Plectranthus amboinicus

Plectranthus amboinicus (Indian Borage / Country Borage)

1. Identity, Taxonomy, and Botanical Description

1.1 Accepted Name and Synonymy

Coleus amboinicus (Lour.), synonymous with Plectranthus amboinicus (Lour.) Spreng., belongs to the Lamiaceae family—a large family of aromatic herbs with many medicinally important species—and is a frequently cited species within the Plectranthus genus, renowned for its traditional uses, phytochemical composition, biological activities, and applications in skin care.

The species was originally classified under the genus Coleus by Loureiro in 1790 but was moved to the Plectranthus genus by Sprengel in 1825, although both names are sometimes seen in the literature today. Because of the lack of clear-cut morphological criteria to discriminate not only among species within the Plectranthus genus but also among the closely related genera, numerous taxonomic problems in the naming of species have resulted in misplacement of species in several closely related genera like Coleus, Solenostemon, and Englerastrum.

Additional accepted synonyms documented in the botanical literature include:

• Coleus amboinicus Lour.; Coleus aromaticus Benth.; Coleus carnosus Hassk.; Coleus crassifolius Benth.; Coleus subfrutectosus Summerh.; Coleus suborbicularis Zoll. & Moritzi.

1.2 Common Names

Plectranthus amboinicus is known by numerous vernacular names: Indian borage, country borage, French thyme, Indian mint, Mexican mint, Cuban oregano, soup mint, and Spanish thyme.

1.3 Botanical Description

P. amboinicus is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia, and Australia. It is a large, succulent, aromatic, perennial herb, shrubby below, hispidly villous or tomentose. Stems are decumbent, up to 1.5 m long and pubescent, with ascending inflorescences. Leaves are petiolate with a fleshy blade, broadly ovate to ovate-deltoid (25–45 × 25–40 mm), densely pubescent on both surfaces, with pale to brownish gland-dots, an obtuse to rounded apex, a truncate to abruptly attenuate base, and a finely crenate margin; the inflorescence is slender and spike-like, 100–300 mm long, with flowers in densely glomerate verticils spaced 10–30 mm apart. Flowers occur in bunches of 10 to 30 cm; the calyx is tomentose, the upper lip oblong, and the corolla is whitish, pink, or lilac-coloured.

The plant is fleshy and succulent with high aromatic properties, resembling oregano in flavor and smell. It is one of the most cited species in the Lamiaceae family, especially for its medicinal properties, accounting for 68% of all customary applications of this genus.

1.4 Common Forms and Preparations

The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The chopped leaves are also used as a substitute for sage (Salvia officinalis) in meat stuffing.

Preparations documented in the ethnobotanical and pharmacological literature include:

• Decoctions and infusions: For asthma, catarrh, or coughs, a decoction or infusion is prepared with 35 grams of leaves in 4 cups (1 litre) of water; for decoctions, the preparation is boiled for 5 minutes in a covered vessel.
• Leaf juice / expressed juice: Plectranthus amboinicus leaf juice was traditionally used topically to treat burns, insect bites, cracks at the corner of the mouth, and skin allergy.
• Essential oil: Extracted from leaves and stems by hydrodistillation for research and antimicrobial applications.
• Solvent extracts: Methanolic, ethanolic, aqueous, acetone, and ethyl acetate extracts are used in pharmacological research.
• Topical cream: ON101, containing 1.25% extracts of Plectranthus amboinicus (0.25%) and Centella asiatica (1%), is applied topically to wounds up to twice daily in a clinical context.

2. Traditional and Historical Use

2.1 Geographic Reach and Cultures of Use

This herb is widely used by indigenous people of tropical rain forests, either in folk medicine or for culinary purposes. In Singapore, local Chinese use Traditional Chinese Medicine (TCM), the Malays use Jamu Medicine, and the Indians practice Ayurvedic, Unani, and Siddha Medicine, all of which incorporate the plant. Herbal medicine employing this plant is practiced widely in folk medicine, Ayurveda, Siddha, Unani, and other traditions.

In its native environment in Kenya, Africa, it is the most frequent Plectranthus species applied to treat burns, wounds, sores, insect bites, and skin allergies.

Most ethnobotanical studies on Plectranthus species were carried out in Africa, South America, and Asia, reflecting the relevance of the genus in the traditional medicine of these continents.

