Asiaticoside: A Comprehensive Reference
1. Identity, Chemical Profile, and Natural Source
Asiaticoside is a triterpene glycoside with the molecular formula C48H78O19. Its triterpenoid saponins belong to two major chemical groups: asiaticosides and madecassosides, derived from the respective aglycones asiatic acid and madecassic acid. The aglycone part of asiaticoside is asiatic acid, a pentacyclic triterpenoid, and multiple hydroxyl (OH) groups confer further complexity to the multi-ring structure. The glycoside portion consists of a trisaccharide chain attached to the triterpenoid backbone. The structural difference between asiaticoside and its close analogue madecassoside lies in the presence or absence of a hydroxyl group at the R1 position, with both sharing a glucose-glucose-rhamnose sugar unit at R2.
Asiaticoside has a molecular weight of 959.12 g/mol and a chemical formula of C48H78O19. It is described physically as a white needle-like crystal. The major bioactive constituents of Centella asiatica are the pentacyclic triterpenoid glycosides asiaticoside and madecassoside, along with their corresponding aglycones, asiatic acid and madecassic acid. Asiaticoside and madecassoside have been identified as the marker compounds of C. asiatica in the Chinese Pharmacopoeia, and these triterpene compounds are recognised for a wide range of pharmacological properties including neuroprotective, cardioprotective, hepatoprotective, wound healing, anti-inflammatory, anti-oxidant, anti-allergic, anti-depressant, anxiolytic, antifibrotic, antibacterial, anti-arthritic, anti-tumour, and immunomodulatory activities.
Asiaticoside is concentrated in the aerial parts of Centella asiatica (L.) Urban. This plant is a stoloniferous perennial herb belonging to the plant family Apiaceae (Umbelliferae), which contains 20 different species. It is a slender, creeping plant rooting at the nodes, growing in damp areas in different tropical countries. Centella asiatica is an ethnomedicinal herbaceous species that grows abundantly in tropical and subtropical regions of China, India, South-Eastern Asia, and Africa. More specifically, it is native to the Indian subcontinent, Pakistan, Southeast Asia, Malaysia, Indonesia, China, Japan, Korea, Taiwan, and the equatorial belt of South Africa, Madagascar, and South-Central America.
The whole plants of C. asiatica contain up to 8% triterpene saponins, including asiaticoside, madecassoside, and their aglycones. By the European Pharmacopoeia standard, dried and fragmented aerial parts are required to contain a minimum of 6.0% of total triterpenoid derivatives, expressed as asiaticoside.
Synonyms and Vernacular Names
C. asiatica is the most pharmaceutically and economically significant species of the genus Centella, often used synonymously with "Gotu Kola" in medicinal and commercial contexts. Centella asiatica is a synonym with Hydrocotyle asiatica L. Further names used include Indian Pennywort (English), Hydrocotyle Asiatique (French), Brahma-manduki and Brahmi-Buti (Hindi), Tsubokusa (Japanese), Tungchian and Luei Gong Gen (Chinese), and Blasteostimulina—the last being a Spanish commercial name specifically for asiaticoside. C. asiatica is known by numerous vernacular names, reflecting its widespread use and cultural integration, underscoring its global recognition and ethnomedicinal importance.
Common Forms and Preparations
Alcoholic or aqueous extracts of Centella, as well as refined and purified extracts, have been used commercially. The most studied standardised extracts are TECA, TTFCA, and TTF, all containing 40% asiaticoside and 60% of the aglycones (asiatic acid and madecassic acid). Clinical studies in particular have been published describing preparations including TTFCA, TECA, and commercial extracts sold under the names Madecassol® (titrated extract of Centella asiatica) and Centellase® (total triterpenoid fraction of Centella asiatica). Centella asiatica is available over the counter in the forms of whole herbs, powder, capsules, or liquid extracts, and is also an ingredient in skincare products.
2. Traditional and Historical Use
Centella asiatica has been used in Ayurvedic medicine in India for almost 2000 years with significant use of its neuropharmacological properties. In Ayurveda, it has been recognized as one of the main herbs for revitalizing the nerves and brain cells and has been administered extensively in treating disorders like depression. Parts of the plant were considered useful in diseases of the skin, nervous system, and blood.
