Crinum latifolium
1. Identity: Botanical Classification, Natural Source, and Forms
Taxonomy and Nomenclature
Crinum latifolium Linn. is a member of the family Amaryllidaceae and is extensively distributed throughout the world in the tropics, subtropics, and warm temperate regions. The genus Crinum belongs to the Amaryllidaceae family and comprises approximately 160 species distributed throughout the tropics and warm temperate regions of the world in Asia, Australia, Africa, and America.
The species epithet latifolium is Latin for "broad-leaved," describing the plant's distinctive leaf morphology. Commonly called Sudarsana in India, its Latin name highlights the broad (latifolium) leaves. In Vietnamese traditional medicine it bears the names Trinh Nữ Hoàng Cung (Imperial Virgin or Virgin in the Palace) and Bạch Tuộc. Crinum latifolium is one of Vietnam's precious medicinal herbs. In the past, it was reserved only for royalty, and was therefore commonly referred to as the "Medicine for the King's Palace" and the "Royal Female Herb" in Vietnam.
A specific cultivar, registered as Crinum latifolium L. var. crilae Tram & Khanh, has been the subject of a focused research program originating in Vietnam since the 1990s. In 1990, pharmacologist Nguyen T.N. Tram began the first scientific study of the Vietnamese plant Crinum latifolium L. to determine if claims from Traditional Vietnamese Medicine were wishful folklore or efficacious fact. Her investigations sought to substantiate Crinum's traditional anti-tumor/anti-cancer use for male and female reproductive organs.
Botanical Description
This herb grows from a subterranean bulb, sending up strap-like leaves up to 1.5 m long and elegant white or pink-tinged blossoms perched on tall scapes. It thrives in damp soils of riverbanks and wet forests across southern China, Vietnam, Thailand, and India. The plant has a bulb-like trunk and a spherical root of 10–15 cm in diameter, whose leaf sheaths together constitute a trunk of approximately 10–15 cm.
Common Forms and Preparations
Preparations of Crinum latifolium take several forms in both traditional and contemporary use. In traditional Chinese and Vietnamese medicine, aqueous leaf extracts made by infusion or decoction have been utilized to cure ovarian and prostate malignant growth. Crinum bulbs and leaves are also utilised in herbal medications. Modern commercial preparations include standardized dry-powder capsules. The dry extract of Crinum latifolium leaves from CriLa® capsules (250 mg), obtained by the Thien Duoc Company Ltd. (Ho Chi Minh City, Vietnam), was standardized with reference to the amount of crinamidine content (70 μg/capsule) using reverse phase high performance liquid chromatography (HPLC). Crila was approved by the Ministry of Health in Vietnam in 2005 as a traditional medicine for the treatment of benign prostatic hyperplasia and uterine fibroids after the 2007 clinical study.
2. Traditional and Historical Use
Indian Traditions (Ayurveda, Siddha, Unani)
The plant is widely utilized as traditional medicines in a few indigenous systems of medicine like Ayurveda, Siddha, and Unani. The Indian species Crinum latifolium (L.) was traditionally used to treat rheumatism, fistula, tumors, earaches, rubefacient, tubercle, and whitlow. In Ayurvedic nomenclature the plant is known as Sudarsana.
Vietnamese and Chinese Traditions
Herbal preparations of Crinum latifolium L. have been used therapeutically for over 1,000 years in Asian folk medicine for their anti-inflammatory, anti-tumour, and anti-microbial effects. In the case of the traditional use against cancer, especially in Vietnamese and Chinese medicine, hot aqueous extracts of C. latifolium are consumed as a remedy for prostate cancer, with successful cases being reported.
Within the Vietnamese royal court, the herb carried a special social status. Crinum latifolium L. was used by royal physicians to treat gynecological disorders for imperial concubines, including dysmenorrhea and tumors. Because most concubines did not give birth, the plant is called Trinh Nu Hoang Cung (Imperial Virgin, or Virgin in the Palace). The herb was also employed more broadly: according to traditional medicine, Crinum latifolium L. is described as pungent, cool, and little toxic; its characteristics are vitality motivation, anti-inflammation, pain relief, heat eradication, detoxication, blood activation, and the ability to cure tumors.