2.2 Traditional Conditions and Preparations

P. amboinicus has been used for decades to treat inflammation-related diseases, particularly for skin, infective, digestive, and respiratory problems. It has been used to treat convulsive, epileptic, and bronchodilator syndromes, as well as cutaneous leishmaniasis, to eliminate microbial and respiratory infections, and to treat animal or insect bites, coughs, sore throats, nasal congestion, and a range of other conditions such as rheumatism and flatulence.

It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever, and skin diseases.

Leaves of Plectranthus amboinicus are consumed in India along with buttermilk (a probiotic source) during pathogen-induced diarrhea; this treatment is known to reduce the number of episodes as well as the duration of diarrhea.

Coleus amboinicus (Plectranthus amboinicus) leaves are a traditional galactogogue used in Indonesia, called torbangun or bangun-bangun in the local languages.

Plectranthus amboinicus has been used in herbal medicines for the treatment of various disorders such as asthma, flu, eczema, and cardiovascular disorders.

For respiratory use, to manage asthma, a decoction or juice produced from leaves is given orally, sometimes together with other medicines. The TRAMIL network—a Caribbean and Latin American organization that scientifically validates traditional medicine—specifies the preparation of a decoction or infusion with 35 grams of leaves in 4 cups (1 litre) of water, boiling for 5 minutes in a covered vessel; for the infusion, boiling water is added to the leaves, previously lightly toasted or not, and covered; after cooling and straining, the preparation is taken up to 3 times a day.

3. Key Constituents and Active Compounds

3.1 Volatile / Essential Oil Fraction

The literature survey revealed the occurrence of 76 volatile and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols, and aldehydes.

High amounts of bioactive compounds are found in the essential oil of its leaves, including carvacrol, thymol, β-caryophyllene, α-humulene, γ-terpinene, p-cymene, α-terpineol, and β-selinene.

The proportions of individual constituents vary markedly by geographic origin and extraction method. One study identified major compounds in the essential oil as carvacrol (23.0%) and camphor (22.2%). In another study, carvacrol accounted for 54.4% of the essential oil from Brazilian P. amboinicus. A third analysis reported linalool (50.3%), carvacrol (14.3%), geranyl acetate (11.7%), and nerol acetate (11.6%) as the major components of an aqueous leaf extract.

The clinical-stage formulation ON101 lists the following as known constituents: carvacrol, p-cymene, γ-terpinene, limonene, linalool, myrcene, thymol, α-amorphene, and β-cubebene.

3.2 Non-Volatile / Polyphenolic Fraction

HPLC analysis revealed rosmarinic acid, naringin, catechol, syringic acid, ellagic acid, and myricetin as significant phenolic compounds in the P. amboinicus extract, while GC-MS analysis found carvacrol as the primary component.

HPLC analysis of an extract confirmed the occurrence of bioactive polyphenols including rosmarinic acid (6.16 mg/g extract), rutin (0.32 mg/g extract), caffeic acid (0.77 mg/g extract), gallic acid (0.26 mg/g extract), p-coumaric acid (0.10 mg/g extract), and quercetin (0.15 mg/g extract).

The plant contains a variety of flavonoids, namely quercetin, apigenin, luteolin, salvigenin, and genkwanin. Ursolic acid is a triterpenoid compound, rosmarinic acid is a phenol compound, and luteolin is a flavonoid compound found in the leaves of Plectranthus amboinicus.

The chemical composition of aqueous leaf extracts has also been reported to contain tannins, flavonoids, saponins, polyuronides, and steroid glycosides.

3.3 Antioxidant Potency by Extract Type

The methanol extract contained the highest total phenolic (94.37 ± 1.24 mg GAE/g) and flavonoid contents (26.90 ± 1.35 mg RE/g) and exhibited the highest DPPH scavenging activity (90.13 ± 3.32%) followed by the acetone extract (80.23 ± 3.26%) at 500 μg/mL concentration.

4. Mechanisms of Action

4.1 Anti-Inflammatory Mechanisms

In vivo studies show that the aqueous extract of P. amboinicus decreases malondialdehyde (MDA) level and production of TNF-α and COX-2 in edema-paw tissue in mice. In vitro studies show that the extract inhibited pro-inflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The extract blocked the degradation of IκB-α and nuclear translocation of NF-κB p65 subunit.

The anti-inflammatory activity of aqueous extracts and ethyl acetate of P. amboinicus has been further demonstrated by showing that expression of oxidative stress markers, iNOS, COX-2, IL-1β, histamine receptor 1, and NF-κB was modulated by pretreatment with the extracts; the same treatments resulted in decreased NO production, indicating inhibition of macrophage activation.

