1. INTRODUCTION:

1.1 Overview of Medicinal Plants in Pharmacy:

Medicinal plants have historically served as a fundamental resource for therapeutic agents and continue to be integral to modern pharmaceutical sciences. Natural products derived from plants contribute significantly to drug discovery due to their structural diversity, biological activities, and comparatively favourable safety profiles. A substantial proportion of approved drugs have originated from plant-derived bioactive compounds or their semi-synthetic analogues, reinforcing the relevance of botanical sources in pharmaceutical innovation. In recent years, research on medicinal plants has expanded beyond traditional usage to include systematic pharmacological evaluation, mechanism-based studies, and advanced formulation development, thereby strengthening their role in pharmaceuticals, nutraceuticals, and cosmeceuticals.^1,2

1.2 Sea Buckthorn: Historical and Traditional Importance:

Sea buckthorn (Hippophae rhamnoides L.), belonging to the family Elaeagnaceae, has a long history of traditional use in Tibetan, Chinese, Mongolian, and Ayurvedic systems of medicine. Historically, various parts of the plant—including berries, leaves, and seeds—were utilized for the management of skin disorders, gastrointestinal ailments, pulmonary conditions, wounds, and inflammatory diseases. Traditional texts describe sea buckthorn oil as a rejuvenating agent capable of enhancing tissue regeneration and promoting overall vitality. The ethnomedicinal relevance of sea buckthorn has laid a strong foundation for its evaluation using modern scientific and pharmaceutical approaches.^3,4

1.3 Global Relevance in Modern Pharmaceutical Research:

In the last decade, sea buckthorn has gained considerable global attention due to its exceptionally rich phytochemical profile. The plant contains high concentrations of vitamins (A, C, E, K), flavonoids (such as quercetin and isorhamnetin), carotenoids, phenolic acids, phytosterols, and essential fatty acids, notably omega-7 (palmitoleic acid), which is rare in most plant sources. These bioactive constituents have demonstrated diverse pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, wound-healing, cardioprotective, hepatoprotective, and anticancer effects. Owing to these properties, sea buckthorn has emerged as a promising candidate for pharmaceutical formulations, functional foods, and cosmeceutical applications worldwide.^2,3,5

1.4 Rationale for Reviewing Sea Buckthorn:

Despite the growing volume of scientific literature on sea buckthorn, existing studies remain dispersed across different domains such as phytochemistry, pharmacology, clinical research, and formulation science. Comprehensive reviews integrating traditional knowledge with contemporary pharmaceutical advancements—particularly novel drug delivery systems and translational research—are limited. Furthermore, issues related to variability in phytochemical composition, lack of standardization, and insufficient large-scale clinical trials present challenges for pharmaceutical development. Therefore, an updated and integrated review is necessary to critically analyse existing evidence, identify research gaps, and highlight opportunities for future drug development based on sea buckthorn.^1,4,6

1.5 Scope of the Review:

The present review aims to provide a systematic and comprehensive overview of sea buckthorn with emphasis on its pharmaceutical relevance. It encompasses botanical and taxonomical aspects, traditional uses, phytochemical composition, pharmacological activities, pharmacokinetics and bioavailability, pharmaceutical dosage forms, novel drug delivery systems, nutraceutical and cosmeceutical applications, safety and toxicity profiles, and regulatory perspectives. By compiling and analysing recent literature published between 2023 and 2025, this review intends to support evidence-based development of sea buckthorn-derived therapeutic products and guide future pharmaceutical research.^2,3,6

2. Botanical and Taxonomical Profile:

2.1 Botanical Description:

2.1.1 Plant Morphology:

Sea buckthorn (Hippophae rhamnoides L.) is a deciduous, dioecious shrub reaching 2–4 meters in height, characterized by extensive branching with stiff, thorny lateral shoots that provide mechanical protection and support in high‑stressor environments such as cold deserts and semi‑arid slopes. Leaf morphology includes narrow, lanceolate leaves with a silvery‑green appearance, primarily due to dense trichomes on the lower surface, which serve to reduce transpiration and facilitate adaptation to sunlight intensity and water deficit conditions observed in native habitats.^1,2

2.1.2 Fruit Characteristics:

The fruits of sea buckthorn are small, round to oblong berries, typically measuring 6–9mm in diameter, with bright orange to yellow pigmentation attributed to high concentrations of carotenoids and flavonoids. These berries possess a juicy pulp with a pronounced acidic flavour resulting from significant amounts of ascorbic acid and organic acids. Internally, each berry contains one to three seeds rich in lipids useful for oil extraction. Fruits are persistent on the plant after leaf fall, enabling delayed mechanical harvesting even under low temperature conditions.^3,4

2.2 Taxonomical Classification:

The accepted taxonomical classification of Hippophae rhamnoides is:

	Classification
Kingdom	Plantae
Clade	Angiosperms
Order	Rosales
Family	Elaeagnaceae
Genus	Hippophae
Species	Hippophae rhamnoides L.

