Spilanthol Based Herbal Ointment: A Review of its Local Anaesthetic and Multifunctional Applications

Spilanthes acmella, is also called as toothache plant, eyeball plant, or occasionally "pancreas," belongs to the Asteraceae (or Composite) family of medicinal plants.¹ It typically grows to a height of 12–15 inches and spreads around 24–30 inches, flourishing in both full sun and partial shade. It prefers soil that is rich, moist, and well-draining, ideally with a pH between 6.1 and 6.5. Seeds can be sown directly in garden beds or indoor containers, with flats being the preferred method. Propagation can also be achieved through stem cuttings. The plant thrives in humid conditions with frequent watering and germinates best at temperatures between 20°C and 24°C (67°F to 75°F).Nicknamed the "toothache plant" due to the numbing sensation it produces when its leaves or flowers are chewed, Spilanthes acmella have a long curative history of medicinal properties, especially in Ayurveda.¹ It has been used to address issues like scurvy, gum and throat infections, scabies, psoriasis, stammering in children, tongue paralysis, and tooth pain. Originally from Brazil, it is now found globally, particularly in North Australia, the Americas, Africa, India, Sri Lanka, Borneo, and Malaya. Though the entire plant is bitter, the flower heads are particularly pungent, producing a tingling, numbing sensation that stimulates salivation. Its key active compounds, "spilanthol" and "acmellonate," are used to alleviate oral discomfort and enhance salivary flow. Traditionally, it's also been employed as an antiseptic, antibacterial, antifungal, antimalarial, and antipyretic remedy. Research has supported its effectiveness in addressing rabies, tuberculosis, the flu, toothaches, coughs, and more.² Spilanthes acmella produces small, conical yellow flowers and is recognized for its medicinal properties throughout the entire plant. In some cultures, its leaves are consumed either raw or cooked like leafy vegetables, producing a tingling and numbing sensation in the mouth upon ingestion. Interestingly, the plant has been traditionally used to stun fish using its crushed leaves. A variety of models, such as intracutaneous wheal development in guinea pigs, nerve plexus anaesthesia in frogs, and antipyretic action in yeast-induced fever models in albino rats, have been used in scientific investigations to assess the local anaesthetic potential of aqueous extracts from Spilanthes acmella. This species is commonly referred to as jambú, Spilanthes acmella, or Acmella oleracea, particularly the variety oleracea. Its bioactive components are extensively studied not only for their roles in plant defence and growth regulation but also for their therapeutic benefits due to antibacterial and antifungal activities. Recent research suggests that cold infusions of jambu flowers may act as effective diuretics and may help dissolve urinary tract stones. ³These extracts also demonstrated potential in reducing inflammatory pain and hypersensitivity, likely by inhibiting prostaglandin synthesis. Topical applications of aerial parts are commonly used to relieve toothaches and sore throats due to their anaesthetic effects. Moreover, wild Acmella species are under investigation for their potential in developing novel antibiotics to treat bacterial infections. A broad range of biological activities has been attributed to extracts from various Spilanthes species, including antioxidant, antimicrobial, anti-inflammatory, enzyme-inhibiting, immunomodulatory, gastroprotective, insecticidal, and larvicidal effects. These findings have sparked interest in the pharmaceutical industry, leading to the development of several medicinal products. Root extracts of the plant have shown promising results in treating conditions such as HIV/AIDS, while other traditional uses include applications as a purgative, diuretic, and remedy for bladder stones. The plant also finds use as an analgesic, bio-insecticide, and treatment for gum diseases, rheumatism, and fever.⁴ Spilanthol (chemical formula: C??H??NO; molecular weight: 221.339 g/mol) is a naturally occurring bioactive compound found in various medicinal plants, many of which are traditionally referred to as toothache plants due to their numbing effects.  It is also referred to as affinin. Its IUPAC designation is (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide. This chemical is amphiphilic, meaning it has both hydrophilic (polar amide) and lipophilic (non-polar fatty acid) sections. It is classified as an alkylamine. It may be effectively extracted from plant material using solvents like ethanol, methanol, hexane, or supercritical carbon dioxide because of its dual solubility. After being extracted, spilanthol can be purified using techniques such as preparative thin-layer chromatography (TLC) or high-performance liquid chromatography (HPLC)⁵.In addition to its well-known analgesic properties, especially for oral pain relief, spilanthol also exhibits antibacterial activity, which supports its inclusion in products like toothpastes and oral gels (e.g., Buccaldol®, Indolphar®). Furthermore, it has gained popularity in the cosmetics industry, where it is used in anti-wrinkle creams as a natural alternative to Botox. Several commercial formulations, including Gatuline®, SYN®-COLL, and ChroNOline™, incorporate spilanthol for its purported anti-aging effects.⁶