Royal physicians used the plant to treat gynecological disorders, and it was additionally used among common people to treat several urinary diseases.
Broader Southeast Asian Use
The Crinum species have commercial, economical, and medicinal importance. Besides its popularity as an ornamental garden plant with beautiful blossoms, the plant attracts considerable attention due to various medicinal properties including antitumor, immune-stimulating, analgesic, antiviral, antibacterial, and antifungal activities.
3. Key Constituents and Active Compounds
Overview of Phytochemical Classes
The plant contains various chemical constituents, including alkaloids, flavonoids, terpenoids, and phenolic compounds. Phytochemical screening of ethanolic extract of the leaves of Crinum latifolium has revealed that it is rich in alkaloids, glycosides, tannins, flavonoids, gums, and mucilages.
Amaryllidaceae-Type Alkaloids
Alkaloids are the dominant and most-studied bioactive class. Phytochemical analysis of Crinum species has revealed more than 170 different compounds, most of which are alkaloids of the Amaryllidaceae type, which exhibit a wide range of biological activity such as analgesic, central nervous system, antitumor, and antiviral effects.
Although chemical analysis of Crinum latifolium alkaloids has been performed mainly on bulbs, which contain the highest concentrations of alkaloids, the presence of alkaloids, especially of the crinane type — e.g., crinamine, crinamidine, crinafoline, and crinafolidine — were also detected in water extracts of Crinum latifolium leaves.
Studies on the bulbs have revealed a particularly rich alkaloid profile. A new base, 3-O-acetylhamayne, was isolated from Crinum latifolium L. (Amaryllidaceae) along with crinamine, powelline, crinine, 1-O-acetyllycorine, hamayne, undulatine, and cherylline. Additional bases including diacetyllycorine, crinamidine, O-acetylcrinine, deacetylbowdensine, and bowdensine were also isolated.
A 2023 investigation of the bulbs found a particularly large alkaloid array: fifty-one Amaryllidaceae alkaloids have been isolated from the bulbs of Crinum latifolium L., eleven of which are previously undescribed. Four novel and potently bioactive Amaryllidaceae alkaloids — 4,8-dimethoxy-cripowellin C, 4,8-dimethoxy-cripowellin D, 9-methoxy-cripowellin B, and 4-methoxy-8-hydroxy-cripowellin B — together with one known alkaloid, cripowellin C, were isolated from the 95% EtOH extract of the bulbs of Crinum latifolium.
Lycorine
Lycorine is among the best-characterized individual alkaloids from Crinum latifolium. Lycorine is a pyrrolophenanthridine alkaloid with the molecular formula C₁₆H₁₇NO₄ and a molecular mass of 287.31 g/mol, occurring as colorless prismatic crystals. It is naturally isolated from various plants in the Amaryllidaceae family, including Lycoris radiata, Leucojum aestivum, Clivia miniata, Crinum latifolium, and Scadoxus puniceus. Lycorine (1) and 6α-hydroxybuphanidrine (2) were identified as the two major alkaloids isolated from the ethanolic leaf extract of C. latifolium. The C. latifolium leaf extract was found to contain 0.279 ± 0.003% lycorine and 0.232 ± 0.004% 6α-hydroxybuphanidrine.
Crinafoline, Crinafolidine, and Related Crinane-Type Alkaloids
Crinafoline and crinafolidine are two anti-tumor alkaloids that have been reported from Crinum latifolium, documented in the Journal of Chemical Research in 1986. These crinane-type alkaloids, along with crinamine and crinamidine, form the structural backbone most associated with the plant's anticancer activity.
Non-Alkaloidal Constituents
In vitro antioxidant activity studies have led to the quantification of oleanolic acid, linoleic acid, and lupeol by HPTLC. The content of oleanolic acid, linoleic acid, and lupeol were found to be higher in aerial parts — 0.015%, 0.048%, and 0.028% respectively — while root extract contained 0.006%, 0.027%, and 0.025% respectively, on a dry weight basis. Additional flavonoid and coumarin-type isolates from methanol extracts include a novel compound 4-senecioyloxymethyl-3,4-dimethoxycoumarin and the flavone 5,6,3'-trihydroxy-7,8,4'-trimethoxyflavone. Six compounds were isolated from the methanol extract of Crinum latifolium by bioassay-guided separation, of which two were new metabolites, with structures established as 4-senecioyloxymethyl-3,4-dimethoxycoumarin and 5,6,3'-trihydroxy-7,8,4'-trimethoxyflavone based on spectroscopic analyses.