Studies investigating the anti-inflammatory mechanisms of P. amboinicus (PA-F4) demonstrated inhibition of the NLRP3 inflammasome. PA-F4 inhibited the ATP-induced release of caspase-1, IL-1β, and IL-18 from LPS-initiated cells by blocking NF-κB activation. Rosmarinic acid, cirsimaritin, salvigenin, and carvacrol are suggested to be the active components of the extract responsible for these effects.

Rosmarinic acid has been shown specifically to inhibit the activation of the transcription factor NF-κB and NFATc1 in bone marrow macrophages.

4.2 Antimicrobial Mechanisms

Studies have investigated the effect of P. amboinicus leaf extracts on catalase activity, reactive oxygen species, lipid peroxidation, cytoplasmic membrane permeability, and efflux pump activity in S. aureus and P. aeruginosa. Because the enzyme catalase protects bacteria against oxidative stress, disruption of its activity creates an imbalance in reactive oxygen species (ROS) levels, which subsequently oxidizes lipid chains, leading to lipid peroxidation.

Combinations of phytochemicals with hydrophobic antibiotics such as rifampicin and erythromycin increase the penetration rate within bacterial cells, thus enhancing antimicrobial action. Isolation of phytochemicals responsible for efflux pump inhibition (EPI) activity could lead to the development of additional plant-based efflux pump inhibitors.

4.3 Wound Healing / Macrophage Regulation

ON101, which is comprised of extracts from Plectranthus amboinicus and Centella asiatica, exerts a wound-healing effect by regulating the balance between M1 and M2 macrophages. An extract of one plant suppresses inflammation, while an extract of the other increases collagen synthesis. In preclinical studies, these two plant extracts had a synergistic effect on balancing the ratio of M1 to M2 macrophages and accelerating wound healing in a mouse model.

5. Scientific Evidence by Area of Application

5.1 Wound Healing and Diabetic Foot Ulcers

This is the area of strongest clinical evidence for any preparation containing P. amboinicus, deriving from a multi-center phase 3 randomized controlled trial of the standardized formulation ON101.

ON101 is composed of two active pharmaceutical ingredients: PA-F4 from an extract of Plectranthus amboinicus and S1 from an extract of Centella asiatica, two medicinal plants reported to have significant pharmacological activities in wound healing. With 48 in vitro and in vivo studies performed, these two ingredients contribute to a synergistic effect on regulation of the M1:M2 macrophage ratio and have been defined and formulated in a cream base using a proprietary formula.

This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients had debrided DFUs of 1 to 25 cm² present for at least 4 weeks and with Wagner grade 1 or 2, and were randomized 1:1 to receive ON101 or control absorbent dressings. ON101 was applied twice daily, or the absorbent dressing was changed once daily or 2–3 times a week, for 16 weeks, with a 12-week follow-up. The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits.

A multicenter, randomized controlled trial demonstrated a significantly higher complete healing rate with ON101 cream (60.7%) versus absorbent dressing (35.1%) over 16 weeks, with an odds ratio of 2.84 and a 95% confidence interval of 1.66–4.84.

A post hoc analysis of 276 patients from this trial found that in the full analysis set, the proportion of patients achieving healing was 61.7% in the ON101 group and 37.0% in the comparator group (p = 0.0001). In subgroup analysis according to risk factors, ON101 demonstrated superior healing capacity on Wagner grade 2 ulcers, plantar ulcers, ulcer size ≥5 cm², ulcer duration ≥3 months, for patients with HbA1c ≥9%, and patients with BMI ≥25.

An earlier, smaller pilot study also used the combination cream. A single-center, randomized, controlled, open-label study was conducted. Twenty-four type 1 or type 2 diabetes patients aged 20 years or older with Wagner grade 3 foot ulcers post-surgical debridement were enrolled between October 2008 and December 2009. Twelve randomly assigned patients were treated with WH-1 cream (containing P. amboinicus and C. asiatica) twice daily for two weeks. Another 12 patients were treated with hydrocolloid fiber dressings. No statistically significant differences were seen in percent changes in wound size at 7- and 14-day assessments. The short 2-week treatment window and small sample size of this earlier study limit its conclusions.

