INTRODUCTION:

Herbal medicine has been an integral part of healthcare systems for centuries, with Ayurveda serving as one of the most widely practiced traditions. Today, global recognition of Ayurveda and its plant-based remedies is steadily increasing, particularly for conditions where conventional medicine offers limited solutions.

Almost all Ayurvedic preparations are derived from plants, either in raw form or as processed extracts, and are often categorized under complementary and alternative medicine (CAM). Their popularity has grown due to their cultural acceptance, affordability, and effectiveness against difficult-to-treat disorders^1,2.

Semecarpus anacardium Linn. (family: Anacardiaceae), commonly known as Bhallataka, Bhilwa, or the “marking nut,” is distributed across tropical and central India, including the sub-Himalayan belt. The plant has significant medicinal value and is extensively used in traditional systems of medicine for a variety of ailments, including dermatological and systemic conditions^3,4.

Background on Hair Growth and Disorders:

Hair growth follows a cyclical process involving anagen (growth), catagen (regression), and telogen (resting) phases, with disruption of this cycle resulting in various forms of alopecia. Common disorders include androgenetic alopecia (hormone-driven follicle miniaturization), alopecia areata (autoimmune-mediated), telogen effluvium (stress or illness-related shedding), anagen effluvium (chemotherapy-induced), tinea capitis (fungal infection), and traction alopecia (mechanical stress). Given the limitations of current therapeutic agents such as minoxidil and finasteride, natural alternatives with multi-targeted actions are increasingly being explored. In this context, S. anacardium has emerged as a promising candidate due to its phytoconstituents with antioxidant, anti-inflammatory, and follicle-stimulating properties^5-8.

Traditional and Ethnomedicinal Use of S. anacardium:

S. anacardium has a long history of use in traditional medicine, being mentioned in the Ramayana and classical Ayurvedic texts where it is referred to as “Ardha-Vaidya,” signifying its importance in holistic healing. Ethnomedicinally, the plant has been widely used for the management of various ailments, including arthritis, skin diseases, piles, asthma, diabetes, and hair disorders^8-10. Its therapeutic reputation in Ayurveda and folk medicine highlights its broad pharmacological potential; however, it is equally recognized for its inherent toxicity if consumed without proper purification. Traditional detoxification methods are therefore considered essential before therapeutic application, ensuring safety while preserving its medicinal efficacy^10-12.

Botanical Characteristics and Taxonomy of S. anacardium:

Semecarpus anacardium Linn. f., commonly known as the marking nut tree or Oriental cashew in English, is also referred to as Bhela, Bhelatuki (Hindi and Bengali) and Balia (Oriya). It is a medium-sized deciduous tree, attaining a height of 12-15m and a girth of approximately 1.25m. The bark is dark brown, rough, and tough. Leaves are rectangular to oblong (18–60cm long), rounded at the apex, cartilaginous at the edges, coriaceous and glabrous on the upper surface, and ashy grey or buff beneath. Flowers are subsessile, greenish-white, fascicled in pubescent panicles, with lanceolate bracts, pilose calyx segments, and ovate acute petals. The fruits are drupes, obliquely ovoid to rectangular, smooth, shiny, and black when mature. The pericarp is caustic, while the fruit is pungent, slightly sweet, and possesses a characteristic acrid odour. Phytochemically, the plant is rich in anacardic acid, cardol, catechol, anacardioside, fixed oils, semecarpol, bhilawanol, biflavonoids, and biflavones^13-17.

Taxonomical Classification:

Table 1. Taxonomical Classification of S. anacardium^14,15.

Kingdom	Plantae
Subkingdom	Tracheobionta
Super division	Spermatophyta
Division	Magnoliophyta
Class	Magnoliopsida
Subclass	Rosidae
Order	Sapindales
Family	Anacardiaceae
Genus	Semecarpus
Species	Semecarpus anacardium Linn. f.

Geographical Distribution and Cultivation:

The genus Semecarpus (family Anacardiaceae) is distributed across tropical Asia and Oceania. S. anacardium is widely found in the outer Himalayas from Sutlej to Sikkim, as well as in several Indian states including Assam, Maharashtra, Karnataka, West Bengal, Odisha, Madhya Pradesh, Bihar, Tamil Nadu (Kanara forests), and the Konkan belt. Globally, it is reported in China, Nepal, Myanmar, Malaysia, North Australia, and parts of East Asia, extending to the Indo-Malaysian region, the Coromandel Coast, and the western peninsular belt. It naturally thrives in dry tropical, moist deciduous, and semi-evergreen forests up to an altitude of 3500 ft^18,19.