Multiple recognized subspecies are adapted to distinct geographic regions, demonstrating variation in morphological and biochemical traits related to ecological occupation.⁵

2.3 Geographical Distribution:

2.3.1 India:

In India, sea buckthorn is predominantly found in the cold arid zones of the Himalayas, particularly in Ladakh (Union Territory), Himachal Pradesh, Uttarakhand, and Sikkim, covering altitudinal ranges from 1,500 to 4,500 m above sea level. Its natural distribution is associated with rocky slopes, river valleys, and sandy plains, where it contributes to soil stabilization and ecosystem resilience.⁶

2.3.2 International-Distribution:

Sea buckthorn is also widely distributed beyond India:

2.3.3 China: Particularly in Xinjiang, Inner Mongolia, and Gansu provinces, where it is extensively cultivated.⁷

· Russia: Notably in Siberian regions and Altai Mountains.⁸

· Europe: Present in countries such as Germany, Ukraine, Austria, and Scandinavia, typically in well‑drained soils near riverbanks and coastal dunes.⁹

2.4 Cultivation and Harvesting:

2.4.1 Climatic Requirements:

Sea buckthorn exhibits remarkable tolerance to temperature extremes (from below −30°C to +40°C), drought stress, and saline soils, making it suitable for harsh environments. Optimal growth occurs under full sunlight with well‑drained, sandy‑loam substrates. Its ability to fix atmospheric nitrogen via symbiotic root bacteria enhances soil fertility and supports ecological restoration programs.¹⁰

2.4.2 Harvesting Methods:

Harvesting is typically conducted between late summer and early autumn (August–October) when berries achieve maximum phytochemical concentration and oil yield. Manual picking is common due to the delicate nature of berries; however, industrial cultivation increasingly uses mechanical shaking and vibrating comb devices to reduce labour intensity while preserving fruit quality.¹¹

2.4.3 Post‑Harvest Handling:

Post‑harvest handling is critical due to the high perishability of berries. Rapid cooling (0–5°C) or freezing is recommended to preserve sensitive phytoconstituents such as vitamin C, carotenoids, and flavonoids. For oil production, berries are washed and separated into seeds and pulp before cold pressing or solvent extraction, processes that influence the yield and stability of final products.¹²

3. Phytochemical Composition:

Sea buckthorn (Hippophae rhamnoides L.) is widely recognized for its exceptionally rich and diverse phytochemical profile, which forms the basis of its broad pharmacological activities. The berries, leaves, seeds, and oils contain a unique combination of vitamins, minerals, polyphenols, fatty acids, and other bioactive compounds that contribute to antioxidant, anti-inflammatory, wound-healing, cardioprotective, and immunomodulatory effects.¹

3.1 Primary Constituents:

3.1.1 Vitamins:

Sea buckthorn is considered one of the most vitamin-rich medicinal plants. The fruits are particularly abundant in vitamin C (ascorbic acid), often exceeding the levels found in common citrus fruits, thereby contributing significantly to antioxidant defence and immune function.²

Vitamin A, primarily present as provitamin A carotenoids such as β-carotene, supports epithelial integrity and visual health.³

Vitamin E, including tocopherols and tocotrienols, plays a crucial role in protecting cellular membranes from lipid peroxidation.⁴

Additionally, sea buckthorn contains vitamin K and several B-complex vitamins (B1, B2, B3, B6) that are involved in metabolic regulation and nervous system function.⁵

3.1.2 Minerals:

Sea buckthorn berries and leaves contain essential macro- and micro-elements such as zinc (Zn), iron (Fe), calcium (Ca), magnesium (Mg), and selenium (Se). These minerals contribute to enzymatic activity, hematopoiesis, bone metabolism, and antioxidant defence mechanisms. The synergistic presence of minerals and vitamins enhances the overall therapeutic potential of sea buckthorn preparations.⁶

