Heliopsis

Heliopsis: A Comprehensive Reference

Overview and Scope

The name Heliopsis refers to a genus of flowering plants in the daisy family (Asteraceae) that has attracted scientific and ethnomedicinal interest across two distinct but related species. Heliopsis longipes (A. Gray) S.F. Blake, commonly called chilcuague or "Aztec root," is the species of primary pharmacological and dietary-supplement relevance; it is a narrowly endemic Mexican herb whose roots are the principal medicinal part. Heliopsis helianthoides (L.) Sweet, commonly called rough oxeye, smooth oxeye, or false sunflower, is a broader North American species with more limited but documented ethnobotanical use. This article covers both species, with the preponderance of scientific evidence relating to H. longipes.

1. Botanical Identity, Classification, and Natural Source

1.1 Heliopsis longipes

Heliopsis longipes is an herbaceous plant native to Mexico, growing particularly in the states of Querétaro, Guanajuato, and San Luis Potosí, where it is known by common names including "Chilcuague," "Chilcuán," "Chilmecatl," "Aztec root," and "Golden root," among others. It is endemic to the Sierra de Álvarez and Sierra Gorda mountain ranges in central Mexico. In Nahuatl, the plant is referred to as Chilcoatl, a portmanteau denoting the root's spicy qualities (chil) and its snakelike shape (coatl). Other names include Chilcuas, Chilcuan, Chilcmecatl, chili de palo, palo de duende, pelitre, golden root, and Aztec root.

It is a perennial herb endemic to the Sierra de Álvarez and Sierra Gorda area, where the states of San Luis Potosí, Guanajuato, and Querétaro converge, and its root is the part with traditional uses. The plant belongs to the tribe Heliantheae within the family Asteraceae. The plant typically grows to a height of 30–60 cm, with lanceolate leaves arranged oppositely along its stem. The roots, which are the most valued part of the plant, are elongated and gnarled, covered in a brownish outer layer that encases a yellow interior.

1.2 Heliopsis helianthoides

Heliopsis helianthoides is a species of flowering plant in the family Asteraceae, known by the common names rough oxeye, smooth oxeye, and false sunflower. It is native to eastern and central North America from Saskatchewan east to Newfoundland and south as far as Texas, New Mexico, and Georgia. It is a rhizomatous herbaceous perennial growing 40–150 cm tall. The toothed leaf blades are oval to triangular or lance-shaped and may be smooth, hairy, or rough in texture. The flowers are produced from midsummer to early autumn.

There are three subspecies of H. helianthoides: ssp. helianthoides, generally occurring east of the Mississippi River; ssp. occidentalis, found in the Great Plains region; and ssp. scabra, which is predominant in the Ozark region of Missouri, Arkansas, and Oklahoma.

1.3 Common Preparations and Dosage Forms

For H. longipes, the commercially and traditionally utilized part is the root, which is available in dried form, as an ethanolic or hydroalcoholic tincture, as a powdered extract, and as a topical spray. In Central Mexico, the roots of this species are widely used as a spice, a home insecticide, and for the treatment of illnesses including toothaches, gingival disease, and muscular pain. When H. longipes roots come into contact with oral cavity tissues, they produce numbness and a tingling sensation of the tongue, associated with a significant increase in salivary flow. For H. helianthoides, traditional preparations included root decoctions and infusions used among North American indigenous peoples (see Section 3).

2. Key Constituents and Active Compounds

2.1 N-Alkylamides (Alkamides) — Primary Bioactive Class

The predominant bioactive molecules found in H. longipes roots are N-alkylamides or alkamides, mainly N-isobutyl-2E,6Z,8E-decatrienamide, also known as affinin or spilanthol. GC–MS analysis of the extract confirmed spilanthol as the major constituent present (63.94%), followed by other minor alkamides, which could also contribute to the biological effects observed.

Affinin (spilanthol) has the molecular formula C₁₄H₂₃NO and a molecular weight of 221.339 g/mol. Spilanthol is a bioactive compound found in many different plants used as traditional remedies throughout the world. It is present in Heliopsis longipes and several species in the genus Acmella, including A. oleracea L., also known as paracress and jambu.

