Introduction

Bisabolol is a common soothing ingredient in cosmetics for sensitive-skin care, after-sun care, post-shave care, and skin-repair products. It is closely associated with German chamomile and can also be obtained from the Brazilian Candeia tree. Commercial production routes now include chemical synthesis and biotechnological fermentation in addition to plant extraction.

Bisabolol exerts effects on the skin at multiple levels. Its lipophilic sesquiterpene structure facilitates partitioning into the lipid environment of the skin; cell and animal studies have shown that (−)-α-bisabolol can affect multiple inflammation-related signaling pathways and reduce certain inflammatory mediators; and in vitro experiments have also demonstrated antimicrobial activity against some bacteria and fungi. In addition, bisabolol can alter the lipid state of the stratum corneum and promote the percutaneous diffusion of certain coexisting molecules, a property that has implications for both formulation applications and safety assessment.

Together, these properties constitute the principal scientific basis for the use of bisabolol as a skincare ingredient.

1 What Is Bisabolol? Sources, Structure, and Stereoisomerism

In cosmetics, the ingredient is designated as Bisabolol. Pharmacological and skin-related research has focused primarily on α-bisabolol, among which naturally occurring (−)-α-bisabolol is an important and extensively studied form, also known as levomenol.

α-Bisabolol is a monocyclic sesquiterpene alcohol with the molecular formula C₁₅H₂₆O and a relative molecular mass of 222.37. The molecule contains one hydroxyl group and a large hydrocarbon framework, giving it pronounced lipophilicity overall. PubChem reports a calculated XLogP of approximately 3.8 and a topological polar surface area of approximately 20.2 Ų.[1]

German chamomile, or chamomile (Matricaria recutita L.), is one of the classic natural sources of (−)-α-bisabolol. Chamomile belongs to the Asteraceae family but is not the same species as the flowers commonly referred to as chrysanthemums. The essential-oil composition varies substantially among different chamomile populations and cultivars. Some chemotypes are rich in α-bisabolol, whereas others contain bisabolol oxides as their major constituents. Gosztola et al. examined 28 wild populations and four cultivated varieties and found that essential-oil content and the composition of major constituents, including α-bisabolol and bisabolol oxides, were influenced by genetic background and environmental conditions.[2]

The Brazilian Candeia tree (Eremanthus erythropappus) is another important natural commercial source. Albertti et al. found that its essential oil can contain relatively high levels of (−)-α-bisabolol and identified the bisabolol synthase EeBOS1 involved in the biosynthesis of this compound.[3]

Commercial bisabolol can currently be produced by plant extraction, chemical synthesis, or biotechnological fermentation. Different production routes may differ in stereoisomer composition, purity, impurity profiles, raw-material sources, and resource consumption. Biotechnological routes can use specific terpene synthases to selectively produce (−)-α-bisabolol. A 2016 metabolic-engineering study achieved production of 9.1 g/L (−)-α-bisabolol in a 50 L fermentation system.[4]

2 Lipophilic Sesquiterpene Structure and Affinity for Skin Lipids

The α-bisabolol molecule contains only one hydroxyl group, which provides a relatively localized polar region, whereas its 15-carbon sesquiterpene skeleton constitutes most of the molecule. Consequently, it has limited compatibility with water and a relatively high affinity for nonpolar and lipid environments.

The stratum corneum, the outermost layer of the skin, consists of corneocytes and intercellular lipids. The ordered lipid structures formed by ceramides, cholesterol, and free fatty acids constitute an important barrier that limits the entry of exogenous substances into the skin. The lipophilicity of bisabolol favors its partitioning into this lipid environment and also enables it to enter the oil phase or other hydrophobic microenvironments in cosmetic formulations.

This physicochemical characteristic primarily influences the partitioning and diffusion of bisabolol within the skin and its interactions with lipid membranes. Its specific effects on inflammatory regulation are further supported by cell-signaling and animal studies.

3 Anti-inflammatory and Soothing Effects: Inflammatory Mediators, Cell Signaling, and Mast-Cell Regulation

When the skin is exposed to ultraviolet radiation, chemical irritation, friction, or other stressors, multiple cell types, including keratinocytes, immune cells, and mast cells, can become activated, leading to the release of inflammatory mediators and cytokines. The soothing effects of bisabolol are associated with modulation of these inflammatory processes.

