Centipeda

Centipeda: A Comprehensive Reference Article

1. Identity and Botanical Classification

Centipeda is a genus of small herbaceous flowering plants belonging to the family Asteraceae (the daisy family). The genus comprises 12 taxa in 10 species, and all but one species occur in Australia. There are documented traditional medicinal uses of five species across Australia, India, and China. Two species dominate the scientific and ethnobotanical literature and are discussed in detail below.

1.1 Centipeda cunninghamii (DC.) A. Braun & Asch.

Centipeda cunninghamii, historically referred to as Myriogyne cunninghamii, is an Australian species of flowering plant belonging to the family Asteraceae. The species was first formally described in 1838 by the Swiss botanist Augustin Pyramus de Candolle, who placed it in the genus Myriogyne. Commonly known as "old man weed," and less commonly referred to as "common sneezeweed" or "scent weed," it is an endemic Australian traditional medicinal plant with over 150 years of documented use.

Known traditionally by the Koori name gukwonderuk, translated into English as "old man weed," the plant has long been recognised by Indigenous communities for its medicinal applications. The plant is identified by its uniquely shaped leaves and a pungent aroma, and it grows naturally on a range of soil types near the edges of waterways and billabongs and in damp areas subject to periodic inundation. The plant is widely distributed and occurs in all states of Australia, although it is more common in southeastern Australia. It can be identified by its unique shaped leaf and its pungent scent, which is pine-like and minty.

1.2 Centipeda minima (L.) A. Braun & Asch.

Centipeda minima (CM), the dried whole plant of Centipeda minima (L.) A. Braun and Aschers, has been used as a traditional Chinese medicinal herb for thousands of years for the treatment of rhinitis, sinusitis, cough, and asthmatic diseases. It is also commonly known as "chicken intestine herb," "stone coriander," or "ground coriander." In Traditional Chinese Medicine (TCM), it is known by the names Ebushicao or Ebushicao (鹅不食草). It is the dried whole plant, collected at flowering in summer and autumn. The rootlets of this herb are slender and pale yellow. The texture is fragile, yellowish-white, and can be broken easily. Leaves are small and often crumpled, which look greyish-green or brown, and the edges are often serrated. The capitulum is yellow or yellowish-brown. The odour is slightly aromatic, and pungent when smelled for a long time; it tastes a little bitter, as described in the Chinese Pharmacopoeia.

1.3 Relationship Between the Two Species

Centipeda cunninghamii is the generally preferred plant for Australian traditional applications, but other species of the Centipeda genus can also be used, including Centipeda minima (spreading sneezeweed, also known as C. orbicularis) and C. thespidioides, known as Desert Sneezeweed. Although they are botanically related and share some constituents, the two species have been studied in largely separate scientific literature and in different cultural traditions, and the medicinal properties of one cannot be automatically assumed to apply to the other.

2. Traditional and Historical Use

2.1 Indigenous Australian Use of C. cunninghamii

Centipeda cunninghamii has a long history of traditional use by Australian Aboriginals for wounds, infections, and inflammation. Traditional methods of use most commonly involve binding leaves of the plant directly to the forehead or other parts of the body, so that body heat may release the plant's oils, which are then absorbed into the skin. It may also be taken orally, sometimes mixing it with emu fat or boiling or soaking it in water to create a tea.

The plant has traditionally been used by boiling in water to produce a tea, which is often taken orally to treat illnesses including tuberculosis. Other known uses of the tea solution or decoction include the treatment of purulent ophthalmia and sandy blight, and for alleviating eye inflammation by bathing the eyes with a cooled solution. Other uses of the plant have been to place the plant around the head of the person for the relief of colds. It has also been administered as an antiprotozoal.

2.2 Traditional Chinese and Indian Use of C. minima

Centipeda minima is known in TCM for its effects in dispersing wind-cold, clearing nasal passages, and relieving coughs. It has a pungent taste and warm nature, acting on the lung meridian, and functions to disperse wind-cold, unblock the nasal passages, and relieve cough. It is a traditional Chinese medicinal material utilized for treating wind-cold syndrome, wind pain, coughs, phlegm, nasal congestion, and runny nose.

