Grindelia

Grindelia (Grindeliae herba): A Comprehensive Reference

1. Identity, Taxonomy, and Botanical Description

1.1 Scientific Names and Taxonomy

Grindelia belongs to the family Asteraceae. The four species most widely recognised for medicinal use and covered under official monographs are Grindelia robusta Nutt., Grindelia squarrosa (Pursh) Dunal, Grindelia humilis Hook. et Arn., and Grindelia camporum Greene. Additional species employed in traditional contexts include G. integrifolia, G. humboldtii, and G. hirsuta (syn. G. humilis). The genus name is attributed to David Hieronymus Grindel, an 18th-century physician and professor of pharmacy.

The genus Grindelia Willd. comprises about 68 species. It is a perennial plant of the family Asteraceae, commonly known as "gumweed," and the genus includes about 50 to 65 species originating from North and South America, although only a few have stood out in natural medicine for their wealth of active compounds and therapeutic applications.

Common names for various Grindelia species include gumweed, field gumweed, hardy grindelia, California gum plant, gum plant, scaly grindelia, resinweed, rosin weed, tarweed, August flower, and Spanish gold.

1.2 Plant Morphology and Habitat

Grindelia is a perennial herb with leafy stems. It bears yellow flowers that are surrounded by bracts, which produce a resinous substance. G. camporum and related species are indigenous to the southwestern United States and Mexico, where they are found in prairies, plains, and along roadsides. Grindelia squarrosa is characterised as an arid-lands herb.

Budding grindelia flowers ooze a thick, creamy resinous latex that has an invigorating, pungent aroma. The milky latex often traps small insects in the budding flowers. When harvesting grindelia buds, the sticky latex adheres to hands and tools.

1.3 Plant Parts Used and Common Preparations

The herbal drug, as defined in official monographs, consists of the dried flowering tops of G. robusta, G. squarrosa, G. humilis Hook. et Arn., or G. camporum Greene. The aerial parts of the plant are the primary material used. They are typically plucked before the flower buds open and dried as quickly as possible.

In traditional medicine, the herb is used orally in the form of a tea, tincture, or liquid extract, or used to make a topical lotion. Modern commercial preparations include:

• Herbal tea / infusion: Prepared by pouring 150 mL of boiling water over 2 to 3 g of finely chopped Grindelia herb, leaving to infuse for 10 to 15 minutes, then straining. Drunk hot several times a day, up to a maximum of 4–6 g per day.
• Tinctures: Hydroalcoholic preparations from the dried aerial parts, typically in ratios such as 1:2 or 1:5.
• Liquid extracts: More concentrated than tinctures.
• Topical preparations: Diluted tinctures of Herba Grindeliae are used externally for acute dermatitis, for example dermatitis caused by Rhus toxicodendron (poison oak/ivy).
• Dried herb capsules/tablets: Standardised or unstandardised powdered aerial parts.

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2. Traditional and Historical Use

2.1 Native American and Indigenous Use

Grindelia has a long history of use among North American Indigenous tribes for respiratory, urinary, kidney, digestive, and skin conditions. The following uses are documented from ethnobotanical sources:

• Southwest Indigenous peoples consumed grindelia to treat asthma, as well as bladder and kidney problems.
• Blackfoot Indigenous peoples consumed a decoction of the dried roots as a spring purge and for liver problems.
• Nevada Indigenous peoples applied a topical wash to measles and smallpox.
• Costanoan Indigenous peoples bathed the skin with grindelia tea to treat boils, burns, wounds, and poison oak.
• Southwestern tribes applied warm preparations of grindelia for burns, blisters, skin eruptions, sore joints, paralysis, and "cold in the bones." The resin was rubbed on the eyes to treat snow blindness.
• The Blackfoot made a decoction or infusion of the above-ground plant for liver trouble; the Cheyenne decocted the flowering tops and applied them topically for sores, skin lesions, skin diseases, and scabs, and applied the flower resin to the outside of the eyes for snow blindness; the Mahona applied a poultice to cuts and used a wash as a disinfectant; and in the Jemez Nation a decoction of the dried and powdered above-ground plant was used to clean cuts on both humans and horses.