Although the leaf was initially given importance in the traditional pharmacopoeia of India, many modern investigators have advocated the use of the entire plant, including root, twigs, leaves, and seeds. The use of this herb can also be traced back to China and other Southeast Asian countries, where it was used for fever, skin conditions, and treating inflammation-related diseases.
This perennial herb from the Apiaceae family has been used for centuries for its multifunctional properties in Indian Ayurvedic medicine, as well as in herbal medicine in Malaysia, China, and other Asian regions. C. asiatica has been traditionally used in the ancient medicinal systems throughout the world as a remedy for a wide range of disorders. It is most popularly used for its neuroprotective activities and in the treatment of disorders concerning the central nervous system, such as mental fatigue, anxiety, and memory enhancement.
Asiaticoside is defined in some historical sources as a compound traditionally used in the treatment of leprosy and tuberculosis, where it was thought to damage the cell walls of the bacteria responsible for these diseases, thereby facilitating their elimination by the body's immune system.
C. asiatica extracts are reported widely in Ayurvedic and Chinese traditional medicine to boost memory, prevent cognitive deficits, and improve brain functions. Traditional preparations included aqueous decoctions, pastes made from fresh or dried leaf material applied topically to wounds, and dried leaf powders. Commonly dried leaf powder of Centella asiatica was used by traditional healers.
3. Key Constituents, Co-occurring Compounds, and the Role of Asiaticoside
Centella contains several pentacyclic triterpenoids, including asiaticoside, brahmoside, and madecassic acid, along with other constituents such as centellose, centelloside, and madecassoside. The main chemical components responsible for its pharmacological activity are triterpenes, mostly asiaticoside, asiatic acid, madecassoside, and madecassic acid.
C. asiatica is also rich in a diverse group of compounds formed by quinic acid esterified to cinnamic acid derivatives and flavonoids, such as kaempferol, quercetin, and related glycosides. Approximately 124 chemical compounds have been isolated and identified from Centella asiatica.
The plant is rich in bioactive compounds such as pentacyclic triterpenes (notably Asiaticoside, Asiatic Acid, Madecassoside, and Madecassic Acid), flavonoids, phytosterols, and phenolic acids, which contribute significantly to its therapeutic effectiveness. Among these, asiaticoside is the most studied individual compound and is considered one of the principal active principles, particularly for dermatological and neurological applications.
4. Mechanisms of Action
4.1 Collagen Synthesis and Wound Healing
Asiaticoside can induce type I collagen synthesis via the activation of the TGF-β receptor I kinase-independent Smad signalling pathway. Specifically, asiaticoside promotes type I collagen (Col1) synthesis in human dermal fibroblasts via Smad 2 and Smad 3 phosphorylation, leading to Smad 3 and Smad 4 binding. Oral administration of both asiaticoside and madecassoside has been shown to enhance collagen type III synthesis by activating skin fibroblasts via the TGF-β/Smad pathway.
Asiaticoside enhances wound healing by promoting fibroblast proliferation, potentially linked to tissue cell migration around the wound or the expression and activation of specific growth factors. Asiaticoside stimulates the synthesis of type I collagen inhibitors in human fibroblast cells, which are crucial in preventing skin aging. It also enhances skin cell behavior during the wound healing process by increasing migration rate, promoting cellular proliferation, improving initial skin cell adhesion, and increasing the number of normal human dermal fibroblasts.
Asiaticoside acts during the inflammatory phase by reducing the synthesis of pro-inflammatory cytokines (TNF-α, IL-6) and growth factors (TGF-β, PDGF, VEGF). Topical application of asiaticoside enhances dermal vascularization and re-epithelialization, accompanied by increased collagen cross-linking and capillary density.
Notably, asiaticoside exhibits dual regulatory properties: while it has been shown to strongly inhibit fibrotic processes involved in pathological scar formation, previous studies have also demonstrated that it can accelerate normal cutaneous wound healing by promoting fibroblast proliferation and collagen synthesis. This dual function — enhancing normal tissue repair while suppressing excessive scar formation — suggests that precise control of the timing and dosage of asiaticoside administration is crucial for its clinical application.
