A review on therapeutic potential of Acmella oleracea (L.): A medicinal Herb

Introduction

The Acmella genus, classified under the Asteraceae family, contain about 30 different species. Among various species, Acmella oleracea is considered one of the most important (Cheng et al., 2015) [4] . The flowers of this plant are golden-yellow in colour with red tips, arranged in a characteristic round and tubular shape called discoid capitulum (Uthpala, & Navaratne 2020) [19] . Acmella has significant medicinal value due to its wide range of bioactive compounds. It is commonly called as the "Toothache Plant" because of its use in relieving tooth pain. The entire plant has various health benefits. In northern regions of Brazil, this plant is called as "Jambu". Because of its medicinal value, this is also used for the traditional cooking. The flowers are often added to vegetable dishes, adding flavour and having a mild numbing effect (Rondanelli et al., 2020) [13] . Traditionally, all parts of the plant including flowers, leaves, and stems are known for their use in folk medicine to relieve a wide range of ailments. In Brazilian homes, especially in the Amazon region, Acmella oleracea is commonly employed in traditional medicine for treating throat infections, mouth ulcers, and even mild fevers. When the flowers and leaves of plants are chewed, they produce a unique tingling, numbing or mouth-watering sensation on the lips and tongue. This sensory effect is arises due to spilanthol content which is a bioactive compound found in high concentration in the plant. Spilanthol is belongs to N-Alkylamide group that acts as a natural local anesthetic and analgesic (Alperth et al., 2024) [3] . It interacts with nerve endings and temporarily blocks pain signals, making it especially useful in treating toothaches, gum inflammation, and oral discomfort.

Scientific classification

The scientific classification of A. oleracea is given in the table below (Table 1). Apart from its pain-relieving activity, spilanthol contain antimicrobial, antifungal and anti-inflammatory properties. These features make Acmella oleracea a valuable for the development of herbal-based dental care products, such as gels, mouthwashes, and toothpaste aimed at reducing oral infections and inflammation (Sawant & Kareppa, 2022) [16] .

Both the leaves and flowers of this species serve as important sources of bioactive compounds and are widely used in traditional remedies and culinary practices.

Leaves

Acmella oleracea leaves are soft, and dark green in colour, and range in shape from oval to lanceolate, with noticeable venation and finely serrated edges. They are arranged alternately along the stem and grow on slender petioles. When the leaves are crushed, a special aroma is released due to the essential oils they contain. The leaves are reservoir of some beneficial constituents, including alkylamides (notably spilanthol), flavonoids, and various phenolic compounds. These chemicals contribute to the pharmacological activities such as antibacterial, anti-inflammatory, antioxidant and pain-relieving properties (Dubey et al., 2013) [6] .

Traditionally, the leaves are used to prepare a decoction to treat fever, oral infections, sore throat and joint pain associated with arthritis. Their ability to stimulate saliva flow also makes them effective in managing oral dryness and speech difficulties (Savant et al., 2022) [16] . The fresh leaves of Acmella oleracea are also consumed as food in some regions and this is used for salads or lightly cooked food as a leafy green in South American and Asian cuisines.

Flowers

Flowers of Acmella oleracea, a member of the Asteraceae family, are unique in their structure and form. They are arranged in a dense, cylindrical, disc-shaped head known as the capitulum. Unlike many flowering plants in this family, Acmella oleracea does not have petal-like ray florets and has only tubular disc florets. These flowers usually display a bright yellow colour with a red or maroon center, which gives them a distinctive look. Flowers are borne on long stalks and are located in the axils of the leaves. They are soft and fleshy, which contributes to their edible and medicinal uses. One of the most significant chemical constituents of the flowers is spilanthol. Spilanthol is a alkaylamide which have anti-wrinkled activity and used in many skin care products. Acmella oleracea flowers are frequently used to treat the mouth ulcer because of its antimicrobial, antioxidant and anti-inflammatory activity (Sanap et al., 2023) [15] .