Overall assessment: The Phase 3 RCT provides robust, clinically meaningful evidence of wound-healing efficacy for the ON101 combination cream containing PA-F4 (the P. amboinicus standardized fraction). However, the preparation is a fixed-combination product, and the independent contribution of P. amboinicus alone cannot be fully disentangled from that of Centella asiatica within the ON101 formula.

5.2 Antimicrobial Activity

P. amboinicus extracts and essential oils exhibit significant antimicrobial activity against both Gram-positive and Gram-negative bacteria, and notable antifungal properties, particularly against dermatophytes.

In vitro antibacterial evidence is extensive. In vitro antimicrobial activity was conducted against Escherichia coli, Proteus vulgaris, Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus, and multiresistant S. aureus using microdilution method. All strains were sensitive to the essential oil, except P. aeruginosa which was resistant to P. amboinicus and P. ornatus. A synergistic effect of all essential oils combined with the aminoglycosides was demonstrated.

Plectranthus amboinicus is a potential source of antimicrobial agents, namely cell permeability enhancers, efflux pump inhibitors, and target bacterial antioxidant systems, giving it a multimodal mechanism of antibacterial activity.

Regarding antifungal interactions with clinical drugs, evaluation of the interference of P. amboinicus essential oil on the anti-Candida activity of clinically used antifungals (itraconazole, ketoconazole, and amphotericin B) showed diverse levels of interference. The essential oil exhibited prominent synergic interference on the activity of itraconazole against C. albicans, C. tropicalis, C. krusei, and C. stellatoidea. Interference with ketoconazole's anti-yeast activity was antagonistic and synergistic depending on the Candida species, while amphotericin B showed only small interference.

Overall assessment: Evidence for antimicrobial activity is extensive but derives almost entirely from in vitro and animal studies. No controlled clinical trials have assessed P. amboinicus preparations for the treatment of microbial infections in humans as a stand-alone intervention. The evidence is preliminary and cannot support human therapeutic claims beyond what has been established in preclinical models.

5.3 Anti-Inflammatory and Analgesic Activity

Plectranthus amboinicus presented the highest prevalence among species in systematic reviews of the Plectranthus genus, confirming its ethnobotanical and pharmacological importance, especially in inflammatory, infectious, and metabolic diseases.

Evaluation of the in vivo (rat model) anti-inflammatory and antitumor activities of an extract from the leaves of P. amboinicus showed significant reduction of edema and confirmed anti-inflammatory properties at specific dosage levels. In a preclinical study, the methanolic extract of Plectranthus amboinicus was given intraperitoneally in the form of suspension in 2% gum acacia at two different doses (250 and 500 mg/kg body weight), and the results showed significant reduction in inflammation (P<0.05–0.01).

P. amboinicus has been reported to have a therapeutic effect for rheumatoid arthritis, as demonstrated in collagen-induced arthritis (CIA) models in rat and mouse. A study revealed active constituents of P. amboinicus possessing AP-1 and TNF-α inhibitory activities, with rosmarinic acid identified as one of the key isolates by repeated HPLC separation.

Carvacrol and rosmarinic acid, secondary metabolites identified in extracts and essential oils of P. amboinicus, are regarded as promising drug candidates in inflammatory conditions.

Overall assessment: Evidence for anti-inflammatory and analgesic properties is based on in vitro mechanistic studies and animal models, with no controlled human clinical trials specifically for pain or inflammation management as stand-alone endpoints. Evidence is mechanistically compelling but remains preclinical in nature for these specific endpoints.

5.4 Antioxidant Activity

The methanol extract exhibited the highest DPPH scavenging activity (90.13 ± 3.32%) followed by the acetone extract (80.23 ± 3.26%) at 500 μg/mL concentration. Similarly, the highest ferric ion reduction potential (849.63 ± 30.95 μM of Fe(II)/g dry weight) was exhibited by the methanol extract.

The species demonstrates anti-inflammatory properties by inhibiting pro-inflammatory cytokines. The plant's rich polyphenolic content contributes to its significant antioxidant properties, with potential relevance to preventing conditions like hyperpigmentation and premature aging.

Overall assessment: Antioxidant activity is well established in in vitro assays across multiple studies but has not been confirmed through clinical trials measuring in vivo antioxidant outcomes in humans.

5.5 Respiratory Conditions

Numerous studies have demonstrated the potential of this plant for treating pulmonary disorders because of its phytochemical and pharmacognostic properties, specifically the activity of its essential compounds against airway inflammation.

