INTRODUCTION:

Skin hyperpigmentation is a disorder in which patches of skin becomes darker in colour. This occurs due to melanin is overproduced in certain spot of skin. Melanin is an important pigment in skin hyperpigmentation the process is known as melanogenesis. Melanin pigmentation in epithelial cell is known as melanosis. Melanin present within the dermis between the bundle of collagen is known as dermal melanosis¹. Melanocyte cell produce two types of melanin pigment- Eumelanin (black or brown), Pheomelanin (yellow reddish) responsible for colour in skin, hair and eye in human^2,3.

There is three type of skin hyper-pigmentation which are melasma, post-inflammatory hyper pigmentation, and age spot⁴. Melasma is caused by sun exposure, Addison’s disease hormonal imbalance, and vitamin B12 deficiency^5,6.

In skin cell, UV radiation produces reactive oxygen species (ROS) which activate the intracellular signaling pathways⁷. Mainly there are two enzymes responsible for melanin production; Tyrosinase and Dopachrome Tatuomerase. Tyrsosinase is a main enzyme in melanin growth and over activity of tyrosinase enzyme causes hyper-pigmentation⁸.

There are many herbs found which has tyrosinase inhibitory properties. Tyrosinase inhibitors demands are increasing on the industrial and clinical scale, so invitro assay and screening technique are also developed for tyrosinase inhibitor^8-10. Herbs like Glycyrrhiza glabra, Panax ginseng, Embica officinalis, Azadiracta indica, Curcuma longa etc. used for treatment of skin hyperpigmentation¹¹. Some phytoconstituents like ellagic acids, quercetin, and some whitening agent like kojic acid, arbutin etc. are used for treatment as skin hyperpigmentation¹².

MELASMA:

The word Melasma originates from the Greek word "melas", which means black, and refers to its brownish clinical presentation¹³. Melasma is an acquired hyper-melanosis personified by asymmetric, brown-coloured, irregular, spots on sun exposed areas of the skin, especially the face. It occurs especially as hyperpigmented macules on the cheeks, forehead, upper lip, nose, and chin¹⁴. Chronic ultraviolet (UV) exposure, female hormone stimulation etc. have all been proposed to play a role in the development of melasma¹⁵.

It is also noticed that a release of histamine from mast cells in response to UV irradiation has been known to stimulate melanogenesis, which is mediated by H2 receptors. Sebocytes have been postulate to contribute to the development of melasma¹⁶. Effect of Hormones play a role in the pathogenesis of melasma, estrogen, and progesterone have an impact in melasma development, because melasma is common in pregnancy, hormonal contraceptive use, estrogen therapy in prostate cancer patients. In females, melasma is more frequent about 9 times more cause than in males. Melasma is an unwanted cutaneous effect of oral contraceptives. Melasma is commonly caused by physiological change in hormone. Estrogens play a major role in both physiological and pathological conditions of the skin in melasma^16,17.

Figure 1. Pigmentation of melasma on the face¹⁸.

HERBAL PLANTS:

1. Aloe^19-26:

The leaf is used for the treatment of melasma, skin burns and other minor burns. Its gel is mainly used as anti-fungal, anti-inflammatory, and hepato-protective effect. The isolates of aloe vera are barbaolin, aloesin, aglycone of aloenin, aloesin, isoaloerresin D etc. shows potent tyrosinase inhibitory properties. Aloesin shows highest inhibition value than other molecules extracted from aloe^3-5. It was discovered that aloesin 34 % lessened pigmentation. This finding indicated that aloesin might be utilised for hypermelanosis, which is brought on by ultraviolet rays⁸.

Figure 2. Aloesin

2. Amla^27-31:

The fruit part is used for the treatment of various skin disease. Sesquiterpenoids, alkaloids, sugars, mucic acids, amino acids, flavonolglycosides, phenolic glycosides, phenolic acids, and tannins are just a few of the numerous compounds that can be found. Compared to other fruit juice, the juice from Emblica officinalis has the highest concentration of vitamins C and E. Tyrosinase may be inhibited by the extract by blocking the expression of Trp-1 and the Microphthalmia-associated transcription factor (MITF), while Trp-2 may be induced when the extract is applied at low doses.

Figure 3. vitamin C

3. Cutch tree^33-35:

The bark is used for the treatment. At a concentration of 120 g mL^-1, the extract showed strong tyrosinase inhibition activity, with an inhibition percentage of 61.58 compared to a favourable kojic acid regulation at a concentration equivalent to 120g mL^-1.