The Native American traditional medicinal use of the plant as a cough medicine and as an antiseptic wash has prompted subsequent scientific investigation.

2.2 19th-Century Western and Eclectic Medicine

The plant had long been used in traditional medicine in both South America and by Native Americans for a range of conditions including bronchitis and various skin complaints. It was not until the middle of the 19th century that the plant was recognised for its medicinal potential and became more widely used in Western practice. While Native Americans used it for various inflammatory conditions, European settlers adopted it for its expectorant and antispasmodic properties.

Pharmaceutical cigars, such as Neumeier's cigarillos from around 1913, contained Grindelia robusta among other botanicals for the treatment of asthma.

2.3 Official Monograph Recognition

The HMPC (EMA's Committee on Herbal Medicinal Products) monograph classifies grindelia herb for traditional use in cough due to cold; the ESCOP monograph lists productive cough and catarrh of the upper respiratory tract; and the German Commission E monograph lists catarrh of the upper respiratory tract.

The HMPC has classified grindelia herb as a traditional herbal medicinal product under Article 16a of Directive 2001/83/EC. ESCOP's indication is for productive cough and catarrh of the upper respiratory tract, based on human experience and long-standing use. Based upon long-standing use, grindelia herb can be used to treat coughs associated with colds.

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3. Key Constituents and Phytochemistry

3.1 Diterpenic Resin (Primary Fraction)

The main therapeutically active constituents in G. camporum appear to be borneol, several grindelic acids (around 30% volume), and several diterpenic acids, all of which appear in the sticky latex resin of the plant.

The aerial parts of G. squarrosa are a rich source of diterpenes. They contain grindelic, 6-oxygrindelic, 18-hydroxy-6-oxygrindelic, 7-alpha-oxodihydrogrindelic, and 8-alpha-oxodihydrogrindelic acids. As the dominant diterpene, grindelic acid has been identified, which may constitute 20–60% of grindelia resin and up to 6% of the dry plant material.

The resin also contains diterpene derivatives, their methyl esters, and stictanonoic acid.

3.2 Flavonoids

Several flavonoids have been identified, including apigenin 4′-methyl ether, quercetin and its 3,3′-dimethyl ether, and kaempferol 3,7-dimethyl ether, as well as significant plant sterols.

The main active flavonoid constituents include quercetin-3-methylether and 6-OH-kaempferol-3,6-dimethylether, which inhibit neutrophil elastase and contribute to the anti-inflammatory activity of grindelia.

Polyphenolic compounds characteristic of the Asteraceae family have been confirmed present, such as caffeoyl quinic acid and dicaffeoyl quinic acids, as well as luteolin and apigenin derivatives.

3.3 Phenolic Acids

Phenolic acids identified in Grindelia include ferulic, chlorogenic, caffeic, p-hydroxybenzoic, vanillic, and p-coumarinic acid.

3.4 Essential Oil Constituents

Compositional analysis of essential oils from the flowers (GEOFl) and leaves (GEOLv) of G. squarrosa revealed that the main components were α-pinene (24.7% and 23.2% in GEOFl and GEOLv, respectively), limonene (10.0% and 14.7%), borneol (23.4% and 16.6%), p-cymen-8-ol (6.1% and 5.8%), β-pinene (4.0% and 3.8%), bornyl acetate (3.0% and 5.1%), trans-pinocarveol (4.2% and 3.7%), spathulenol (3.0% and 2.0%), myrtenol (2.5% and 1.7%), and terpinolene (1.7% and 2.0%).

Enantiomer analysis showed that α-pinene, β-pinene, and borneol were present primarily as (−)-enantiomers, with 100% enantiomeric excess (ee) for (−)-α-pinene and (−)-borneol in both flower and leaf oils, while limonene was present primarily as the (+)-enantiomer.