4. Mechanisms of Action
Immunomodulation via IDO Suppression
Aqueous leaf extracts of C. latifolium were shown to modulate immune activation in human peripheral blood mononuclear cells (PBMCs) by reducing neopterin production in cells stimulated with mitogens or interferon-γ, thereby indicating suppression of excessive cell-mediated immune activation. The extract was also found to inhibit indoleamine-2,3-dioxygenase (IDO)–mediated tryptophan degradation in unstimulated and mitogen-stimulated PBMCs, further supporting its immunomodulatory and anti-inflammatory capacity. Mechanistically, in human macrophages, IFN-γ induces the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyses the rate-limiting step of tryptophan degradation via the kynurenine pathway. IDO plays a central role in the suppression of intracellular bacteria and viruses during an antimicrobial immune response, and also in growth control of malignant cells, as ongoing tryptophan degradation limits protein biosynthesis by depriving cells of this essential amino acid.
Antiproliferative and Antitumor Mechanisms
Lycorine demonstrates significant anticancer activity by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis in various cancer types, such as bladder, breast, and colorectal cancers, with in vitro IC₅₀ values ranging from 0.8 to 50 μM and in vivo tumor growth inhibition at doses of 5–30 mg/kg.
The pathological mechanism of BPH is associated with the induction of prostate stromal cell proliferation through transforming growth factor-beta (TGF-β). Standardization and investigation of the potential anti-BPH activity of C. latifolium extract could benefit the further development of BPH-related analyses. At the cellular level, the crude extract was more potent than either lycorine or 6α-hydroxybuphanidrine alone against TGF-β-treated WPMY-1 cell proliferation, and the greatest synergistic effect of the two alkaloids was achieved at a 1:1 ratio.
Antiangiogenic activity has also been identified. The compound 4-senecioyloxymethyl-3,4-dimethoxycoumarin was found to be strongly inhibitory against in vitro tube-like formation of human umbilical venous endothelial cells (HUVECs) while manifesting no cytotoxicity in tumor cell lines (B16F10, HCT116). Significant inhibitory activity (53.5% inhibition) was still observed at concentrations as low as 1 μg/mL.
Antioxidant Activity
In vitro antioxidant activity of an aqueous Crinum latifolium extract was demonstrated by an oxygen radical absorbance capacity (ORAC) value of 1610 ± 150 μmol Trolox equivalents/g. For context, analysis of water extracts of 45 herbs traditionally used in Chinese medicine revealed a range of ORAC activity (40–1990 μmol TE/g), of which only two herbal extracts — Spatholobus suberectus (1990 μmol TE/g) and Sanguisorba officinalis (1940 μmol TE/g) — showed a higher ORAC value than the Crinum latifolium extract in that study.
Cholinesterase Inhibition
Among the 51 alkaloids isolated from C. latifolium bulbs, alkaloid 51 exhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition more potent than galanthamine. This finding is of interest because galanthamine — also an Amaryllidaceae alkaloid — is an approved pharmaceutical agent for Alzheimer's disease.
5. Scientific Evidence by Area of Use
5.1 Benign Prostatic Hyperplasia (BPH)
Crinum latifolium L. (Amaryllidaceae) has been used in Southeast Asian traditional medicine to alleviate the symptoms of benign prostatic hyperplasia (BPH).
In vitro evidence: Dose-dependent inhibitory effects of an aqueous Crinum latifolium extract on cell proliferation were demonstrated in highly metastatic human prostate carcinoma PC3 cells (IC₅₀ = 4.5 ± 0.8 mg/ml), androgen-sensitive prostate adenocarcinoma LNCaP cells (IC₅₀ = 2.3 ± 0.1 mg/ml), and benign prostate hyperplasia BPH-1 cells (IC₅₀ = 2.1 ± 0.04 mg/ml). A separate study at Chulalongkorn University demonstrated that the C. latifolium leaf extract contained 0.279 ± 0.003% lycorine and 0.232 ± 0.004% 6α-hydroxybuphanidrine, and the crude extract was more potent than either alkaloid alone against TGF-β-treated WPMY-1 cell proliferation. The drug combination study revealed that the greatest synergistic effect was achieved at a 1:1 ratio of the two alkaloids. The results support the anti-BPH activity of C. latifolium in traditional medicine.
