Ethnopharmacological insight and therapeutic potential of Nymphaea alba: A Comprehensive Review of Its Therapeutic Applications

Introduction
Nymphaea albaL., also known as the European White-Water Lily and referred to as Neelofar in Unani medicine, is an aquatic perennial plant recognized for its therapeutic value in both traditional and modern healthcare systems. A member of the Nymphaeaceae family, this hydrophyte naturally grows in calm freshwater environments such as ponds, lakes, and slow-flowing rivers throughout Europe, North Africa, and parts of Asia. Its ability to adapt to various aquatic habitats contributes to its widespread availability and utilization in medicinal and ecological contexts. Within the Unani medical framework—an ancient system based on Greco-Arabic medical philosophy—Nymphaea alba is characterized by a Barid (cold) and Ratab (moist) temperament. This classification is rooted in the humoral theory, which emphasizes maintaining a balance among the body’s four essential fluids: Dam (blood), Balgham (phlegm), Safra (yellow bile), and Sauda (black bile). The plant is traditionally employed to correct imbalances associated with excess heat and dryness, thereby supporting overall health and well-being[1][2]. Neelofar is utilized in the Unani system in multiple dosage forms, including powders, syrups (Sharbat-e-Neelofar), electuaries (Majoon-e-Neelofar), decoctions, and topical applications like poultices. These preparations are traditionally prescribed for a range of health conditions such as insomnia, anxiety, anovulatory infertility, diabetes, urinary tract issues, and inflammatory disorders. Its therapeutic efficacy is attributed to its ability to alleviate imbalances caused by excessive Hararat (heat) and Yabusat(dryness), thereby restoring humoral equilibrium in the body.[3][4].

The broad therapeutic potential of Nymphaea alba is largely due to its diverse phytochemical profile, which encompasses alkaloids, flavonoids, phenolic acids, glycosides, tannins, and steroidal constituents, as recognized in both classical literature and contemporary research [5][6]. These naturally occurring compounds form the basis for its wide range of pharmacological effects, including antioxidant, antidiabetic, analgesic, anxiolytic, anticancer, antimicrobial, and antifertility properties—many of which support its traditional usage within Unani medicine. Emerging clinical investigations, especially those examining its utility in stimulating ovulation, have yielded encouraging results. These findings indicate comparable efficacy to standard therapies like clomiphene citrate, suggesting Nymphaea alba as a potentially safer and effective therapeutic option [7]. In addition to its medicinal applications, the plant plays a valuable role in aquatic ecosystems by limiting algal proliferation and acting as a bioindicator for environmental heavy metals, underscoring its importance across both medical and ecological disciplines [8][9].

Unani Description and Ethnobotanical Uses

In the Unani system of medicine, Nymphaea alba—commonly referred to as Neelofar—is regarded as a significant medicinal plant, primarily due to its Barid (cold) and Ratab (moist) temperament, which corresponds with the humoral concept of maintaining equilibrium among the four bodily fluids: Dam (blood), Balgham (phlegm), Safra (yellow bile), and Sauda (black bile) [1]. Its therapeutic actions include cooling, astringent, sedative, and rubefacient effects. These properties support its traditional classification as a Muqawwi-e-Bah (aphrodisiac), Mudirr-e-Baul (diuretic), Musakkin (sedative), and Musakkin-e-Alam (analgesic). As such, it is utilized in the treatment of reproductive health issues, neurological conditions like anxiety and insomnia, urinary disorders, diabetes (Ziabetus), and inflammatory conditions, including dermatological inflammations.[2][3][7][19]. Its rhizomes, flowers, seeds, and leaves are used in powders, syrups (Sharbat Neelofar), electuaries (Majoon-e-Neelofar), decoctions, and poultices for boils, while its starch-rich rhizomes and seeds are processed into flour or boiled for nutritional purposes, serving both medicinal and dietary roles [20][5].

Temperament (Mizaj): Cold (Barid) and Moist (Ratab) in the second degree, making it suitable for balancing hot and dry conditions in the body [3][21].

Part Used: Rhizomes, flowers, seeds, and leaves, with rhizomes and flowers being the most commonly used in Unani formulations [22].

Therapeutical Uses:

Muhalil e awram (Anti-inflammatory): Neelofar contains bioactive compounds like tannins and flavonoids that reduce inflammation in the respiratory tract [23]. In Unani medicine, it is used to soothe irritated airways in conditions such as bronchitis and asthma (Zeeq-un-NafasSho’abi), providing relief from symptoms like swelling and discomfort in the lungs [3].

