Regimen Lab Skincare Encyclopedia ?

Alpha Bisabolol

1.0 Last Updated February 21, 2022

Ingredient Profile

Common Name: Bisabolol, Levomenol
INCI: Bisabolol
Source: German Chamomile, Candeia Tree

kligman ingredient evaluation

Penetration: Good penetration
Level of Evidence:

Level B; Good Quality Evidence
Reduces II-6 and TNF-⍺, blocks pain receptors

Regimen's Take

Bisabolol is a potent anti-inflammatory that has been used in cosmetics and other dermatologic preparations for decades. We are currently using Bisabolol in our C.R.E.A.M. for several purposes: 1) It helps soothe the skin 2) It has some anti-bacterial and anti-fungal properties to combat other ingredients’ effect on acne 3) It has some penetration enhancing properties, useful for improving the action of the active ingredients in C.R.E.A.M. It is an oil-soluble active so we only use it with our C.R.E.A.M. for now, but it definitely has a bright future for upcoming products.

TLDR

  • Bisabolol is a potent anti-inflammatory agent that reduces redness and sting sensation
  • It acts as a penetration enhancer for hard-to-penetrate actives
  • It has some antibacterial and anti-fungal properties

What is Bisabolol?

Bisabolol is a naturally occurring plant extract that was first isolated from the German chamomile, Matricaria chamomilla. It has since been identified in various aromatic plants around the world, and is a major component of the African alpine sage Salvia runcinata essential oil (1). Bisabolol and bisabolol-rich oils are found in skincare products and pharmaceuticals as both an active and inactive constituent due its well-established beneficial properties such as anti-inflammatory and antibacterial. While the German chamomile and African alpine sage may contain up to 50 and 90% bisabolol, respectively, the Brazilian Eremanthus erythropappus is also another bisabolol-rich source containing up to 85% of it. It is colourless in nature and has a mild floral scent making it a common ingredient in decorative cosmetics (1). 

What is Bisabolol used for?

  • Anti-inflammatory
  • Anti-irritant
  • Antibacterial and Anti-fungal
  • Penetration Enhancer
  • Anti-pigmentation

The major biological activities of bisabolol such as anti-inflammatory, anti-irritant, antibacterial, and low toxicity, drug permeation and non-allergenic properties make it a preferred active ingredient in topical formulations used to treat inflammation and hyperpigmentation. In addition to dermatological benefits, bisabolol also exhibits pharmacological properties such as analgesic, antibiotic, anti-parasitic, antioxidant, anticancer, and anti-anxiety, and is used in treating sleep disorders (2). Bisabolol is also found in cosmetics such as fragrances and shampoos, and non-cosmetics such as household cleaners and detergents.

Clinical studies using topical formulations containing bisabolol have been assessed on different areas of the skin. Following 8 weeks of applying cream containing 0.5% bisabolol to pigmented areas on human back skin, adverse reactions such as burning, erythema, or pruritus were not observed. Dermal toxicity was also not observed in studies using rat models. Aside from being an active ingredient in certain formulations, bisabolol is also used in combination with other ingredients, specifically propylene glycol, as a penetration enhancer. According to the Cosmetic Ingredient Review (CIR) panel, bisabolol is safe for its intended use in cosmetic and dermatological formulations (3).

Hyperpigmentation is a distressing concern that is common among people who are susceptible to eczema, exposure to ultraviolet light, and chronic skin inflammation. The anti-inflammatory and whitening properties of bisabolol make it a useful ingredient as an adjunctive therapy for the treatment of hyperpigmentation-related disorders. A topical cream containing 0.5% bisabolol after 8 weeks of application was shown to have strong whitening effect on UV-exposed pigmented skin when compared to a control formulation without the ingredient. Bisabolol is also effective as a component in after-sun products to alleviate inflammation post-UV exposure (4,9).Bisabolol can be used as an adjunctive therapy for treating hyperpigmentation and various other medical conditions. It also demonstrates synergism with propylene glycol to enhance penetration of other ingredients into the skin. The typical concentration of bisabolol in cosmetic formulations is between 0.1-0.2%, and is well-absorbed following dermal exposure (3). 
Aside from dermatological benefits in depigmentation and wound-healing activity, bisabolol is also used in nociception attenuation, and in treating inflammation and arthritis (5). Additional medicinal properties include gastroprotective, antibacterial, antifungal, and antioxidant (6). Studies using cell model systems also show efficacy in antitumor activity using different human brain cancer cell lines (7). 