Regulatory status: Crila was approved by the Ministry of Health in Vietnam in 2005 as a traditional medicine for the treatment of benign prostatic hyperplasia.
Evidence strength: Preclinical in vitro evidence is consistent and mechanistically grounded (TGF-β pathway, antiproliferative). However, large-scale randomized controlled trials in humans are not yet published in the peer-reviewed literature indexed on PubMed. Evidence remains largely at the in vitro and animal stage, with a Vietnamese regulatory approval based on clinical data not fully accessible in international peer-reviewed journals.
5.2 Uterine Fibroids and Gynecological Applications
Clinical evidence: Of the varieties of C. latifolium, one specific variety — "Crila" (C. latifolium L. var. crilae Tram & Khanh) — has been studied in women with uterine fibroids. A 3-month study of 195 women with uterine fibroid tumors was conducted in three hospitals in Vietnam in 2007, in which C. latifolium decreased the size or stopped the growth of fibroid tumors in 79.5% of the women.
Estrogenicity assessment: Crila showed no estrogenic or antiestrogenic activity when evaluated using Ishikawa cell-based assays, indicating that this botanical is probably not estrogenic in vivo. The same study showed that when estradiol was added to the extract before treating Ishikawa cells, the estrogenicity of the extract was enhanced.
Combination research: The combination of natural compounds Crila and epigallocatechin gallate (EGCG) showed enhanced antiproliferative effects on human uterine fibroid cells compared to single treatments.
Evidence strength: The 2007 Vietnamese multi-hospital clinical study (n=195) provides the most substantial human-level data, but this study was conducted within Vietnam's regulatory context and is not published in major peer-reviewed international journals as a full RCT. The study design and blinding procedures are not fully described in currently accessible English-language literature, which limits independent evaluation. The in vitro estrogenicity data from Fertility & Sterility Science is peer-reviewed and informative.
5.3 Immunomodulation
In vitro / ex vivo human cell evidence: One study evaluated the effects of powdered Crinum latifolium leaves extracted in water on the T-cell/macrophage interplay by measuring influence on PBMCs stimulated with phytohaemagglutinin (PHA), which activates formation of IFN-γ in T-cells and subsequently tryptophan degradation and neopterin production in macrophages. Significant anti-inflammatory effects were shown by the extract's potential to suppress IDO-mediated tryptophan degradation in unstimulated and mitogen-stimulated PBMC at IC₅₀ doses of 241 ± 57 μg/ml and 92 ± 20 μg/ml, respectively. Concentrations of the immune activation marker neopterin were slightly diminished in unstimulated PBMC, whereas a dose-dependent inhibition of neopterin formation was observed in mitogen-stimulated PBMC (IC₅₀ = 453 ± 86 μg/ml).
The researchers concluded that both effects — inhibition of tumor cell growth and recovery of immune functions — are important for the antitumor properties of Crinum latifolium.
Evidence strength: The immunomodulatory evidence is derived from well-characterized in vitro/ex vivo experiments using human PBMCs, published in peer-reviewed journals (Scientia Pharmaceutica, 2011; International Immunopharmacology, 2001). These findings are mechanistically coherent but do not constitute clinical evidence in intact human subjects.
5.4 Antioxidant Activity
The antioxidant capacity of Crinum latifolium extracted in water was evaluated using the ORAC assay, which measures the direct capacity of chain-breaking antioxidants based on the hydrogen atom transfer mechanism. The ORAC value of 1610 ± 150 μmol Trolox equivalents/g places the aqueous leaf extract among the higher-ranking traditional medicinal herb extracts evaluated with this assay.
All isolates from the bulbs were in vitro evaluated for their cytotoxic activity against seven lung cancer cell lines, in addition to antimicrobial activity for eight bacteria, scavenging potential using ABTS·⁺ and DPPH tests, and anti-inflammatory activity for COX-1 and COX-2.