3.2 Secondary Metabolites:

3.2.1 Flavonoids:

Flavonoids constitute a major group of secondary metabolites in sea buckthorn. Predominant flavonoids include quercetin, isorhamnetin, kaempferol, and their glycosides. These compounds exhibit strong antioxidant and anti-inflammatory activities by scavenging free radicals and modulating key cellular signalling pathways.⁷

3.2.2 Phenolic Acids:

Phenolic acids such as gallic acid, ferulic acid, caffeic acid, and p-coumaric acid have been identified in sea buckthorn. These compounds contribute to antioxidant capacity and antimicrobial activity, supporting the plant’s protective and therapeutic roles.⁸

3.2.3 Carotenoids:

Sea buckthorn is particularly rich in carotenoids, including β-carotene, lycopene, lutein, and zeaxanthin. These pigments are responsible for the characteristic orange-yellow colour of the berries and provide antioxidant protection while also serving as precursors of vitamin A.⁹

3.2.4 Phytosterols:

Phytosterols, mainly β-sitosterol, campesterol, and stigmasterol, are present in sea buckthorn oils. These compounds are known for their cholesterol-lowering properties and anti-inflammatory effects, making them valuable for cardiovascular health applications.¹⁰

3.2.5 Tannins:

Tannins present in sea buckthorn leaves and berries contribute to antimicrobial, astringent, and wound-healing activities. They play a supportive role in tissue repair and protection against microbial invasion.¹¹

3.3 Fatty Acid Profile:

Sea buckthorn oil possesses a unique fatty acid composition that distinguishes it from most plant oils.

3.3.1 Omega-3 and Omega-6 Fatty Acids:

Omega-3 (α-linolenic acid) and omega-6 (linoleic acid) are essential polyunsaturated fatty acids present in sea buckthorn seed oil. These fatty acids are involved in inflammatory regulation, cardiovascular protection, and maintenance of skin barrier function.¹²

3.3.2 Omega-7 (Palmitoleic Acid – Key Highlight):

One of the most distinctive features of sea buckthorn is its high content of omega-7 (palmitoleic acid), particularly in pulp oil. Omega-7 is relatively rare in plant sources and is associated with skin regeneration, mucosal healing, metabolic regulation, and anti-inflammatory activity, making sea buckthorn highly valuable for dermatological and gastrointestinal formulations.¹³

3.3.3 Omega-9 Fatty Acids:

Omega-9 (oleic acid) contributes to membrane stability and cardiovascular health and enhances the bioavailability of lipophilic bioactive compounds.¹²

3.4 Bioactive Compounds of Pharmaceutical Interest:

3.4.1 Quercetin:

Quercetin is a potent flavonoid with antioxidant, anti-inflammatory, anticancer, and cardioprotective properties. It exerts its effects through modulation of oxidative stress pathways and inflammatory mediators.⁷

3.4.2 Isorhamnetin:

Isorhamnetin, a methylated derivative of quercetin, exhibits enhanced bioavailability and strong antioxidant, anti-tumour, and Vaso-protective effects, making it a compound of high pharmaceutical interest.^7,14

3.4.3 β-Sitosterol:

β-Sitosterol is a key phytosterol known for its lipid-lowering, immunomodulatory, and anti-inflammatory properties. It has been widely investigated for its role in managing dyslipidaemia and inflammatory conditions. ¹⁰

3.4.4 Tocopherols:

Tocopherols (vitamin E isomers) present in sea buckthorn oils protect lipids from oxidative degradation and are extensively used in pharmaceutical and cosmeceutical formulations for skin protection and anti-aging applications.⁴

4. Pharmacological Activities:

Sea buckthorn (Hippophae rhamnoides L.) exhibits diverse pharmacological activities attributed to flavonoids, carotenoids, vitamins, phytosterols, and unsaturated fatty acids. This bioactive act synergistically to provide antioxidant, anti-inflammatory, wound healing, cardioprotective, and anticancer effects, validated through recent experimental studies.^1,3

4.1 Antioxidant Activity:

Sea buckthorn shows strong antioxidant potential by scavenging free radicals and enhancing endogenous antioxidant enzymes. Phenolics, flavonoids, vitamin C, and tocopherols neutralize ROS and reduce lipid peroxidation through electron donation and metal chelation mechanisms ^[1,2]. In vivo studies report increased SOD and catalase levels with reduced malondialdehyde (MDA), confirming oxidative stress mitigation.^2,3