Centipeda species have been used as a traditional medicine in India and China. In China and India, C. minima has been used to treat inflammation associated with colds, haemorrhoids, malaria, toothache, and headaches. C. minima has also been used as an antimicrobial for conjunctivitis, ophthalmia, skin rashes, epididymitis, white patches on the skin, dyspnoea, cough, and toxicosis. Central Australian Aboriginal tribes used C. minima, C. cunninghamii, C. thespidioides, C. craterformis, and C. pleiocephala to treat colds.

3. Key Constituents and Active Compounds

3.1 Overall Chemical Profile of C. minima

A total of 191 compounds have been isolated and identified from C. minima, including terpenes, flavonoids, sterols, phenols, organic acids, and volatile oils. The primary bioactive constituents of Centipeda minima are volatile oils, terpenes, flavonoids, and organic acids, all exhibiting extensive pharmacological effects.

3.2 Sesquiterpene Lactones

Sesquiterpene lactones are widely regarded as the most pharmacologically significant class of compounds in C. minima. C. minima contains a large number of terpenoids, of which guaiacolane sesquiterpene lactones are the main active constituents with biological activities such as anti-tumour, anti-inflammatory, anti-viral, anti-microbial, anti-malarial, anticancer, anti-diabetic, and analgesic effects, in addition to monoterpene glycosides, sesquiterpenes, and triterpene constituents.

Among these, the sesquiterpene lactones brevilin A, arnicolide D, and arnicolide C constitute the principal active constituents of C. minima. Sesquiterpene lactones are built from three isoprene units, contain one or more lactone rings, and exhibit potent anti-cancer, anti-oxidant, and anti-inflammatory activities. Brevilin A is a sesquiterpene lactone isolated from C. minima and has been reported to exhibit multiple biological activities, including antibacterial and anti-cancer effects.

Brevilin A (also called 6-O-angeloylplenolin, or 6-OAP) is the most abundant sesquiterpene lactone in the plant. HPLC-UV and UHPLC-Q-TOF-MS analysis detected four compounds in an emulsion extract of C. minima: arnicolide D, arnicolide C, microhelenin C, and brevilin A. Among them, brevilin A was the main component and its content was more than double that of the other compounds combined.

Compounds including brevilin A, arnicolide C, arnicolide D, and helenalin are proposed as candidate Quality Markers for C. minima, providing a scientific basis for elucidating its pharmacologically active substances and establishing quality evaluation criteria.

3.3 Flavonoids

Chemical constituents isolated from ethyl acetate and n-butanol extracts of C. minima include the flavonoids (2R,3R)-(+)-7,4′-di-O-methyldihydrokaempferol, iristectorin A, 4′,5,8-trihydroxy-7-methoxyisoflavone, 3-trimethoxyquercetin, quercetin, and hispidulin, among others. C. minima is rich in flavonoids with significant pharmacological activity, and these compounds are commonly used in clinical treatment of allergic rhinitis; the anti-allergic effect of flavonoids is reported to be slightly stronger than that of volatile oil components.

3.4 Organic Acids

Organic acids represent another important class of bioactive compounds. Key organic acids identified in C. minima extracts include caffeic acid, chlorogenic acid, and isochlorogenic acids A, B, and C. Chlorogenic acid in particular has attracted attention as a potential anti-cancer compound. Chlorogenic acid, a representative organic acid in C. minima, reportedly possesses anticancer potential and inhibits tumor growth by affecting the tumor microenvironment, and has been approved for Phase II clinical trials in patients with glioma in China.

3.5 Volatile Oils — C. cunninghamii

The essential oil composition of C. cunninghamii, principally chrysanthenyl and sabinyl acetates, has been known for some time, though there was historically little scientific information regarding its broader phytochemistry and biological activity. The steam-distilled volatile oil from C. cunninghamii has been reported to contain thymol, myrtenyl acetate, myrtenol, cis-chrysanthenyl acetate, and cis-chrysanthenol.

Seventeen compounds were isolated from C. cunninghamii and subsequent bioassays indicated that the anti-inflammatory activity was linked to flavonoids and terpenoids, whilst the antioxidant activity was attributed to both flavonoids and a group of novel heptenedioic acid caffeoyl esters.

