Spanish needle

Spanish Needle (Bidens pilosa L.): A Comprehensive Reference

1. Identity

1.1 Botanical and Taxonomic Classification

Bidens pilosa L. is a plant of the Asteraceae family and belongs to the Bidens genus, which comprises approximately 280 species. Bidens pilosa is an annual plant that originated from South America, but it is now widely distributed in most pantropical areas of the world. It is native to the Americas but is widely distributed as an introduced species in other regions including Eurasia, Africa, Australia, South America, and the Pacific Islands, and is classified as an invasive species in some regions of the world.

The generic name Bidens came from the Latin and means "two teeth": bis means double or two, and dens means tooth, which refers to the typical twin barbs at the tip of the achene. Bidens pilosa was identified by Carl Linnaeus in 1753.

Its variants include pilosa var., minor var., radiata var., odorata var., alba var., bimucronata var., bisetosa, calcicola, and alausensis.

1.2 Common Names

Bidens pilosa grows with numerous ridged branches, reaching over two meters under favorable conditions, and is commonly called by many vernacular names, such as hairy beggartick, Spanish needles, devil needles, black jack, railway daisy, and pitchforks. Bidens species are also sometimes known as xian feng cao ("all bountiful grass") in Chinese because of their prosperous growth. Regional names documented across cultures include Xian Feng Cao, Gui Zhen Cao, Beggarticks, Cobbler's Pegs, Farmer's Friend, Blackjack, Herbe à aiguilles (French), Zweizahn (German), Kumut, Ketul, Ko-sendangusa, Picão-preto, Mugwenga, Aceitilla, Amor seco, Chipaca, Kichoma mguu, Puen nok sai, and Đơn kim (Vietnamese). In Latin American countries it is also known as amor seco, masaquía, sillcao, chipaca, cadillo, and picao preto.

1.3 Plant Morphology

Bidens pilosa is a branched annual forb of gracile habit, growing up to 1.8 meters tall. It grows aggressively on disturbed land and often becomes weedy. The leaves are all oppositely arranged and range from simple to pinnate in form, the upper leaves with three to five dentate, ovate-to-lanceolate leaflets. It is an erect plant with green leaves, white or yellow flowers, and tiny black seeds.

1.4 Common Preparations and Dosage Forms

All parts of the B. pilosa plant — the whole plant, the aerial parts (leaves, flowers, seeds, and stems), and/or the roots, fresh or dried — are used as ingredients in folk medicines. It is frequently prepared as a dry powder, decoction, maceration, or tincture. Generally, the plant is applied as dry powder or tincture when used externally, and as a powder, maceration, or decoction when used as an internal remedy.

B. pilosa is used as an herb and as an ingredient in teas or herbal medicines. Its shoots and leaves, dried or fresh, are utilized in sauces and teas. The plant has significant ethnobotanical value as both a food and beverage supplement; various parts, including the leaves, flowers, stems, and entire plant, are consumed as food. In Africa, the leaves and young shoots are commonly used in meals, either cooked in soups and stews or added fresh to salads. In many other countries, the young shoot tips and leaves are utilized for preparing beverages, juices, or dried to make tea.

In the 1970s, the United Nations Food and Agriculture Organization (FAO) promoted the cultivation of B. pilosa in Africa because it is easy to grow, edible, palatable, and safe.

2. Traditional and Historical Use

2.1 Geographic Scope and Ethnobotanical Reach

Bidens pilosa has been used in traditional medicine across 15 countries spanning Latin America (Cuba, Trinidad and Tobago, Colombia, Peru, and Brazil), Africa (Côte d'Ivoire, Nigeria, Cameroon, Zimbabwe, Kenya, and Ethiopia), Asia (China, India, and the Philippines), and Oceania (Fiji). A synthesis of the ethnobotanical literature reveals 60 documented indications, which can be classified into 14 disease categories, including animal bites, circulatory system diseases, dermatological infections, ear/nose/eye problems, endocrine system disorders, excretory and reproductive system disorders, fever, gastrointestinal ailments, hair care, hepatobiliary system diseases, neurological disorders, respiratory diseases, skeleto-muscular disorders, and tumors and cancer.