Mukhrijbalgham (Mucolytic and Expectorant): The astringent and resolvent properties of Neelofar aid in clearing mucus from the respiratory system [24]. It is commonly included in Unani formulations like Sharbat-e-Neelofar to alleviate cough and chest congestion, particularly in conditions like chronic bronchitis and pleurisy (Zat-ul-Janb) [25].

Neelofar is combined with herbs like Unnab and Banafsha in Unani syrups and decoctions to treat cough and respiratory irritation [25]. Its flowers, known for their cooling and narcotic effects, are particularly valued for easing symptoms like chest tightness and persistent cough [24].

Munawwim (Sedative) and Musakkin-e-a’asab (Calming Effects): Neelofar’s sedative action helps calm the respiratory system, reducing bronchial spasms that cause breathing difficulties [26]. Its alkaloids contribute to relaxing bronchial muscles, making it effective for managing asthma symptoms and improving airflow [27]. It is also prescribed for insomnia, anxiety, and restlessness due to its sedative (Munawwim) and analgesic (Musakkin-e-A’asab) properties, often used in decoctions or pastes to calm the nervous system [3].

Mubarrid (Cooling): Its cold temperament makes it effective for fever, liver inflammation, and burning sensations. It is used in Nutool (irrigation) with cooling herbs like Khatmi (Althaea officinalis) and Banafsha (Viola odorata) for tremors and inflammatory conditions [21].

Muqawwiqalb (Cardioprotective and Cardiac Tonic): The flowers act as a cardiac tonic, used for palpitations and cardiac weakness [22].

Mudir e Bol (diuretics): Seeds and rhizomes serve as diuretics, treating urinary tract inflammations, kidney stones, and burning micturition [28].

Muqawwi Bah (Aphrodisiac and Reproductive Health): Noted for its aphrodisiac properties, Neelofar is used in formulations to enhance sexual health and treat seminal weakness [3].

Qabiz for Dermatological Uses: Applied externally as a paste (Zimad), it treats skin inflammations, burns, and eruptions due to its cooling and astringent (Qabiz) effects [29].

Preparations in Unani:

Joshanda (Decoctions): Used for fever and insomnia.

Zimad (Paste): Applied externally for skin inflammations.

Nutool(Irrigation): Combined with other cooling herbs for tremors and inflammation.

Sufoof (Powders and Confections): Incorporated in formulations for cardiac and urogenital health [22].

Compound formulations of Neelofar: Sharbat Neelofar, Majoon Supari Paak, ArqMurakkabMusaffiKhoon, MajoonDabeedul Ward.

Vernacular Names

Nymphaea alba is known by various names across different languages, reflecting its cultural and medicinal significance:

• Urdu/Unani: Neelofar [2]
• Arabic: Nilufar [1]
• Persian: Nilupar [10]
• Hindi: Kumudini, Kanwal [5]
• Bengali: Shapla [11]
• Tamil: Alli [12]
• Telugu: Kaluva
• Kannada: Tavare
• Malayalam: Ambal
• English: European White-Water Lily [9].

Cultivation: Nymphaea alba, widely known as the white-water lily, is a perennial aquatic species cultivated for its ornamental beauty, therapeutic applications, and ecological significance. It flourishes in still or slow-moving shallow waters and depends on particular environmental conditions for optimal development.

Habitat Requirements: Nymphaea alba thrives in calm aquatic environments such as ponds, lakes, and marshes, ideally at water depths ranging from 30 to 150 cm. It grows best under full sun to partial shade, needing a minimum of six hours of direct sunlight each day. The optimal water pH for its growth lies between 6.0 and 7.5, favoring slightly acidic to neutral conditions. Well adapted to temperate regions, this species can withstand cold climates, with its rhizomes remaining viable even in frozen substrates during winter. As such, it is well suited for cultivation in USDA hardiness zones 4-10.[13][14].

Soil and Substrate: The plant requires nutrient-rich, muddy, or silty substrates. A loamy soil mixed with clay is ideal for anchoring rhizomes. In artificial ponds, a heavy clay-loam mix in submerged containers is recommended to support growth and prevent nutrient leaching [14].

Climate and Distribution: Native to Europe, North Africa, and parts of Asia, including a notable presence in India’s Bengal, Orissa, and Kashmir regions, Nymphaea alba grows at elevations up to 1500 m [9]. It thrives in neutral to alkaline waters of ponds, lakes, and slow-moving rivers at depths of 0.5–5.5 m over muddy or silty substrates [8]. Its ecological role includes reducing algal growth by shading water bodies, making it valuable for both medicinal and environmental applications, as well as Unani formulations across diverse regions [5][10].