3.6 Other Compounds

Compounds previously reported in C. minima in the older literature include isobutyroylplenolin, senecioylplenolin, lupeol acetate, hexacosanol, β-sitosterol, stigmasterol, taraxasteryl palmitate, taraxasteryl acetate, taraxasterol, arnidiol, arnicolide, breviofolin, helenanin, florilenalin isobutyrate, florilenalin isovalerate, and florilenalin angelate. Compounds known specifically for C. cunninghamii from the older literature include myriogenin and cis-chrysanthenyl acetate.

4. Established Mechanisms of Action

4.1 Anti-Inflammatory Mechanisms

Detailed investigations suggest that aqueous ethanolic extracts of C. cunninghamii act against a range of inflammatory markers including PGE₂, COX, NO, and TNF-α, but not through the lipoxygenase pathway. The same profile — acting against COX-1, COX-2, NO, and TNF-α, but not through the lipoxygenase pathway — has been confirmed for C. cunninghamii extracts.

For brevilin A specifically, brevilin A significantly attenuates the activation of caspase-1 and the subsequent secretion of interleukin-1β (IL-1β) in mouse macrophages and human THP-1 cells, showing an inhibitory effect on NLRP3 inflammasome activation. Brevilin A exhibits a broad spectrum of pharmacological properties, including anticancer, anti-inflammatory, treatment of alopecia areata, antifibrotic, and antiviral activities.

4.2 Anticancer Mechanisms

Sesquiterpene lactones, such as 6-O-angeloylplenolin (6-OAP, or brevilin A) and arnicolide D, have similar structures and anticancer mechanisms. As the most abundant sesquiterpene lactone in C. minima, 6-OAP exhibits anticancer activities mainly by targeting Skp1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase and signal transducers and activators of transcription 3 (STAT3).

Mechanistically, brevilin A primarily induces cell apoptosis, triggers autophagy, and disrupts signaling pathways. Brevilin A has also been demonstrated to enhance the anticancer properties of drugs like paclitaxel and cisplatin, leading to reversal of chemotherapy resistance and increased sensitivity.

6-O-angeloylplenolin and arnicolide D were found to be the active compounds responsible for the activation of the Nrf2 signaling pathway and inhibition of ROS production. The sesquiterpene lactones that abundantly distributed in C. minima extracts, including 6-OAP, arnicolide D, and arnicolide C, were demonstrated to decrease Skp2 while increasing p27 protein level, thereby significantly inducing cell cycle arrest and suppressing migration of NSCLC cells.

4.3 Antioxidant Mechanisms

The antioxidant activity of C. cunninghamii was attributed to both flavonoids and a group of novel heptenedioic acid caffeoyl esters. For C. minima, 6-O-angeloylplenolin and arnicolide D were found to be the active compounds responsible for the activation of the Nrf2 signaling pathway and inhibition of ROS production.

4.4 Immunomodulatory and Anti-Allergic Mechanisms

Studies using an ovalbumin-induced allergic rhinitis mouse model found that fresh C. minima extract predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas dried C. minima extract enhanced Th1 activity (increasing IFN-γ). This differential immunomodulation suggests that plant processing may meaningfully alter the therapeutic profile of the herb.

5. Scientific Evidence by Area of Use

5.1 Allergic Rhinitis and Sinusitis

Reports suggest that Centipeda minima extracts possess anti-inflammatory, anti-bacterial, and anti-allergic effects, and the herb has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. The evidence base for this application is the most developed of any area, and it spans laboratory, animal, and limited clinical investigation.

A 2015 PubMed-indexed study on a rat allergic rhinitis model examined the volatile oil constituent. The study analysed the volatile oils from seven geographic areas and their therapeutic effects on allergic rhinitis; Sprague-Dawley rat allergic rhinitis models (n = 10 per group) were treated with 100 μL per nostril of 0.1% C. minima volatile oil, with blank and model groups receiving the same amount of normal saline. After 15 days, serum inflammatory factors were detected by ELISA and nasal mucosa tissues were examined by haematoxylin-eosin staining and immunohistochemistry. The results suggested that C. minima volatile oil operates via multi-target and multi-pathway mechanisms in the treatment of allergic rhinitis.