How does Bisabolol work?

Bisabolol, or more specifically (-)-α-bisabolol, is an unsaturated, optically active sesquiterpene alcohol obtained by distillation of essential oils from natural source plants (1). The dermatological and pharmaceutical versatility of bisabolol is apparent when examining the variety of its biochemical targets with each target responsible for carrying out a different function. Some of the most well-characterized functions of bisabolol are clinically studied in humans and rodents to examine the biochemical basis of each. The most notable functions are anti-inflammatory, antibacterial, anti-nociceptive, anti-tumor, and its use in hyperpigmentation treatment.

Anti-inflammatory

Several mechanisms behind the anti-inflammatory properties of bisabolol have been investigated. The established premise is that bisabolol inhibits the production of the pro-inflammatory cytokines, mainly IL-6 and TNF-α, and bind strongly to their receptors on our cells, thereby blocking them from transmitting pro-inflammatory signals (8). Bisabolol also controls inflammation by decreasing the migration of TNF-α and leukocytes to the site of the injury (6).

Anti-nociceptive (Soothing)

Bisabolol-induced anti-nociception can be related to the anti-inflammatory properties of the compound. The analgesic properties of bisabolol were assessed ex vivoin mice and compared to those of lidocaine, a common topical anaesthetic. Both compounds were demonstrated to have similar effects in anti-nociceptive activity and reduction of neuronal excitability by blockage of sodium and potassium channels, which are responsible for peripheral pain perception (8). In vivo studies in mice also demonstrate efficacy in reducing pain perception by decreasing prostaglandin synthesis, an important step in inflammatory response (10).

Antibacterial

Bisabolol presents a modulatory synergistic effect against bacterial infections when it is used in combination with certain antibiotics. Similar to its role in enhancing permeation of dermatological products into our skin, bisabolol allows permeation of exogenous compounds, such as antibiotics, into the bacterial cell. This is achieved by targeting the bacterial cell membrane and disrupting its normal barrier function. Once the integrity of the bacterial membrane is compromised, antibiotics are allowed to enter and reach their biochemical targets (1).

Hyperpigmentation Treatment

Epidermal and dermal hyperpigmentation is generally caused by an increased number of melanocytes or melanogenic enzyme activity (9). Thus, bisabolol targets the mediators that are involved with these processes to block them from occurring. An important hormone responsible for pigmentation in mammals is the α-melanocyte-stimulating hormone (α-MSH). Bisabolol inhibits α-MSH-induced melanogenesis by suppressing CREB phosphorylation, which is induced by protein kinase A (4). As a result, the inactivation of this cAMP signaling pathway inhibits the expression of enzymes that are important for melanocyte development and differentiation

Anti-inflammatory

Inflammation is a natural and common biological response to a variety of stimuli such as local injury. It is a complex pathological process mediated by signaling molecules that trigger a series of events leading to a cascade of further molecular events which ultimately result in immune cells migrating to the site of infection or injury. The inflammatory response is an example of our host defense mechanism and plays a vital role in immunity. However, the consequences with inflammation can sometimes be unpleasant and may require medical attention. Skin-related conditions such as rashes, itchiness, dermatitis, rosacea, and psoriasis are the result of the body’s inflammatory response. Known for its anti-inflammatory, analgesic, and antibacterial properties, bisabolol is incorporated in various topical formulations to alleviate the effects of such dermatological conditions. A major mechanism bisabolol utilizes to achieve this is through the inhibition of pro-inflammatory cytokine production, particularly IL-6 and TNF-α, and exhibiting high binding affinity to their cellular receptors. This phenomenon is observed in macrophages post-LPS-induced inflammation (5). As it is widely recognized that cytokine secretion in response to injury or infection is an example of cutaneous inflammatory response, inhibition of pro-inflammatory cytokines by bisabolol and its molecular interaction with their receptors demonstrated therapeutic efficacy in skin inflammation (10). In addition, bisabolol is also known to inhibit other events that are responsible for inflammatory response, such as leukocyte migration and neutrophil degranulation (6)

How does it help in apoptosis?

