Selaginella

Other Names

African clubmossBryodesmaChinese resurrection plantclub spike mosscushion spikemossdinosaur plantDiplostachyumDiplostachyum apodumdoradillaEuselaginellafalse rose of Jerichofern alliesfern allyflower of stonegemmiferous spikemossgolden clubmossJuan baiJuàn bǎiKrauss's spike mosslesser club mosslesser clubmosslittle-club-mosslycophyteLycopodioidesLycopodioides apodumLycopodioides tamariscinaLycopodioides uncinatumLycopodium apodumLycopodium caulescensLycopodium imbricatumLycopodium involvensLycopodium lepidophyllumLycopodium selaginoidesLycopodium tamariscinumMrithasanjeevaniPalillopeacock mossPolycoccaPolypodium tamariscinumrainbow mossresurrection fernresurrection mossresurrection plantrock selaginellarose of JerichoSandhanakaraniSanjeevaniSanjeevani bootiSanjeeviniSanjivini bootiSapo maguiSavarnyakaraniSelaginella apusSelaginella caulescensSelaginella imbricataSelaginella involvensSelaginella japonicaSelaginella spinosaSelaginella tamariscina var. pulvinataSelaginella veitchiiSelaginellaceaeSelaginoidesSelagoShi Shang Baisiempre vivaspike mossspikemossspreading club mossStachygynandrumStachygynandrum tamariscinumstarry spike-mossstarry spikemossstone flowertamariskoid spikemossVishalyakarini卷柏石上柏

Synopsis

Selaginella: A Comprehensive Reference Article

1. Identity and Botanical Classification

Taxonomic Classification

Selaginella, also known as spikemosses or lesser clubmosses, is a genus of lycophyte. It is usually treated as the only genus in the family Selaginellaceae, with over 750 known species. The plant family Selaginellaceae includes only one genus, Selaginella, which corresponds to a group of early vascular plants with an important place in evolutionary history. They belong to the Lycopodiophyta division, which is the oldest lineage of vascular plants on Earth. There are more than 700 Selaginella species distributed worldwide in a diverse range of habitats, from deserts to tropical rain forests and mountainous regions.

These primitive vascular plants, commonly known as spikemosses or lesser clubmosses, are characterized by branched stems that are either prostrate and creeping or erect and ascending, bearing tiny, scale-like microphylls arranged in four longitudinal rows. Each leaf features a distinctive ligule — a small, tongue-like outgrowth at its base — and many species produce rhizophores, specialized, leafless structures that bear roots. Selaginella species are heterosporous, producing two types of spores — smaller microspores and larger megaspores — within compact, spike-like strobili at the tips of branches, marking an evolutionary advancement toward the seed habit seen in higher plants.

The Lycopodiophyta lineage has been evolving independently of other vascular plants for over 400 million years, and in that time have evolved several convergent features like leaves, wood, trees and seed-like structures, making them extremely important in the understanding of plant evolution.

Medicinal Species of Primary Interest

The genus contains numerous species with recorded medicinal relevance, but the most extensively studied include:

Selaginella tamariscina (P.Beauv.) Spring — the most widely researched species, native to rocky mountain habitats in East and Southeast Asia, and a central ingredient in Traditional Chinese Medicine (TCM).
Selaginella doederleinii Hieron. — a perennial herb found in South and Southwest China, extensively investigated for anticancer properties.
Selaginella lepidophylla (Hook. & Grev.) Spring — the "resurrection plant" or "Rose of Jericho," native to the Chihuahuan Desert, traditionally used in Mexican and Mesoamerican folk medicine.
Selaginella uncinata (Desv.) Spring — a folk herbal medicine used in South China, also known as "peacock moss" or Cuiyuncao.
Selaginella bryopteris (L.) Baker — known as "Sanjeevani" in Indian traditions, with uses documented in South Asian ethnobotany.
Selaginella moellendorffii Hieron. — an important model organism whose genome has been fully sequenced.
Selaginella labordei Hieron. ex Christ — traditionally used in Chinese medicine as an antiviral agent, including in chronic hepatitis.

The Selaginella plant belongs to the family Selaginellaceae in the major group Pteridophytes, and is a rare single-family single-genus plant in the plant kingdom.

Common Names and Synonyms

Common names for Selaginella lepidophylla include flower of stone, false rose of Jericho, rose of Jericho, resurrection plant, resurrection moss, dinosaur plant, siempre viva, stone flower, and doradilla. In Chinese traditional medicine, S. tamariscina is variously referred to as Juan Bai (卷柏), meaning "curled cypress," in reference to its habit of curling tightly when desiccated. S. uncinata is called Cuiyuncao, Lvrongcao, and Landibo in China.

