Understanding Hyperpigmentation: Melanin Pathways, UV Influence, and Treatment Targets

Hyperpigmentation is a condition causing uneven dark spots or patches on the skin due to increased eumelanin production by melanocytes (Vashi and Kundu, 2013). As such, understanding melanin production and skin tone is central to developing effective hyperpigmentation treatment skincare. There are several types of hyperpigmentation, typically classified by aetiology (Vashi and Kundu, 2013). Post inflammatory hyperpigmentation (PIH) occurs after cutaneous injury or inflammation and is especially common in darker skin tones. Melasma is often triggered hormonally and presents as symmetrical brown patches on the face, making it one of the most common concerns associated with melasma and uneven skin tone. Solar lentigines are flat spots varying in colour which form due to cumulative sun exposure. Ephelides, or freckles, are small light brown spots that darken with sun exposure and are more common in lighter skin tones. Maturational dyschromia, or general uneven tone, can be seen in mature dark skin and is a diffuse hyperpigmentation, typically affecting the cheekbones and lateral forehead. Many other types of hyperpigmentation exist, and the commonality is increased eumelanin synthesis causing uneven skin tone (Vashi and Kundu, 2013).

Hyperpigmentation can pose aesthetic concerns for an individual, affecting their psychological well-being, due to feelings of self-consciousness. This can lower self-esteem, especially if the hyperpigmentation is persistent. Furthermore, hyperpigmentation can sometimes be an indicator of underlying conditions such as metabolic imbalances and inflammatory disorders (Vashi and Kundu, 2013). Inflammatory hyperpigmentation such as PIH can be hard to manage, and discolouration may take an extended time to fade (Vashi and Kundu, 2013). Social pressures to have even skin tone provide cosmetic companies with the opportunity to produce products preventing hyperpigmentation occurrence, especially those aiming to reduce dark spots naturally or utilise natural skin brightening actives.

In order to create products to prevent hyperpigmentation, it is vital to understand the process of melanogenesis (Wong et al., 2025). This aids understanding of how melanin formation can occur in excess due to upregulation of eumelanin synthesis, as seen in hyperpigmentation disorders (Wong et al., 2025). Alpha-Melanocyte-Stimulating Hormone (α-MSH) is secreted by keratinocytes upon UV exposure. After secretion, α-MSH binds to MC1R receptors on melanocytes and stimulates protein cascades which result in transcription of tyrosinase (TYR) (Wong et al., 2025). This α-MSH and MC1R pathway is central to melanin regulation skincare science, particularly in developing new generation tyrosinase inhibitors skincare solutions. This activation ultimately leads to melanin synthesis.

Figure 1:

Figure 1: Melanogenesis. α-MSH binds to MC1R receptors on melanocytes, activating them. This activates adenylate cyclase. Adenylate cyclase catalyses the conversion of ATP to cAMP. Upregulation of cAMP levels in melanocyte cytosol activates PKA, which activates CREB, causing its translocation into the nucleus. Here, CREB binds to MITF transcription factors, marking TYR and DCT genes for transcription. Tyrosinase catalyses the conversion of tyrosine to DOPA. DOPA is converted to eumelanin by DCT (Wong et al., 2025).

Since hyperpigmentation occurs due to dysregulation of eumelanin synthesis, the most typically targeted route to preventing hyperpigmentation is by modulating the processes that lead to eumelanin production. A key target for downregulation when preventing hyperpigmentation is α-MSH (Wong et al., 2025). Downregulating α-MSH will consequently downregulate eumelanin production by preventing gene transcription of melanin-synthesising enzymes. Upregulation of α-MSH inhibitors can downregulate α-MSH action and therefore eumelanin synthesis. For example, agouti signalling protein (ASIP) is a competitive inhibitor of α-MSH, antagonising its action via negative regulation (Wong et al., 2025). This will consequently prevent downstream cascades which cause melanin synthesis, reducing hyperpigmentation prevalence.

Understanding the interactions between pigmentation and UV exposure, melanin synthesis pathways, and inhibitory molecules is key to developing effective hyperpigmentation treatment skincare formulations. Incorporating targeted pathways such as the α-MSH/MC1R route, tyrosinase activity regulation, or ASIP modulation enables cosmetic scientists to engineer sophisticated systems to manage melasma and uneven skin tone. Ultimately, combining biochemical regulation with natural skin brightening actives provides a balanced approach to reducing hyperpigmentation and supporting clearer, more even skin tone.