The major components of the oil of G. robusta were oxygenated terpenoids (57.4%), of which borneol (14.8%) was the largest constituent. In an analysis of G. robusta aerial parts from central Italy, 45 components were identified, with borneol (15.2%), α-pinene (10.3%), trans-pinocarveol (7.0%), bornyl acetate (4.5%), and limonene (4.3%) as the main components.

3.5 Saponins

The plant also contains flavonoids, phenolic acids, essential oils, polyacetylenes, and saponins. A saponin-enriched fraction of G. robusta, combined with polyphenols, has been the subject of in vitro anti-inflammatory studies (see Section 5 below).

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4. Mechanisms of Action

4.1 Anti-inflammatory Activity via NF-κB Pathway

G. squarrosa extract has been shown to produce significant modulation of pro-inflammatory functions of LPS-stimulated nasal and bronchial epithelium. Treatment with the extract resulted in a decrease of TLR-4 expression and p65 NF-κB concentration and inhibition of cytokine synthesis (IL-8, TNF-α, IL-1β, and IL-6) in both nasal and bronchial cellular models.

Studies with a G. robusta extract enriched in saponins and polyphenols examined its effect on LPS-induced inflammatory mediator secretion (IL-6, TNF-α, RANTES, MCP-1, PGE₂) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in all tested mediators. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1, and to a lesser extent PGE₂ and TNF-α. Inhibition was also observed for MMP-1, -3, -7, -8, -9, and -13. This ability was associated with a reduction of NF-κB p65 activation.

Whole plant methanolic extracts of Grindelia robusta showed up to 4.5-fold inhibition of nitric oxide (NO) production in J774 murine macrophage cells challenged with LPS without cytotoxicity. These selected extracts significantly reduced the protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) as observed by Western blot analysis.

4.2 Neutrophil Immunomodulation

Little was known about the immunomodulatory activity of essential oils from G. squarrosa prior to dedicated investigation. Researchers therefore isolated essential oils from the flowers and leaves of G. squarrosa and evaluated their chemical composition and innate immunomodulatory activity.

Treatment with Grindelia essential oils inhibited activation of neutrophils by the N-formyl peptide receptor 1 (FPR1) agonist fMLF and the FPR2 agonist WKYMVM. The principal active component was identified as (−)-borneol, recognised as a novel modulator of human neutrophil function.

Methylated exudate flavonoids quercetin-3-methylether and 6-OH-kaempferol-3,6-dimethylether inhibit neutrophil elastase, contributing to the anti-inflammatory activity of grindelia.

4.3 Macrophage Stimulation (Anti-inflammatory Cytokine Induction)

G. squarrosa extract slightly modulated ICAM-1 expression, affecting the attachment of macrophages to epithelium. Only G. squarrosa extract (not isolated grindelic acid alone) was able to stimulate the anti-inflammatory functions of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Grindelic acid, identified as a dominant compound in the plant extract, modulated pro-inflammatory functions of epithelium and macrophages only slightly, suggesting a synergistic multi-compound effect.

4.4 Expectorant and Antispasmodic Properties

Due to its antispasmodic, expectorant, and hypotensive effects, G. squarrosa has been suggested for the treatment of asthmatic and bronchial conditions, especially when these are associated with rapid heartbeat and nervous responses. These properties are attributed to the resin and volatile oil fractions, though the specific receptor-level mechanisms for expectorant action have not been fully characterised in peer-reviewed clinical research.

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5. Scientific Evidence by Area of Use

5.1 Respiratory Conditions (Cough, Bronchitis, Catarrh)

Regulatory/monograph status: The ESCOP monograph characterises grindelia as having a resin consisting of diterpenic acids, various grindelic acids, and borneol as its main characteristic constituents, with therapeutic indications of productive cough and catarrh of the upper respiratory tract. Gumweed herb (G. camporum) is indicated for cough and bronchitis under official herbal medicine frameworks.

In vitro evidence: Based on the traditional use of G. squarrosa aerial parts, researchers hypothesised that successful treatment of cold-related diseases may arise from modulation of the pro-inflammatory functions of respiratory epithelium and human monocytes/macrophages. The biological activity of the extract and grindelic acid were compared with clarithromycin and budesonide as positive controls in cellular assays.