4.2 Anti-Inflammatory Activity:

Anti-inflammatory effects are mediated through inhibition of COX-2 and LOX pathways, leading to reduced prostaglandin and leukotriene synthesis. Sea buckthorn extracts down-regulate pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in cellular and animal models.^4,5

4.3 Wound Healing and Skin Regeneration:

Sea buckthorn oil promotes collagen synthesis, angiogenesis, and re-epithelialization due to omega fatty acids and carotenoids. Accelerated healing has been observed in burn and ulcer models, along with improvement in psoriasis and eczema through restoration of skin barrier function and reduced inflammation.^6,7

4.4 Anticancer Activity:

Sea buckthorn exhibits anticancer effects by inducing apoptosis and cell cycle arrest. Flavonoids and carotenoids activate caspase-mediated pathways and inhibit cancer cell proliferation. In vitro studies demonstrate reduced viability of melanoma and skin cancer cell lines with minimal toxicity to normal cells.^8,9

4.5 Cardioprotective Activity:

Cardioprotective effects include reduction of total cholesterol, LDL, and triglycerides, alongside improved endothelial function. Antioxidant and anti-inflammatory actions inhibit LDL oxidation and atherosclerotic progression.^10,11

4.6 Hepatoprotective Activity:

Sea buckthorn protects against chemically induced liver damage by normalizing AST and ALT levels and enhancing hepatic antioxidant defences, thereby reducing oxidative stress–mediated injury.^12,13

4.7 Antimicrobial and Immunomodulatory Effects:

Extracts exhibit broad-spectrum antibacterial and antifungal activity due to phenolic compounds, with preliminary antiviral effects reported. Immunomodulatory actions include enhanced macrophage activity and balanced cytokine production, supporting host defence mechanisms.^14,15

5. Pharmacokinetics and Bioavailability:

Sea buckthorn (Hippophae rhamnoides L.) contains a wide range of bioactive constituents, including lipophilic fatty acids, carotenoids, tocopherols, and hydrophilic flavonoids. The pharmacokinetic behaviour and bioavailability of these compounds are significantly influenced by their physicochemical properties, metabolic stability, and formulation approaches.^1,4

5.1 Absorption Challenges of Lipophilic Constituents:

Sea buckthorn seed and pulp oils are rich in lipophilic compounds such as palmitoleic acid (ω-7), oleic acid, linoleic acid, carotenoids, and vitamin E. These constituents exhibit poor aqueous solubility, which limits their dissolution in gastrointestinal fluids and subsequently reduces intestinal absorption.¹ Their absorption depends largely on bile salt–mediated micelle formation and the presence of dietary lipids. In addition, first-pass hepatic metabolism and inter-individual variability in gastrointestinal physiology contribute to low and inconsistent systemic availability. As a result, conventional oral formulations of sea buckthorn oil often demonstrate suboptimal bioavailability.⁴

5.2 Metabolism of Flavonoids:

Flavonoids present in sea buckthorn, including quercetin, isorhamnetin, kaempferol, and their glycosidic derivatives, undergo extensive metabolic transformation after oral administration. These compounds are subjected to phase II metabolism in the intestine and liver, involving glucuronidation, sulfation, and methylation reactions.² Intestinal microbiota also plays a crucial role in de-glycosylation and biotransformation of flavonoids into smaller phenolic metabolites. Although plasma concentrations of parent flavonoids are generally low due to rapid metabolism and elimination, their metabolites may contribute significantly to the observed pharmacological effects.^2,3

5.3 Bioavailability Enhancement Strategies:

To overcome pharmacokinetic limitations, various strategies have been explored to enhance the bioavailability of sea buckthorn constituents. Lipid-based delivery systems such as nano-emulsions, self-emulsifying drug delivery systems (SEDDS), and liposomes have demonstrated improved solubility and intestinal absorption of lipophilic compounds.^1,16,17 Encapsulation approaches using cyclodextrins, biopolymeric carriers, solid lipid nanoparticles, and phytosome complexes protect sensitive phytoconstituents from degradation and first-pass metabolism.^16,17Additionally, co-administration with dietary lipids and nano-formulation-based approaches have been shown to enhance systemic exposure and sustained release, thereby improving the therapeutic potential of sea buckthorn-based formulations.^3,16

6. Pharmaceutical Dosage Forms and Formulations:

Sea buckthorn (Hippophae rhamnoides L.) has been formulated into a variety of dosage forms to maximize its therapeutic potential, stability, bioavailability, and patient compliance. Various conventional and novel drug delivery systems have been investigated to effectively deliver its bioactive constituents.