Spilanthus acmella⁷

 Spilanthes acmella, a common medicinal herb in the Asteraceae family, is sometimes referred to as Acmella oleracea, akarkara, paracress, or the eyeball plant. This plant, which is frequently called the "toothache plant," is easily identified by its eyeball-shaped, bright yellow flowers with a dark crimson centre. This plant is very useful in dental care because of its many therapeutic benefits, which include analgesic, anaesthetic, antibacterial, and anti-inflammatory qualities. Both the leaves and the flower heads (capitula) are traditionally used in northern India to treat throat and oral pain. A natural effect of chewing them is to cause a tingling and numbing feeling on the lips and tongue.⁸

Plant description

The Spilanthes genus includes around 35 species native to tropical regions, with three varieties cultivated in India. Spilanthes acmella is a hardy herbaceous plant that typically grows between 20 and 50 centimetres in height. Although it thrives in many climates, it is sensitive to frost and behaves as a perennial in warmer regions.⁹ This compact, upright plant produces vibrant, cone-shaped flowers with golden-yellow heads and reddish centres, creating a striking visual. It can be successfully grown in both garden beds and pots. For best growth, it prefers nutrient-rich, well-composted soil and a warm environment, ideally around 70°F (21°C). The stems of the plant have a strong, pungent flavour and are coated in glandular hairs. The taste of the entire plant is bitter and harsh. Notably, S. acmella does not have traditional flower petals; instead, it develops distinctive golden flower heads with rust-coloured centres. Its leaves are arranged oppositely, with petioles, broad ovate shapes that narrow at the base and taper to either an acute or blunt tip. Flowering and fruiting typically occur between March and April¹⁰

Geographical distribution                                                                                

 India, Australia, North America, Africa, Sri Lanka, Borneo, and Malaya are just a few of the tropical and subtropical places where this plant is found in the wild. It is primarily found in the central and southern parts of India.¹¹

Sensory quality

Despite having no discernible smell, Spilanthes acmella has a distinct flavour that changes from pleasantly salty and pleasant to extremely tingly, spicy, and slightly burning—finally leaving the mouth feeling numb.¹²

Phytochemistry of spilanthus acmella

To better understand the link between a plant's therapeutic effects and its chemical makeup, it's essential to study its phytochemical composition. Numerous studies have focused on identifying and analysing the structure of the pungent alkylamides found in Spilanthes acmella. Spilanthol, the most noticeable component, is an isobutyl amide with a strong flavour and insecticidal qualities. Because of its bitterness, it can also increase salivation. Apart from alkylamides, the plant has also yielded triterpenoids. The IUPAC name for Spilanthol, also known as N-isobutylamide, is (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide. One study involving an ethanol-based extract of the plant showed that 9.04% of the extract consisted of total N-alkylamides, of which spilanthol made up a significant 88.84%.

Composition and its properties

Numerous physiologically active substances found in Spilanthes acmella can be extracted from the plant as a whole or from particular sections such the roots, leaves, and flowers. To identify these compounds, researchers commonly use gas chromatography–mass spectrometry (GC-MS), including instruments like the Thermo Finnigan system. This technique allows for the detailed analysis of chemical constituents present in the plant's extracts. In samples from southern India, studies have identified over 45 different chemical components within the essential oil derived from fresh plant material. One of the most significant constituents is spilanthol, which is recognized for its analgesic, anti-inflammatory, and local anaesthetic effects. Experiments using insect pupae have shown that spilanthol can disrupt normal nervous system activity, causing symptoms such as twitching, spinning, and lack of muscle coordination—suggesting that the compound affects nerve signal transmission. The compounds found in the essential oil are typically arranged according to their order of elution from a polar GC column (similar to DB-5 columns), with their relative concentrations measured using peak area percentages from the GC-MS analysis.