As documented in the ethnobotanical record, B. pilosa, either as a whole plant or different parts, has been reported to be useful in the treatment of over 40 categories of illnesses.

2.2 Africa

In South Africa, Bidens pilosa is an important traditional medicine used by various cultural groups for a wide range of treatments. A leaf decoction is used to treat headaches, ear infections, kidney problems, and flatulence. The leaf extract is also used to cure malaria, stomach and mouth ulcers, diarrhea, and hangover; the whole plant is also used as a poison antidote. In West Africa, traditional use of the plant for skin ailments such as applying crushed leaves to eczema patches or minor wounds has been documented in ethnobotanical surveys.

The plant is used in folk medicine for its anti-inflammatory, antiseptic, liver-protective, anti-hypoglycemic, and blood-pressure-lowering effects. It has been widely used in Taiwan as a traditional medicine, being also the major ingredient of an herbal infusion believed to prevent inflammation and cancer.

2.3 Asia

In China, B. pilosa is traditionally considered to cure enteritis, bacterial dysentery, and pharyngitis. In Japan, a traditional drug known as Kampo-tea® is made from dried B. pilosa. The plant has long been recognized for its medicinal properties across diverse regions, including India, Africa, China, Cuba, Uganda, the Caribbean, and several parts of Asia and South America.

2.4 Latin America

Young leaves and flowers have been used in Mexican folk medicine to treat stomach disorders, hemorrhoids, and diabetes. In Brazil, the plant remains a popular home remedy for diarrhea. Traditional medicine systems across Africa, Asia, and South America have utilized Bidens pilosa for treating infections, inflammation, hypertension, and metabolic disorders.

2.5 Use in Childbirth and Reproductive Contexts

In tropical zones, B. pilosa has been traditionally utilized worldwide in herbal medicine, with one documented use during childbirth as a labour facilitator. The results of experimental studies explain why B. pilosa leaves are used as a folk medicine to enhance labor in many countries. Due to oxytocic effects, decoctions of B. pilosa have been warned against for use by pregnant women.

3. Key Constituents and Active Compounds

3.1 Overview of Phytochemical Complexity

Major chemical constituents — including 301 compounds — belonging to polyacetylenes, polyacetylene glycosides, flavonoids, flavone glycosides, aurones, chalcones, okanin glycosides, phenolic acids, terpenes, pheophytins, fatty acids, and phytosterols have been identified or isolated from the different parts of this plant.

Polyacetylenes and flavonoids, typical metabolite classes in the Bidens genus, predominate in the phytochemistry of B. pilosa. Additional chemical constituents include polyacetylenic glycosides, aurones, aurone glycosides, p-coumaric acid derivatives, caffeoylquinic acid derivatives, pheophytins, diterpenes, tannins, phytosterols, ascorbic acid, carotene, essential oils, saponins, and steroids.

3.2 Polyacetylenes

34 polyynes (polyacetylenes) have been found in B. pilosa so far. The most pharmacologically studied of these is cytopiloyne, a polyacetylenic glucoside. Cytopiloyne (CP) is a bioactive polyacetylenic glucoside purified from B. pilosa that has been shown to increase the percentage of macrophages in the spleen. In the Asteraceae family, the acetylene moiety is widely distributed in the Heliantheae tribe, and some representatives, such as 1-phenylhepta-1,3,5-triyne, are noted for their biological activity and strong long-wave UV radiation absorbance.

3.3 Flavonoids

B. pilosa is an extraordinary source of phytochemicals, particularly flavonoids and polyynes. Plant flavonoids are commonly reported to possess anticancer, anti-inflammatory, antioxidant, and other bioactivities. However, the bioactivities of only seven of the 60 flavonoids present in B. pilosa have been studied; the bioactivities of the remaining 53 flavonoids are poorly understood and deserve further investigation.