G. squarrosa extract and grindelic acid had no direct antimicrobial effect in the tested conditions. However, significant modulation of pro-inflammatory functions of LPS-stimulated nasal and bronchial epithelium was observed. Treatment with G. squarrosa extract resulted in decreased TLR-4 expression and p65 NF-κB concentration and inhibition of cytokine synthesis (IL-8, TNF-α, IL-1β, and IL-6) in both cellular models.

The results of this in vitro study support the traditional use of Grindelia squarrosa preparations for treatment of cold-associated disease symptoms, with the biological effect likely a consequence of the synergistic effect of all compounds present in the extract.

Evidence strength: The safety profile is generally favourable, but robust clinical evidence is still limited. The respiratory indication rests upon a strong traditional use record, monograph recognition by EMA HMPC (as a traditional herbal medicinal product), ESCOP, and German Commission E, and supporting in vitro mechanistic data. No published randomised controlled trials (RCTs) in human subjects for respiratory endpoints have been identified in the peer-reviewed literature.

5.2 Antimicrobial Activity

Grindelia species have been shown to exert antimicrobial activity, especially against gram-negative E. coli. The extract of G. squarrosa flowers showed inhibition diameters in excess of 19.3 mm of A. caviae, M. luteus, and P. alvei. Different extract solvents (CCl₄ and 1-BuOH) confirmed antimicrobial properties of G. squarrosa: CCl₄ extract inhibited E. coli, S. aureus, and C. albicans growth, whereas 1-BuOH extract inhibited S. aureus, P. aeruginosa, and K. pneumoniae.

The major essential oil components were screened for antimicrobial activity against respiratory and dermal pathogens. (−)-β-Pinene showed strong antibacterial activity against Streptococcus pneumoniae (MIC 39.1 μg/mL) and (−)-borneol showed strong activity against Staphylococcus aureus (MIC 78.1 μg/mL).

Furthermore, (±)-α-pinene and (−)-β-pinene have shown strong activity against methicillin-resistant S. aureus (MRSA) with IC₅₀ values of 68.6 and 51.4 μg/mL, respectively, and both α-pinene and β-pinene were active against Klebsiella pneumoniae with MIC values of 178 μg/mL and 170 μg/mL, respectively.

Evidence strength: Antimicrobial evidence is in vitro only, using isolated essential oil components and crude extracts. Results are variable depending on the extraction solvent and species tested; one study using 60% ethanol extract at 25–100 μg/ml and grindelic acid at 10–50 µM found no bacteria growth inhibition and no detectable minimal inhibitory concentration. Clinical antimicrobial evidence is absent.

5.3 Skin and Topical Applications

Grindelia has been used to relieve respiratory ailments and was also applied topically for wounds, burns, and skin irritation. Diluted tinctures of Herba Grindeliae are used externally for acute dermatitis, including dermatitis caused by Rhus toxicodendron (poison oak).

While no clinical data currently supports these uses, several studies and authoritative herbalists support the use of other Grindelia species as a topical anti-inflammatory, particularly when prepared as an aqueous decoction.

Evidence strength: Topical use is supported primarily by ethnobotanical records and traditional practice. No controlled clinical trials have been identified.

5.4 Anti-inflammatory and Immunomodulatory Activity

A 2022 study published in Molecules by Schepetkin et al. investigated essential oils isolated from flowers and leaves of G. squarrosa and their innate immunomodulatory activity on human neutrophils. Compositional analysis revealed the main components were α-pinene, limonene, borneol, β-pinene, bornyl acetate, trans-pinocarveol, spathulenol, myrtenol, and terpinolene. Treatment with Grindelia essential oils inhibited activation of neutrophils by FPR1 and FPR2 agonists, and (−)-borneol was identified as a novel modulator of human neutrophil function.

An earlier study (La et al., 2010, published in Phytotherapy Research) examined a G. robusta extract enriched in saponins and polyphenols tested on monocyte-derived macrophages. At concentration range 25–100 μg/mL, the extract inhibited dose-dependently the secretion of IL-6, MCP-1, and, to a lesser extent, PGE₂ and TNF-α. Inhibition was also observed for MMP-1, -3, -7, -8, -9, and -13 production. This ability was associated with a reduction of NF-κB p65 activation.