4.2 Anti-inflammatory Mechanisms
Asiaticoside has been found to inhibit the NF-κB signalling pathway and reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in macrophages. CA extracts and their pentacyclic triterpenes have been reported to be effective against acne, burns, atopic dermatitis, and wounds by modulating the NF-κB and mitogen-activated protein kinase (MAPK) signalling pathways through regulation of inflammatory responses and oxidative stress in both in vitro and in vivo models.
4.3 Neuroprotective Mechanisms
Multiple mechanisms are known to be responsible for the cognitive enhancement attributed to C. asiatica, involving the inhibition of acetylcholinesterase activity, reduction of phospholipase A2 (PLA2) activity, protection against β-amyloid formation, and protection from brain damage. Mechanistic investigation suggests that asiaticoside may ameliorate cognitive impairment by inhibiting the activation of the p38 MAPK pathway and promoting synaptic repair.
In the central nervous system, asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. In vivo studies demonstrated that it could attenuate neurobehavioural, neurochemical, and histological changes in transient focal middle cerebral artery occlusion animals. Asiaticoside also showed anxiolytic effects in acute and chronic stress animal models.
In cerebral ischaemia-reperfusion injury, asiaticoside reduces oxidative stress and neuroinflammation through NOD2/MAPK/NF-κB pathway modulation and microglial regulation. Asiaticoside prevents neuronal apoptosis by modulating apoptotic signalling pathways, including caspase-3 inhibition and upregulation of anti-apoptotic proteins like Bcl-2.
Asiaticoside is reported to be highly blood-brain-barrier permeable.
4.4 Bioavailability and Metabolic Conversion
Following oral administration, madecassoside and asiaticoside are converted to their respective aglycones in the intestine and are absorbed into the stomach, liver, kidney, brain, and skin within minutes, where they exert various pharmacological and biological activities. The main explanation for differences between human and animal pharmacokinetics is that there is β-glycosidase in the human intestine, which can hydrolyse glycosides, while the animal β-glycosidase cannot hydrolyse these glycosides. Because asiaticoside and madecassoside are glycosides, they cannot be easily absorbed by the gastrointestinal tract intact.
The absolute bioavailability of asiaticoside has been reported to be very low, at approximately 1.86%. When asiaticoside was administered orally in rats, the Cmax, T1/2, AUC0–t, and Tmax were 658.17 ± 597.56 μg/L, 4.20 ± 0.91 h, 1937.19 ± 464.40 μg h/L, and 0.62 ± 0.79 h, respectively. Asiaticoside appeared to degrade through a first-order reaction and had low biotoxicity; however, the pharmacokinetic properties differed according to species.
5. Scientific Evidence by Area of Use
5.1 Wound Healing and Skin Repair
This is arguably the most extensively documented area of asiaticoside research, with evidence spanning in vitro cell studies, animal models, and some clinical trials.
Preclinical evidence: Both in vivo and in vitro studies have demonstrated that asiaticoside has significant healing properties in normal and chronic wound models. Enhancement in collagen synthesis has been observed in human dermal fibroblasts (HDFs), where cells were treated with 30 μg/mL of asiaticoside; expression of collagen was improved after 2 hours of treatment and maintained for 48 hours. Topical treatment with asiaticoside and madecassoside induced collagen synthesis, proliferation, and cell growth while stimulating burn wound healing in male ICR mice.
Clinical evidence: Topical application of Centiderm ointment made from C. asiatica ethanol extract significantly improved objective scores (pliability, vascularity, pigmentation, height, and visual acuity) and subjective signs (dryness, itching, and irritation) in patients with second-degree burn wounds on their limbs. The means of re-epithelialization and complete healing were significantly better in the Centiderm group than in the control group.
Clinical evidence also substantiates the efficacy of asiaticoside in accelerating wound closure, enhancing tissue regeneration, and minimising scarring, with a favourable safety profile. Among the triterpenoid compounds of C. asiatica, the glycosides (asiaticoside and madecassoside) themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognised as the main active constituents responsible for burn wound healing.