Propagation of S. anacardium:

Propagation is usually seed-based. Mature fruits are harvested, and seeds with hard shells are selected (Figure 1). Seeds are soaked in water for 24 h to soften the testa, dried briefly, and then sown 1-2 cm deep in a well-draining potting mix of sand, soil, and compost. Germination generally occurs within 2-4 weeks at 25-30 °C. Once seedlings produce true leaves, they can be transplanted into field conditions with partial shade and well-draining soil. Regular irrigation, mulching, and organic fertilization enhance growth. Pests such as mealybugs and aphids, as well as fungal infections, may affect cultivation and can be managed with insecticidal soaps or organic practices. Fruiting typically commences after 4-5 years, and mature fruits are harvested when yellow-brown with brittle outer shells. The kernels, once carefully separated from the caustic pericarp, are collected for medicinal applications²⁰.

Figure 1. Marking nut (seed) of S. anacardium¹⁷.

Phytochemistry of S. anacardium:

Phytochemical Profile:

The phytochemical composition of S. anacardium is diverse, comprising a wide range of secondary metabolites responsible for its pharmacological activity. The nut shell extract is particularly rich in bioactive constituents such as anacardic acid, biflavonoids, and phenolic compounds. The biflavonoids include biflavone-A, biflavone-C, biflavone-A1, biflavone-A2, tetrahydrorobustaflavone, jeediflavanone, semecarpuflavanone, galluflavanone, and anacardoflavanone. Phenolic derivatives such as bhilawanols, semecarpol, and anacardol also contribute to its biological activity (Table 2). Bhilawanol, one of the characteristic toxic and medicinally relevant constituents, is a mixture of 3-pentadec(en)yl catechols, primarily 8Z,11Z-diene and 8Z-monoene derivatives, which are associated with both therapeutic and irritant effects²¹.

Major Phytoconstituents and Therapeutic Roles

Table 2. Phytoconstituents of S. anacardium, their pharmacological roles.

Name of Phyto-constituent	Class	Parts used	Therapeutic effect	Reference
Anacardic acid	Phenolic compound	Nut	Antimicrobial, anti-inflammatory, anticancer	21
Bhilwanol	Phenolic lipid	Nut	Immunomodulatory, anti-arthritic	21,22
Semecarpol	Alkyl phenol	Nut	Antioxidant, antitumor	21
Flavonoids	Polyphenol	Nut, Leaf	Antioxidant, anti-inflammatory	21,23
Cardol	Phenolic compound	Nut	Cytotoxic, antibacterial	21
Glycosides	Glycoside compound	Bark, Nut	Cardioprotective, antidiabetic	22
Tannins	Polyphenolic compound	Bark, Leaf	Astringent, antimicrobial	22
Saponins	Glycoside compound	Nut, Bark	Anti-inflammatory, immuno-boosting	22
Proteins & amino acids	Protein class	Nut	Nutritional, tissue repair	22
Essential oils	Volatile compounds	Leaf, Nut	Antimicrobial, aromatic	22

Mechanistic Insights into Hair Growth Promotion:

Hair Growth Cycle:

Hair growth is a dynamic and cyclical process consisting of three principal phases: anagen (growth), catagen (regression), and telogen (resting). During anagen, rapid proliferation of hair matrix cells occurs adjacent to the dermal papilla (DP), leading to follicular elongation and hair shaft production. In catagen, follicular regression begins, matrix cell apoptosis occurs, and melanin synthesis ceases, though dermal papilla cells (DPCs) remain viable. Finally, in telogen, follicles remain quiescent until re-entry into the anagen phase, where DP–stem cell interactions trigger regeneration and the emergence of new hair alongside the retained telogen shaft. Compound follicles, often observed in the human scalp, contribute to multiple hairs sharing a single external orifice (Figure 2)^13,24.

Molecular and Cellular Mechanisms:

Antioxidant and Anti-inflammatory Effects:

Excessive oxidative stress and scalp inflammation are associated with follicular damage and miniaturization. S. anacardium phytoconstituents, particularly flavonoids and phenolics, exhibit strong ROS-scavenging and anti-inflammatory properties, thereby preserving follicular microenvironments conducive to regeneration^25,26.

Cytokine Modulation:

Chronic inflammation in the follicular niche is mediated by cytokines such as IL-1β, IL-12, and the activation of NF-κB. By suppressing these pathways, plant-derived bioactives restore DPC survival, reduce perifollicular fibrosis, and sustain anagen duration^26,27.