A more recent study aimed to compare the therapeutic effects of fresh and dried C. minima against allergic rhinitis, using an ovalbumin-induced AR mouse model treated with fresh (CMF) or dried (CMD) extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components.

A PubMed-indexed histopathological study on allergic rhinitis treated with C. minima reached the conclusion that C. minima is effective in treating allergic rhinitis. However, the overwhelming majority of available evidence comes from animal models and in vitro studies. Robust, placebo-controlled human clinical trials specifically on Centipeda for rhinitis have not been identified in the peer-reviewed literature at the time of this writing, and the strength of the clinical evidence is therefore considered preliminary.

5.2 Anticancer Properties

Accumulated evidence suggests that C. minima extracts and their active components possess therapeutic potentials for treating human diseases, especially cancers. This body of evidence is, to date, largely preclinical.

Triple-Negative Breast Cancer (in vitro): In an investigation of anti-cancer activity in TNBC, in MDA-MB-231 cells, the total extract of C. minima (CME) could significantly reduce cell viability and proliferation, induce apoptosis, and inhibit cancer cell migration and invasion, in a dose- and time-dependent manner.

Non-Small Cell Lung Cancer (in vitro and in vivo): At doses of 200–600 mg/kg, ECM significantly inhibited tumor growth and metastasis in A549-luciferase cell orthotopic xenografts by suppressing Skp2 expression. The sesquiterpene lactones, including 6-OAP, arnicolide D, and arnicolide C, were also demonstrated to decrease Skp2 while increasing p27 protein level, thereby significantly inducing cell cycle arrest and suppressing NSCLC cell migration. A supercritical fluid extract of C. minima (CM-SFE), mainly consisting of 6-OAP, arnicolide D, and arnicolide C, exhibited stronger anti-NSCLC activity than the ethanol extract in orthotopic xenograft models.

Nasopharyngeal Carcinoma (in vitro): One study investigated the anticancer activities of C. minima ethanol extracts (CME) against nasopharyngeal carcinoma cell CNE-1. CNE-1 cells were treated with different concentrations (15–50 μg/mL) of CME for different time intervals (24, 48, and 72 h), and cytotoxicity was determined by MTT assay. Volatile oils from C. minima extracted by steam distillation and supercritical fluid extraction induced CNE cell death via induction of intrinsic apoptosis by regulating the expression of the Bcl-2 family of proteins.

Multiple Myeloma (in vitro): Small compound 6-O-angeloylplenolin has been reported to induce mitotic arrest and exhibit therapeutic potentials in multiple myeloma (PLoS ONE, 2011).

Gastric Cancer (in vitro): Brevilin A isolated from Centipeda minima has been reported to induce apoptosis in human gastric cancer cells via an extrinsic apoptotic signaling pathway.

Lung Cancer Mechanism Study: Results from network pharmacology analysis of brevilin A's anti-lung-cancer activity highlight STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets.

Clinical translation: Clinical trials have assessed the potential of 6-OAP in patients with vertex balding and alopecia areata, given its effect on JAK-STAT signaling. Chlorogenic acid, a representative organic acid in C. minima, reportedly possesses anticancer potential and inhibits tumor growth by affecting the tumor microenvironment, and has been approved for Phase II clinical trials in patients with glioma in China. The totality of anticancer evidence remains preclinical (in vitro and animal studies) with the exception of these early-phase or niche clinical evaluations.

5.3 Skin and Wound Applications

The extract of C. cunninghamii has been found to be an effective anti-inflammatory composition, antifungal composition, UV-blocking or sunscreen composition, and a promoter of cell renewal as a healing agent. The topical anti-inflammatory (antihistaminic, antiallergic), sunscreen, and cell renewal properties have reportedly been proved clinically, with a significant difference (p < 0.005) obtained. The extract is preferably diluted with 20% ethanol to obtain a final concentration of 0.2% sesquiterpene lactones calculated as brevilin A. This claim originates from a US patent filed by Bio-Botanica Inc. (US 5,804,206) and represents proprietary, not peer-reviewed, clinical data; no independently published randomised controlled trial of topical C. cunninghamii extract has been identified in the peer-reviewed medical literature.