Evidence strength: In vitro and animal data for wound healing and collagen stimulation are robust. Clinical evidence is supportive but primarily derived from small trials and observational studies. Large-scale randomised controlled trials specifically isolating asiaticoside are limited.
5.2 Chronic Venous Insufficiency (CVI) and Venous Microangiopathy
This area contains the strongest and most consistently reported human clinical evidence for Centella asiatica triterpene preparations containing asiaticoside.
Clinical evidence: During the 1980s, several clinical studies showed that the Total Triterpenic Fraction of Centella asiatica (TTFCA = TECA) at the oral dose of 60–120 mg daily for 30–90 days was able to improve subjective and objective outcomes in patients with venous insufficiency. A single-blind, placebo-controlled, randomized study was performed on the effects of different doses of TTFCA in patients with venous hypertensive microangiopathy, using a combined microcirculatory model including laser Doppler flowmetry (LDF) and transcutaneous oxygen and carbon dioxide tension measurements. All tests provided a significant difference between drug-treated groups and the placebo group, distinguishing between the higher (120 mg daily) and lower (60 mg daily) dose of TTFCA. Transcutaneous PO2-PCO2 measurements were significantly modified by drug treatment while no variation was detected in the placebo group. Significant symptomatologic effects (by subjective scores) followed TTFCA administration, especially at the higher dose.
TTFCA was found effective in venous insufficiency, reducing ankle oedema, foot swelling, and capillary filtration rate while improving microcirculatory parameters. TTFCA displays significant activity in venous hypertensive microangiopathy and its effects are dose-dependent.
Systematic review: A systematic review by Chong and Aziz assessed the efficacy of Centella asiatica for improvement of the signs and symptoms of CVI, searching 13 electronic databases including the Cochrane Central Register of Controlled Trials for randomised controlled trials; eight studies met the inclusion criteria. Two included trials showed a statistically significant effect on ankle swelling in favour of the TTFCA group after eight weeks (MD −0.84; 95% CI −0.94 to −0.74) and four weeks (MD −0.77; 95% CI −0.78 to −0.76) of treatment.
Regulatory recognition: Medicinal products containing triterpenic extract from Centella asiatica have been authorised in Europe for cutaneous use (powder, cream, and ointment) since 1968. Active constituents of Centella asiatica are components of many cosmetic preparations worldwide in the area of skin care.
Evidence strength: Moderate. Multiple RCTs support benefit in CVI-related oedema and microcirculatory parameters, but as one review noted, there is not enough evidence to globally support the efficacy of phlebotonics for chronic venous insufficiency, and there is a need for further randomised, controlled clinical trials with greater attention to methodological quality.
5.3 Neuroprotection, Cognitive Function, and Neurological Disorders
Preclinical evidence: In vivo studies indicate that asiaticoside and madecassoside support cognitive function and synaptic integrity, as demonstrated by improved memory and learning outcomes in Alzheimer's disease (AD) animal models, likely via enhanced synaptic plasticity and cholinergic support. In conclusion, these triterpenoids show multifaceted neuroprotective effects in preclinical models of AD. Asiaticoside displays broad bioactivities in cell culture and animal models including neuroprotection, antidepressant activity, anti-oxidation, anti-inflammation, protection of DNA damage, and regulation of apoptotic factors in cortical neurons. Neuroprotective effects include repairing spinal cord injury and protecting neuronal damage induced by ischaemia hypoxia.
C. asiatica extract, asiatic acid, and asiaticoside could effectively increase the content of brain-derived neurotrophic factor (BDNF) in preclinical models. Recent studies indicate that asiaticoside might provide protection against neural damage in neurological disorders such as Parkinson's disease and Alzheimer's disease, potentially through mechanisms like synaptic remodelling, neurotransmitter balance restoration, cell apoptosis inhibition, and inflammation reduction.
Clinical evidence: Clinical studies found that C. asiatica effectively improved the cognitive function of stroke patients. Patients were divided into three groups and administered 1,000 mg/day or 750 mg/day of C. asiatica extract, or 3 mg/day of folic acid, respectively. In patients with vascular cognitive impairment, doses used were 750 mg and 1,000 mg of extract per day.