Recent studies show bisabolol is able to kill by apoptosis human glioma cell lines that are normally highly resistant to common antitumor treatments. Rather than through the receptor-mediated pathway, bisabolol induces apoptosis through the mitochondrial intrinsic pathway whereby mitochondrial damage activates a cascade of events leading to programmed cell death (7). Bisabolol exhibits preferential apoptotic action as it is highly toxic to tumor cells while remaining non-toxic to normal cells. This may be related to the different plasma membrane lipid composition of normal and tumor cells and their cellular uptake efficiency of bisabolol, which is hydrophobic in nature. Thus, bisabolol is easily incorporated into the reportedly abundant lipid rafts of the tumor cell plasma membrane. Once absorbed into the plasma membrane Bid is recruited from the cytoplasm to the lipid rafts, and mediates trafficking of bisabolol to the mitochondrial membrane (7). Hence, bisabolol is rapidly distributed in the cytosol after its uptake. 
An increase in the release of cytochrome c is observed post-treatment with bisabolol in human glioma cell lines (7). Another early event in bisabolol-induced apoptotic cell death is the loss of mitochondrial cell membrane potential from the change in the concentrations of pro- and anti-apoptotic proteins. As a result, mitochondrial membrane integrity is compromised, and opening of the mitochondrial permeability transition pore (mPTP) with a consequent release of mitochondrial constituents ultimately leads to cell death. The inference that mPTP is a target apoptotic mechanism of bisabolol is supported by the prevention of cell death when mPTP is inhibited and in the absence of bisabolol. While the viability of human glioma cells drastically declined post-treatment with bisabolol, the viability of human fibroblasts was minimally affected. In clinical studies using the human glioma cell model, bisabolol induces rapid apoptosis at a concentration of 2 µM, and completely kills the same cells in only a few hours at 10 µM (7). 
 

Clinical trials 

Actives

Conclusion 

Source

0.5% bisabolol

Subjects: Human, n = 28

Tested area: Back, topical application

Strong whitening effect after 8 weeks of application on back skin following UV exposure; useful as an adjunctive therapy for treatment of hyperpigmentation-related disorders; no adverse effects were observed

Lee, J., Jun, H., Jung, E., Ha, J., Park, D. (2009). Whitening effect of α-bisabolol in Asian women subjects. International Journal of Cosmetic Science, 32, 299-303. doi: 10.1111/j.1468-2494.2010.00560.x

0.7 and 1.4 mg bisabolol

Subjects: Mice, n = 8

Tested area: Ear, topical application

Significant reduction in Croton oil-, arachidonic acid-, and phenol-induced edema; in vivo evidence showing suppression of mustard oil-induced visceral pain by targeting cytochrome P450 (anti-nociception activity); effective ingredient in anti-inflammatory agents for treating acute dermatitis by inhibiting prostaglandin synthesis

Leite, G. D. O., Leite, L. H. I., Sampaio, R. D. S., Araruna, M. K. A., Menezes, I., R. A. D., Costa, J. G. M. D., Campos, A. R. (2011). (-)-α-Bisabolol attenuates visceral nociception and inflammation in mice. Fitoerapia, 82, 208-211. doi:10.1016/j.fitote.2010.09.012

50, 100, and 200 mg bisabolol/kg

Subjects: Rodents, n = 5-8 per group

Tested area: Intraplantar injection 

Pre-treatment with bisabolol (100 and 200 mg/kg) significantly reduced carrageenan-, serotonin- and dextran-induced paw edema; bisabolol was able to decrease the intensity of inflammatory hypernociception by reducing TNF-α levels after induced peritonitis; in vitro evidence showing decrease of neutrophil degranulation

