Role of Ancient Ayurvedic drugs and their formulations in treatment of hyperpigmentation of skin

Abstract

Hyperpigmentation disorders, including melasma and post-inflammatory hyperpigmentation (PIH), are prevalent dermatological concerns that significantly affect quality of life, particularly among individuals with darker skin tones. Conventional therapies—such as hydroquinone, retinoids, corticosteroids, chemical peels, and laser treatments—often provide inconsistent outcomes and carry risks of side effects or recurrence. This has stimulated growing interest in Ayurvedic medicine, a holistic system with a long tradition of using botanicals for enhancing skin complexion and restoring balance. This review synthesizes classical Ayurvedic perspectives alongside modern pharmacological evidence, focusing on key herbs such as Curcuma longa (turmeric), Rubia cordifolia (manjistha), Symplocos racemosa (lodhra), Santalum album (sandalwood), and Glycyrrhiza glabra (liquorice). These botanicals exhibit antioxidant, anti-inflammatory, and melanogenesis-regulating activities, supported by preclinical and emerging clinical studies. Challenges including phytochemical variability, lack of large-scale randomized controlled trials, and formulation-related issues highlight the need for rigorous standardization and innovative delivery systems. By bridging Ayurvedic wisdom with contemporary research, this review underscores the potential of these botanicals as safe, sustainable, and effective alternatives or adjuncts for managing hyperpigmentation, while outlining future directions for integrative dermatology.

Keywords

melanin, melanocytes, hyperpigmentation, Ayurveda,tyrosinase,skin disorders, melasma, proinflammatory Hyperpigmentation

Introduction

Prevalence : PIH is consistently reported at higher rates in skin-of-color populations than in Caucasians.Prevalence also varies within Asian populations, with darker-skinned groups (e.g., Malays, Indians) more affected than lighter-skinned groups (e.g., Chinese), highlighting that pigmentation depth, not ethnicity alone, increases risk.

1. Prevalence of hyperpigmented spots (according to age group) assessed clinically by dermatologists (N = 1,204). (b) Prevalence of hyperpigmented spots (according to age group) assessed from photographs (N = 1,196)

Ayurvedic Perspective of Pigmentary Disorders :

Vyanga is the Ayurvedic term for a skin condition on the face that causes painless, thin, bluish-black patches, reducing the natural glow of the skin. It is traditionally classified as a minor disease (Kshudra Roga) but is a significant cosmetic concern.  According to Ayurvedic theory, this happens when the bodily energies (Doshas) – especially Pitta (heat) and Rakta (blood) – become unbalanced, affecting skin color.

Ayurvedic theory explains Vyanga as arising from imbalanced Pitta and blood (Rakta) due to stress or emotional factors like anger, grief, or exhaustion. These imbalances disturb the normal pigment formation in the skin, causing the dark patches.Foundational Ayurvedic works such as the A????ga H?daya, Yoga Ratn?kara, Su?ruta Sa?hit?, and Chakradatta discuss both causation and therapeutic approaches for vyanga (the Ayurvedic correlate of melasma) Ayurvedic skin care is portrayed as multifaceted: internal purification and rejuvenation through Pañcakarma (bio-cleansing procedures) and Ras?yana (rejuvenation therapy), together with pathya ahara-vih?ra (dietary and lifestyle measures), form the foundation. These systemic approaches are complemented by local therapies such as abhyanga (therapeutic massage) and topical lepa (medicinal pastes).

Ayurvedic Drugs and Classical Formulation in Hyperpigmentation :

A wide range of Ayurvedic herbs and formulations have been historically prescribed for improving skin complexion and reducing pigmentation.

Haridra (Curcuma longa) – Turmeric (Curcuma longa) are the dried rhizomes of Curcuma longa Linn. Family: Zingiberaceae is a commonly used herb in Ayurvedic medicine and a ubiquitous culinary spice. India stands as the leading producer, exporter, and consumer of turmeric, recording a yield of 8.46 lakh tonnes in 2014–2015.The term “turmeric” originates from the Latin expression terra merita, meaning “meritorious earth.” Commonly referred to as “yellow root,” “golden spice,” and “Indian saffron,” it has been valued for over 6,000 years in traditional medicine as well as in religious rituals. In Sanskrit, turmeric is known by 55 different names, each reflecting its medicinal or spiritual significance.The earliest mention of turmeric can be traced back to the Atharvaveda.Its primary.bioactive constituent, curcumin, is a hydrophobic polyphenolic compound that confers the characteristic yellow color of turmeric.

Compounds in turmeric (curcuminoids) show antioxidant, anti-inflammatory and lightening effects in laboratory tests and can block enzymes that break down skin matrix (like collagenase and elastase).Curcumin shows promise for inflammatory conditions (for example, PIH.Laboratory work suggests curcumin interferes with inflammatory pathways (like NF-κB) and enzymes involved in psoriasis.