Habitat

Acmella oleracea is primarily native to Peru and Brazil, but they also grow in China, Taiwan, India. It can also be planted in moist continental climates such as the Moscow region as an annual plant (Matyushin et al., 2017) [10] . [8] .

Ethnobotanical Uses of Acmella oleracea

A. oleracea is widely cultivated and used in indigenous communities of Asia, Africa, and South America due to its medicinal value. (

Secondary Metabolites:

Acmella oleracea is rich in secondary metabolites, namely triterpenoids, steroidal, steroidal glycosides, phenolic compounds, coumarins, volatile compounds and Nalkylamides, etc. (Table 3).

Pharmacological activity of A. oleracea

A. oleracea has a diversity of pharmacological activity, including antimicrobial activity, antioxidant potential, antinociceptive properties, diuretic effect, immunomodulatory activity and pancreatic lipase inhibition (Figure 1), details of these activities are as follows:

Antimicrobial Activity

Antimicrobials are chemicals commonly used to prevent or treat infections by killing or inhibiting the growth of harmful microorganisms, such as bacteria, viruses, fungi, and parasites. They work by targeting vital biological processes such as enzyme function, genetic mutations or cell wall formation (Russell et al., 1991) [14] . In a study conducted on Acmella oleracea, methanolic leaf extracts were evaluated for antibacterial activity through the disc diffusion technique. It was tested against both Gram positive as well as gram negative bacteria. The inhibition zone ranged from 10 mm to 26 mm, showing that the plant extract has mild to moderate antibacterial activity. The strongest effect was observed against Vibrio mimicus, with a maximum inhibition zone of 23 mm (Alam and Akash 2023) [2] . These findings suggest that A. oleracea has the potential to be used as a natural antimicrobial agent. Further studies showed that both hydroethanolic and aqueous extracts of Acmella oleracea were effective against Streptococcus mutants, bacteria associated with dental plaque. These extracts had a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 125 µg/ml. The leaves and flowers of the plant were found to contain high amounts of spilanthol-a major active compound (Aktar et al., 2024) [1] . In a biofilm reduction test, using 500 µg/ml of the extract reduced S. mutants activity by more than 50%, a result similar to that obtained with chlorhexidine mouthwash (0.12%). This suggests that this extract rich in spilanthol may be useful in dental products for the prevention of dental caries. Different extraction solvents ethanol, water and petroleum ether were used to test the antibacterial properties of dried Acmella oleracea flower buds. Ethanolic extracts obtained from cold water dried flowers showed greater antibacterial effects than sun dried flowers. These extracts produced inhibition zones of 12-18.8 mm against several harmful microbes including E. coli, Staphylococcus auress, and Pseudomonas aeruginosa. The research also tested extracts of A. oleracea on skin and intestinal bacteria found in animals. Whole and fragmented plant parts were active against a variety of bacteria and fungi when used at various concentrations (up to 1000 mg/mL). Spilanthol was identified in the extract using chromatography methods. A study showed that chloroform extract of A. oleracea reduced the growth of Salmonella typhi at an MIC of 31.25 mg/mL Plates treated with 100 mg/ml extract showed bacterial inhibition after 18 h. Through the well diffusion method, the antibacterial activity of the plant was evaluated against several pathogens such as Streptococcus salivarius, Pseudomonas aeruginosa, S. viridian, S. mutans, Neisseria catarrhalis and Bacillus megaterium .The chloroform extract was particularly potent against S. viridians, whereas the aqueous extract worked well against N. catarrhalis and S. mutans. The methanol extract was effective against B. megaterium and P. aeruginosa. However, the water extract had no significant antimicrobial effect on the microorganisms tested (Thompson et al., 2012 and Uthpala et al., 2021) [17,18] .