Chemically, alkamides are low molecular weight (<400 Da) N-substituted α-unsaturated acyl amides. They consist of a straight α-unsaturated C8–C18 acyl chain condensed to different amines. The most abundant alkamide acyl chain reported is C10. N-alkylamides are a class of secondary metabolites of increasing pharmacological interest due to their anti-inflammatory, immunomodulatory, analgesic, and antitumor properties. Their presence is characteristic of some botanical families, mainly Asteraceae species commonly used in folk medicine, distributed within the Heliantheae tribe, especially Heliopsis and Acmella (syn. Spilanthes), which are likely to synthesize olefinic alkamides.

2.2 Phenolic Compounds in Heliopsis helianthoides

Chemical analysis of H. helianthoides using HPLC has identified a wider variety of phenolic constituents. Using HPLC, researchers studied the chemical composition and antioxidant activity of bioactive substances in the roots, leaves, flowers, and seeds of H. helianthoides. The results showed the presence of 5 phenolic compounds in the roots, 4 in the leaves, 10 in the flowers, and 8 in the seeds; the highest content of identified compounds was found in the leaves at 3192.20 ± 79.78 mg/kg. The dominating hydroxycinnamic acid was chlorogenic acid, with its highest concentration (1537.21 ± 38.43 mg/kg) found in the leaves. Among flavonoids, luteolin prevailed in the roots, apigenin-7-glucoside prevailed in the seeds, and rutin prevailed in the leaves and flowers, with a maximum rutin content of 1426.64 ± 35.67 mg/kg found in the leaves.

2.3 Other Phytochemical Classes

Guaianolide sesquiterpenoids, N-alkylamides, and lignans have been isolated and characterized from H. helianthoides. The shared presence of N-alkylamides across the genus links both species to the broader pharmacological profile of this compound class, though the concentrations and specific profiles differ between species.

3. Traditional and Historical Use

3.1 Mesoamerican Traditions — Heliopsis longipes

The local population in central Mexico has been familiar with the potent analgesic, anesthetic, antimicrobial, and anti-inflammatory action of chilcuague since Aztec times. Heliopsis longipes (Asteraceae) is a broadly used species in Mexican, Central, and South American traditional medicine for its anesthetic, analgesic, anti-inflammatory, and anti-ulcerative properties.

Heliopsis longipes is a perennial herb whose root is used as a condiment in sauces and spicy meals because it has a flavor similar to chili; in addition, it is used in traditional medicine to alleviate tooth and muscle pains, and also as an insecticide. Chilcuague is used against parasites by adding roots over food. Historically, roots were traded year-round at traditional markets (tianguis). Its diverse traditional uses are supported by year-round sales at the traditional markets of San Luis de la Paz, Dr. Mora, and San José Iturbide, Guanajuato; Rioverde and San Ciro, San Luis Potosí; and Jalpan, Querétaro.

Extracts from the roots of Heliopsis longipes have reportedly been used for treating colds and pneumonia, and an alcoholic extract has been tested for use as an anesthetic for tooth extraction. The root was also chewed directly: the root is chewed to numb the tongue and relieve pain in the teeth and throat.

3.2 North American Indigenous Traditions — Heliopsis helianthoides

The Chippewa took a decoction of the roots of H. helianthoides as a stimulant. The Cherokee used the roots in combination with Scutellaria incana "for young women," presumably for menstruation-related discomforts, and sore feet were relieved by soaking in an infusion of what was called "swamp sunflower." A tea from this plant has been used as a cure for various lung ailments. The plant has been harvested from the wild for local use as a medicine and also has potential for use as an insecticide.

4. Mechanisms of Action

4.1 Pain Signaling: TRP Channels, GABA, and Opioidergic Pathways

Affinin (spilanthol) is the main bioactive alkylamide present in Heliopsis longipes roots, exerting antinociceptive and anti-inflammatory effects that involve the activation of TRP channels. This activity was attributed to the modulation or blocking of transient receptor potential channels subfamily V member 1 (TRPV1) and subfamily A member 1 (TRPA1) and the increased release of gamma-aminobutyric acid (GABA).