Morphology and Common Preparations

S. tamariscina is an evergreen perennial plant native to mountain rock walls and belongs to the order Selaginellales, the family Selaginellaceae, and the genus Selaginella. They reach a height of approximately 20 cm. They have spores that are egg-shaped triangles with serrated edges and four rows of scaly leaves.

Preparations encountered in research and traditional practice include:

Decoctions (water extracts) — the whole plant boiled in water, the most traditional preparation across Asian and Mesoamerican cultures.
Ethanol/ethyl acetate extracts — the forms most commonly used in laboratory and pharmacological studies.
Dried powder — used in some TCM formulations and as a nutritional ingredient.
Carbonized form (S. tamariscina carbonisatus) — a specific carbonized extract has shown hemostatic effects, whereas standard extract can promote blood circulation.
Tablets — in clinical application, S. doederleinii is commonly used in several famous antitumor prescriptions (such as TCM Yiqi Yangyin for treatment of lung cancer), or has been prepared into tablets (mainly consisting of SD alcohol extract) for the treatment of digestive tract cancer, nasopharynx cancer, and lung cancer.
Cosmetic preparations — Jericine is a commercially available aqueous extract from S. lepidophylla recommended for anti-aging and regenerative moisturizing creams.
Infusion/tea — S. lepidophylla has been used as a herbal medicine. An infusion is made by steeping a tablespoon of dried material in hot water, and the resulting tea is used to treat colds and sore throat. In Mexico, S. lepidophylla is sold as a diuretic.

2. Traditional and Historical Use

Traditional Chinese Medicine

Selaginella tamariscina has been used for centuries as a Traditional Chinese Medicine to treat various human diseases, including inflammation, human cancer, and hyperglycemia. In oriental medicine, it has been used for the treatment of dysmenorrhea, chronic hepatitis, hyperglycemia, amenorrhea, hematuria, prolapse of the anus, and metrorrhagia.

S. tamariscina is used in folk medicine to treat the side effects of mental instability, tumor prevention and healing, renal function enhancement, stones, asthma, bronchial disease, and radiation therapy. It is also used to treat bleeding and maintain hemostasis.

The whole plants of S. uncinata are a popular ethnic medicine and folk herb in south China. It has been used medicinally for at least 400 years for the treatment of jaundice, diarrhea, edema, gonorrhea, bones and muscles ache, hematemesis, hemoptysis, hematochezia, trauma bleeding, hemorrhoids, burns and snake bites. It is mainly used in Chinese traditional medicine, especially as the most-used folk herbal medicine by China's ethnic minorities.

As a commonly used medicine among ethnic minorities, S. uncinata has been widely used in clearing heat and dampness, eliminating blood stasis, detoxifying, and stopping bleeding, but it mostly remains at the level of folk experience medication.

The Selaginella plants are generally used by tribal communities to cure fever, jaundice, hepatic disorders, cirrhosis, diarrhea, cholecystitis, sore throat, cough of the lungs, promote blood circulation, remove blood stasis, and stop external bleeding after trauma and after separation of the umbilical cord.

South and Southeast Asia

S. bryopteris is also very popular as "Sanjeevani" and is used in various therapeutic medicines. Traditionally, the plant is used in jaundice treatment, in easy delivery of women and restoring menstrual regularities, and in relief from heat stroke and burning sensation during urination.

In Java and the Indonesian Archipelago, approximately 200 of the 700–750 world species of Selaginella are found. Field research and literature reviews indicate that Selaginella is used traditionally to heal wounds, bloody stools, internal hemorrhoid bleeding, menstrual and uterine disorder, blood expediting, enhancing body endurance and longevity, headache, etc.

Mesoamerica and Mexico

Selaginella lepidophylla is found in the Middle East and Mexico. The species is popularly known as "resurrection plant," "rose of Jericho," siempre viva, flor de piedra, doradilla, "flower of rock," "stone flower," or magóra (Tarahumara) and grows particularly in well-drained soils.

The plant's ability to survive extreme desiccation was noted by Spanish missionaries when they reached the New World. The missionaries used S. lepidophylla to demonstrate to potential native converts the concept of being reborn. Because of its properties, the false rose of Jericho was considered a lucky charm, and was passed on in families from generation to generation.