6.1 Conventional Dosage Forms:

Capsules:

Capsules are widely used to deliver sea buckthorn oils and extracts, particularly soft gelatine capsules for oil formulations rich in fatty acids and carotenoids. Capsules protect sensitive lipophilic compounds from oxidation and allow precise dosing for antioxidant and cardiovascular support supplements.^1,2

Tablets:

Tablets containing sea buckthorn extract or powdered berries are used for antioxidant and metabolic health applications. The manufacturing process requires careful selection of binders and disintegrants to avoid degradation of heat-sensitive phytocompounds during compression.^2,3.

Syrups:

Liquid syrups prepared from aqueous sea buckthorn extracts or berry juice provide a palatable dosage form, especially useful in paediatric and geriatric populations. These formulations enhance oral uptake of hydrophilic vitamins and flavonoids but require stabilizers to prevent microbial growth.⁴

Oils:

Sea buckthorn oils (seed and pulp) are used as standalone oral formulations for cardiovascular, metabolic, and mucosal healing benefits. Topical use of sea buckthorn oil promotes skin regeneration and wound healing, but oxidation remains a major formulation challenge.^1,5

6.2 Novel Drug Delivery Systems (Highly Novel):

Nano emulsions:

Nano emulsions are fine oil-in-water dispersions that significantly enhance the solubility, bio accessibility, and intestinal uptake of lipophilic compounds like carotenoids and fatty acids from sea buckthorn oil.¹⁶

Liposomes:

Liposomes encapsulating sea buckthorn bioactive improve protection against degradation and facilitate targeted delivery of both hydrophilic and lipophilic constituents. This can improve antioxidant availability and cellular uptake.¹⁷

Transferosomes:

Transferosomes are deformable vesicles that penetrate deeper skin layers, enhancing topical and transdermal delivery of fatty acids and antioxidants. Sea buckthorn-loaded transferosomes show improved skin permeation and therapeutic action.¹⁸

Ethosomes:

Ethosomal systems utilize high ethanol content to fluidize the skin barrier, enabling enhanced delivery of sea buckthorn phytoconstituents. These systems are promising for dermal therapy and anti-inflammatory applications.¹⁸

Solid Lipid Nanoparticles (SLNs):

SLNs provide enhanced stability and controlled release of sea buckthorn bioactive. Their solid lipid matrix protects sensitive compounds and improves shelf-life for topical and oral use.⁹

Nanostructured Lipid Carriers (NLCs):

NLCs offer higher drug loading and lower leakage compared to SLNs. Sea buckthorn-loaded NLCs improve bioavailability and sustained release, making them ideal for pharmaceutical and cosmetic formulations.^9,10

6.3 Topical and Transdermal Formulations:

Gels:

Sea buckthorn gels are hydrogel-based topical systems used for skin repair, inflammation, and wound healing. Their aqueous base provides good spread ability and rapid release of active constituents.¹¹

Creams:

Cream formulations with sea buckthorn oil offer balanced hydration and enhanced penetration of bioactive compounds, making them suitable for anti-aging and moisturizing applications.¹²

Ointments:

Occlusive ointments containing sea buckthorn extracts or oil are used for chronic ulcers and dermatological conditions due to their prolonged skin contact and regenerative effects.¹³

Wound Dressings:

Advanced wound dressings incorporating sea buckthorn extracts or nanocarriers offer antioxidant, anti-inflammatory, and antimicrobial benefits, supporting faster healing and reduced infection risk.^11,14

7. Sea Buckthorn in Cosmeceuticals:

Sea buckthorn (Hippophae rhamnoides L.) has emerged as a valuable ingredient in cosmeceutical formulations due to its rich content of bioactive compounds such as carotenoids, flavonoids, tocopherols, phytosterols, and essential fatty acids. These constituents contribute to multiple skin-beneficial effects, including anti-aging, hydration, photoprotection, and acne control, making sea buckthorn widely used in modern cosmetic and dermatological products.^1,2

7.1 Anti-Aging Formulations:

Sea buckthorn oil and extracts are extensively incorporated into anti-aging formulations because of their strong antioxidant properties. The presence of vitamins C and E, carotenoids, and flavonoids helps neutralize free radicals, reduce oxidative stress, and prevent premature skin aging.^2,3 This bioactive support collagen synthesis, improve skin firmness, and reduce the appearance of fine lines and wrinkles. Regular application of sea buckthorn-based creams and serums has been associated with enhanced skin elasticity and improved overall skin texture.^4.