In 2011, Kim et al. investigated the effects of (−)-α-bisabolol in lipopolysaccharide-stimulated RAW264.7 macrophages. They found that bisabolol reduced the production of nitric oxide and prostaglandin E₂ and decreased the expression of inducible nitric oxide synthase and cyclooxygenase-2.[5]

Further analyses showed that bisabolol reduced nuclear factor κB (NF-κB)- and activator protein-1 (AP-1)-related transcriptional activity while attenuating the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase. JNK phosphorylation did not change significantly in this experiment.[5]

In 2014, Maurya et al. further investigated the effects of α-bisabolol on skin inflammation. Bisabolol reduced macrophage production of tumor necrosis factor-α and interleukin-6 and, in a mouse ear inflammation model induced by 12-O-tetradecanoylphorbol-13-acetate, reduced ear thickness and weight while attenuating lipid peroxidation and histological damage.[6]

A 2022 study further examined mast cells. In a dinitrochlorobenzene-induced atopic dermatitis-like mouse model, topical application of (−)-α-bisabolol alleviated skin lesions and epidermal thickening and reduced mast-cell activation in the lesions. In immunoglobulin E-mediated bone marrow-derived mast-cell experiments, bisabolol reduced the release of β-hexosaminidase, histamine, and tumor necrosis factor-α while inhibiting JNK- and NF-κB-related signaling. In this model, ERK and p38 phosphorylation did not change significantly.[7]

The signaling changes observed in different experimental models are not entirely identical. Macrophage studies mainly found effects involving ERK, p38, NF-κB, and AP-1, whereas mast-cell studies primarily implicated JNK and NF-κB. These findings support a modulatory effect of bisabolol on multiple inflammation-related processes, but current evidence remains insufficient to attribute its effects to a single, highly selective molecular target.

Human evidence for bisabolol remains relatively limited. In 2017, Werner et al. investigated sunscreen formulations containing bisabolol or panthenol. During a 48-hour observation period in a human ultraviolet-induced erythema model, the bisabolol-containing test formulation did not produce statistically significant inhibition of erythema relative to the base formulation.[8]

Existing cell and animal studies support a mechanistic basis and preclinical activity for the anti-inflammatory and skin-soothing effects of bisabolol; however, human evidence remains limited, and specific effects are influenced by concentration, formulation vehicle, skin condition, type of stimulus, and evaluation endpoint.

4 Antimicrobial Activity: Sensitivity Varies Among Microorganisms and Strains

α-Bisabolol also exhibits a certain degree of antimicrobial activity.

In 2011, De Lucca et al. studied natural α-bisabolol and the synthetic bisabolol mixture Dragosantol. The experiments included multiple species of Aspergillus, Fusarium, dermatophytes, as well as Pseudomonas aeruginosa and Staphylococcus aureus. The results showed that α-bisabolol exerted marked fungicidal or inhibitory effects against some of the tested fungi and bacteria, with substantial differences in sensitivity among microorganisms.[9]

Subsequent studies have also shown that the direct antibacterial activity of bisabolol is influenced by strain characteristics.

In 2020, Pereira da Cruz et al. studied Staphylococcus aureus strains carrying the TetK or NorA efflux pumps. The minimum inhibitory concentration of α-bisabolol alone was 1024 μg/mL or higher, indicating relatively weak direct antibacterial activity. At subinhibitory concentrations, however, it enhanced the effects of tetracycline or norfloxacin against certain strains. The findings suggested that bisabolol or its β-cyclodextrin complex can affect processes associated with certain bacterial efflux pumps.[10]

Thus, the antimicrobial activity of bisabolol shows clear microorganism- and strain-dependent differences, and sensitivity cannot be directly extrapolated among different bacteria, fungi, and drug-resistant strains.

For cosmetic products that require preservative protection, bisabolol cannot replace a validated preservative system. Microbiological safety should still be assessed on the basis of water activity, pH, packaging, and the overall formulation, with preservative efficacy testing performed where appropriate.

5 Stratum Corneum Penetration Enhancement: Increased Lipid Fluidity and Molecular Diffusion

The effects of bisabolol on the stratum corneum are not limited to its own entry into the skin; it can also alter the percutaneous diffusion of certain coexisting molecules.

In 1991, Kadir and Barry investigated the penetration-enhancing effects of α-bisabolol using excised human skin. After pretreatment with a 1:1 α-bisabolol/propylene glycol system, the skin permeability of the model drugs 5-fluorouracil and triamcinolone acetonide was approximately 17-fold and 73-fold that of untreated skin, respectively.[11]

The researchers further analyzed the stratum corneum by differential scanning calorimetry and found a marked decrease in the enthalpy of the stratum corneum lipid phase transition after bisabolol treatment, suggesting reduced lipid order and increased fluidity.