Antioxidant Potential:

When free radicals accumulate in excess in the body, they cannot be neutralized, resulting in oxidative stress, which is an imbalance between harmful oxidative processes and protective antioxidant defenses. Free radicals are unstable molecules, formed primarily in mitochondria, which can damage proteins and other cellular structures, potentially leading to a number of health problems. Antioxidants help by neutralizing these radicals, thereby reducing the damage they cause to the body (Mo et al., 2021) [12] . It has been found that adding Acmella oleracea extract to bearberry, using a technique called supercritical extraction, significantly increases its antioxidant capacity. Scientists use different testing methods like ABTS, DPPH and ORAC to measure this activity (da Silva et al., 2023) [5] . Spilanthol, one of the major bioactive compounds, was identified through advanced techniques such as GC-FID (gas chromatography-flame ionization detection), TLC (thin layer chromatography), and FTIR-ATR (Fourier transform infrared-attenuated total reflectance). In another study, extract of jambu flower (Acmella oleracea) was found to have powerful antioxidant properties, suggesting it could be used as a natural preservative in beer. The researchers treated the plant powder with a mixture of hydrochloric acid and methanol to separate the phenolic compounds and then assessed the antioxidant capacity through DPPH and ABTS tests. The radical scavenging capacity of each sample was measured using Trolox (µmol/g dry weight) and compared with a standard reference. Among the different plant parts, leaves, stems and flowers of A. oleracea showed significantly higher levels of antioxidants (Weintraub et al., 2020) [20] . In particular, the methanolic extract obtained from the stem of A. oleracea showed strong antioxidant activity when tested with hydrogen peroxide and hydroxyl radical scavenging methods. This extract also showed the effect of neutralizing free radicals in a concentration dependent manner. Moreover, MTT assay indicated that the extract could decrease the survival of cancer cells, such as HeLa and V79 cell lines. Of all the plant parts tested, stem extracts had the strongest activity against superoxide radicals, while leaves were most effective in neutralizing DPPH radicals (Aktar et al., 2024) [1] .

Antinociceptive Properties

Given the variation in pain perception between individuals, understanding the underlying mechanisms of antinociception is essential for effective pain management. Tools such as the Temporal Summation of Pain (TASP) help identify individuals with increased or decreased sensitivity to pain, which is important for developing personalized treatment strategies. The growing body of research targeting neuropathic and inflammatory pain has emphasized the importance of tailored approaches for varying patient populations experiencing chronic or internal pain syndromes (Aktar et al., 2024) [1] . The antinociceptive potential of the methanolic extract of Acmella oleracea has been validated through both in vivo and in silico methods. These effects are primarily due to inhibition of the neurogenic and inflammatory responses seen in formalin-induced nociceptin mode Molecular docking analysis further demonstrated that the plant alkylamides functionally bind to CB1/CB2 and TRPV1 receptors, which play key roles in nociceptive modulation Importantly, the crude methanol extract did not induce the adverse effects associated with cannabinoid-based treatments, such as seizures or hyper locomotion These findings highlight the therapeutic promise of A. oleracea alkylamides as new antinociceptive agents. For the first time, this study establishes a link between these compounds and the modulation of the endocannabinoid and vanilloid signaling pathways. Further pharmacological investigations into the hexanic fraction (HF) and isobutylalkylamide (IBA) demonstrated significant antinociceptive (0.1 µg) and pronociceptive (30 µg) effects via intraplantar administration in murine models. In the context of glutamate-induced nociception, low doses of HF and IBA significantly decreased pain responses in both the neurogenic and inflammatory phases. This analgesic effect was mediated via TRPV1 (transient receptor potential vanilloid 1) regulation and was independent of endogenous opioid system activation. Additionally, compound 48/80induced nociception and mast cell degranulation in the hind paw were reduced following high-frequency stimulation (HF). According to Dallazzane et al., (2018), both agents were shown to decrease nociceptive responses through mechanisms involving TRPA1 activation.