Rocha, N. F. M., Rios, E. R. V., Carvalho, A. M. R., Cerqueira, G. S., de Arajo Lopes, A., Leal, L. K. A. M., Dias, M. L., de Sousa, D. P., de Sousa, F. C. F., (2011). Anti-nociceptive and anti-inflammatory activities of (-)-α-bisabolol in rodents. Naunyn-Schmiedeberg’s Arch Pharmacol. 384:525-533. doi: 10.1007/s00210-011-0679-x

0.5, 1, 5, and 10 mM Bisabolol

Subjects: Mice

Tested area: Ex vivo, sciatic nerve 

Anti-nociceptive effects of bisabolol implicated in reduced neuronal excitability and the blockade of sodium channels, which are widely expressed in sensorial peripheral fibers; effect was similar to lidocaine

Alves., A. M. H., Gonçalves., J. C. R., Cruz, J. S., Araújo, D. A. M. (2010). Evaluation of the sesquiterpene (-)-α-bisabolol as a novel peripheral nervous blocker. Neuroscience Letters, 472, 11-15. doi:10.1016/j.neulet.2010.01.042

5 µM Bisabolol

Subject: In vitro, Human glioma T67 cell line, Human fibroblasts

Treatment with 5 µM bisabolol decreased mitochondrial membrane potential, and Increased reactive oxygen species levels as a result of apoptosis in human glioma cells, but not in fibroblasts; the solubility of bisabolol in lipid rafts of the tumor cell membrane underlies it readily uptake and apoptotic activity

Cavalieri, E., Bergamini, C., Mariotto, S., Leoni, S., Perbellini, L., Darra, E., Suzuki, H., Fato, R., Lenaz, G. (2009). Involvement of mitochondrial permeability transition pore opening in α-bisabolol induced apoptosis. FEBS Journal. 276, 3990-4000

0.1, 0.15, 0.25, 0.35, 0.55, and 5 µM Bisabolol

Subject: In vitro, Human umbilical vein endothelial cells (HUVEC)

Death-inducing effect and cytotoxicity was observed in HUVEC cells after treating with 5 µM bisabolol, however, treating with 0.1 and 0.25 µM bisabolol showed ability of the cells to organize in a capillary-like structure (angiogenesis initiation) 

Magnelli, L., Caldini, R., Schiavone, N., Suzuki H., Chevanne, M. (2010). Differentiating and Apoptotic Dose-Dependent Effects in (-)-α-Bisabolol-Treated Human Endothelial Cells. J. Nat. Prod, 73, 523-526. doi:10.1021/np9003933

0.1, 0.3, and 1.0% bisabolol

Subject: Mice

Tested area: Ear, topical application

Significant reduction of ear edema, oxidative stress and pro-inflammatory cytokine production in 1% bisabolol-treated mice demonstrated amelioration of skin inflammation; not an irritant to rabbit skin in primary skin irritation test 

Maurya, A. K., Singh, M., Dubey, V., Srivastava, S., Luqman S., Bawankule, D. U. (2014). α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production and Ameliorates Skin Inflammation. Current Pharmaceutical Biotechnology, 15, 173-181

1, 3, and 10 µg/mL bisabolol

Subject: In vitro, Mice peritoneal macrophage cells

Pro-inflammatory cytokine production was significantly decreased in bisabolol-treated cells in LPS- and TPA-induced inflammation, but no significant change in cell viability at any concentration compared with untreated cells

Maurya, A. K., Singh, M., Dubey, V., Srivastava, S., Luqman S., Bawankule, D. U. (2014). α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production and Ameliorates Skin Inflammation. Current Pharmaceutical Biotechnology, 15, 173-181

Does it penetrate the skin?

The structure of the epidermis is a formidable barrier against harmful substances from entering the body. However, its complex architecture is also a challenge to overcome in allowing penetration of topicals and drug delivery through the percutaneous route. A common approach is to incorporate permeation enhancers such as bisabolol in dermatological and pharmaceutical formulations. Bisabolol and propylene glycol, a common emollient, have been shown to exhibit synergism in enhancing skin penetration of other ingredients (3). Bisabolol is also found in high levels in chamomile oil to improve transdermal drug permeation in the skin (1). On its own, it is well-absorbed shortly after dermal exposure (3).