Drug-partitioning experiments further showed that the enhancement of 5-fluorouracil could not be explained by changes in the stratum corneum–vehicle partition coefficient. The increase in the solubility of triamcinolone acetonide in the penetration-enhancing system was also far smaller than the increase in skin permeability. The researchers therefore concluded that the increased flux of both drugs was primarily attributable to enhanced diffusivity within the altered stratum corneum barrier.[11]

The experiment used a high-proportion bisabolol/propylene glycol pretreatment system, which differs substantially from the lower use levels and different vehicles found in ordinary cosmetic formulations. Therefore, the 17-fold and 73-fold increases are specific to the experimental system and cannot be used directly to estimate the magnitude of penetration enhancement in routine skincare formulations.

The penetration-enhancing properties of bisabolol also need to be considered in formulation safety assessment. In its safety evaluation, the Cosmetic Ingredient Review (CIR) noted that bisabolol can enhance skin absorption and advised formulators to consider the possibility of increased absorption of other coexisting ingredients, particularly ingredients whose safety assessments are based on low percutaneous absorption.[12]

For formulations containing irritating ingredients, or ingredients whose safety is closely associated with the level of percutaneous exposure, skin tolerability and exposure should be evaluated using the complete formulation.

6 Safety and Formulation Stability

6.1 Safety in Cosmetic Use and Skin-Sensitization Risk

In its 1999 safety assessment, CIR concluded that bisabolol was safe under the cosmetic conditions of use at that time. In 2015, the Expert Panel re-reviewed the ingredient using newly available research data and updated information on frequency and concentration of use and maintained its original safety conclusion.[12]

The Research Institute for Fragrance Materials (RIFM) classified α-bisabolol as a weak skin sensitizer in its 2020 safety assessment based on animal and human data and established a No Expected Sensitization Induction Level of 5500 μg/cm² using a weight-of-evidence approach. In a human repeat-insult patch test, 10% α-bisabolol did not induce sensitization, although a small number of cases of contact dermatitis have been reported.[13,14]

Available evidence supports relatively good skin tolerability of bisabolol under normal cosmetic exposure conditions, although the possibility of contact allergy in individual users cannot be excluded.

6.2 Formulation Stability and Influencing Factors

Bisabolol is a lipophilic, oily ingredient that is generally incorporated into the oil phase of formulations such as emulsions, creams, and oils. Because its molecule contains unsaturated carbon–carbon double bonds, the stability of finished products can still be influenced by oxygen, light, temperature, coexisting ingredients, and packaging conditions.

In practical product development, long-term and accelerated stability testing is required to evaluate bisabolol content, color, odor, phase state, and other physicochemical parameters. Good compatibility with the oil phase does not necessarily mean that bisabolol will exhibit high stability under all formulation and storage conditions.

7 Combination Applications: Moisturization, Barrier Support, and Multi-Ingredient Soothing

7.1 Combination with Moisturizing and Barrier-Supporting Ingredients

Bisabolol can be used in combination with moisturizing ingredients such as glycerol and hyaluronic acid, as well as barrier-lipid-related ingredients such as ceramides, cholesterol, and fatty acids. Glycerol and hyaluronic acid mainly improve hydration of the stratum corneum, barrier-lipid-related ingredients mainly support the intercellular lipid structure of the stratum corneum, and bisabolol primarily contributes soothing and inflammation-modulating effects.

These ingredients act on different aspects of skin condition and can be combined to form formulation systems that integrate moisturization, barrier support, and soothing effects. The specific effects of such combinations still depend on ingredient concentrations, ratios, and the complete formulation.

7.2 Combination with Other Soothing Ingredients in Multi-Ingredient Systems

Bisabolol can also be combined with soothing ingredients that have different functional characteristics. In 2024, Tan et al. studied a four-component system consisting of allantoin, bisabolol, D-panthenol, and dipotassium glycyrrhizinate. In a human keratinocyte model stimulated with ultraviolet B radiation, the combination reduced prostaglandin E₂ and multiple inflammation-related mediators and attenuated changes associated with oxidative stress.[15]

This study showed that combinations of multiple soothing ingredients can simultaneously affect inflammation- and oxidative-stress-related processes. Because the experiment evaluated a specific ratio of four ingredients, the findings cannot be directly extrapolated to other ratios, nor can they be used to conclude that arbitrary bisabolol-containing combinations are synergistic.