Carvacrol and thymol are phenol compounds found in the essential oil of Plectranthus amboinicus and have been shown to have anti-inflammatory, antimicrobial, and antioxidant properties. Ursolic acid is a triterpenoid compound, rosmarinic acid is a phenol compound, and luteolin is a flavonoid compound in the leaves; these compounds have been studied for their potential therapeutic effects in respiratory disorders such as asthma and COPD.

C. amboinicus remains a primary remedy for respiratory conditions, supported by studies confirming antimicrobial and bronchodilatory properties.

Overall assessment: Use in respiratory conditions is supported by a rich ethnobotanical record and by in vitro and animal-based mechanistic evidence for the anti-inflammatory and antimicrobial properties of key constituents. However, no published human clinical trials have specifically evaluated P. amboinicus preparations as a treatment for asthma, COPD, or other respiratory conditions.

5.6 Digestive Health and Prebiotic Effects

In the background of its ethnobotanical use in diarrhea, an investigation was carried out to determine whether the leaves, in addition to antimicrobial activity on pathogens, could also have a positive effect on beneficial gut microflora. The growth-stimulating activity of the hot water extract (HWE) of P. amboinicus leaves on probiotic Lactobacillus plantarum was determined by microbroth dilution technique.

HWE of P. amboinicus leaves inhibited growth of pathogens (Escherichia coli and Salmonella typhimurium) while stimulating the growth of L. plantarum. SDS-PAGE gel showed the presence of phenolic acid decarboxylase enzyme induced in the presence of HWE in L. plantarum, indicating the utilization of polyphenols by the bacteria. Cells grown on HWE also showed β-galactosidase activity, indicating their ability to utilize sugars present in HWE.

Overall assessment: Evidence for digestive health applications is preliminary, limited to in vitro studies demonstrating prebiotic-like activity. No human clinical trials have confirmed efficacy for diarrhea or gut health.

5.7 Galactogogue (Breast Milk Production)

Coleus amboinicus (Plectranthus amboinicus) leaves are a traditional galactogogue used in Indonesia (called torbangun or bangun-bangun). Human studies of poor quality and some rodent studies indicate that it might have some efficacy as a galactogogue, but the studies are inadequate to establish activity.

No data exist on the excretion of any components of Coleus amboinicus into breast milk or on the safety and efficacy of Coleus amboinicus in nursing mothers or infants, although it has been used for hundreds of years in Indonesia with apparent safety.

Overall assessment: This is an area of traditional use supported only by low-quality human studies; evidence is insufficient to establish galactogogue activity.

5.8 Anticancer / Cytotoxic Activity

P. amboinicus exhibits cytotoxic activity against various cancer cell lines. Ethanolic extract nanoparticles of the leaves have been studied for anti-proliferative and pro-apoptotic properties against cancer cell lines. Clinical studies are considered necessary to confirm anticancer effects, particularly when combined with other treatments.

Overall assessment: Anticancer evidence is entirely limited to in vitro cell-line studies. No human clinical trials have been conducted. Evidence is preliminary only.

5.9 Skin Care and Dermatology

The species demonstrates remarkable mosquito repellent and anti-parasitic effects, comparable to DEET, and potent anti-inflammatory properties by inhibiting pro-inflammatory cytokines. The plant's rich polyphenolic content contributes to its significant antioxidant properties, with potential relevance to preventing conditions like hyperpigmentation and premature aging.

In dermatophyte infections, the essential oil has demonstrated notable antifungal properties in laboratory settings. The Phase 3 ON101 clinical trial (described under wound healing, above) provided the most clinically rigorous evidence for a dermatological application of a P. amboinicus-containing formulation, specifically for chronic diabetic foot ulcers.

Overall assessment: The strongest human evidence in dermatology is for the combination cream ON101 in diabetic foot ulcers (Phase 3 RCT). Skin care, anti-aging, and insect-repellent claims are supported only by preclinical data.

6. Body Systems Associated with Plectranthus amboinicus

Studies have cited numerous pharmacological properties including antimicrobial, anti-inflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant, and analgesic activities. It has also been found to be effective against respiratory, cardiovascular, oral, skin, digestive, and urinary diseases. The principal body systems for which research and traditional use have been documented are:

• Integumentary (skin): Wound healing, burns, insect bites, skin infections, dermatophyte infections, and anti-aging.
• Respiratory: Asthma, cough, catarrh, nasal congestion, respiratory infections, and potential bronchodilatory effects.
• Gastrointestinal: Diarrhea, flatulence, digestive infections, and prebiotic support of beneficial microflora.
• Musculoskeletal / Immunological: Rheumatism, rheumatoid arthritis, and general inflammatory conditions.
• Cardiovascular: Traditional use recorded; limited modern mechanistic data available.
• Endocrine / Metabolic: Antidiabetic activity and wound healing in diabetic contexts.
• Reproductive: Traditional galactogogue use (Indonesia).