Evidence strength: Antioxidant data are in vitro only. Numerous assays (DPPH, ABTS, ORAC, hydrogen peroxide) have been applied; results are consistent across studies. No controlled human trials on antioxidant endpoints have been published.
5.5 Anti-inflammatory Activity
C. latifolium exhibits various pharmacological effects including anti-inflammatory, anti-diarrhoeal, hypoglycemic, antioxidant, hepatoprotective, antipyretic, and antimicrobial activities.
At the cellular level, plants rich in lycorine, an alkaloid, have shown promise as analgesics; however, the exploration of their CNS side effects and analgesic effectiveness remains incomplete. In a mouse study, lycorine at 3, 10, and 30 mg/kg (intraperitoneal) did not affect motor coordination, and doses of 3 and 10 mg/kg did not lead to any impairment in spontaneous locomotor activity. However, the highest dose (30 mg/kg) demonstrated a significant impairment in rearing behavior and an increase in immobility.
Evidence strength: Anti-inflammatory activity is supported by in vitro and animal studies. Human clinical trial data for inflammatory conditions specifically attributable to Crinum latifolium are absent from the indexed peer-reviewed literature.
5.6 Antidiabetic Activity
Ethanol and aqueous extracts of Crinum latifolium Linn.'s leaves have demonstrated considerable anti-diabetic potential in preclinical models. An in vitro antioxidant and antidiabetic activity study was conducted on the ethanolic extract of Crinum latifolium leaves. Phytochemicals of the extract were analysed by qualitative methods. In vitro antioxidant and antidiabetic studies were done by hydrogen peroxide (H₂O₂) assay and glucose uptake in yeast cells method, respectively. The results for the glucose uptake in yeast cells method showed significant uptake of glucose across the plasma membrane of yeast cells at concentrations of 0.2 to 1.2 mg/ml at 5 mM glucose concentration.
Evidence strength: Limited to in vitro methods (enzyme inhibition assays, yeast cell models). No animal or human intervention studies on blood glucose outcomes have been indexed for C. latifolium specifically.
5.7 Anticancer / Cytotoxic Properties
Scientific evidence for an antitumor effect of Crinum latifolium constituents emerged from an aqueous extract of Crinum latifolium leaves, which was found to retard growth of chemically induced 20-methylcholanthrene tumors in rats.
Aqueous extracts from C. latifolium leaves in Vietnam showed in vitro and in vivo T-lymphocyte activation and retarded growth of chemically induced tumors (sarcomas) in rats. The alkaloids isolated from C. latifolium are known to possess antitumor and immune-stimulating activities.
Several phytochemical and biological studies on this species have been conducted, and pharmacological studies have revealed its promising anti-inflammatory, antioxidant, and anticancer properties using different in vitro and in vivo models.
Evidence strength: Evidence is grounded in in vitro cell-line studies (PC3, LNCaP, BPH-1, B16F10, HCT116) and limited animal studies. No published RCTs or phase II/III human oncology trials for C. latifolium as a standalone anticancer agent appear in the indexed peer-reviewed literature. The Vietnamese regulatory approval for BPH is for a benign condition; extrapolation to malignant cancer requires clinical validation.
5.8 Antimicrobial and Antifungal Activity
Extracts of Crinum species are reported to exert antitumor, immunostimulating, analgesic, antiviral, antibacterial, and antifungal effects, which have been mainly attributed to the more than 150 alkaloids of the Amaryllidaceae type present in Crinum species. Extracts of C. latifolium have been shown to exhibit anti-oxidative, anti-inflammatory, anti-microbial, cytotoxic, anti-diabetic, anthelmintic, analgesic, and anti-cholinesterase activities across a range of published studies.
Evidence strength: Antimicrobial data are in vitro only. No human clinical trials for infectious disease indications have been published.
5.9 Cholinesterase Inhibition and Neurological Interest
Galanthamine, a drug from the Amaryllidaceae family, is clinically relevant in treating the neurocognitive disorder Alzheimer's disease, which underscores the importance of Amaryllidaceae alkaloids. The fact that C. latifolium contains cholinesterase inhibitors surpassing galanthamine in isolated assays is of pharmacological interest, but no clinical investigation of Crinum latifolium in dementia or cognitive decline has been published.