Wnt/β-catenin Activation:

The Wnt/β-catenin signaling pathway is a master regulator of hair follicle morphogenesis and regeneration. Activation of this cascade promotes the transition from telogen to anagen, leading to follicular proliferation and shaft elongation. Polyphenolic compounds of S. anacardium may directly or indirectly stimulate this pathway, thereby enhancing hair cycling²⁸.

Sonic Hedgehog (Shh) Pathway:

The Shh pathway is essential for follicular neogenesis and matrix keratinocyte proliferation. Evidence suggests that S. anacardium phytochemicals may influence Shh signaling, supporting the proliferation and differentiation of follicular stem cells²⁹.

Hormonal Modulation:

Hair cycle balance is highly dependent on androgen, estrogen, and thyroid hormone signaling. Overexpression of 5-α reductase, leading to increased dihydrotestosterone (DHT), drives androgenic alopecia through follicular miniaturization. By contrast, estrogen prolongs anagen and increases follicular diameter, while thyroid hormones regulate follicular stem cell activation. Phytoconstituents of S. anacardium may counter DHT-induced miniaturization and stabilize hormonal homeostasis, thereby supporting hair density and regeneration³⁰.

Growth Factors and Cytokines:

A wide spectrum of growth factors including FGF-1, FGF-2, FGF-7, FGF-10, IGF-1, IGF-2, and EGF is integral to follicular regeneration. These stimulate matrix cell proliferation, protect against chemotherapeutic or UV-induced damage, and sustain the multipotency of follicle-derived mesenchymal stem cells. Cytokinins such as zeatin, naturally occurring in plants, further augment follicular proliferation through enhanced cell division and bud initiation³¹.

Although pathways such as Wnt/β-catenin and Sonic Hedgehog (Shh) are central to hair follicle biology, evidence specifically connecting S. anacardium phytoconstituents to these mechanisms is now emerging. Anacardic acid, a major bioactive, has been shown to modulate Wnt signaling by enhancing β-catenin stability and transcriptional activity, thereby promoting hair follicle stem cell proliferation and transition into the anagen phase²⁸. Similarly, biflavonoids and phenolic compounds from S. anacardium exert immunomodulatory effects that indirectly support Shh signaling, enabling dermal papilla-epidermal interactions crucial for follicular regeneration²⁹. These mechanistic insights provide a more direct pharmacological basis for its traditional reputation as a hair growth promoter, distinguishing it from general plant antioxidants.

Pharmacological Evidence:

Preclinical Studies:

Extracts of Semecarpus anacardium have demonstrated promising preclinical activity in hair growth promotion. Petroleum ether and ethanolic extracts were evaluated in albino rats and compared with a standard 2% minoxidil formulation. The results indicated follicular stimulation and accelerated hair regrowth, with some formulations showing activity comparable to minoxidil³². Furthermore, the pharmacological potential of S. anacardium nuts has been linked to their bioactive phytoconstituents, although detailed structure-function relationships remain to be elucidated. Isolation of active principles and well-designed controlled clinical trials are warranted to confirm their therapeutic value³³.

Antimicrobial Activity:

In addition to growth-promoting effects, S. anacardium petroleum ether seed extracts exhibited broad-spectrum antimicrobial activity, particularly against dandruff-causing fungi and bacteria. Thin-layer chromatography revealed distinct phenolic compounds and fractions contributing to this antimicrobial efficacy. Such activity supports its ethnomedicinal use in managing scalp disorders, though further investigations are required to validate clinical safety and efficacy³⁴.

Comparative Data:

Polyherbal formulations combining S. anacardium with other botanicals such as Trigonella foenum-graecum (fenugreek) and Aloe vera demonstrated synergistic effects. In rat models, these formulations significantly enhanced hair growth parameters, including earlier initiation of regrowth and improved shaft elongation compared with individual extracts or minoxidil alone³⁵. The synergism highlights the potential of S. anacardium as a valuable component in modern herbal formulations for hair care.

Molecular Mechanism of Hair Follicle Stimulation by S. anacardium:

S. anacardium extract demonstrated significant immunomodulatory and anti-inflammatory effects relevant to hair follicle biology. The extract did not affect TNF-α or IL-6 production at either protein or mRNA level but significantly reduced pro-inflammatory cytokines IL-1β and IL-12p40, both spontaneously and in response to LPS stimulation. Furthermore, it inhibited nuclear translocation of transcription factors AP-1 and NF-κB through suppression of IκBα phosphorylation and also reduced nitric oxide production in LPS-induced RAW macrophage cells³⁶.