Evidence strength: Some clinical studies suggest a modest benefit in a few cognitive functions, but a meta-analysis showed a lack of benefit. In preclinical studies, the compound reduced oxidative stress, Aβ levels, and apoptosis, while promoting mitochondrial health. Evidence in rodent models and a limited number of human trials confirms the traditional reputation of C. asiatica as a cognitive enhancer, and its anxiolytic and anticonvulsant properties. Overall, the neuroprotective evidence is predominantly preclinical; human clinical data remain preliminary and heterogeneous. Further clinical research is warranted to confirm safety, optimize dosing, and translate preclinical results into effective human treatments.
5.4 Hepatoprotection
Asiaticoside and madecassoside have shown significant protection against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury in preclinical studies. Asiaticoside and madecassoside are considered promising hepatoprotective agents for acute liver injury.
Evidence strength: This application is supported primarily by preclinical in vitro and in vivo data. Controlled human clinical trials specifically evaluating asiaticoside's hepatoprotective effects are lacking in the published literature, and this area cannot be considered clinically established.
5.5 Pulmonary Protection
Studies have found that asiaticoside could attenuate hyperoxia-induced lung injury and effectively protect from septic lung injury induced by cecal ligation and puncture (CLP). Asiaticoside also has a protective effect against bleomycin-induced pulmonary fibrosis in animal models. Wang et al. demonstrated in an earlier study that asiaticoside can attenuate the development of pulmonary hypertension (PH) in hypoxia-induced PH rat models by attenuating pulmonary cardiovascular remodelling and preventing right ventricular hypertrophy. These results were concluded to be mediated by asiaticoside blocking the hypoxia-induced overactivity of the TGF-β1/SMAD2/3 signalling pathway and inhibiting the aberrant proliferation and migration of pulmonary arterial smooth muscle cells.
Evidence strength: Exclusively preclinical. No human trials have evaluated asiaticoside for pulmonary indications as of available evidence.
5.6 Anti-tumour Activity
Asiaticoside has shown anti-cancer effects in a series of human malignancies in preclinical studies, including multiple myeloma, melanoma, glioma, and breast cancer. Asiaticoside may be a potential anti-cancer agent. In hepatocellular carcinoma (HCC) cell lines, asiaticoside significantly inhibited cell proliferation in a dose- and time-dependent manner, significantly induced apoptosis, and caused G1 cell cycle arrest. Western blot assay results indicated the mechanism involves inhibiting the activity of the PI3K/Akt and MAPK/ERK pathways. Further evidence is needed to confirm these results, particularly in vivo efficacy and eventual human studies.
Evidence strength: Currently limited to in vitro cell-line studies and a small number of animal experiments. No human clinical data exist for oncological applications.
5.7 Anti-inflammatory and Antioxidant Activity
Asiaticoside and madecassoside show anti-inflammatory activity through inhibition of inflammatory mediators such as NO, TNF-α, and IL-6, and are able to reduce oxidative stress and inflammatory processes in different cell lines including macrophages and endothelial cells. Asiaticoside increases wound healing activity through collagen synthesis in fibroblasts of the vascular walls, improving their flexibility and blood vessel tension. It has also demonstrated anti-inflammatory activity and improvement of capillary permeability, and it leads to an increase in antioxidant levels.
5.8 Skin Ageing and Cosmeceutical Applications
Asiaticoside and madecassoside are considered cosmetically beneficial for their roles in anti-ageing, skin hydration, collagen synthesis, UV protection, and curing scars. At the molecular signalling level, asiaticoside and madecassoside activate the TGF-β/Smad pathway to drive extracellular matrix synthesis, thereby enhancing collagen deposition and improving skin elasticity and hydration.
6. Body Systems Associated with Asiaticoside
- Integumentary (skin): Wound healing, burn repair, anti-inflammatory, anti-oxidant, antifibrotic, and antibacterial activities are all associated with asiaticoside in the skin.
- Central nervous system: C. asiatica has shown antistress, antidepressant, anxiolytic, and antiseizure properties in preclinical studies. In animal models, asiaticoside showed neuroprotective, anti-depressive, and anxiolytic effects.