Diuretic Effect

Acmella oleracea, particularly its fresh flowers, has been investigated for its potential diuretic activity. In experimental studies, aqueous extracts prepared by cold maceration of fresh flowers were evaluated for their effects on urinary output. Administration of high doses of the extract resulted in a significant increase in urine volume following a single dose, indicating a pronounced diuretic response. The observed effect was comparable in magnitude to that of furosemide, a widely used loop diuretic. In addition to increased urine output, a significant elevation in urinary sodium (Na⁺) and potassium (K⁺) excretion was recorded, suggesting enhanced electrolyte elimination. Furthermore, the urine produced following extract administration exhibited a slightly acidic pH, indicating that the extract may exert a mechanism of action similar to that of loop diuretics. Phytochemical analyses of A. oleracea flowers have revealed the presence of bioactive constituents such as N-isobutylamides, alkaloids, and amino acids, which may collectively contribute to the observed diuretic activity.The extract was also characterized by a rapid onset and prolonged duration of action, which may reduce the frequency of administration required for therapeutic efficacy. These findings support the traditional use of A. oleracea flowers as a natural diuretic and suggest their potential application as a safer alternative for managing conditions associated with fluid retention. However, further studies focusing on dose optimization, mechanism of action, and clinical safety are required to validate its therapeutic utility (Dubey et al., 2013 and Aktar et al., 2024) [6,1] .

Immunomodulatory Activity

Studies have shown that hexane and chloroform extracts of Acmella oleracea can reduce the production of nitric oxide in activated immune cells called macrophages. When used at a concentration of 80 micrograms per milliliter (mcg/mL), the hexane extracts reduced nitric oxide levels by 72%, while the chloroform extract caused a greater reduction of up to 85%. Animal and plant immunomodulatory drugs increase the body's responsiveness against infections by primarily activating the non-specific immune system. The leaves functions as immunomodulatory, adaptogenic, toothpaste, lithotriptic, antiscorbitic, ailagogine, and digestive. Acmella oleracea leaves are reported to be used traditionally as a tonic for the immune system stimulation. Internally consumed, the herb is known to exhibit general immunomodulatory activity, promoting white blood cell production (leucocytes) and antiviral interferon production and phagocytic function. Leaf ethanolic extract exhibited macrophage immunostimulation and increased function compared to control, demonstrating the herb's potential as a herbal immunomodulatory compound (Dubey et al., 2013 and Joseph et al., 2013) [6,7] .

Pancreatic Lipase inhibition

The ethanolic flower extract of Acmella oleracea demonstrated a 40% inhibition of pancreatic lipase activity in vitro at a concentration of 2 mg/mL. In comparison, Aframomum melegueta exhibited a higher inhibition rate of approximately 90%, indicating greater lipase inhibitory activity. Furthermore, an extract concentration of 0.75 mg/mL from A. melegueta produced stronger pancreatic lipase inhibition than A. oleracea (Dubey et al., 2013) [6] .

Conclusions

The accumulated ethnobotanical knowledge and experimental evidence clearly indicate that Acmella oleracea is a pharmacologically significant medicinal plant with multifunctional therapeutic potential. Its bioactivity is largely attributed to spilanthol and related N-alkylamides, along with a diverse array of secondary metabolites that collectively confer antimicrobial, antioxidant, analgesic, anti-inflammatory, diuretic, immunomodulatory, and metabolic regulatory effects. The demonstrated efficacy of leaf and flower extracts, particularly in oral health management and pain modulation, supports the plant's longstanding traditional use and its relevance in modern phytotherapy. Despite encouraging preclinical findings, the translation of A. oleracea into evidence-based medicinal applications remains limited by the lack of standardized extracts, comprehensive toxicological assessments, and well-controlled human clinical studies. Future research should therefore focus on bioavailability, mechanism-based pharmacology, formulation development, and clinical validation to facilitate the safe and effective integration of A. oleracea-derived products into contemporary healthcare systems.

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