Topical forms may help lesions and can speed wound healing in animal studies by reducing inflammation and boosting collagen and new blood-vessel formation.Topical curcumin preparations have been reported to improve sun-damaged skin and some pigmentary changes when used for long periods. Preclinical research has identified multiple biological activities of curcumin, notably anti-inflammatory and antineoplastic effects..In two clinical split-face trials:Caucasian women, a cream containing turmeric extract + niacinamide significantly improved fine lines and wrinkles and showed directional improvement in pigmentation. In Asian women, a turmeric-extract-only cream reduced hyperpigmentation by approximately 14.16% at 4 weeks and 14.91% at 8 weeks (both highly significant, P < 0.0001). Tetrahydrocurcumin (THC) another metabolite of curcumin is recognized for its potent antioxidant activity, suggesting its potential role in alleviating oxidative stress-related disorders such as skin hyperpigmentation. Recent investigations utilizing an in vitro B16F10 melanoma cell model revealed that THC effectively suppressed α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis. This effect was associated with a marked downregulation of the key melanogenic enzymes tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). Complementary studies using a human keratinocyte model further demonstrated that THC exerted a protective effect against hydrogen peroxide (H?O?)-induced oxidative injury. Specifically, THC improved cell viability and reduced intracellular ROS accumulation. To enhance topical delivery, THC was incorporated into a lecithin-based nanoemulsion.nanoemulsion markedly improved membrane permeation compared with a conventional THC suspension.

Manjistha (Rubia cordifolia) – It is the roots and stem of Rubia cordifolia Linn. family: Rubiaceae In Ayurveda, root of Manjistha (Indian Madder) has traditionally been prescribed to enhance facial complexion (Ayurvedic Pharmacopoeia of India, 2001). It is a key component of Kumkumadi taila, a classical polyherbal formulation valued for rejuvenating skin texture (Hazra & Panda, 2013). Ethnomedicinally, its root has been applied externally to manage a variety of skin conditions, including wounds, ulcers, and acne (Joshan et al., 2010).. In classical texts, Acharya Charaka described Manjistha as a rejuvenative herb with detoxifying properties, while Acharya Sushruta, the renowned surgeon, recommended its use for maintaining balance among the body’s bio-elements.Beyond dermatological applications, extracts of Manjistha have demonstrated diverse pharmacological activities such as antioxidant, anti-inflammatory, radioprotective, and hepatoprotective effects.while modern phytochemical investigations attribute these effects to active constituents such as anthraquinones and glycosides. The roots of this plant are particularly rich in purpurin, an anthraquinone compound along with  it’s glycosides (Mouri and Laursen, 2012). Additionally, several other anthraquinones—such as xanthopurpurin, mollugin, alizarin, lucidin primeveroside, ruberythric acid, and rubiadin—are also found in varying amounts (Son et al., 2008). anthraquinones that prevent oxidative stress and protect cells from damage, are comparable to vitamin E.The plant is rich in antioxidants such as alizarin, rubiadin, and other hydroxyl-anthraquinones. Extracts protect against oxidative damage by scavenging free radicals, boosting glutathione levels, and improving enzyme activity, comparable to vitamin C and E supplementation.Studies suggest that R. cordifolia may serve as an antioxidant and anti-inflammatory agent, particularly because of its antioxidant and free-radical scavenging properties, which are beneficial in treating hyperpigmentation However, the conventional isolation of active compounds from the plant can be slow and labor-intensive.To address this challenge, modern strategies such as cell suspension cultures and genetic manipulation are recommended to boost the production of valuable secondary metabolites.

Lodhra (Symplocos racemosa) – It is the stem bark of Symplocos racemosa Roxb.family Symplocaceae.In Ayurveda, Lodhra is highly valued for its astringent (Kashaya rasa) and cooling (Sheeta veerya) qualities. These properties help in reducing excessive secretions, controlling bleeding, and promoting quick wound healing. Because of its Ruksha (drying) and Laghu (light) nature, it removes excess moisture and stickiness from the skin, which helps in reducing inflammation, acne, and other skin eruptions.Lodhra is  beneficial in treating Kushtha (skin diseases) and especially Pittaja skin disorders due to its cooling effect that balances aggravated Pitta dosha, a common cause of pigmentation and skin discoloration. Flavonoids from Symplocos racemosa possess structural features (phenolic groups, glycosidic linkages) that enable them to scavenge free radicals and reduce oxidative stress, a property central to their antioxidant action. Certain flavonoids in S. racemosa were able to suppress nitric oxide production in immune cells, indicating their role in controlling inflammation. Though their activity was weaker than dexamethasone, this still highlights therapeutic potential.Therefore, the flavonoids in Symplococus racemosa may help regulate melanin synthesis by limiting oxidative and inflammatory pathways, suggesting a potential role in skin-lightening and pigmentation control therapies.Quercetin, kaempferol, and catechin are well-established antioxidants known to inhibit melanogenesis and calm inflammation in skin cells. Eriodictyol also possesses UV-protective and anti-inflammatory properties, potentially reducing melanocyte overstimulation.

