Alpha Bisabolol

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 

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