7.2 Skin Hydration and Elasticity:

Sea buckthorn is particularly rich in palmitoleic acid (ω-7), an essential fatty acid naturally present in human skin lipids. This fatty acid helps restore the skin barrier, improve moisture retention, and enhance skin elasticity ^1,5 Cosmeceutical formulations containing sea buckthorn oil promote deep hydration, reduce trans epidermal water loss, and support skin regeneration. These properties make sea buckthorn suitable for dry, sensitive, and aging skin formulations.⁵

7.3 UV Protection:

The carotenoids, flavonoids, and tocopherols present in sea buckthorn provide protective effects against ultraviolet (UV)-induced skin damage. These compounds help absorb UV radiation and reduce oxidative damage caused by sun exposure.^3,6Sea buckthorn-based sunscreens and after-sun products have shown potential in reducing erythema, preventing photoaging, and supporting skin repair following UV exposure.⁶

7.4 Acne and Pigmentation Control:

Sea buckthorn exhibits anti-inflammatory, antimicrobial, and sebum-regulating properties, making it beneficial in acne management. The flavonoids and fatty acids present in sea buckthorn help reduce inflammation, inhibit acne-causing microorganisms, and promote faster healing of acne lesions.^4,7 Additionally, its antioxidant content supports skin brightening and helps regulate melanin synthesis, contributing to the reduction of hyperpigmentation and uneven skin tone.^7,8

8. Nutraceutical and Functional Food Applications:

Sea buckthorn (Hippophae rhamnoides L.) has gained significant importance in the nutraceutical and functional food industries due to its exceptional nutritional profile and wide range of health-promoting bioactive compounds. The berries, seeds, and leaves are rich in vitamins (C, E, A, K), essential fatty acids, polyphenols, flavonoids, amino acids, and minerals, which contribute to its functional and therapeutic value.^1,2

8.1 Health Supplements:

Sea buckthorn is extensively used in the form of nutraceutical supplements such as capsules, soft gels, powders, and extracts. These supplements are primarily formulated using seed oil, pulp oil, or standardized berry extracts. Regular consumption of sea buckthorn supplements has been associated with improved cardiovascular health, enhanced immune response, gastrointestinal protection, and metabolic regulation.^2,3The presence of omega-7 fatty acid (palmitoleic acid) plays a key role in maintaining mucosal integrity and lipid metabolism, while polyphenols and flavonoids contribute to antioxidant and anti-inflammatory effects.³

8.2 Beverages:

Sea buckthorn-based functional beverages, including juices, squashes, syrups, and fermented drinks, are popular due to their high vitamin C content and refreshing taste. These beverages provide antioxidant support, improve digestion, and enhance overall vitality.^1,4 However, the acidic nature and astringent taste of sea buckthorn juice require formulation optimization through blending with other fruit juices, sweeteners, or fermentation processes. Recent developments in beverage technology, such as encapsulation of bioactive and controlled processing, have helped preserve nutritional quality and improve sensory acceptance.^4,5

8.3 Fortified Foods:

Sea buckthorn extracts and powders are increasingly incorporated into fortified food products such as bakery items, dairy products, cereals, confectionery, and nutrition bars. Fortification with sea buckthorn enhances the nutritional profile of foods by increasing their antioxidant capacity, vitamin content, and essential fatty acid levels.^2,5Functional foods fortified with sea buckthorn have shown potential benefits in improving lipid profiles, glycaemic control, and gut health. Microencapsulation techniques are often employed to improve stability, mask unpleasant Flavors, and protect sensitive bioactive compounds during processing and storage.⁵

9. Clinical Studies and Human Evidence:

Recent clinical investigations have provided growing human evidence supporting the therapeutic potential of sea buckthorn (Hippophae rhamnoides L.), particularly in skin health, cardiovascular protection, and metabolic regulation. Most available studies indicate beneficial outcomes; however, further large-scale and long-term clinical trials are required to establish standardized therapeutic recommendations.^1,2