- Cardiovascular and venous: C. asiatica is an important herbal medicine that has been widely used for many years in the treatment of cardiovascular diseases. Asiaticoside has particular documented effects on venous tone and microcirculation.
- Hepatic: Preclinical evidence for protection against acute liver injury as described above.
- Pulmonary: Preclinical data for protection against acute lung injury and pulmonary fibrosis.
- Musculoskeletal/periodontal: In vitro experiments found that asiaticoside effectively promoted the osteogenic differentiation of human periodontal ligament cells and inhibited RANKL-induced osteoclast formation, indicating therapeutic potential for periodontal tissue regeneration and osteolytic diseases.
7. Dosage Forms and Dosages Reported in Studies
In adults, the dosages most frequently used clinically are in the range of 60–180 mg/day, in divided doses three times daily, of TTFCA (TECA). The duration of use ranges between 2–8 weeks. The posology of powdered leaf is 0.5–1 g daily.
Dose ranges noted in the literature were 30–90 mg/day for extracts and 1.5–4.0 g/day for the crude form; much higher doses have been tested in clinical studies. For example, doses used in patients with vascular cognitive impairment were 750 mg and 1,000 mg of extract per day.
Regarding the safety and pharmacokinetics of C. asiatica in healthy volunteers from Thailand, daily oral doses (single or multiple) of 250 mg and 500 mg were found to be safe for patients, with only mild to moderate adverse events reported.
With respect to standardised extracts in venous insufficiency trials, a significant distinction was made between the higher (120 mg daily) and the lower (60 mg daily) dose of TTFCA in a randomized placebo-controlled trial for venous hypertensive microangiopathy.
For topical formulations, the leaves of Centella asiatica have found application in clinical practice for dermatological disorders and in particular for improving the healing process of wounds, burns, and skin conditions. Semi-solid preparations for topical use typically contain 1% extract. It is important to note that the dosages above pertain to whole-plant extracts standardised to include asiaticoside alongside other triterpenes; isolated asiaticoside dosing in humans has not yet been well-characterised in clinical trials.
8. Safety, Toxicology, and Notable Interactions
8.1 General Safety Classification
Due to the lack of any reported adverse effects of C. asiatica in any clinical studies, the plant is categorised as a Class 1 herb (one that can safely be consumed when used appropriately) in the Botanical Safety Handbook.
8.2 Acute Toxicity
Several researchers have verified the safety of asiaticoside for human use. In 2012, Sampath et al. demonstrated the safety of asiaticoside and pointed out that the lethal dose (LD50) of asiaticoside is over 2000 mg/kg by acute oral administration in animal studies.
8.3 Adverse Effects Reported
In clinical studies with C. asiatica, patients experienced different degrees of side effects such as constipation, skin itching, and abdominal distension. Both asiaticoside and madecassoside are regarded as safe, but some individuals may have allergic reactions or intestinal upset.
In some clinical trials, contact dermatitis has been documented with topical application. The Cosmetic Ingredient Review (CIR) expert panel has reviewed dermal sensitisation data from guinea pig sensitisation studies (OECD 406) and human repeat-insult patch tests on formulations containing Centella asiatica extract.
8.4 Pharmacokinetic Considerations Affecting Safety
The pharmacokinetics of human studies are inconsistent with animal studies. The main explanation is that there is β-glycosidase in the human intestine, which can hydrolyse glycosides, while the corresponding enzyme in animals cannot hydrolyse these glycosides. This means that asiaticoside ingested orally by humans is substantially converted to its aglycone (asiatic acid) before systemic absorption, which has implications for interpreting animal-derived safety and efficacy data.
Asiaticoside is highly blood-brain-barrier permeable. It has a variety of pharmacological effects including anti-neural inflammation and anti-cancer properties, as well as protective properties for the skin, cardiovascular system, and pulmonary system.
8.5 Bioavailability Challenge and Research Directions
Future investigation should focus on improving the bioavailability of asiaticoside and conducting more rigorous clinical assessment. Various drug delivery approaches including nanocarrier systems are being investigated to address the documented poor oral bioavailability of intact asiaticoside.
References
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