Figure 4. Catechin

4. Green tea^36-40:

Steamed, dried, and rolled leaves are used to make green tea in order to deactivate endogenous polyphenol oxidase (PPO). Researchers assessed Camellia sinensis activity, melanin formation, and expression of the melanogenic enzyme at the protein and mRNA levels in melan-A cells. -[-]-epigallocatechin-3-gallate [EGCG], -[-]-epigallocatechin[EGC], -[-]-catechin[C], -[-]-gallocatechingallate [GCG], and -[-]-epicatechingallate [ECG] are active components found in green tea. In mouse melanoma cells, EGCG suppresses melanin synthesis. Gallic acid and EGCG have more tyrosinase inhibitory action through cell proliferation.

Figure 5. Epigallocatechin gallate [EGCG]

5. Indian sarasparila^31,42:

It is a member of the Asclepiadaceae family and is frequently called anantmul. By preventing the synthesis of L-dopa to dopachrome, Hemidesmus indicus reduces the monophenol and diphenol activity of tyrosinase, which in turn inhibits the generation of melanin. L-tyrosine was used as a substrate for the study of 2-hydroxy-4-methoxybenzaldehyde MBALD's suppression of monophenolase activity. Vanillin, lupeal, and hemidesminine are the active ingredients that have antioxidant properties.

Figure 6. Heminine

6. Jamaica cherry^43,44:

Muntingia calabura extracts are made by decocting various plant components, such as leaves, flowers, and fruits, in various solvents, including ethanol, water, hydro-ethanol, and petroleum ether. As a consequence, the leaf extract of Muntingia calabura in hydroethanol had the highest level of anti-thyrosinase and antioxidant activity. The melanogenesis process is inhibited by plant extracts. Reactive oxygen species produced by the human body promote DNA damage, melanin production, and melanocyte proliferation.

Figure 7. 1-Deoxy-d-Mannitol

7. Liquorice^45-48:

The antioxidant activity of Glycyrrhiza glabra extracts, particularly the potent antioxidant glycyrrhizin, triterpene saponins, and flavonoids, has a significant impact on the skin. The hydrophobic portion of Glycyrrhiza's root extract contains gabridin, which can prevent UVB induction and lower tyrosinase activity in cultures of melanocytes. By preventing L-DOPA from being oxidised, the liquorice extract inhibits the activity of tyrosinase with an IC50 value of 53 g mL^-1. The maximum tyrosinase inhibition activity is seen in glabridin content. The first oxidation of tyrosine was shown to have the most-inhibitory activity, with an IC50 value of 0.9g mL^-1.

Through the action of its main active ingredient, glabridin, liquorice extract has the capacity to block tyrosinase activity, which suppresses melagonesis. Other two well-known liquorice active ingredients include liqueritin and iso-liquirtin, which both remove or disperse epidermal melanin.

Figure 8. Glabridin

8. Lotus^49-52:

Alkaloids, saponine, and phenols found in its seed and leaf extract exhibit antioxidative activity against tissue oxidation. Lotus seeds and leaves exhibit defence mechanisms for protection of skin from UVB radiation, anti-aging impact, and effect of skin whitening.

Figure 9. Nuciferine

9. Neem oil^53-54:

Additionally, to having antibacterial and antioxidant properties, Azadirachta indica exhibits activity against the tyrosinase enzyme. It also contains azadirachtin, isomeldenin, nimbin, nimbinene, 6-desacetyllnimbinene, and nimbandiol.

Figure 10. Azadirachitin

10. Papaya^55-57:

Papain, chymopapain A, and B are present, and they have antioxidant action. Additionally, it contains malic acids, calcium, sugar, fiber, vitamin C, thiamine, riboflavin, and niacin. Additionally, it contains proteins and lipids. Carica fruit extract has been reported to have 87% antioxidant activity. There were two main types of phenolic chemicals in papaya fruit. These phenolic chemical families are the most significant natural antioxidant groupings.

Figure 11. Papain

11. Saffron^58-60:

Utilizing 70 % ethanol, the antioxidant activity of the extract was 81 %. The crocus sativus reduces the skin's melanin pigment. Emulsion is utilised as a skin-whitening agent and in cosmetic and pharmaceutical preparations to treat skin hyperpigmentation. With an IC₅₀of 1.84mm, isorhamnetin-3, 49-diglucoside has a 55.7% concentration at 2666.7g mL^-1.