References

1

Kamatou, G. P. P., Vijoen, A. M. (2010). A Review of the Application and Pharmaological Properties of α-Bisabolol and α-Bisabolol-Rich Oils. J Am Oil Chem Soc, 87:1-7. doi:10.1007/s11746-009-1483-3

2

Ghasemi, M., Jelodar, N. B., Modarresi, M., Bagheri, N., Jamali, A. (2016). Increase of Chamazulene and α-Bisabolol Contents of the Essential Oil of German Chamomile (Matricaria chamomile L.) Using Salicylic Acid Treatments under Normal and Heat Stress Conditions, 5, 56. doi: 10.3390/foods5030056

3

International Journal of Toxicology. (1999). Final Report on the Safety Assessment of Bisabolol. Cosmetic Ingredient Review, 18(3):33-40

4

Lee, J., Jun, H., Jung, E., Ha, J., Park, D. (2009). Whitening effect of α-bisabolol in Asian women subjects. International Journal of Cosmetic Science, 32, 299-303. doi: 10.1111/j.1468-2494.2010.00560.x

5

 

Kim, S., Jung, E., Kim, J., Park, Y., Lee, J., Park, D. (2011). Inhibitory effects of (-)-α-bisabolol on LPS-induced inflammatory response in RAW264.7 macrophages. Food and Chemical Toxicology. 49, 2580-2585. doi: 10.1016/j.fct.2011.06.076

6

Rocha, N. F. M., Rios, E. R. V., Carvalho, A. M. R., Cerqueira, G. S., de Arajo Lopes, A., Leal, L. K. A. M., Dias, M. L., de Sousa, D. P., de Sousa, F. C. F., (2011). Anti-nociceptive and anti-inflammatory activities of (-)-α-bisabolol in rodents. Naunyn-Schmiedeberg’s Arch Pharmacol. 384:525-533. doi: 10.1007/s00210-011-0679-x

7

Cavalieri, E., Bergamini, C., Mariotto, S., Leoni, S., Perbellini, L., Darra, E., Suzuki, H., Fato, R., Lenaz, G. (2009). Involvement of mitochondrial permeability transition pore opening in α-bisabolol induced apoptosis. FEBS Journal. 276, 3990-4000

8

Alves., A. M. H., Gonçalves., J. C. R., Cruz, J. S., Araújo, D. A. M. (2010). Evaluation of the sesquiterpene (-)-α-bisabolol as a novel peripheral nervous blocker. Neuroscience Letters, 472, 11-15. doi:10.1016/j.neulet.2010.01.042

9

Werner, M., Herling, M., Garbe, B., Theek, C., Tronnier, H., Heinrich, U., Braun, N. (2017). Determination of the Influence of the Antiphlogistic Ingredients Panthenol and Bisabolol on the SPF Value in vivo. Skin Pharmacol Physiol, 30:284-291. doi 10.1159/000480301

10

Leite, G. D. O., Leite, L. H. I., Sampaio, R. D. S., Araruna, M. K. A., Menezes, I., R. A. D., Costa, J. G. M. D., Campos, A. R. (2011). (-)-α-Bisabolol attenuates visceral nociception and inflammation in mice. Fitoerapia, 82, 208-211. doi:10.1016/j.fitote.2010.09.012

11

Magnelli, L., Caldini, R., Schiavone, N., Suzuki H., Chevanne, M. (2010). Differentiating and Apoptotic Dose-Dependent Effects in (-)-α-Bisabolol-Treated Human Endothelial Cells. J. Nat. Prod, 73, 523-526. doi:10.1021/np9003933

12

Maurya, A. K., Singh, M., Dubey, V., Srivastava, S., Luqman S., Bawankule, D. U. (2014). α-(-)-bisabolol Reduces Pro-inflammatory Cytokine Production and Ameliorates Skin Inflammation. Current Pharmaceutical Biotechnology, 15, 173-181

?
The Skincare Encyclopedia aims to improve public understanding of the biology and chemistry of skincare. The Encyclopedia is rooted in core scientific principles and extensive research, in many cases in collaboration with the authors of the original studies referenced. This is a project of Regimen Lab, maintained by a group of multidisciplinary scientists, MDs, and researchers.