Hair follicle development is tightly regulated by Wnt/β-catenin signalling. Wnt10b activation triggers β-catenin, facilitating the transition of hair follicles from the telogen (resting) phase to the anagen (growing) phase, thereby promoting stem cell proliferation. In androgenetic alopecia (AGA), dihydrotestosterone (DHT) suppresses Wnt10b and Wnt5a expression while increasing the Wnt inhibitor Dkk-1, leading to impaired follicle stem cell activity. Supplementation with Wnt10b reverses this androgen-mediated repression and supports follicular regeneration³⁶.

In addition, Sonic Hedgehog (Shh) signalling plays a pivotal role in sustaining hair follicle stem cell activity and inducing anagen initiation. Shh stimulation promotes follicle regeneration, synchronises dermal–epidermal interactions, and even induces de novo follicle formation in wounded skin. Conversely, inhibition of Shh signalling prevents regrowth, underscoring its therapeutic relevance in hair loss management³⁷.

Preliminary in vitro evidence also supports the potential of S. anacardium in stimulating follicular cell proliferation and differentiation, indicating its promise as a natural candidate for hair growth promotion³⁸.

Comparative Perspective with Other Hair-Promoting Plants:

Several medicinal plants are traditionally recognized for hair growth promotion, including Eclipta alba (Bhringraj), Aloe vera, and Trigonella foenum-graecum (fenugreek). While these botanicals primarily act via antioxidant activity, improvement of scalp circulation, and nutritional support, S. anacardium offers a unique multi-targeted profile:

· Unlike Eclipta alba, which mainly enhances keratinocyte proliferation and pigment restoration, S. anacardium modulates Wnt/β-catenin and Shh signaling in addition to antioxidant and anti-inflammatory pathways^28,29.

· Compared with Aloe vera, which functions largely as a soothing and hydrating agent with mild proteolytic effects, S. anacardium demonstrates direct cytokine suppression (IL-1β, IL-12) and NF-κB inhibition, indicating stronger immunomodulatory potential^26,27.

· In contrast to fenugreek, which acts through phytoestrogens and nutritional proteins, S. anacardium provides distinct phenolic lipids (bhilawanols, anacardic acid) that target both microbial scalp disorders and follicular signaling cascades³¹.

This comparative distinction highlights S. anacardium as not merely another antioxidant-rich herb but as a potent mechanistic candidate capable of targeting multiple regulatory checkpoints in follicular biology.

Formulation Approaches:

Traditional Formulations:

S. anacardium has long been incorporated into topical preparations such as oils and shampoos for scalp disorders and hair promotion. Two herbal antidandruff shampoos were developed using petroleum ether extract of S. anacardium seeds at concentrations of 10%, 20%, and 30%. Formula I contained sodium lauryl sulphate, stearic acid, sodium hydroxide, biosulfur, water, perfume, and preservative; Formula II included sodium lauryl sulphate, selenium disulfide, bentonite, water, and perfume. Both formulations demonstrated promising antidandruff activity when tested against scalp pathogens^39,40. Traditional medicated oils were also prepared by cooking S. anacardium (purified fruit) along with Trigonella foenum-graecum (seeds) and Azadirachta indica (leaves) in coconut oil, a process that ensured full integration of phytoconstituents into the lipid base⁴¹.

Novel Formulations:

Aloe vera gel has been employed as a novel vehicle for delivering S. anacardium bioactives. Fresh aloe vera leaves were processed by the fillet method, stabilized with sodium benzoate (0.5% w/w) and ascorbic acid (0.5% w/w), and then used as the base for preparing herbal gels. Formulations containing 10% petroleum ether and ethanolic extracts of S. anacardium, Trigonella foenum-graecum, and Trigonella corniculata demonstrated enhanced follicle stimulation and favorable physicochemical stability^42,43.

Stability Considerations:

Ayurvedic literature describes nearly 40 Bhallataka formulations, including Bhallataka Kshaudra, prepared with honey, oil, and ghee in the ratio 1:8:16. Accelerated stability testing under conditions of 40±2°C and 75±5% relative humidity showed no significant changes in microbiological, heavy metal, or physicochemical parameters. The estimated shelf life of Bhallataka Kshaudra was ~4.49 years, confirming the long-term stability of such formulations⁴⁵.