Toxicological analysis

The toxicity profile of Spilanthes acmella was evaluated using zebrafish embryos as a biological model. In this study, an aqueous crude extract prepared from the plant’s leaves was applied to newly fertilized zebrafish embryos to assess potential adverse effects. At 48 hours post-fertilization (hpf), the lowest observed effect concentrations (LOEC) were found to be 20% for malformations and 10% for sublethal outcomes. Meanwhile, the no observed effect concentrations (NOEC) were recorded as 20% for lethality, 10% for malformations, and 1% for sublethal effects. Notably, even at the highest tested concentration of 20%, no embryo mortality was observed, suggesting that the extract did not produce lethal toxicity at that level.

Mechanism of action of spilanthus acmella as local anaesthetic¹³

The local anaesthetic effect is brought on by the action of spilanthol, an isobutyl amide chemical called acmellonate. According to certain researches, alkyl amides are present in spilanthus acmella. Because it contains alkylamides, a few studies have demonstrated the local anaesthetic qualities of spilanthus acmella. The potential mechanism of action of spilanthus acmella as a topical anaesthetic may be related to conduction obstruction in nerve fibers. The antinociceptive properties of Spilanthus acmella have been investigated; the suggested mechanism of action involves enhanced gamma-aminobutyric acid release and modification or blockage of transient receptor potential channels subfamily V member 1 (TRPV1) and subfamily A member 1 (TRPA1).

Medicinal values of spilanthus acmella¹⁴

Throughout history, Spilanthes acmella has been used medicinally in a number of places, including Malaysia, Thailand, Brazil, India, and Spain. The medicinal properties of many plant components, such as the leaves, flowers, and roots, have been used in medicine. Extracts from the leaves and blossoms have long been used to treat toothaches and stomatitis, an infection of the mouth, because of its inherent anaesthetic qualities. In addition to its use in dentistry, the plant has been used to cure a variety of illnesses, including fever, rabies, throat infections, coughs, and TB. Its use extends to managing fever, rheumatism, and urinary conditions, with evidence suggesting it acts as a diuretic and may help in dissolving urinary stones.¹⁵ In addition, S. acmella is recognized for its antiseptic, antibacterial, and antimalarial activities. It has been incorporated into pharmaceutical products aimed at oral health, including treatments for gum infections, periodontitis, and as a component in mouthwashes and toothache relief formulations.

Synonyms

Table No. 01: Synonyms

Taxonomic classification  ¹⁴

Table No. 02: Taxonomic classification

Table No. 03: Morphology¹⁶

Medicinal Applications of Spilanthes acmella¹⁷

Spilanthes acmella is a well-known medicinal herb that is sometimes referred to as the "toothache plant" because of its capacity to increase salivation and reduce dental discomfort. Historically valued across cultures, it has been cultivated for not just medicinal use, but also culinary, horticultural, and insect-repelling purposes. Its therapeutic potential stems from a rich variety of secondary metabolites present throughout the plant. Here are several established and traditional uses of the plant:

1. Antimalarial Activity¹⁸

In traditional African medicine, Spilanthes species have been used to combat microbial infections. The compound spilanthol, found in S. acmella, has demonstrated activity against Plasmodium falciparum, the parasite responsible for malaria.

2. Relief from Rheumatism

Used particularly among older adults, the whole plant is believed to help ease joint pain and inflammation, making it beneficial in cases of gout and rheumatism.

3. Digestive Health

Chewing on the roots of S. acmella is a traditional remedy for gastrointestinal issues, offering relief from digestive tract discomfort. ¹⁶

4. Toothache and Oral Health

The plant is widely recognized for its numbing effect. Chewing the flower heads can alleviate toothaches, sore throats, and even temporary paralysis of the tongue, thanks to the action of spilanthol.¹⁹

5. Local Anaesthetic Effect

Extracts from the plant act as local anaesthetics, providing temporary loss of sensation in targeted areas without affecting consciousness.