Macroscopic Characters:

Rhizome: Thick, creeping, and tuberous, 5–20 cm long, dark brown to black externally, white internally when cut (Fig. 1), with numerous rootlets and a rough surface bearing scars of old leaves and roots (Fig. 2) [15].

Nymphaea alba rhizome.

Leaves: The leaves are floating and nearly circular in shape, measuring approximately 10–30 cm in diameter, and feature a pronounced basal sinus. Their upper surface is dark green, smooth, and coated with a waxy layer (Fig. 3), while the underside displays a purplish to reddish hue. The petioles are elongated, submerged, and notably flexible, allowing the leaves to adapt to water movement.[13].

Flowers: Large (7–15 cm in diameter), solitary, white, and fragrant, with 4 sepals and numerous spirally arranged petals (Fig. 4). Flowers float on the water surface and bloom during the day [16].

Seeds:Small, ovoid, 1–2 mm, enclosed in a spongy aril aiding flotation and dispersal (Fig. 5) [13].

Fruit:

Microscopic Characters:

Rhizome:

• Epidermis: Single-layered with thick-walled cells.
• Cortex: Large, loosely arranged parenchymatous cells with air spaces (aerenchyma) for buoyancy, containing starch grains and calcium oxalate crystals (raphides).
• Vascular Bundles: The vascular bundles are scattered and collateral in arrangement, comprising xylem elements (tracheids and vessels) along with phloem components (sieve tubes and companion cells) [17].

Leaf:

• Epidermis: Upper epidermis is waxy, lacking stomata; lower epidermis has numerous stomata. Trichomes are absent.
• Mesophyll: Spongy parenchyma with large air spaces, lacking a palisade layer.
• Vascular Tissue: Veins embedded in mesophyll with small vascular bundles [18].

Flower: Petals and sepals consist of thin-walled parenchymatous cells with pigments (anthocyanins in sepals) (Fig. 7). Anthers contain pollen grains with spiny exine [17].

Useful components: Alkaloids, glycosides, resin, tannins

Phytochemical Composition:

These constituents underpin its Unani applications for balancing humors and treating conditions associated with heat and dryness Table 1 [2].

Pharmacological Properties

Modern research has validated the pharmacological activities of Nymphaea alba, many of which corroborate its traditional Unani uses. The following sections provide a detailed analysis, integrating Unani perspectives and additional references from primary studies.

Antioxidant Properties

Ethanolic rhizome extracts of Nymphaea alba exhibits robust antioxidant activity, with IC50 values of 63.9 µg/ml (DPPH assay), 9.21 µg/ml (nitric oxide scavenging), and 79.56 µg/ml (superoxide radical scavenging) [5]. These effects are attributed to tannins and phenolic compounds, which neutralize reactive oxygen species, reducing oxidative stress [35][36]. In Unani medicine, Neelofar’s cooling (Barid) properties are used to counteract excessive heat (Hararat), aligning with its antioxidant capacity [2]. A study in Wistar rats demonstrated that Nymphaea alba mitigates potassium bromate-induced renal oxidative stress, reducing lipid peroxidation and enhancing antioxidant enzyme activity [37][38][39]. This supports its Unani use for conditions involving humoral imbalances caused by oxidative stress [3].

Antidiabetic Effects

In Unani medicine, Neelofar is employed to manage diabetes (Ziabetus) by restoring humoral balance and reducing excessive heat [2][40]. Scientific investigations have confirmed that nymphal, a steroidal constituent isolated from the flowers, promotes insulin secretion and supports the regeneration of pancreatic β-cells in streptozotocin-induced diabetic rat models [30]. This effect is associated with improved glucose metabolism, demonstrated by a significant reduction in blood glucose levels and enhanced β-cell recovery. [41][42]. These findings support Neelofar’s traditional use in Unani formulations for diabetes management [4].

Analgesic Effects

Ethanolic extract of the rhizome at a dose of 600 mg/kg exhibits notable analgesic effects in murine models, showing superior efficacy compared to standard drugs in both acetic acid-induced writhing and formalin-induced pain tests by significantly decreasing licking responses [5]. This aligns with Neelofar’s Unani classification as a Musakkin-e-Alam (pain reliever) for conditions like headaches and joint pain [2][43]. The analgesic effects are likely mediated by flavonoids and phenolic compounds, which inhibit prostaglandin synthesis and modulate pain pathways [44][45].

