibroblasts). This extract inhibited proliferation of all cell lines, with GR50 values of 72, 48, 38, and 32 µg/mL for HS27, HCT116, PC3, and BMel cells, respectively, after 48 h exposure.
At the time of publication of the breast cancer cell study, no anticancer activity of B. sempervirens extracts had yet been described in human subjects.
Limitations: All anticancer evidence is limited to in vitro cell line experiments. No animal model studies or human clinical trials have evaluated boxwood extracts for oncological outcomes.
Scientific Evidence (Level: Preclinical)
Buxus alkaloids exhibit various biological effects including antimalarial, antibacterial, antifungal, antiviral, and enzyme inhibitory activities. Among gemmotherapy extracts studied, boxwood (Buxus sempervirens) was included in a group of plants featuring antimicrobial effects. A few alkaloids from Buxus have shown interesting biological activities including antibacterial, antimycobacterial, antimalarial, and acetylcholinesterase (AChE) inhibitory activities. All current evidence is from in vitro or preclinical studies.
Scientific Evidence (Level: Preclinical — Animal Models Only)
Animal studies conducted in Morocco investigated the effects of aqueous leaf extracts of B. sempervirens on lipid profiles in diabetic rats. In preparation, 1 g of powdered leaves mixed with 100 mL distilled water was boiled for 10 min and then cooled for 15 min in a Soxhlet apparatus. While these animal studies suggest a possible antidiabetic or lipid-modifying effect, no human clinical trial data exist to support this use.
People use chemicals (extracts) from the leaf of boxwood to make medicine. The following dosages appear in peer-reviewed research:
No established human therapeutic dose has been validated through multiple clinical trials for any indication. The SPV30 HIV trial remains the sole human dosing reference available in the peer-reviewed literature.
All parts of the plant are poisonous, particularly the bark and leaves. The use of common boxwood for herbal purposes is not recommended due to the presence of potent steroidal alkaloids (such as cyclobuxine), which have significant toxicity.
Buxus sempervirens aerial parts contain buxine, cyclobuxine, and several related steroidal alkaloids; toxic effects include contact dermatitis, initially exciting effects followed by paralysis and hypotension, nausea, vomiting, dizziness, diarrhea, spasms, and death by respiratory arrest.
The main toxins in boxwood are various steroidal alkaloids, with buxine identified as the primary alkaloid; other alkaloids such as buxinidine, cyclobuxine, and cycloprotobuxine are also present. These alkaloids are classified as highly toxic according to toxin classification, as they can have toxic effects even at concentrations of 5 to 50 mg/kg body mass. The lethal dose (LD) of pure buxine is approximately 0.1 g/kg body mass, while in dogs, approximately 5 g of leaves per kg body weight is considered a lethal dose.
Human ingestion of boxwood is rare, but in cases of large ingestions it would most likely cause gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. The primary toxin found in Buxus species is a bitter alkaloid called buxine; contact with skin can cause mild irritation, but is otherwise generally safe to handle.
A 1999 study of B. sempervirens revealed toxic effects on humans. Intoxication in humans and animals was not uncommon. Initial excitement was followed by growing mobilization and finally death was caused by paralysis, i.e., respiratory failure.
The leaf itself should not be used for medicine, as it can cause serious harm, including death.
The alkaloids have cardiotoxic effects by impairing cardiac conduction and contractility; it is suspected that they affect sodium and potassium channels in heart muscle cells, which can lead to arrhythmias. At higher doses, liver and kidney damage can also occur due to the breakdown and accumulation of metabolic byproducts.
No severe side effects were reported in any of the three groups in the SPV30 HIV trial; the authors concluded that SPV30 990 mg/d has beneficial effects in HIV-asymptomatic patients. This suggests that standardized, controlled extracts at the 990 mg/d dose level did not produce severe adverse events in the short term, though this was a single trial in a specific patient population.
Boxwood may cause poisoning, causing miscarriage and affecting the fetus; boxwood is completely contraindicated during pregnancy, lactation, and for those under 15 years of age.
Boxwood is not commonly used in herbal medicine and is a toxic plant that can cause serious poisoning. Its internal use is restricted to express medical prescription and under the supervision of health professionals.
The body of scientific literature on Buxus sempervirens as a medicinal agent is characterized by a single human randomized controlled trial (the SPV30/HIV study by Durant et al., published 1998 in Phytomedicine), a substantial body of phytochemical characterization work identifying over 200 steroidal alkaloids, and a growing number of preclinical (in vitro and animal) studies across anticancer, antiprotozoal, and cholinesterase-inhibitory domains. Plants of the family Buxaceae are widely used in traditional medicine and constitute rich sources of terpenoidal alkaloids; compounds of this family have been the subject of numerous chemical and pharmacological studies over past decades because of their interesting biological activities such as cholinesterase inhibition.
People use boxwood extract for conditions such as HIV/AIDS, malaria, and arthritis, and as a "blood-detoxifying agent," but there is no good scientific evidence to support these uses. Boxwood might stop the parasite that causes malaria from reproducing; it might also stop viruses, but there isn't enough scientific evidence to support these theories.
In summary, promising pharmacological signals exist at the preclinical level, particularly for antiprotozoal, anticancer, and cholinesterase-inhibitory effects. Human evidence, however, is essentially limited to the single HIV trial, which, while randomized and controlled, predates modern antiretroviral standards and has not been replicated. The narrow margin between pharmacological and toxic doses of the plant's alkaloids represents a fundamental challenge for its therapeutic development.
Health conditions that Boxwood may help support.
Body systems that Boxwood may help support.
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