6. Body Systems and Health Areas of Association
- Male urogenital system: BPH symptom management; antiproliferative effects on prostate stromal and carcinoma cells.
- Female reproductive system: Uterine fibroids, ovarian cysts, dysmenorrhea — primary areas of traditional use and the subject of the 2007 Vietnamese clinical study.
- Immune system: Modulation of PBMC activation via IDO inhibition and neopterin suppression; T-lymphocyte stimulation reported in earlier studies.
- Musculoskeletal system: Traditional use in rheumatism; analgesic properties supported in animal models.
- Metabolic/endocrine: Preliminary antidiabetic signals from in vitro enzyme inhibition assays.
- Neurological: Cholinesterase inhibitory alkaloids present; not yet clinically studied in neurological conditions.
- Dermatological/wound care: Traditional use for whitlow, abscesses, and wound healing (bulb poultices).
7. Dosage Forms and Dosages Reported in Studies
The following dosage information is derived directly from published research or regulatory sources; it is not prescriptive.
Standardized capsules (CriLa® / Crila®): The CriLa® capsule contains 250 mg of dry leaf extract, standardized to 70 μg crinamidine per capsule. Total alkaloids, calculated with reference to lycorine, were measured at 1.25 ± 0.13 mg total alkaloids per capsule.
BPH dosing (per product information based on Vietnamese regulatory data): For treatment of benign prostatic hyperplasia: 4 capsules, two times daily, after meals. The usual course is 8 weeks.
Uterine fibroid dosing (per product information based on Vietnamese regulatory data): For treatment of fibroid uterus: 5 capsules, two times daily, after meals. The usual course is 9 weeks, with a further course possible if necessary.
Extract concentration in laboratory studies: The extract used in the PMC 2011 laboratory study was standardized to contain 0.3 μg crinamidine/mg of dry extract.
Alkaloid content in leaf extract: The C. latifolium leaf extract in the 2022 Chulalongkorn University study contained 0.279 ± 0.003% lycorine and 0.232 ± 0.004% 6α-hydroxybuphanidrine.
8. Safety Considerations
Acute Toxicology
Acute toxicology studies in mice have shown that with levels that were 20, 30, 80, and 100 times the usual human doses — up to 25 g/kg per day of dried extract of C. latifolium — toxicity was not detected at 48 hours. The LD₅₀ was reported as 49.7 g/kg. The findings of low toxicity were confirmed in rats, rabbits, and dogs, and in physiological models.
Reported Adverse Effects
Reported undesirable effects include slight dizziness and indigestion, which may occur but are described as rare cases that resolve within one to two days of taking the medicine. With the prevalent use of standardized Crila® internationally, there have been no reported adverse events requiring medical care.
Lycorine-Specific Considerations
Because lycorine is a principal active alkaloid of C. latifolium, its individual safety profile is relevant. In a mouse study, lycorine at 3, 10, and 30 mg/kg (intraperitoneal) did not affect motor coordination, and doses of 3 and 10 mg/kg did not lead to any impairment in spontaneous locomotor activity; however, the highest dose (30 mg/kg) demonstrated a significant impairment in rearing behavior and an increase in immobility. These animal-derived CNS findings are not directly extrapolable to typical oral supplement doses in humans.
Traditional Toxicity Classification
According to traditional Vietnamese medicine, Crinum latifolium L. is described as pungent, cool, and little toxic. This characterization aligns with the low acute toxicity figures derived from experimental animal studies.
Estrogenicity
Crila showed no estrogenic or antiestrogenic activity when evaluated using Ishikawa cell-based assays, indicating that this botanical is probably not estrogenic in vivo. This finding is important because the plant's primary historical use in women's reproductive conditions raised the question of hormonal activity.
Evidence Gaps
Although Amaryllidaceae provide a plethora of biologically active compounds, there is tardiness in their development into clinically pliable medicines. Long-term safety data in humans, drug interaction studies, and safety data for specific populations such as pregnant women, children, and immunocompromised individuals are not available in the peer-reviewed literature. Data on toxicity and clinical efficacy remain sparse across the broader genus, and this applies equally to C. latifolium.
References
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