7. Dosage Forms and Dosages Reported in Studies

The following dosages are reported strictly as they appear in identified sources, without extrapolation or interpretation:

• Traditional oral decoction (TRAMIL network): 35 grams of leaves in 4 cups (1 litre) of water; for decoctions, boil for 5 minutes; drink up to 3 times per day as indicated by symptoms.
• Animal anti-inflammatory study (intraperitoneal): Methanolic extract administered intraperitoneally in the form of suspension in 2% gum acacia at doses of 250 and 500 mg/kg body weight.
• Animal toxicity assessment (oral): Rats were able to tolerate oral doses of up to 3,000 mg/kg of their body weight of the ethanolic extract without signs of toxicity.
• Antifungal in vitro study: The methanolic extract was assessed at concentrations of 150, 250, and 500 µg/mL; these concentrations were found to have higher inhibition over fungal species, with significant antifungal activity (P<0.05–0.01) compared with the positive control (fluconazole).
• ON101 topical cream (Phase 3 RCT): ON101, containing 1.25% total extracts consisting of Plectranthus amboinicus (0.25%) and Centella asiatica (1%), applied topically to wounds up to twice daily.
• ON101 sub-acute mouse study (oral equivalent): In sub-acute toxicity studies, mice were treated with 200 and 400 mg/kg doses of methanolic extract over 28 days; progressive increase in body weight at these doses indicated improvement in nutritional state of the animal.

8. Safety Considerations and Interactions

8.1 Acute and Sub-Acute Toxicity

In toxicology studies, rats were able to tolerate oral doses of up to 3,000 mg/kg of their body weight of the ethanolic extract of P. amboinicus without signs of toxicity. A slight cytotoxicity was observed when the hydroalcoholic extract and the ethyl acetate fraction were incubated with RAW 264.7 macrophages; their half-maximal inhibitory concentrations (IC50) were 817.0 μg/mL and 99.6 μg/mL respectively. Although the hydroalcoholic extract showed a relatively high in vitro cytotoxicity, this was not observed with any significant alterations in in vivo toxicity studies.

8.2 Interactions with Conventional Antifungal Drugs

Little is known of derivatives and their effectiveness when used together with conventional drugs. In evaluating the interference of P. amboinicus essential oil on the anti-Candida activity of some clinically used antifungals (itraconazole, ketoconazole, and amphotericin B), it showed a diverse level of interference. The essential oil exhibited prominent synergic interference on the activity of itraconazole against several Candida species. Interference on the anti-yeast activity of ketoconazole was antagonistic and synergic with some species. Amphotericin B showed only small interference. These interactions have been observed only in vitro; no human pharmacokinetic or pharmacodynamic interaction studies have been conducted.

8.3 Synergism with Antibiotics

A synergistic effect of P. amboinicus essential oil combined with the aminoglycosides was demonstrated in vitro. Combinations of phytochemicals from P. amboinicus with hydrophobic antibiotics such as rifampicin and erythromycin increase the penetration rate within bacterial cells, thus enhancing antimicrobial action against bacteria that otherwise fail to be penetrated. The clinical significance of these interactions in humans has not been established.

8.4 Pregnancy, Breastfeeding, and Pediatric Use

The TRAMIL network, which systematically reviews traditional Caribbean and Latin American medicinal plants, states that the plant is not for use during pregnancy, breastfeeding, or in children under 3 years of age.

The NIH LactMed database (Drugs and Lactation Database) notes that no data exist on the excretion of any components of Coleus amboinicus into breast milk or on the safety and efficacy of Coleus amboinicus in nursing mothers or infants, although it has been used for hundreds of years in Indonesia with apparent safety.

8.5 Status of Scientific Validation

Scientific validation of many traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This comprehensive exploration of P. amboinicus validates its diverse therapeutic potential across infectious diseases, oncology, and wound care, but further research and clinical trials are warranted to fully elucidate its mechanisms of action and optimize its therapeutic applications. Further clinical studies are essential to establish therapeutic mechanisms and validate its traditional uses.

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