Flavonoids, a major class of polyphenolic compounds present in Bidens pilosa, exhibit extensive pharmacological properties, including antioxidant, anti-inflammatory, and antimicrobial effects. The flavonoids, specifically aurones and chalcones, have been reported as good sub-tribal level markers.

3.4 Phenolic Acids and Phenylpropanoids

The major bioactive components found in Bidens pilosa contributing to its antioxidant activity are phenylpropanoid glucosides, polyacetylenes, diterpenes, flavonoids, and flavone glycosides. Vanillin, hydroxybenzaldehyde, caffeic acid, coumaric acid, and ferulic acid have been found in methanol extracts of the plant.

3.5 Terpenoids and Essential Oils

Forty-four compounds, including the major terpenes β-caryophyllene (10.9% and 5.1% in the leaves and flowers, respectively) and τ-cadinene (7.82% and 6.13% in the leaves and flowers, respectively), were identified in the yellowish essential oils obtained from B. pilosa.

4. Established Mechanisms of Action

4.1 Anti-Inflammatory Mechanisms

Phenolics and polyynes are major anti-inflammatory phytochemicals present in B. pilosa. Phenolics such as luteolin and ethyl caffeate, which are major constituents of B. pilosa, have been reported to possess anti-inflammatory activity. Luteolin was reported to exhibit anti-inflammatory activity in macrophages; it inhibited the release of inflammatory cytokines TNF-α and interleukin-6 in RAW 264.7 cells following LPS stimulation. It inhibited TNF-α production with an IC₅₀ value of 1 μM. The underlying anti-inflammatory mechanism of luteolin was reported to be the inactivation of Akt and NF-κB activation.

Cyclooxygenase-2 (COX-2) is a physiologically important enzyme that converts arachidonic acid to prostaglandin (PGE2); its expression is induced by a wide variety of external stimuli, indicating its involvement in inflammatory diseases. Research showed that the aqueous extracts of B. pilosa aerial parts affected the production of COX-2 and PGE2 as well as the activation of mitogen-activated protein kinases (MAPKs) in normal human dermal fibroblasts in response to the inflammatory cytokine IL-1β. This work showed that IL-1β activated MAPKs such as ERK1/2, p38, and JNK and induced COX-2 expression.

Across preclinical reports, aqueous B. pilosa reduces lipid peroxidation, restores endogenous antioxidant defenses (superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione), and improves histopathology in organs affected by diet-induced stress. These effects coincide with favorable changes in metabolic and inflammatory markers, including attenuation of NF-κB and TNF-α signaling, consistent with broad cytoprotective activity in the liver and kidney.

4.2 Antidiabetic Mechanisms

Among the polyacetylenes, cytopiloyne identified from B. pilosa had better glucose-reducing activities in diabetic mice than other polyynes. It was demonstrated that B. pilosa and cytopiloyne lowered blood glucose via insulin secretion and islet protection. Mechanistic studies showed that cytopiloyne and, probably, B. pilosa exerted antidiabetic action via regulation of β-cell function.

Cytopiloyne inhibits the differentiation of CD4+ cells into Th1 cells but promotes their differentiation into Th2 cells, presenting it as a potent antidiabetic agent. Cytopiloyne is reported to inhibit IFN-γ expression and promote Th2 cell differentiation and the transcription of the cytokine Interleukin-4 (IL-4).

4.3 Immunomodulatory Mechanisms

Human CD4+ T cells cultured in vitro under Th1 or Th2 polarizing conditions were exposed to a butanol fraction (ButF) of B. pilosa extract. The extract altered cell differentiation — it inhibited Th1 but favored Th2 polarization by activating the transcription factor GATA-3.

Cytopiloyne was shown to enhance macrophage-mediated extinction of Candida through PKC-dependent phagocytosis and intracellular Candida elimination based on phagolysosomal integration, acidification, and activation of lysosomal enzyme. In vitro, cytopiloyne improved the Candida parapsilosis-engulfing and eliminating capacities of RAW264.7 macrophages, while in vivo it enhanced the survival rate for Candida-infected mice and weakened the severity of hepatic and splenic microscopic lesions through a macrophage-based mechanism.