9.1 Summary of Clinical Trials:

Randomized and controlled clinical trials evaluating sea buckthorn oil, berry extracts, and standardized supplements have typically been conducted over 8–12 weeks. These studies assessed biochemical, physiological, and clinical parameters and reported improvements in lipid metabolism, inflammatory status, and skin-related outcomes. Variability in formulation and extract standardization limits direct comparison across trials.^1,2

9.2 Skin Disorders:

Clinical studies have demonstrated that oral supplementation with sea buckthorn oil improves skin hydration, elasticity, and barrier function compared to placebo. Topical formulations containing sea buckthorn extracts have also shown enhanced wound healing, reduced erythema, and improved skin regeneration in mild inflammatory skin conditions. These effects are attributed to omega-7 fatty acids, carotenoids, and antioxidant flavonoids.^3,4

9.3 Cardiovascular Health:

Human trials suggest cardioprotective effects of sea buckthorn supplementation, particularly in individuals with dyslipidaemia. Significant reductions in total cholesterol, LDL cholesterol, and triglycerides, along with modest increases in HDL cholesterol, have been reported. Improvements in oxidative stress markers and endothelial function further support its cardiovascular benefits.^5,6

9.4 Metabolic Disorders:

Clinical evidence indicates that sea buckthorn supplementation improves fasting blood glucose, insulin sensitivity, and inflammatory biomarkers in individuals with metabolic syndrome or insulin resistance. Reductions in waist circumference and serum triglyceride levels suggest its potential role as an adjunct dietary intervention for metabolic disorders.^2,7

Overall, available clinical evidence supports the beneficial role of sea buckthorn in human health; however, well-designed, long-term clinical studies are needed to confirm efficacy and establish standardized dosage guidelines.

10. Safety, Toxicology, and Regulatory Status:

10.1 Toxicological Studies:

Acute Toxicity:

Preclinical studies have shown that sea buckthorn extracts and oils exhibit low acute toxicity. Oral administration in rodents at doses up to 5 g/kg body weight did not result in mortality or significant behavioural changes, indicating a wide margin of safety for human consumption.^2,3

Sub-Chronic Toxicity:

Sub-chronic studies over 28–90 days in animal models demonstrated no significant alterations in haematological, biochemical, or histopathological parameters at doses relevant to human supplementation. Some studies reported minor changes in liver enzyme levels, but these were within physiological limits and not considered toxicologically relevant.^3,4 These findings support the safe use of standardized extracts in nutraceutical and cosmeceutical applications.

10.2 Drug–Herb Interactions:

Anticoagulants:

Sea buckthorn contains bioactive compounds that may have mild antiplatelet or anticoagulant activity. While clinical evidence is limited, caution is advised when co-administered with anticoagulants such as warfarin or heparin due to potential additive effects on bleeding risk.⁵

Antihypertensives:

Some studies suggest that omega fatty acids and flavonoids in sea buckthorn may have blood pressure–modulating effects. While beneficial in hypertensive patients, concurrent use with antihypertensive drugs may enhance hypotensive effects, requiring monitoring of blood pressure.^5,6

10.3 Regulatory Status:

India (AYUSH, FSSAI):

Sea buckthorn is recognized as a safe herbal ingredient by the Ministry of AYUSH in India and is included in several traditional formulations. FSSAI approves its use as a food ingredient, nutraceutical, or functional food additive under prescribed limits.^1,7

FDA (United States):

Sea buckthorn is generally recognized as safe (GRAS) when used in food products and dietary supplements. Its oils and extracts are permitted as food ingredients, provided quality and purity standards are maintained.⁷

EMA (Europe):

In the European Union, sea buckthorn is listed in the European Medicines Agency (EMA) herbal monographs as a traditional herbal medicinal product for use in nutritional and skin-related applications. Regulatory approval requires standardization of bioactive constituents and compliance with safety requirements.^7,8

11. Challenges and Limitations:

Despite the growing interest in sea buckthorn for pharmaceutical, nutraceutical, and cosmeceutical applications, several challenges remain: Variability in Phytochemical Content Seasonal, geographical, and genetic variations result in differences in bioactive compound concentrations, affecting consistency and therapeutic efficacy. ^[2,3]Stability Issues Lipophilic compounds such as carotenoids, omega fatty acids, and vitamin E are prone to oxidation, limiting shelf life and bioavailability ^[3,4].Standardization Problems Lack of universally accepted standardization protocols for extracts complicates quality control and clinical reproducibility.^4,5.Lack of Large-Scale Clinical Trials While small clinical studies indicate beneficial effects, there is a paucity of large, well-controlled trials, limiting definitive conclusions about long-term efficacy and safety.^1,2,6Addressing these challenges through advanced formulation techniques, rigorous standardization, and high-quality clinical research is essential for wider therapeutic and commercial adoption.