Figure 12. Picrocrocin

12. Sandalwood oil^61-65:

Numerous medical benefits of sandalwood include anti-inflammatory, anti-phlogistic, antiseptic, antispasmodic, carminative, diuretic, emollient, hypotensive, memory-enhancing, sedative, and more. The characteristics of sandalwood oil include skin anti-aging, smoothing, moisturising, and moisturising. The oil contains DPPH radical scavenging properties as well as the ability to inhibit the oxidative enzyme 5-lipoxygenase. Sandalwood oil's main component is alpha-santalol. It is a more powerful tyrosinase inhibitor than kojic acid and arbutin [IC₅₀ = 171 g mL^-1].

Figure 13. α-Santalol

13. Turmeric^66-72:

Some of the active ingredients in curcuma longa, such as curcumin, demethylcurcumin, and bisdemethylcurcumin, have tyrosinase inhibitory or depigmenting properties. The most tyrosinase inhibition of any of these is found in curcumin. When compared to a synthetic curcumin analogue, natural curcuminoides have strong inhibitory activity. With compound o-diphenols and m-diphenols, curcumin analogue exhibits stronger tyrosinase activity than other compounds. Curcuminoids reduce tyrosinase activity by preventing L-dopa oxidation. MITF, TRP-1, and other tyrosinase protein levels are inhibited by partially purified curcuma longa (PPC), which also suppresses cells that have been activated by MSH. Activation of ERK or PI3K/Akt in the signalling pathway by a PPC-related melanogenesis-suppressing mechanism.

Figure 14. Curcumin

14. Vitex negundo^73-74:

Local cosmetic doctors diagnose hyperpigmentation as melasma or ephelides using a poultice made from this plant. Negundin has a functional lactone at position C-2 and has a strong IC₅₀ value of 10.06 mM for the tyrosinase enzyme. Vitex negundo is used as a tyrosinase inhibitor, a skin lightening agent, and to prevent the production of post-inflammatory pigmentation. Negundin A is one of several chemical components found in Vitex negundo.

Figure 15. Negudin-A

15. White mulberry^75-80:

Morus alba extract contains flavonoids that have antioxidant and tyrosinase-inhibiting effects. Mulberry extract's ability to inhibit tyrosinase is comparable to that of HQ and kojic acid. From the roots of Morus alba, two compounds called oxyresveratrol and mulberroside-A block the generation of monophenolase and the activity of the enzyme mushroom tyrosinase, which is involved in the manufacture of melanin. They have anti-fever, liver-protective, and blood pressure-lowering qualities. The leaves' polyphenols have anti-pigmentation properties.Mulberroside F is inhibited by 51.6 % at a concentration of 1 g mL^-1 compared to an IC₅₀ value of 0.29g mL^-1.

Figure 16. β-Sitosterol

CONCLUSION:

In this review, we covered a variety of plants and the chemical components found in them that are utilised as tyrosinase inhibitors and skin lightening agents. The most vital organ on our bodies is the skin, and the amount of melanin therein determines the colour of the skin. Melanin, a pigment found in skin, gives mammals skin its distinctive colour. Hyperpigmentation of the skin results from an increase in melanin levels in the skin. Tyrosinase enzyme is primarily responsible for melanin synthesis. In order to manufacture melanin in the epidermal layer of skin and impact skin colour, it converts L-tyrosine in L-DOPA and L-DOPA to dopaquinone. plants include Glycyrrhiza glabra, Curcuma longa linn, Cape aloe, vitex negundo, and Azadiracta indica. Aloin, gallic acid, catechin, tocopherol, glabradin, and many more phytoconstituents are employed as anti-hyperpigmentation ingredients in herbal cosmetics. These herbs include flavonoids and triterpenoids, some of which have been shown to have antioxidant and skin-whitening properties.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGEMENT:

The authors express their sincere thanks to Dean, Teaching and non-teaching staff of Dr. Subhash University, Junagadh, Gujarat, India for providing all facilities to conduct this work.

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Received on 24.11.2023 Modified on 12.04.2024

Asian J. Pharm. Res. 2024; 14(3):289-294.

DOI: 10.52711/2231-5691.2024.00045