4.4 Hepatoprotective Mechanisms

The antioxidant activity of the flavonoids found in B. pilosa was correlated with its hepatoprotective effects through their inhibition of NF-κB activation, which may lessen the oxidative stress caused by the production of free radicals during liver injury. This activity might also be due to the anti-inflammatory effects of the aqueous extracts of B. pilosa aerial parts on the inhibition of COX-2 and PGE2 production.

A network pharmacology study found that the possible mechanism of active components against liver fibrosis is to regulate the PI3K-AKT, MAPK, and other signaling pathways by acting on core targets such as PIK3R1, HSP90AA1, SRC, TP53, AKT1, RELA, and to induce the apoptosis of activated hepatic stellate cells to reverse and improve liver fibrosis.

5. Scientific Evidence by Area of Use

5.1 Anti-Inflammatory and Antinociceptive Activity

Evidence strength: Predominantly preclinical (in vitro and animal). One Phase I/II human clinical trial in the specific context of oral mucositis.

Several scientific works have demonstrated and confirmed that different chemical compounds of B. pilosa modulate the synthesis of inflammatory mediators (IL-1β, IL-6, TNF-α) and reactive oxygen species (ROS) in vitro. In addition, in vivo studies in animal models have shown that the anti-inflammatory and antinociceptive properties of B. pilosa are associated with polyacetylenes and phenolic compounds.

An in vivo study evaluated the analgesic and anti-inflammatory properties of the ethyl acetate fraction of an extract obtained from the leaves of B. pilosa in models of chemical and thermal nociception in mice and Wistar rats. Oral administration of this fraction at doses of 50, 100, and 200 mg/kg showed a significant antinociceptive effect in four different models.

Regarding human evidence, until recently there has only been one clinical trial in phase I and II associated with the anti-inflammatory activity of Bidens in mucositis. These studies tested a B. pilosa-derived pharmaceutical product combined with curcuminoids (FITOPROT) and showed its anti-inflammatory and antioxidant effects on cellular and animal models of intestinal mucositis. Phase I clinical trials to evaluate toxicity and side effects of FITOPROT showed that no participant experienced toxicity or systemic or local effects in patients when used topically as a mouthwash at doses of 10 mg/mL of curcuminoids plus 20% v/v of B. pilosa L. or 20 mg/mL of curcuminoids plus 40% v/v of B. pilosa, three times daily for ten consecutive days. The laboratory and clinical parameters were in normal conditions. Side effects observed were low-intensity and temporary mucosa/dental surface pigmentation (n=7) and tooth sensitivity (n=4).

Most of the scientific information analyzed in the immunomodulatory literature supports the potential use of B. pilosa mainly as an anti-inflammatory, antioxidant, antitumoral, antidiabetic, and antimicrobial immune response modulator. It is considered necessary that this biological activity be corroborated through the design of specialized clinical trials that demonstrate effectiveness in the treatment of autoimmune diseases, chronic inflammation, and infectious diseases.

5.2 Antidiabetic Activity

Evidence strength: Substantial preclinical evidence; one small human pilot study.

Although B. pilosa has long been purported to have antidiabetes activity, for some time no human clinical trials had been conducted. A pilot study evaluated the effect of a B. pilosa formulation on fasting blood glucose (FBG), fasting serum insulin, and glycosylated hemoglobin A1c (HbA1c) in diabetic subjects. The B. pilosa formulation reduced the level of FBG and HbA1c in diabetics but increased fasting serum insulin in healthy subjects. Moreover, combination of the B. pilosa formulation with antidiabetic drugs had better glycemic control in diabetics. The homeostatic model assessment (HOMA) data suggested that the antidiabetic activity of this formulation was via improvement of β-cell function.