Evidence strength: All anti-inflammatory evidence is preclinical (in vitro, cell culture models). No human clinical trials evaluating anti-inflammatory endpoints have been identified. The evidence base is preliminary and mechanistic.

5.5 Antioxidant Activity

The chemical composition of the essential oil obtained from Grindelia robusta aerial parts from central Italy was analyzed; 45 components were identified, with borneol, α-pinene, trans-pinocarveol, bornyl acetate, and limonene as the main components. The essential oil showed antioxidant activity in that study. A bioassay-guided phytochemical analysis of the ethanolic extract of Grindelia argentina allowed the isolation of a known flavone, hispidulin, and three new oleanane-type saponins, named grindeliosides A–C.

Evidence strength: Antioxidant data are limited to in vitro assays. No clinical evidence is available.

5.6 Homeopathic Use

In homeopathy, Grindelia is used for asthmatic conditions, chronic bronchitis, emphysema, and as a spleen remedy. This represents a separate tradition of use, and the evidence base for homeopathic formulations is distinct from and not addressed by the phytotherapy literature reviewed above.

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6. Body Systems Associated with Grindelia

• Respiratory system: Herbalists and naturopaths primarily use Grindelia as a natural remedy for respiratory conditions, particularly for mucus and phlegm buildup, chronic bronchitis, asthma, and spasmodic cough.
• Immune system: The wide-spread use of G. squarrosa in traditional medicine and effectiveness during cold-related disease treatment may be explained by modulation of pro-inflammatory responses.
• Integumentary system (skin): Applications to wounds, burns, skin eruptions, and inflammatory skin reactions such as poison oak contact dermatitis are documented in traditional records.
• Urinary/renal system: North American Indigenous peoples used grindelia for urinary and kidney conditions.
• Gastrointestinal system: Used traditionally as a stomachic preparation; large doses are associated with GI irritation due to the resin content (see Safety section).
• Musculoskeletal system: Southwestern tribes applied warm preparations of grindelia for sore joints.

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7. Dosage Forms and Reported Dosages

The following dosages are reported from official and published sources. No clinically validated optimal dosage exists for any indication.

• Herbal tea (infusion): Daily dose: 4 to 6 g of dried herb. Prepared by pouring approximately 150 mL of boiling water over 2 to 3 g of finely chopped grindelia herb and straining after 10 to 15 minutes.
• Tincture (1:5): Typically 1–3 mL taken two to three times daily, as reported in various herbal medicine references.
• Liquid extract (1:1): A recommended dosage for liquid extract of between 1.8 and 3.6 mL per day has been reported.
• Preclinical study concentrations: Preclinical studies have used dry extract (80% ethanol) at 100–200 mg/kg orally in rats; in vitro extracts at 25–100 μg/mL; or 50 µM grindelic acid.

There is no established dosage window for all species of Grindelia; however, no toxic effects have been observed in animal studies. Conservative prescribing is encouraged in initial treatment stages.

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8. Safety Considerations

8.1 General Safety Profile

According to the EMA Community herbal monograph, no adverse reactions have been reported, no fertility data are available, no drug interactions are known, and no case of overdose has been reported.

8.2 Adverse Effects

Known potential adverse effects include allergic reaction and irritation of the gastrointestinal tract. If taken in large doses, it may produce irritation in the stomach or kidney. Large doses may irritate the kidneys and stomach due to the high resin content, and use may not be suitable long-term for this reason.

8.3 Contraindications and Special Populations

Quality is defined in the European Pharmacopoeia, which permits use of the herb of G. hirsutula and G. squarrosa. Contraindications include pregnancy and lactation, and caution is warranted in children.

The Botanical Safety Handbook suggests limiting use in pregnancy to short term and with caution. There is a hypothetical concern that selenium accumulated from the soil in Grindelia could cause toxicity, although this has never been reported in humans — only in grazing animals.