5.4 Alopecia Areata and Hair Growth

A clinical trial combined with network pharmacology-based analysis evaluated the stimulatory effect of the extract of C. minima on hair regrowth. HPLC-UV and UHPLC-Q-TOF-MS detected four compounds — arnicolide D, arnicolide C, microhelenin C, and brevilin A — in the CMX emulsion extract. Brevilin A was the main component, with content more than double that of the other compounds combined. An emulsion extract prepared from C. minima (CMX), containing 6-OAP, ArC, ArD, and microhelenin C, was tested in clinical trials for patients with alopecia areata and vertex balding. While these constitute human trials, the complete methodology, sample sizes, blinding, and outcomes of these trials are not fully reported in the available open literature, and evidence strength for this application is therefore considered preliminary.

5.5 Neuroprotection and Neuroinflammation

In an experimental study on a neurodegenerative mouse model, C. minima extract sustained the expression levels of postsynaptic density 95 (PSD95) and synaptophysin (SYN), activated the Nrf2 signaling pathway, and restored the levels of cellular antioxidants in the hippocampus of mice. Four sesquiterpene lactones isolated from C. minima, particularly 6-O-angeloylplenolin and arnicolide D, were found to be the active compounds responsible for the activation of the Nrf2 signaling pathway and inhibition of ROS production. This holds promise for the treatment of neurodegenerative disease. This evidence is entirely preclinical (animal and in vitro).

5.6 Antimicrobial Activity

Volatile oil from C. minima has demonstrated properties of relieving allergic rhinitis, anti-inflammatory responses, and activity against cancer cell lines, with its ethanol extracts showing antimicrobial activity. Older pharmacognostic work by Taylor and Towers (1998) identified antibacterial constituents of the Nepalese medicinal herb C. minima (Phytochemistry, 47:631–634). All antimicrobial evidence identified is in vitro; no controlled clinical trials of Centipeda for infectious disease have been found in the peer-reviewed literature.

5.7 Osteoarthritis (Preclinical)

Research has found that brevilin A reduced the progression of osteoarthritis in a mouse model by inhibiting inflammation and ferroptosis via the SIRT1/Nrf2/GPX4 signaling pathway. This evidence is preclinical.

6. Body Systems and Health Areas of Association

• Respiratory system: Centipedae Herba, the dried whole plant of C. minima, has documented bioactivities including anti-rhinitis, anti-sinusitis, anti-inflammation, anti-cough, and anti-asthma properties.
• Immune/allergic system: Extracts of C. minima have various pharmacological effects including anti-allergic rhinitis, anti-tumor, anti-allergic, anti-inflammatory, and anti-mutagenic features.
• Integumentary system (skin): Indigenous Australian communities have long valued C. cunninghamii for its medicinal properties, applying it in treatments for wounds, infections, inflammation, and respiratory symptoms.
• Oncology: Scholars have conducted extensive studies on C. minima's clinical applications, especially its potential efficacy in cancer treatment.
• Central nervous system (preclinical): Studies in animal models support potential neuroprotective effects mediated through Nrf2 activation and reduction of oxidative stress in hippocampal tissue.
• Musculoskeletal system (preclinical): Brevilin A has demonstrated activity against osteoarthritis-related inflammation in animal models.
• Hair follicle biology: JAK-STAT signalling inhibition by brevilin A has been explored in clinical trials for alopecia areata and vertex balding.

7. Dosage Forms and Reported Dosages

Dosage information in the scientific literature varies considerably between applications and species.

7.1 Traditional Preparations

• Traditional methods of use include topical application, where leaves are bound to parts of the body, allowing released oils — facilitated by body heat — to permeate the skin. Oral preparations involve boiling or soaking leaves to produce a tea, or mixing with emu fat to create a medicinal preparation.

7.2 Preclinical/Research Dosages

• In a rat allergic rhinitis model, the treatment group was given 100 μL per nostril of 0.1% C. minima volatile oil, with treatment continued for 15 days.
• In A549-luciferase cell orthotopic xenograft mouse models, ECM at doses of 200–600 mg/kg was found to significantly inhibit tumor growth and metastasis.
• In vitro, CNE-1 nasopharyngeal carcinoma cells were treated with concentrations of 15–50 μg/mL of C. minima ethanol extract for time intervals of 24, 48, and 72 hours.