The safety of the B. pilosa formulation was tested in healthy subjects and no obvious side effects were observed. The authors concluded that B. pilosa has potential as an antidiabetes treatment. This was a small, open-label pilot study, and the 14 volunteers whose fasting blood glucose was more than 126 mg/dL and/or whose 2-hour postmeal prandial blood glucose was more than 200 mg/dL were diagnosed as diabetics based on the American Diabetes Association criteria.

Like all anti-diabetic drugs, cytopiloyne failed to prevent or cure diabetes completely but reduced diabetic complications in animal models. A study conducted in non-obese diabetic (NOD) mice showed that a butanol fraction of B. pilosa, administered intraperitoneally at a dose of 10 mg/kg three times per week, could maintain the normal morphology of the pancreatic islets. The fraction inhibited β-cell death and pancreatic tissue infiltration by leukocytes. These data suggested that the plant extract ameliorated Th1-mediated autoimmune diabetes in NOD mice.

Despite these promising preclinical and pilot data, clinical translation is currently absent for the antioxidant and metabolic effects documented in rodent models, and larger, randomized controlled trials remain necessary.

5.3 Antimicrobial and Antiparasitic Activity

Evidence strength: In vitro and animal studies only. No human clinical trials identified.

Ethanolic extract of Bidens pilosa has been shown to contain flavonoids and acetylenes which are responsible for its antiplasmodial activity. Bidens pilosa has been demonstrated to have antimalarial efficacy at doses less than 500 mg/kg in animal models. B. pilosa ethyl acetate extract and its most effective fraction were reported to be highly active against P. falciparum in vitro and noncytotoxic against L929 cells using the MTT assay. However, in vitro tests assume direct action on parasites and are not sufficient to attest antimalarial efficacy; results obtained under in vitro conditions cannot be extrapolated in vivo taking into consideration biotransformation, interaction with food, enzymatic material, and absorption observed in vivo.

Regarding antifungal activity, the methanol, acetone, and water extracts from the root of B. pilosa showed significant activity against bacteria and some fungi species tested. The acetone, methanol, and water extracts exhibited low activity against Aspergillus flavus but suppressed the growth of Penicillium notatum 100% at 0.1 mg/mL. However, none of the phytochemicals have been confirmed as definitive active compounds against fungi; further investigation of active compounds from B. pilosa is necessary to further understand the antifungal efficacy of this plant.

In a mouse model of Candida infection, cytopiloyne (CP) treatment improved the survival rate of infected mice and lowered the severity of microscopic lesions in livers and spleens via a macrophage-dependent mechanism. With CP treatment, the fusion and acidification of phagolysosomes were accelerated and the lysosome enzyme activity of RAW264.7 macrophages was elevated.

The crude methanolic extract of B. pilosa showed larvicidal effect against third-instar larvae of Culex quinquefasciatus. The methanolic extract exhibited 100% mortality rate after 12 hours of incubation at a concentration of 1000 ppm.

5.4 Hepatoprotective Activity

Evidence strength: Animal studies and in vitro network pharmacology. No human trials identified.

Three variants of B. pilosa, including B. pilosa L. var. Minor, protect the liver from injury by various hepatotoxins and have potential as broad-spectrum hepatoprotective agents. The aqueous extract of B. pilosa displayed protection against liver damage induced by chronic obstructive cholestasis in young rats and was proposed for use as a treatment of an analogous disease in children.

5.5 Cardiovascular and Hypotensive Activity

Evidence strength: Animal models only. No human trials identified.

Early studies used three rat models — normotensive Wistar rats, salt-loading hypertensive rats, and spontaneously hypertensive rats — to investigate the hypotensive effect of the methanol crude extract of B. pilosa leaves. The extract lowered systolic blood pressure in hypertensive rats to a greater degree than in normotensive rats.

5.6 Antioxidant Activity

Evidence strength: Well-established in vitro; consistent animal data; no human trials.

The B. pilosa extract showed DPPH radical scavenging activity in vitro. Essential oils from B. pilosa flowers and leaves are also reported to possess antioxidant activity. The coherence of the preclinical antioxidant evidence is limited by methodological heterogeneity, including variable extract composition and dosing, uneven biomarker panels, and limited mechanistic depth for aqueous fractions compared with organic extracts. Few studies link quantified phytochemistry with in vivo exposure-response, and pharmacokinetic data remain scarce.