Affinin-induced antinociception (30 mg/kg, i.p.) was blocked by naltrexone, p-chlorophenylalanine, and flumazenil, suggesting that its pharmacological effect could be due to the activation of opioidergic, serotoninergic, and GABAergic systems. These animal-model findings collectively point to a multitarget analgesic mechanism involving several distinct receptor and channel systems simultaneously, which may account for the potency described in traditional use.

4.2 Anti-inflammatory Mechanisms

The ethanolic extract of H. longipes contains alkamides, mainly affinin (spilanthol). This family of compounds exerts an in vitro inhibitory action on the cyclooxygenase and lipoxygenase enzymes. Previous studies have also indicated that affinin reduces the LPS-induced increase in pro-inflammatory cytokine production in murine macrophages.

4.3 Vasodilatory Mechanisms

The ethanolic extract of Heliopsis longipes roots and its main alkamide, affinin, elicit a vasorelaxant effect through a mechanism involving activation of the gasotransmitter pathways and stimulation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. Affinin induces vasodilation by mechanisms that involve gasotransmitters and prostacyclin signaling pathways. These findings indicate that this natural alkamide has therapeutic potential in the treatment of cardiovascular diseases.

4.4 Endocannabinoid System Engagement

Evidence indicates that affinin or spilanthol activates vascular endothelial cannabinoid receptors (CB1 and eCB), as well as endothelial TRPA1 and TRPV1 channels. The most important affinin-producing plants belong to the genera Acmella (Spilanthes), Heliopsis, and Wedelia, particularly A. oleracea and H. longipes. The engagement of cannabinoid receptor 1 (CB1) has also been noted in the context of antinociceptive and vasorelaxant studies in rodent models.

5. Scientific Evidence by Area of Use

5.1 Analgesia and Antinociception

This is the most extensively studied area for Heliopsis longipes, though all evidence to date is preclinical (animal or in vitro). The antinociceptive effect of H. longipes has been studied in multiple rodent models; intraperitoneal administration of extract and affinin produced a dose-dependent antinociceptive effect in mice subjected to acetic acid and capsaicin tests.

Oral administration of the H. longipes ethanolic extract (HLEE) at doses of 3–100 mg/kg produced a dose-dependent antinociceptive effect in both the writhing and hot-plate tests in mice. The ethanol extract and affinin displayed analgesic action similar to ketorolac and a stimulating effect comparable to caffeine on the nervous system of adult mice.

A solution of 10 μg/mL of dichloromethane extract from this plant showed analgesic activity determined by means of GABA release in mice brain slices. Through a bioassay-directed separation, fractions G-1, G-2, G-4, and G-6 at the same concentration were active. Affinin was the unique and common active compound, evoking GABA release 0.5 min after administration at 1 × 10⁻⁴ M concentration.

A study exploring synergistic interactions found that there is a synergistic interaction between H. longipes ethanolic extract (HLEE) and diclofenac in the Hargreaves model of thermal hyperalgesia, with data suggesting that low doses of the HLEE–diclofenac combination can interact synergistically at the systemic level and may represent a therapeutic advantage for the clinical treatment of inflammatory pain. These findings are entirely rodent-based; no controlled human clinical trials for analgesia have been published as of the available literature.

5.2 Anti-inflammatory Activity

Studies investigating the anti-inflammatory effect of H. longipes extract and its main bioactive component affinin evaluated the mouse ear edema test using two irritating agents, arachidonic acid (AA) and phorbol myristate acetate (PMA). Results confirmed topical anti-inflammatory activity attributable to alkamide inhibition of the arachidonic acid cascade. Results from pharmacological studies demonstrate that affinin induces antinociceptive, anti-hypothermic, and anti-inflammatory activities, which involve the CB1 receptor and the TRPV1 and TRPA1 channels and the suppression of pro-inflammatory cytokines. All evidence in this area is preclinical, primarily from murine models.