8 Representative Chemicals Related to Bisabolol Structure and Sources, Mechanisms of Skin Action, and Formulation Research

Table 1. Chemicals Related to Core Bisabolol Components, Source Quality Control, and Skincare Combinations

Table 2. Chemicals Related to Bisabolol Penetration Enhancement and Skin-Inflammation Mechanism Research

Note: The products listed above are representative Aladdin products relevant to scientific research. Specific applications should be determined according to product specifications, batch COAs, and the intended reaction or evaluation system. Additional information on product specifications, grades, and COAs can be found on the Aladdin website by searching by “product name/CAS/catalog number.”

References

[1] PubChem. alpha-Bisabolol, PubChem CID 10586. National Center for Biotechnology Information.

[2] Gosztola B, Sárosi S, Németh E. Variability of the essential oil content and composition of chamomile (Matricaria recutita L.) affected by weather conditions. Natural Product Communications. 2010;5(3):465–470. DOI: 10.1177/1934578X1000500325.

[3] Albertti LAG, Delatte TL, Souza de Farias K, et al. Identification of the Bisabolol Synthase in the Endangered Candeia Tree (Eremanthus erythropappus (DC) McLeisch). Frontiers in Plant Science. 2018;9:1340. DOI: 10.3389/fpls.2018.01340.

[4] Han GH, Kim SK, Yoon PKS, et al. Fermentative production and direct extraction of (−)-α-bisabolol in metabolically engineered Escherichia coli. Microbial Cell Factories. 2016;15:185. DOI: 10.1186/s12934-016-0588-2.

[5] Kim S, Jung E, Kim JH, Park YH, Lee J, Park D. Inhibitory effects of (−)-α-bisabolol on LPS-induced inflammatory response in RAW264.7 macrophages. Food and Chemical Toxicology. 2011;49(10):2580–2585. DOI: 10.1016/j.fct.2011.06.076.

[6] Maurya AK, Singh M, Dubey V, Srivastava S, Luqman S, Bawankule DU. α-(−)-Bisabolol reduces pro-inflammatory cytokine production and ameliorates skin inflammation. Current Pharmaceutical Biotechnology. 2014;15(2):173–181. DOI: 10.2174/1389201015666140528152946.

[7] Li G, Wu H, Sun L, et al. (−)-α-Bisabolol alleviates atopic dermatitis by inhibiting MAPK and NF-κB signaling in mast cell. Molecules. 2022;27(13):3985. DOI: 10.3390/molecules27133985.

[8] Werner M, Herling M, Garbe B, et al. Determination of the influence of the antiphlogistic ingredients panthenol and bisabolol on the SPF value in vivo. Skin Pharmacology and Physiology. 2017;30(6):284–291. DOI: 10.1159/000480301.

[9] De Lucca AJ, Pauli A, Schilcher H, Sien T, Bhatnagar D, Walsh TJ. Fungicidal and bactericidal properties of bisabolol and dragosantol. Journal of Essential Oil Research. 2011;23(3):47–54. DOI: 10.1080/10412905.2011.9700457.

[10] Pereira da Cruz R, Sampaio de Freitas T, do Socorro Costa M, et al. Effect of α-bisabolol and its β-cyclodextrin complex as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. Antibiotics. 2020;9(1):28. DOI: 10.3390/antibiotics9010028.

[11] Kadir R, Barry BW. α-Bisabolol, a possible safe penetration enhancer for dermal and transdermal therapeutics. International Journal of Pharmaceutics. 1991;70(1–2):87–94. DOI: 10.1016/0378-5173(91)90167-M.

[12] Fiume MM. Bisabolol. International Journal of Toxicology. 2017;36(5 Suppl 2):24S–25S. DOI: 10.1177/1091581817716644.

[13] Api AM, Belsito D, Biserta S, et al. RIFM fragrance ingredient safety assessment, α-bisabolol, CAS Registry Number 515-69-5. Food and Chemical Toxicology. 2020;141 Suppl 1:111238. DOI: 10.1016/j.fct.2020.111238.

[14] Russell K, Jacob SE. Bisabolol. Dermatitis. 2010;21(1):57–58. DOI: 10.2310/6620.2010.09072.

[15] Tan C, Peng K, Lim TY, et al. The combination of allantoin, bisabolol, D-panthenol and dipotassium glycyrrhizinate mitigates UVB-induced PGE₂ synthesis by keratinocytes. International Journal of Cosmetic Science. 2024;46(5):691–701. DOI: 10.1111/ics.12951.

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