5.7 Anticancer Activity

Evidence strength: In vitro and animal studies only. No human clinical trials identified.

B. pilosa is documented as cytotoxic against various cancer cell lines. A structured cross-referencing analysis of the ethnobotanical and pharmacological literature reveals that 26 (43.33%) of 60 documented traditional applications are supported by verified pharmacological mechanisms mediated by 19 classes of bioactive compounds, principally flavonoids, polyacetylenes, and phenolic acids. Among these, anti-inflammatory, antidiabetic, antitumor, and antimicrobial activities are the most consistently validated. Current anticancer data, however, are entirely preclinical and cannot be extrapolated to human therapeutic efficacy.

5.8 Immunomodulatory Activity

Evidence strength: Mechanistically complex preclinical data; one Phase I/II clinical trial (combined product).

Studies have revealed B. pilosa possesses multiple bioactivities of importance to human health, such as antioxidant, anti-inflammatory, antidiabetic, anticancer, hepatoprotective, and immunomodulatory activities. Extracts and isolated compounds exhibit anti-inflammatory effects by reducing the levels of anti-inflammatory cytokines — such as interleukin-6, interleukin-1β, and tumor necrosis factor-α — through reduction of the expression of inflammatory genes such as inducible nitric oxide synthase and cyclooxygenase-2.

The immunological effects of B. pilosa are not universally anti-inflammatory. Under certain conditions, the plant promotes a Th2-skewed immune response with elevated IgE levels, implying potential allergenic or pro-inflammatory consequences under specific immunological contexts.

6. Body Systems and Health Areas

• Metabolic/Endocrine System: Antidiabetic, anti-hyperglycemic, potential insulin secretagogue and β-cell protectant.
• Hepatobiliary System: Hepatoprotective against chemical- and disease-induced liver injury; anti-fibrotic potential in network pharmacology models.
• Immune System: Immunomodulatory via Th1/Th2 balance regulation, macrophage activation (phagocytosis), and cytokine synthesis modulation.
• Cardiovascular System: Hypotensive activity documented in animal models; potential antihypertensive use in traditional medicine.
• Gastrointestinal System: Used traditionally for stomach disorders, diarrhea, ulcers, dysentery, and enteritis; mucositis-related use explored in the only human trial.
• Infectious/Antimicrobial: Antibacterial, antifungal, antiplasmodial (antimalarial), and antiparasitic activities demonstrated in vitro and in some animal models.
• Musculoskeletal/Pain: Antinociceptive properties documented in rodent chemical and thermal pain models.
• Dermatological: Topical use for wounds, skin infections, and eczema documented ethnobotanically.
• Reproductive System: Oxytocic/uterotonic effects documented in animal models, consistent with traditional use as a labor facilitator.
• Oncology (Preclinical): Cytotoxic against various cancer cell lines in vitro; anti-angiogenic activity reported.

7. Dosage Forms and Reported Dosages

In traditional usage, the plants are consumed either dried or fresh, or prepared as decoctions or infusions in water, or as tinctures in alcohol. No universally standardized clinical dosing protocol has been established for any indication.

In the only identified human pilot study, a B. pilosa formulation was evaluated for its effect on fasting blood glucose, fasting serum insulin, and HbA1c in diabetic subjects. The formulation reduced FBG and HbA1c in diabetics and increased fasting serum insulin in healthy subjects; combination with antidiabetic drugs showed better glycemic control.

In the Phase I/II mucositis clinical trial, FITOPROT was used topically as a mouthwash at doses of 10 mg/mL of curcuminoids plus 20% v/v of B. pilosa L. or 20 mg/mL of curcuminoids plus 40% v/v of B. pilosa, three times daily for ten consecutive days.

In anti-inflammatory animal studies, oral administration of an ethyl acetate fraction was used at doses of 50, 100, and 200 mg/kg and showed a significant antinociceptive effect in four different pain models.