12. Future Perspectives:

Sea buckthorn (Hippophae rhamnoides L.) shows strong potential as a nutraceutical, cosmeceutical, and pharmaceutical agent owing to its diverse bioactive profile. Future advancements are expected to focus on nanotechnology-based delivery, targeted therapies, combination approaches, and commercialization strategies to enhance therapeutic outcomes.

12.1 Nanotechnology-Based Formulations:

Nanocarrier systems such as nano emulsions, liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) offer promising solutions to improve the stability, bioavailability, and controlled release of sea buckthorn bioactive.^1,2 Encapsulation protects lipophilic compounds from degradation and enhances systemic and topical absorption, leading to improved therapeutic efficacy and patient compliance.

12.2 Targeted Drug Delivery in Skin Disorders:

Given its strong antioxidant, anti-inflammatory, and regenerative properties, sea buckthorn is an ideal candidate for targeted delivery in dermatological applications. Advanced vesicular systems, including transferosomes, ethosomes, and microneedle-based formulations, are being explored to enhance penetration through the stratum corneum and deliver bioactive to deeper skin layers.^2,3These targeted strategies have the potential to improve efficacy in the management of burns, chronic wounds, psoriasis, and photoaging while minimizing systemic exposure.

12.3 Combination Therapy Approaches:

Combining sea buckthorn with other herbal or synthetic bioactive may produce synergistic antioxidant and anti-inflammatory effects, improving outcomes in metabolic, cardiovascular, and dermatological disorders ^[3,4] Such combinations support the development of personalized nutraceutical and cosmeceutical products.

12.4 Patentability and Commercialization:

Growing global demand for natural bioactive has increased patent activity and commercialization of sea buckthorn-based products. Innovations in nano formulations, standardized extracts, and combination therapies represent areas with high commercial and intellectual property potential.^4,5,20Regulatory acceptance and scalable processing further enhance its market prospects.

Future studies should emphasize:

· Standardization of bioactive components

· Advanced formulation development

· Large-scale clinical validation

· Regulatory and commercialization frameworks

· These efforts will help fully realize the therapeutic and economic potential of sea buckthorn.

CONCLUSION:

Sea buckthorn (Hippophae rhamnoides L.) is a pharmacologically significant medicinal plant characterized by a rich profile of bioactive constituents, including vitamins, minerals, flavonoids, carotenoids, phytosterols, and polyunsaturated fatty acids, notably omega-7 palmitoleic acid. These compounds collectively contribute to its diverse therapeutic properties such as antioxidant, anti-inflammatory, cardioprotective, wound-healing, and skin-regenerative activities, validating both its traditional applications and modern pharmaceutical relevance.

Despite its promising therapeutic potential, the clinical utilization of sea buckthorn is limited by challenges related to poor solubility, stability, and bioavailability of its bioactive compounds. Recent advances in pharmaceutical formulation technologies, particularly nanotechnology-based delivery systems, have shown significant promise in overcoming these limitations by enhancing bioavailability, targeted delivery, and therapeutic efficacy.

Overall, sea buckthorn holds strong potential as a nutraceutical, cosmeceutical, and pharmaceutical agent. Future research should prioritize standardized formulations, advanced drug delivery approaches, and well-designed clinical trials to ensure safe, effective, and scalable pharmaceutical applications of sea buckthorn.

REFERENCES:

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2. Singh B, Sharma HK, Sarkar BC. Sea buckthorn: A multifunctional medicinal plant with emerging pharmaceutical applications. Int J Food Sci Nutr. 2024; 75(6): 601–616. doi:10.1080/09637486.2024.2321145

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Received on 02.04.2026 Revised on 20.04.2026

Accepted on 05.05.2026 Published on 08.07.2026

Available online from July 13, 2026

Res. J. Pharmacognosy and Phytochem. 2026; 18(3):300-308.

DOI: 10.52711/0975-4385.2026.00043

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