Toxicity and Safety Profile:

The toxicity and allergenicity profile of S. anacardium is well documented (Table 3). The fresh juice or sap acts as a potent irritant and can induce blisters, ulcers, severe burning sensations, and eczematous eruptions upon contact with the skin or mucosa, resembling poison-ivy dermatitis⁴⁶. Oral ingestion of 5–10g of nuts (equivalent to ~6–8 seeds) has been reported to cause serious systemic manifestations, including gastrointestinal injury, throat burning, hypotension, tachycardia, cyanosis, delirium, coma, and even death within 12–24 hours⁴⁷. Experimental studies revealed nephrotoxicity in rats, evidenced by reduced haemoglobin, altered kidney enzyme levels, and histopathological changes indicating nephritis⁴⁸.

In contrast, Ayurvedic purification (Shodhana) methods including processes such as boiling in doses of milk or other media significantly attenuate toxicity. For instance, a Siddha-type milk-processed formulation was safe at doses up to 2g/kg, though chronic administration at 500 mg/kg/day over 30 days induced minor disturbances in lipid metabolism and renal biomarkers without causing overt organ damage⁴⁹. Computational toxicology further classifies urushiol II and bhilawanol B as class II toxicants with potent irritant and allergenic potential, with predicted oral rat LD₅₀ values of ~4000mg/kg and ~2700mg/kg, respectively⁵⁰.

Research Gaps and Future Prospects:

Despite promising preclinical and traditional evidence, several pivotal gaps hinder the scientific advancement and therapeutic deployment of S. anacardium:

· Insufficient Clinical Evidence: The translational gap remains wide due to a scarcity of well-designed, large-scale human clinical trials, limiting evidence-based validation⁵¹.

· Standardization Challenges: Current inconsistencies in quality and purity occur due to variable extraction methods, adulteration, and lack of globally accepted standards, underscoring the urgent need for standardized extracts and validated Sodhana (detoxification) procedures⁵².

· Novel Drug Delivery Approaches: Advanced delivery platforms like nanocarriers, hydrogels, and nanogels offer promising strategies for targeted, safe topical administration, particularly in skin and hair applications^53,54.

· Synergistic Potential: Exploration into polyherbal or synergistic formulations may help enhance therapeutic efficacy while minimizing toxicity, but systematic evaluations remain limited⁵⁵.

· Molecular Insights: To fully harness the therapeutic potential of S. anacardium, further molecular-level research is essential for elucidating mechanisms such as hair follicle stimulation and modulatory pathways⁵⁶.

CONCLUSION:

Semecarpus anacardium exhibits diverse pharmacological activities that support its potential in promoting hair growth, primarily through antioxidant, anti-inflammatory, and follicle-stimulating mechanisms. Despite encouraging preclinical and traditional evidence, its therapeutic translation remains restricted due to toxicity concerns, variability in extraction methods, and the lack of robust human clinical studies. Advancing this plant as a natural hair growth promoter will require the development of safe and standardized formulations, integration of modern drug delivery approaches, and rigorous clinical validation to establish efficacy and safety.

In summary, Semecarpus anacardium represents a next-generation candidate among herbal interventions for alopecia. Unlike conventional herbal remedies that act predominantly through nutritional or surface-level antioxidant mechanisms, S. anacardium integrates deep mechanistic actions (Wnt/β-catenin, Shh, NF-κB modulation) with antimicrobial and immunoregulatory effects. This multi-dimensional pharmacological profile, if harnessed through safe, standardized, and modern delivery platforms, positions it as a unique and superior alternative for evidence-based natural hair therapeutics.

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Received on 23.08.2025 Revised on 03.10.2025

Accepted on 10.11.2025 Published on 10.04.2026

Available online from April 13, 2026

Asian J. Res. Pharm. Sci. 2026; 16(2):154-160.

DOI: 10.52711/2231-5659.2026.00024

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Exposure Route	Observed Effects	Findings	Reference
Topical (sap/juice)	Blisters, dermatitis	Contact allergenicity, similar to poison ivy	46
Oral (raw nut/seeds)	GI irritation, hypotension	Toxic dose: ~6–8 seeds; systemic toxicity	47
Subacute (rat model)	Kidney toxicity, altered labs	Dose-dependent nephrotoxicity and biochemical disturbances	48
Siddha preparation	Mild metabolic disturbance	500 mg/kg × 30 days → mild lipid/glucose/renal effects	48
In silico (compounds)	Irritant, allergic potential	Urushiol II LD₅₀ ~4000 mg/kg; Bhilawanol B LD₅₀ ~2700 mg/kg	48