6. Antibacterial Properties²⁰

Ethanolic extracts have shown antimicrobial effects against a variety of harmful bacteria including Salmonella typhi, E. coli, Streptococcus pyogenes, and Staphylococcus aureus. Notably, the extracts were also active against antibiotic-resistant strains carrying the Bla gene.

7. Antifungal Effects

Though limited, S. acmella has shown some effectiveness against fungi like Microsporum gypseum and Cryptococcus neoformans, which commonly infect immunocompromised individuals, such as those with HIV/AIDS.

8. Treatment for Periodontitis

Chewing the roots and flowers may help reduce gum inflammation, offering a natural remedy for periodontitis.

9. Cosmetic Uses

The plant has gained popularity in the cosmetic industry for its ability to relax facial muscles and reduce the appearance of wrinkles, resulting in visibly smoother skin.

10. Other Traditional Uses

Additionally, Spilanthes acmella has long been used to treat fevers, TB, rabies, stomatitis, cough, flu, colds, and headaches. Extracts from the leaves and flowers are typically prepared for these purposes.

Pharmacological Activities of Spilanthus acmella

Spilanthus acmella demonstrates a wide range of pharmacological activities across various plant parts. The leaves and flowers are known for their antibacterial, antiseptic, and antimalarial properties, making them useful in a variety of medical conditions. . This plant has long been used in Ayurvedic medicine to cure ailments like scabies, psoriasis, scurvy, and gum infections. Its flower heads are very helpful for analgesic effects. Below are some of the key pharmacological effects demonstrated by Spilanthus acmella:

1. Anti-inflammatory Activity^22,23

The spilanthol compound from Spilanthus acmella has been found to significantly reduce inflammatory responses in murine macrophages, particularly by inhibiting NF-κB activation. Animal models using aqueous extracts of the plant's aerial parts have demonstrated notable anti-inflammatory and analgesic properties, including a dose-dependent reduction in paw edema and increased pain threshold.

2. Antipyretic Properties²⁰

Studies have indicated that Spilanthus acmella can effectively reduce fever induced by yeast, with flavonoids from the plant contributing to this activity. The mechanism of action involves the inhibition of cyclooxygenase (COX) enzymes, which prevent the hypothalamus from releasing prostaglandin E2 (PGE2), a mediator of fever.

3. Local Anaesthetic Effect

Spilanthus acmella has shown significant potential as a local anaesthetic. Animal studies using plexus anaesthesia in frogs and intracutaneous applications in guinea pigs have demonstrated its ability to block Na+ channels, similar to the mechanisms of commonly used anaesthetics such as lidocaine.

4. Analgesic Effects²⁵

Animal studies have confirmed the analgesic potential of the aqueous extract of Spilanthus acmella. These studies, including tail flick and hot plate tests, show that the plant can provide both peripheral and central analgesic effects, possibly acting through sedative and analgesic pathways.

5. Vasorelaxant Effects²⁶

Spilanthus acmella has demonstrated a vasorelaxant effect in rat thoracic aortas pre-contracted with phenylephrine. The extract, particularly from chloroform and ethyl acetate, induced a dose-dependent relaxation of vascular tissues, supporting its potential role in cardiovascular health.

6. Anti-cancer Activity²⁷

Preliminary in-vitro studies have shown that extracts of Spilanthus acmella possess anticancer properties. These extracts demonstrated growth inhibition in liver (HEP-2) and colon (HT-29) cancer cell lines. The plant’s bioactive compounds may help reduce free radicals and induce apoptosis, offering potential as a preventative or therapeutic agent for cancer.

7. Neuroprotective Effects²⁸

Research has indicated that extracts from the aerial parts of Spilanthus acmella may help protect neurons from degeneration caused by pirimicarb-induced neurotoxicity. The plant’s bioactive compounds are thought to maintain calcium homeostasis, which is crucial for protecting neuronal health.

Fig 1: Spilanthus acmella