5.3 Cardiovascular Effects (Vasodilation / Antihypertensive)

Dichloromethane and ethanolic extracts of H. longipes roots, and affinin isolated from these roots, produce a concentration-dependent vasodilation of rat aorta. The median effective concentration to produce vasodilation (EC50 = 27.38 µg/mL) falls within the concentration ranges at which this compound elicits other biological and pharmacological activities. A 2024 study in Planta Medica further examined antihypertensive potential: the aim was to determine the effect of oral administration of the ethanolic extract of H. longipes and affinin on systolic blood pressure of NG-nitro-L-arginine methyl ester-induced hypertensive rats, exploring the participation of cannabinoid receptors and TRP channels in the mechanism of action. This body of evidence is entirely preclinical (rat models), and no human trials for cardiovascular endpoints are available.

5.4 Antimicrobial and Antifungal Activity

Researchers demonstrated the fungistatic and bacteriostatic activities of affinin, the main alkamide of H. longipes roots, and two alkamides obtained by its catalytic reduction. The bioactivity was tested against fungi including Rhizoctonia solani, Sclerotium rolfsii, Sclerotium cepivorum, Fusarium sp., Verticillium sp., Phytophthora infestans, Saccharomyces cerevisiae; and bacteria including Escherichia coli, Erwinia carotovora, and Bacillus subtilis. Four of the assayed fungi showed an important sensitivity to the presence of affinin: S. rolfsii, S. cepivorum, P. infestans, and R. solani AG-3 and AG-5, displaying a growth inhibition of 100%. S. cerevisiae showed a similar growth inhibition with affinin. The alkamide affinin inhibited growth of E. coli and S. cerevisiae at concentrations as low as 25 μg/mL. Higher concentrations of affinin were necessary to inhibit growth of P. solanacearum and B. subtilis. This evidence is in vitro; no human clinical data on antimicrobial applications exist.

5.5 Insecticidal and Larvicidal Activity

Heliopsis longipes has been recognized as a potential source of insecticidal compounds called alkamides, which can be used to control populations of insect vector transmitters of several diseases affecting human health. Crude extracts of H. longipes roots exert paralyzing action and toxic effects against houseflies, codling moth larvae, and several leaf-eating insects. Studies have evaluated affinin against mosquito larvae: crude extract of H. longipes roots and affinin were obtained and evaluated against third instar larvae of Anopheles albimanus and Aedes aegypti. Results show that the crude extract of H. longipes possesses larvicidal activity against larval stages of An. albimanus and Ae. aegypti. This evidence is laboratory-based (in vivo insect models) rather than human clinical.

5.6 Anticancer / Antiproliferative Activity

Significant growth inhibition was found in cancer cell lines, with emphasis on K-562 and MCF-7 cells, exhibiting IC50 values of 87.14 and 134.25 μg/mL, respectively, without inducing substantial damage to HaCaT cells after 48 hours of treatment. Spilanthol displayed a more pronounced inhibitory effect on cell lines. Furthermore, real-time PCR revealed that the H. longipes extract activated caspase 3 and caspase 8 after treatment for 48 hours. These results confirm the induction of apoptosis by Heliopsis longipes and the potential usefulness of the species and their alkamides as compounds to develop new anti-cancer agents. This evidence is exclusively in vitro (cell culture); no animal or human studies on anticancer efficacy have been reported.

5.7 Antioxidant Activity (Heliopsis helianthoides)

Research on H. helianthoides using HPLC has characterized the antioxidant phenolic content across different plant parts. The highest content of identified phenolic compounds was found in the leaves of H. helianthoides at 3192.20 ± 79.78 mg/kg. The presence of high concentrations of chlorogenic acid, rutin, luteolin, and apigenin-7-glucoside provides a theoretical basis for antioxidant activity, as these are well-characterized antioxidant flavonoids and hydroxycinnamic acids. Direct antioxidant efficacy studies in humans specific to H. helianthoides have not been identified in the literature.