In the NOD mouse immunomodulatory study, a butanol fraction of B. pilosa was administered intraperitoneally at a dose of 10 mg/kg three times per week.

In the long-term animal toxicology study, 24-week oral toxicity of B. pilosa was investigated at doses of 0%, 0.5%, 2.5%, 5%, and 10% of food in mice.

Clinical studies are lacking to provide definitive dosing recommendations for human use.

8. Safety Considerations and Interactions

8.1 General Safety Profile in Animals

In a 24-week study, mortality, body weight, organ weight, food intake, water consumption, hematology, serum biochemistry, urinalysis, genotoxicity, and organ histopathology of animals of both sexes were analyzed. No significant difference in these parameters was observed between control and B. pilosa-fed mice except that body weight and food intake in those fed with 10% B. pilosa were significantly less than controls. Similar results were seen in chickens fed with B. pilosa for 28 days.

Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), total protein (TP), albumin, blood urine nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) showed no statistically significant difference between control and B. pilosa-fed mice in the 24-week study.

An acute toxicity study using female mice found that the LD50 of Bidens pilosa was greater than 5000 mg/kg body weight.

In vivo tests of acute toxicity showed a weak toxic effect for both leaf extracts in rats, with the toxicity of the ethanol extract (LD50 = 6.15 g/kg) being greater than that of the aqueous extract (LD50 = 12.30 g/kg).

8.2 Uterotonic and Pregnancy-Related Concerns

The experimental data on oxytocic effects explain why B. pilosa leaves are used as a folk medicine to enhance labor in many countries. Due to these oxytocic effects, decoctions of B. pilosa have been advised against for use by pregnant women. The plant's ability to accumulate heavy metals such as cadmium and arsenic necessitates careful sourcing from uncontaminated environments to ensure consumer safety. Additionally, its estrogenic and uterotonic properties warrant careful consideration, especially in contexts related to pregnancy and reproductive health.

In a study of pregnant rats, higher doses resulted in elevated biochemical markers such as AST and ALT, alongside histopathological alterations in the liver, kidneys, and gravid uterus. Information regarding safety and efficacy during pregnancy and lactation is lacking.

8.3 High-Dose Cardiovascular Concern

The F3 chromatographic fraction of the leaf extract of B. pilosa has been shown to induce hypotension followed by death of rabbits at high doses.

8.4 Immunological Caution

Research using ovalbumin-sensitized BALB/c mice found that a butanol fraction of B. pilosa increased the levels of IgE and Th2 cytokines in serum, increased IgE and IL-5 levels in bronchoalveolar lavage, and increased infiltration of the respiratory tract by eosinophils and mast cells. This finding — the potential for Th2-skewing — is of relevance in individuals with pre-existing allergic or atopic conditions, though it has not been studied in humans.

8.5 Human Clinical Safety

Clinical data regarding adverse effects of B. pilosa are limited; however, a small clinical study reported no adverse effects following administration of a B. pilosa formulation for 90 days.

8.6 Subpopulation Considerations (Allergenicity)

As a member of the Asteraceae (daisy/composite) family, individuals with documented hypersensitivity to this plant family may be at increased risk of cross-reactive responses, though this has not been formally quantified in clinical studies.

8.7 Heavy Metal Accumulation

Bidens pilosa's ability to accumulate heavy metals like cadmium and arsenic necessitates careful sourcing from uncontaminated environments to ensure consumer safety.

8.8 Long-Term Toxicology Gap

Toxicology studies require assessments in experimental animals and humans, but thorough examinations in sufficient numbers are still lacking to definitively classify B. pilosa as non-toxic and safe across all use contexts.

9. Overall State of the Evidence

Despite its ecological invasiveness, Bidens pilosa possesses a long history of traditional use and substantial resource potential that remains incompletely synthesized. Systematic ethnobotanical compilation documents 60 traditional medicinal indications across 14 disease categories spanning Latin America, Africa, Asia, and Oceania.