Chandana (Santalum album) –Sandalwood, known as Chandana in Sanskrit, has been deeply rooted in Indian traditions for centuries.It is the heartwood obtained from Santalum album Linn.belonging to family Santalaceae In Ayurveda, the paste made from its heartwood is valued not only for religious and spiritual purposes but also for enhancing beauty and skin health.Sandalwood is traditionally regarded as a symbol of vitality and is widely used in cosmetics and skincare, being suitable for all skin types.Sandalwood oil (SWO) has long been an important ingredient in Ayurvedic medicine. The oil and paste are considered natural coolants; the paste Is used as an ointment to relieve body heat and simultaneously works as a cosmetic to improve complexion and radiance. Its essential oil, which contains 80–90% sesquiterpenoid alcohols, is a key component in many skin-brightening formulations and has demonstrated low acute oral and dermal toxicity in laboratory studies.Active phytochemicals in Sandalwood for skin lightening are Α-Santalol and β-Santalol,Santalene (α- and β-santalene)Santalene derivatives (santalone,santalenic acid)phenolic compounds.(minor constituents).Recent research highlights that α-santalol, the principal constituent of sandalwood oil, acts as a strong tyrosinase inhibitor (IC?? = 171 μg/mL), comparable to established agents such as kojic acid and arbutin (IC?? ≈ 149 μg/mL), underscoring its potential application in skin-care products. In a 2022 study Santalol inhibited tyrosinase isolated from the mushroom Agaricus bisporus  in a dose-dependent and competitive manner, with maximum inhibition at ~50 µM. It likely occupies the enzyme’s active site, preventing the natural substrate (L-DOPA) from binding.Another clinical study evaluated the efficacy of Indian sandalwood oil (Santalum album L.) in protecting skin against oxidative stress induced by urban dust and blue light (412 nm). In a randomized, double-blind trial with 22 participants, formulations containing 0.1%, 1%, and 10% sandalwood oil were compared with placebo and α-tocopherol. The protective effect was assessed by measuring squalene monohydroperoxide (SQOOH), a lipid peroxidation marker. Lipid peroxidation matters because it is a key biochemical marker of oxidative stress in the skin.Results showed a dose-dependent reduction in SQOOH, with 1–10% concentrations significantly reducing oxidative damage and outperforming α-tocopherol. This study provides the first in vivo evidence that sandalwood oil has potent antioxidant and anti-aging properties, supporting its application in cosmetic formulations targeting pollution- and light-induced skin damage.

Liquorice(Glycyrrhiza glabra Linn.) – These are the roots and stolons of Glycyrrhiza glabra Linn.family Fabaceae (Leguminosae) In Ayurveda, Yashtimadhu (liquorice) is described as Varnya, meaning it supports skin complexion.It is also described as wound healing and skin repair (Ropana, Sandhaneeya).Anti-itching and skin comfort (Kandughna):Its use in relieving itching also adds to its dermatological and cosmetic significance.This property links directly to its use in improving pigmentation and maintaining an even skin tone.Liquorice root contains phytochemicals such as glabridin, liquiritin, and isoliquiritin, which have been reported to inhibit melanin synthesis.The herb is highlighted for its skin-regenerating and antioxidant properties, which further contribute to its role in depigmentation.One study conducted in vitro using Murine melanoma B16F10 cells – to assess melanin production, tyrosinase activity, and expression of melanogenesis-related genes (MITF, TYR, TRP-1, TRP-2) showed that heat-treated (Glycyrrhiza glabra × G. uralensis),licorice extract (WH-130) showed higher phenolic content, stronger antioxidant activity, and more effective inhibition of melanin production than non-heated extract. This effect was linked to increased isoliquiritigenin levels and suppression of melanogenesis-related genes, supporting its potential as a natural skin-whitening agent.The findings suggest that heat treatment enhances the bioactivity of licorice extracts,A clinical trial on 38 women with malar melasma measured the Melasma Area and Severity Index (MASI) scores at baseline and biweekly. After eight weeks, licorice extract significantly reduced MASI scores from 10.59 to 2.59,though hydroquinone cream produced a greater reduction.