5.8 Mutagenicity Assessment (Safety-Relevant Efficacy Data)

In the Ames test, neither the H. longipes extract nor affinin induced mutations in the Salmonella typhimurium strains TA98, TA100, or TA102, with or without the S9 microsomal fraction. The acetone extract of Heliopsis longipes roots (10–80 μg/Petri dish) and its active compound affinin (6.25–50 μg/Petri dish) were not mutagenic as evaluated by the Ames test. These negative results are reassuring but do not substitute for comprehensive human genotoxicity data.

6. Body Systems and Health Areas Associated with Heliopsis

• Nervous System / Pain: Analgesia and anesthesia (primarily oral/dental); demonstrated in rodent models via opioidergic, GABAergic, serotoninergic, and TRP channel mechanisms.
• Immune and Inflammatory Response: Cyclooxygenase and lipoxygenase inhibition; suppression of pro-inflammatory cytokines in macrophages; demonstrated in vitro and in murine models.
• Cardiovascular System: Vasodilation via gasotransmitter and prostacyclin signaling pathways, CB1 receptor activation; studied in rat aorta ex vivo and in vivo hypertension models.
• Antimicrobial Defense: Antifungal and antibacterial activity demonstrated against a range of plant and human-pathogenic organisms; all data in vitro.
• Oncology (Preclinical): Antiproliferative and apoptosis-inducing activity in cancer cell lines; in vitro only.
• Insect Pest and Vector Control: Larvicidal activity against malaria- and dengue-associated mosquito species; entomological research models.
• Antioxidant / Phenolic: High phenolic content (particularly in H. helianthoides), including rutin, chlorogenic acid, and luteolin; theoretical antioxidant capacity measured in vitro.

7. Dosages Reported in Preclinical Studies

No standardized human dosages have been established for either Heliopsis species. The following dosages are reported exclusively from animal (rodent) studies:

• Affinin at 30 mg/kg administered intraperitoneally to mice was used to evaluate antinociceptive effects and to probe the mechanism of action by receptor antagonism.
• Oral administration of H. longipes ethanolic extract at 3–100 mg/kg (per os) produced dose-dependent antinociceptive effect in mice in both writhing and hot-plate tests.
• The derived theoretical ED30 value for the HLEE–diclofenac combination in mice was 54.4 ± 9.4 mg/kg body weight, while the actually observed experimental ED30 value was 8.6 ± 4.0 mg/kg body weight.
• Affinin at 20 mg/kg was used in mice to evaluate anti-inflammatory activity and behavioral effects in LPS-induced hypothermia models.
• A solution of 10 μg/mL of dichloromethane extract showed analgesic activity as determined by GABA release in mice brain slices.
• An EC50 of 27.38 µg/mL was established for the vasodilatory effect of affinin in ex vivo rat aorta preparations.
• Affinin inhibited growth of E. coli and S. cerevisiae at concentrations as low as 25 μg/mL in antimicrobial assays.

These figures are from preclinical models and cannot be directly extrapolated to human use. No official monograph (e.g., WHO, ESCOP, Commission E) has been identified for either Heliopsis species that establishes human dosing recommendations.

8. Safety Considerations

8.1 Acute Toxicity Data (Animal Models)

The acetone extract of Heliopsis longipes roots had an LD50 of 62.14 mg/kg (per os) in mice, whereas its active compound affinin had an LD50 of 113.13 mg/kg (per os) in mice. The ethanol extract of H. longipes roots had an LD50 of 288 mg/kg (per os) in mice. These differing LD50 values across extract preparations reflect variations in the concentration and purity of affinin and other constituents in each preparation type.

An aqueous solution of affinin prepared from a powder of an ethanol extract of H. longipes roots has been reported as having an analgesic effect when administered orally to mice at doses of 2.5 to 10.0 mg/kg, with severe depression of normal motor activity and two out of five deaths occurring at the highest dose. This observation underscores that central nervous system depression has been documented at high doses in rodents.

8.2 Mutagenicity and Genotoxicity

Neither the H. longipes extract nor affinin induced mutations in Salmonella typhimurium strains TA98, TA100, or TA102 with or without the S9 microsomal fraction in the Ames test. This negative mutagenicity result is based on the standard bacterial reverse mutation assay. In vivo genotoxicity (micronucleus test) data in mice have also been investigated alongside histopathological organ examination.