The coherence of the preclinical evidence is limited by methodological heterogeneity, including variable extract composition and dosing, uneven biomarker panels, and limited mechanistic depth for aqueous fractions compared with organic extracts. Few studies link quantified phytochemistry with in vivo exposure-response, and pharmacokinetic data remain scarce. Clinical translation is currently absent for most pharmacological areas.

Most of the scientific information analyzed supports the potential use of B. pilosa mainly as an anti-inflammatory, antioxidant, antitumoral, antidiabetic, and antimicrobial immune response modulator. It is necessary that this biological activity be corroborated through the design of specialized clinical trials that demonstrate the effectiveness in the treatment of autoimmune diseases, chronic inflammation, and infectious diseases.

References

• Hadacek F et al. "Chemistry and pharmacology of Bidens pilosa: an overview." PMC / European Journal of Medicinal Plants, 2020.
• Bartolome AP, Villaseñor IM, Yang W-C. "Bidens pilosa L. (Asteraceae): Botanical Properties, Traditional Uses, Phytochemistry, and Pharmacology." Evidence-Based Complementary and Alternative Medicine, 2013.
• International Journal of Pharmaceutical Sciences. "A Comprehensive Review of Bidens Pilosa: Botanical Features, Phytochemical Constituents, Pharmacological Properties, and Safety Profile." 2026.
• MDPI Diversity. "Diverse Utilization of Bidens pilosa and Prospects for Sustainable Management." 2026.
• Silva FL et al. "Compilation of Secondary Metabolites from Bidens pilosa L." Molecules, 2011. Via PMC.
• Chang CL-T et al. "Bidens pilosa Formulation Improves Blood Homeostasis and β-Cell Function in Men: A Pilot Study." PMC, 2015.
• Etukudo EM et al. "Exploring the phytochemical profile, antioxidant and anti-inflammatory potential of Bidens pilosa: A Systematic Review." Frontiers in Pharmacology, 2025.
• Immunomodulatory Properties of Natural Extracts and Compounds Derived from Bidens pilosa L.: Literature Review. Pharmaceutics, 2023.
• Liang Y-C et al. "Toxicity study of Bidens pilosa in animals." Journal of Traditional and Complementary Medicine, 2020. Via PMC.
• "In Vivo and In Vitro Effects of Bidens Pilosa L. (Asteraceae) Leaf Aqueous and Ethanol Extracts on Primed-Oestrogenized Rat Uterine Muscle." PMC, 2010.
• "Antimalarial Activity of Ethyl Acetate Extract and Fraction of Bidens pilosa against Plasmodium berghei (ANKA)." PMC, 2020.
• Deba F et al. "Pharmacological potential of Bidens pilosa L. and determination of bioactive compounds using UHPLC-QqQLIT-MS/MS and GC/MS." BMC Complementary Medicine and Therapies, 2017. Via PMC.
• Chung CY et al. "Cytopiloyne, a polyacetylenic glucoside from Bidens pilosa, acts as a novel anticandidal agent via regulation of macrophages." Journal of Ethnopharmacology, 2016.
• "Exploring the mechanism of action of Bidens pilosa L. in combating hepatic fibrosis through network pharmacology and molecular docking." PMC, 2024.
• "Antioxidant Effects of Aqueous Bidens pilosa in Fructose-Fed Rats." PMC, 2025.
• "Unraveling the reproductive potential of selected flavonoids in Bidens pilosa: A comprehensive review." ScienceDirect, 2025.
• "Mucoadhesive formulation of Bidens pilosa L. (Asteraceae) reduces intestinal injury from 5-fluorouracil-induced mucositis in mice." PMC, 2017.
• Drugs.com Natural Products Database. "Bur Marigold Uses, Benefits & Dosage." 2026.
• "Mechanistic insight into pharmacological effects of secondary metabolites from Bidens pilosa." Phytochemistry Reviews, Springer Nature, 2024.
• Wikipedia. "Bidens pilosa." (Taxonomic and morphological reference.)