Safety, Standardization, and Quality Concerns:

Although Ayurvedic herbs are generally regarded as safe when used traditionally, concerns regarding raw material variability, adulteration, and contamination have been consistently reported (Wahab et al., 2021). Such challenges highlight the need for stringent quality control measures to ensure the safety and efficacy of herbal formulations. Standardization through phytochemical markers, authentication methods such as DNA barcoding, and adherence to Good Manufacturing Practices (GMP) are essential to achieve reproducibility and global acceptance (Rajput et al., 2024). For example, studies on Symplocos racemosa and its flavonoid content emphasize the importance of profiling bioactive markers to minimize inconsistencies across samples (Jung et al., 2014; Shukla et al., 2024). Similarly, the stability and bioavailability challenges observed with curcumin formulations stress the necessity of advanced delivery systems and rigorous standardization (Tabanelli et al., 2021). Furthermore, systematic reviews of botanical therapies for melasma underscore that the therapeutic potential of Ayurvedic herbs must be coupled with robust safety validation and reproducible quality benchmarks before widespread clinical translation (Wang et al., 2022).

Challenges and Future Perspectives :

The main challenges include lack of large-scale randomized controlled trials,systematic reviews of herbal treatments for melasma and topical botanical trials point out the small sample sizes, short durations, and inconsistent endpoints used across studies.for example,many active constituents (e.g., curcuminoids, anthraquinones, glabridin) are chemically unstable or poorly skin-penetrant; trials therefore require advanced delivery systems and stability testing.

Turmeric - evidence of curcuminoids in humans is limited to small, short studies (e.g., a 4-week, 50-participant RCT of 0.25% tetrahydrocurcumin vs 4% hydroquinone) and scattered pilots, making it hard to power larger follow-ups and estimate realistic effect sizes and endpoints. curcumin rapidly decomposes (light, pH), producing multiple degradation products; this confounds which molecule causes observed bioactivity in vitro.Simple co-administration with absorption enhancers (notably piperine) can inhibit metabolism and raise plasma curcuminColloidal lipid systems: Micelles, emulsions, nanoemulsions, liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) are widely studied and have shown substantial increases in curcumin plasma AUC in human and animal studies.  

Simplocos Racemosa - mechanistic work is often limited to general antioxidant/anti-inflammatory assays without direct melanogenesis or signaling pathway studies.multiple classes (phenolics, triterpenoids, glycosides) are reported but few studies fully profile or quantify putative actives across samples, complicating mechanistic attribution.Future work needs to focus on signal transduction pathways, receptor interactions, and gene expression profiles that are modulated by its phytochemicals (e.g., quercetin, betulinic acid, symplocoside).

Manjistha (Rubia cordifolia) -multiple anthraquinones / naphthohydroquinones (e.g., rubiadin, purpurin) exist; mechanistic studies often use crude extracts, making it unclear which constituent drives an effect. some anthraquinones are cytotoxic at concentrations near those used for mechanistic assays, blurring anti-melanogenic vs general cytotoxic effects. modern methodological improvements: the use of metabolomics, network pharmacology, and spectrum–effect correlations to pinpoint active compounds, plus better-standardized extracts and rigorous experimental designs.

Sandalwood – α- and β-santalol content varies by source, adulteration and distillation — mechanistic studies using different oils are not comparable. Many studies test whole oil/extracts (mixtures with many volatiles); specific molecular targets in melanocytes are little studied.synthetic/biotechnological alternatives (microbial santalol production) that can supply chemically defined material for reproducible mechanistic experiments. Chemical standardization (santalol profiling, ISO standards), DNA-barcoding and traceability approaches that let mechanistic studies use authenticated, chemically consistent sandalwood oil/fractions.

Liquorice – glabridin, liquiritigenin, glycyrrhizin and others have distinct activities and ADME; mechanistic studies sometimes focus on one molecule while extracts contain many. In vivo metabolites differ from parent compounds studied in vitro, complicating translation.while glabridin-rich fractions show promise, commercial extracts vary and many clinical reports use proprietary standardized extracts (hard to compare).encapsulation targets delivery to melanocytes and mitigates bioavailability/metabolism issues of single actives.

Future directions involve integrative dermatology, phytochemical-based drug development, and personalized approaches considering Prakriti [Ref: Ayurveda-modern integration papers].

CONCLUSION:

Ayurvedic herbs and formulations present promising alternatives for managing hyperpigmentation, particularly melasma and post-inflammatory hyperpigmentation, due to their antioxidant, anti-inflammatory, and melanogenesis-regulating properties. Botanicals such as turmeric, manjistha, lodhra, sandalwood, and liquorice align with both traditional Ayurvedic wisdom and emerging experimental evidence. However, their broader clinical acceptance is limited by challenges in standardization, quality control, and the scarcity of large-scale, well-controlled clinical trials. Future directions must prioritize phytochemical profiling, advanced delivery systems, and integration of Ayurvedic principles with modern pharmacological research

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