8.3 CNS-Modifying Effects at High Doses

Affinin extracted from H. longipes was evaluated for its psychopharmacological activity in several models. The H. longipes extract and affinin demonstrated antinociceptive effect, modified anxiety behavior, and prolonged the time of sodium pentobarbital-induced hypnosis. Affinin elicited these activities at high doses. Both the extract and affinin decreased the time of clonic and tonic PTZ-induced seizures. These CNS effects at high doses in rodents have potential relevance to human safety at elevated intake levels.

8.4 Toxicological Flagging in Literature Reviews

A literature review of medicinal plants from North and Central America identified Heliopsis longipes among a list of plant species that have shown effects considered highly toxic, including hepatotoxicity, teratogenic, and cardiotoxicity, or with high toxicity in acute studies. The authors noted that a total of 22 plants of 216 cited in the review should be extensively studied in terms of their toxicity, placing H. longipes within a category requiring further safety evaluation before human therapeutic use.

8.5 Potential Drug Interactions

Based on established mechanisms of action, several interaction concerns arise from preclinical data, though these have not been directly studied in humans:

• NSAIDs: Synergistic interaction between H. longipes ethanolic extract and diclofenac has been demonstrated in a mouse model of thermal hyperalgesia. This synergy could theoretically potentiate NSAID effects and side effects.
• CNS depressants: The extract and affinin modified anxiety behavior and prolonged sodium pentobarbital-induced hypnosis, with affinin eliciting these activities at high doses. Concurrent use with sedatives or anxiolytics requires caution.
• Antihypertensive drugs: Given that affinin and H. longipes extracts produce vasodilation through CB1, TRPA1, TRPV1, NO, H₂S, and prostacyclin pathways in animal models, additive blood-pressure-lowering effects with antihypertensive medications are plausible, though unconfirmed in humans.
• Opioid analgesics: The observation that naltrexone blocked affinin-induced antinociception in mice implies involvement of opioidergic pathways, raising the theoretical possibility of interaction with opioid medications.

8.6 Asteraceae Allergy

Both species belong to the Asteraceae (Compositae) family. Individuals with known hypersensitivity to other members of this family (e.g., ragweed, chrysanthemum, chamomile, echinacea) may be at elevated risk for cross-reactive allergic responses, consistent with the broader pattern of Asteraceae hypersensitivity documented in the allergy literature.

8.7 Conservation Note

The use of chilcuague has implicated the total destruction of the plant, so the populations of this species have diminished, with some local populations disappearing. Wild harvesting pressure represents an ecological concern for the narrow endemic range of H. longipes.

9. Strength of Evidence Summary

The overall evidence base for Heliopsis species as a dietary supplement or therapeutic agent remains preliminary and preclinical. The following summary characterizes the state of evidence across domains:

• Analgesic/Antinociceptive: Multiple consistent rodent studies with dose-response data and mechanistic characterization; no human clinical trials.
• Anti-inflammatory: In vitro enzyme inhibition data and rodent edema models; no human clinical trials.
• Vasodilatory/Antihypertensive: Ex vivo rat aorta and in vivo rodent hypertension models; no human data.
• Antimicrobial/Antifungal: In vitro only; no clinical infection treatment studies.
• Anticancer: In vitro cell culture only; no animal efficacy models or human data.
• Antioxidant (H. helianthoides): Chemical profiling and in vitro antioxidant assays; no human bioavailability or efficacy data.

Such species are considered as important sources of lead compounds for food supplements, cosmeceuticals, and drugs. However, the transition from lead compound to validated clinical intervention requires controlled human trials that, as of the available literature, have not yet been conducted for either Heliopsis species.

References

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• PMC Article (2025). The Multitarget Antinociceptive Compound Affinin and Its Effects on Hypothermia, Hypolocomotion, and Sickness Behavior in Lipopolysaccharide-Treated Mice. PMC
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