Anxiolytic and Sedative Effects

In Unani medicine, the Musakkin (sedative) effects of Neelofar are traditionally employed in the management of insomnia and anxiety [2][1]. Experimental studies show that ethanolic extracts of its rhizome enhance diazepam-induced sleep and significantly reduce head-dipping behavior in the hole-board test, demonstrating effects comparable to diazepam [46]. Additionally, in the elevated plus maze model, the extract increases the time spent in open arms, suggesting pronounced anxiolytic activity. These effects are likely attributed to the presence of flavonoids, which are believed to modulate GABAergic pathways [47][48]. These findings support Neelofar’s use in Unani formulations like Sharbat Neelofar for calming the nervous system [10].

Anticarcinogenic Effects

Nymphaea alba has shown chemo preventive potential in studies involving Wistar rats, where it mitigated renal carcinogenesis by reducing oxidative stress and suppressing the hyperproliferative effects induced by potassium bromate [37]. The presence of flavonoids and phenolic compounds contributes to its antitumor activity, primarily through free radical scavenging and regulation of key cellular signaling pathways [49][50]. In the Unani system, Neelofar is traditionally valued for its Barid (cooling) temperament, which is believed to counteract abnormal tissue growth, thus aligning with its observed anticancer effects [2][3].

Antimicrobial Effects

Methanolic extracts derived from the flowers and rhizomes of Nymphaea alba have demonstrated antibacterial properties against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, with minimum inhibitory concentrations (MICs) ranging from 0.25 to 2 mg/ml [6]. The activity is attributed to flavonoids and phenolic acids, which disrupt bacterial cell membranes [51][52]. This aligns with Unani’s use of Neelofar to purify the body of morbid matter (Madda-e-Fasida) [2][53].

Antifertility and Contraceptive Effects

Neelofar is a key Unani herb for reproductive health, used in contraceptive formulations and ovulation inducers [2][10]. A clinical study confirmed its efficacy in ovulation induction, achieving ovulatory rates of 70%, 75.3%, and 76.8% over three cycles in women with anovulatory infertility, comparable to clomiphene citrate [7]. The mechanism may involve hormonal modulation, supporting its Unani classification as a Muqawwi-e-Bah [7][54].

Anti-solar Effects

The ethyl acetate extract exhibits UV-blocking activity due to its flavonoid content, with measurable sun protection factor (SPF) values [20]. In Unani, Neelofar’s cooling properties are used externally for skin protection, supporting its application in dermatological conditions [2][3].

Anti-urolithiatic Effects

The ethanolic rhizome extract reduces bladder stone weight in ethylene glycol-induced urolithiatic rats, likely due to its diuretic (Mudirr-e-Baul) and antioxidant properties [55][56]. This supports its Unani use for urinary disorders [2][43].

Bioindicator Potential

Nymphaea alba serves as a bioindicator for environmental metals (e.g., Ba, Co, Mn, Cu), with plant concentrations correlating with environmental levels, supporting its ecological monitoring applications [9][57][58].

6. Clinical Studies

Although clinical investigations on Nymphaea alba remain limited, emerging evidence—especially within the context of Unani medicine—is encouraging. One notable study assessed the effectiveness of a Unani polyherbal formulation comprising Neelofar, Withaniasomnifera, Anogeissus latifolia, and Barleriaprionitis in promoting ovulation among women aged 20 to 40 years diagnosed with anovulatory infertility[7]. Administered as a 12 g powder daily for five days over three menstrual cycles, it achieved ovulatory rates of 70%, 75.3%, and 76.8%, with conception rates of 10% and 17.8% in the first and third cycles, respectively [7]. These outcomes were comparable to clomiphene citrate, with no adverse effects, highlighting Neelofar’s potential as a safe reproductive therapy [7][59]. The study’s success aligns with Unani’s use of Neelofar as a Muqawwi-e-Bah for reproductive health [10][1]. Additional clinical studies are required to evaluate its therapeutic potential for other Unani indications, including its roles in managing diabetes, inducing sedation, and alleviating pain.[3].

7. Conclusion

Nymphaea alba (Neelofar) is a versatile medicinal plant with significant applications in Unani medicine and modern pharmacology. Its antioxidant, antidiabetic, analgesic, anxiolytic, anticancer, antimicrobial, and antifertility properties, driven by a rich phytochemical profile, align with its Unani uses for balancing humors and treating diverse ailments. Clinical evidence supports its efficacy in ovulation induction, with potential for broader applications in diabetes, pain management, and nervous disorders. This review, backed by a comprehensive set of references, offers a solid framework for future research on Neelofar, integrating traditional Unani insights with contemporary scientific findings to promote its clinical relevance and therapeutic development.

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