8.4 Allergy and Cross-Reactivity

As a member of the Asteraceae (Compositae) family, individuals with known hypersensitivity to other members of this family (such as ragweed, chrysanthemums, marigolds, or daisies) may be at risk of cross-reactive allergic responses. This represents a theoretical risk, consistent with patterns established for other Asteraceae members, though specific case reports for grindelia have not been identified in the reviewed literature.

8.5 Drug Interactions

Potential interactions with other herbal medicines, foods, and/or medications are currently unknown, based on available evidence. No drug interactions are known according to the EMA monograph.

8.6 Kidney Considerations

High resin content at large doses has been noted to carry a potential for renal irritation. Use should be approached with particular caution in people with kidney problems.

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9. Evidence Summary and Limitations

The evidence base for Grindelia can be summarised as follows:

• Traditional/monograph support: Strong, multi-cultural traditional use record spanning centuries; formally recognised by EMA HMPC (as traditional herbal medicinal product), ESCOP, German Commission E, and the European Pharmacopoeia for respiratory indications.
• Preclinical mechanistic evidence: Moderate body of in vitro data from multiple research groups demonstrating anti-inflammatory mechanisms (NF-κB suppression, cytokine inhibition, MMP inhibition, neutrophil modulation), specifically in respiratory epithelial cell models and macrophage models.
• Human clinical trials: Absent. No published RCTs or clinical trials in human subjects have been identified for any indication. All pharmacological evidence is preclinical (in vitro or animal).
• Antimicrobial evidence: Mixed and contradictory between different extraction methods; not clinically relevant on available data.
• Antioxidant and skin applications: Preliminary in vitro data only; no controlled clinical evidence.

Although G. squarrosa extracts are present in the pharmaceutical market, there is still a lack of studies fully explaining their antimicrobial and anti-inflammatory properties. The classification of grindelia herb as a "traditional use" product by the EMA explicitly reflects this absence of clinical trial data while recognising the long-standing documented safe use.

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References

• European Medicines Agency (EMA). Grindeliae herba — Community Herbal Monograph (EMA/HMPC/748220/2011, 2012)
• European Scientific Cooperative on Phytotherapy (ESCOP). Grindeliae herba Monograph, 2015
• Gierlikowska B, Filipek A, Gierlikowski W, et al. Grindelia squarrosa Extract and Grindelic Acid Modulate Pro-inflammatory Functions of Respiratory Epithelium and Human Macrophages. Frontiers in Pharmacology. 2021;11:534111. PMC7848105
• Schepetkin IA, Özek G, Özek T, Kirpotina LN, Khlebnikov AI, Quinn MT. Neutrophil Immunomodulatory Activity of (−)-Borneol, a Major Component of Essential Oils Extracted from Grindelia squarrosa. Molecules. 2022;27(15):4897. PMC9369983
• Essential Oil Composition of Grindelia squarrosa from Southern Idaho. Molecules. 2023;28(9):3854. PMC10180262
• La VD, Lazzarin F, Ricci D, et al. Active Principles of Grindelia robusta Exert Antiinflammatory Properties in a Macrophage Model. Phytotherapy Research. 2010;24(11):1687–1692.
• Naturopaths & Herbalists Association of Australia (NHAA). Herb of the Month: Grindelia camporum or Gumweed. 2024.
• LearningHerbs. Grindelia Uses and Plant Profile (with ethnobotanical citations).
• Altmeyer's Encyclopedia of Dermatology and Phytotherapy. Grindeliae herba.
• Essential Oil Composition of Grindelia squarrosa from Southern Idaho. MDPI Molecules 2023.
• Schepetkin et al. Neutrophil Immunomodulatory Activity of (−)-Borneol from Grindelia squarrosa. MDPI Molecules 2022;27:4897.
• Gierlikowska et al. G. squarrosa Extract and Grindelic Acid: Full text, Frontiers in Pharmacology 2021.
• La et al. Active Principles of Grindelia robusta: Semantic Scholar record.
• Carahealth. Grindelia (Grindelia robusta) Herbal Monograph.