7.3 Topical Extract (Patent)

• The extract described in the Bio-Botanica patent is preferably diluted with 20% ethanol to a final concentration of 0.2% sesquiterpene lactones calculated as brevilin A, and further contains approximately 3% by volume glycerol. The extract can be applied topically to the skin or combined with other standard components used in preparing lotions or creams.

No standardized human oral dosage has been established by any pharmacopoeial body or regulatory agency for either species at this time. The Chinese Pharmacopoeia lists C. minima as an official medicinal herb, though specific dosage ranges were not reproduced in the reviewed open-access literature.

8. Safety Considerations

8.1 General Safety Profile of C. minima

No documented toxicity exists in historical records of TCM, indicating that C. minima is a relatively mild and safe medicinal herb with significant therapeutic value, and it is widely used in TCM practice. However, clinically, only a low incidence of adverse reactions has been observed.

Pharmacological experiments revealed that oral administration in mice showed no signs of weight loss or hepatorenal toxicity, as evidenced by the levels of serum transaminases, alanine aminotransferase, creatinine, and blood urea nitrogen concentrations, demonstrating a favourable safety profile.

ECM extracts can protect neurons from oxidative stress-induced damage, and the percentage of adverse effects is relatively low during clinical use.

8.2 Limitations in Safety Data

Previously, there were limited studies on the potential organ-specific toxicity of Centipeda minima and insufficient scientific data to assess its potential effects on target organs. To better evaluate the safety and possible side effects, additional studies such as toxicity studies and clinical trials are necessary. Therefore, it is not fully evident that C. minima has low toxicity without further investigations.

Current research on C. minima is limited, and to better assess its safety and potential side effects, further systematic toxicological studies are warranted.

8.3 Potential Toxicity at High Doses — C. cunninghamii

Owing to potential toxicity in large quantities, traditional custodians and contemporary herbal practitioners emphasise careful dosage control when the plant is consumed orally. No specific toxic dose or mechanism has been characterised in the peer-reviewed clinical literature.

8.4 Sesquiterpene Lactone Class Considerations

Sesquiterpene lactones as a chemical class are known to be capable of causing contact allergic reactions. Sesquiterpene lactones contain one or more lactone rings and exhibit potent biological activities. The allergenic potential of sesquiterpene lactones from Asteraceae family plants is an established pharmacological concern, though specific published sensitization data for Centipeda species were not identified in the reviewed sources.

8.5 Drug Interactions

No specific drug–herb interaction studies for Centipeda species have been identified in the peer-reviewed literature reviewed for this article. Given the documented inhibitory effects on STAT3 and JAK-STAT signaling, as well as documented effects on cell cycle kinase systems, interactions with immunosuppressive therapies or targeted anticancer agents are a theoretical concern that has not been formally evaluated in clinical studies.

8.6 Quality and Phytogeographic Variation

Differences in the content of volatile oil have been found across seven geographic growing areas of C. minima. Quality control for medicinal plant production of C. cunninghamii has utilised the levels of phenolics, flavonoids, and sesquiterpenes to optimise growing and extraction parameters. This phytochemical variability implies that the potency and safety of Centipeda-based preparations may differ significantly across commercial products.

9. Current Research Status and Limitations

Reviews in the field highlight intriguing anticancer properties mediated by active compounds isolated from C. minima extracts, particularly sesquiterpene lactones, which might provide clues for developing novel anticancer drugs. Relevant clinical trials on chlorogenic acid and 6-OAP may promote anticancer clinical applications. Nevertheless, it remains worth comprehensively elucidating underlying anticancer mechanisms and conducting further clinical trials on C. minima and its active components.

The body of scientific work on C. minima is substantially larger than that on C. cunninghamii. The Australian species has received limited peer-reviewed study relative to the Chinese species. Cutting-edge technology and systems biology could provide a more comprehensive understanding of the therapeutic effects, constituting components, and toxicity of C. minima, which are prerequisites for its translation into therapeutics for various disease treatments.

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