Summary of Traditional Applications Across Cultures

Bleeding and hemostasis: Used across TCM, Indonesian, and Indian traditions to stop bleeding, treat hematuria, and menorrhagia.
Menstrual and reproductive disorders: Used to regulate menstruation, treat amenorrhea, and facilitate childbirth.
Inflammation and infections: Applied for hepatitis, jaundice, sore throat, cholecystitis, and pyrexia.
Cancer (historical TCM use): S. doederleinii in particular has a longstanding folk reputation as an anticancer plant in southern China.
Metabolic disorders: Used for diabetes (hyperglycemia) in Chinese medicine traditions.
Wound healing: Applied as a poultice or decoction externally in multiple traditions.
Tonics and longevity: Incorporated in Indonesian jamu formulations for endurance and longevity.

3. Key Constituents and Active Compounds

Biflavonoids (Primary Active Class)

Biflavonoids, such as amentoflavone, sumaflavone, robustaflavone, ginkgetin, hinokiflavone, and isocryptomerin, are the most important valuable natural products of Selaginella and show various pharmacological activities including antioxidant, anti-inflammatory, and antitumor effects.

Investigation of the phytochemical constituents of S. tamariscina revealed it to be an abundant source of biflavonoids (e.g., amentoflavone, hinokiflavone, isocryptomerin, sumaflavone, and robustaflavone). The biflavonoids isolated from S. tamariscina are known to display a variety of biological activities involving anti-inflammatory, anti-allergic, antitumor, antioxidant, antidiabetic, antiviral, and anticancer activities, and osteogenesis.

Amentoflavone is considered the principal bioactive compound across most medicinally relevant species. S. tamariscina contains flavones, phenols, polysaccharides such as amino acids and trehalose, and small amounts of tannins, such as apigenin, amentoflavone, hinokiflavone, and isocryptomerin.

Delicaflavone, a biflavonoid specific to S. doederleinii, has received particular attention. Delicaflavone was proved to induce apoptosis in cervical cancer HeLa cells, colorectal cancer cells, and lung cancer cells.

Selaginellins (Class-Specific Pigments)

A group of unique compounds named selaginellins, which possess a p-quinone methide and alkynylphenol functional groups, have also been identified from various species of Selaginella. Selaginellins are predominantly colored compounds; the first selaginellin was isolated as a racemic mixture from Selaginella sinensis.

Several biflavonoids (chiefly amentoflavone) and phenolic compounds (selaginellin derivatives) are primarily responsible for the observed pharmacological properties. Potent inhibitors of protein tyrosine phosphatase 1B (PTP1B), phosphodiesterase-4 (PDE4), and repressors of pro-inflammatory cytokines expression have been identified from S. tamariscina extract (STE).

Other Phytochemical Classes

The genus has a large number of bioactive compounds, which include alkaloids, phenols, sterols, aliphatic acids, and terpenoids. These plants contain numerous bioactive natural products, including flavonoids, (neo)lignans, phenols, and alkaloids.

Various Selaginella species have been reported to contain high content of different phytochemicals, such as flavonoids, phenylpropanoids, steroids, pigments, oxygen heterocycle, lignans, coumarins, quinoids, chromones, benzenoids, carbohydrates, and alkaloids.

Antioxidant capacity was presumed to be correlated with the content of flavonoids, (neo)lignans, and selaginellins.

In S. lepidophylla, desiccation-protective primary metabolites include trehalose and betaines. The trehalose produced by the plant acts in place of evaporating water, preventing salts from causing damage and protecting against death due to an excess of salinity. S. lepidophylla also uses betaines, substances which have the same function as trehalose. Once water is restored to the plant tissues, the sugar crystals dissolve and the plant's metabolism, until then paralyzed, reactivates.

Key Compound: Amentoflavone — Mechanisms of Action

Amentoflavone is the most comprehensively characterized compound in the genus. Established in vitro and in vivo mechanisms include:

Anticancer: The effects of extracts on cell proliferation and apoptosis in different cells were apparent on HeLa cells. DNA laddering analysis and caspase-3 expression confirmed that inducing cell apoptosis was one of antitumor mechanisms and antitumor activities of Selaginella species were related to apoptosis induced by caspase family.
Anti-metastatic: Inhibition of epithelial-mesenchymal transition (EMT) was confirmed by increased levels of E-cadherin and downregulation of downstream Snail and Twist transcription. In vivo, metastasis development in nude mice injected with A549-luc cells and co-treated with TGF-β and amentoflavone showed decreased lung metastatic nodule formation.
Antidiabetic: The determination of protein expression of peroxisome proliferator activated receptor γ (PPAR-γ) in adipose tissue and insulin receptor substrate 1 (IRS-1) in hepatic and skeletal muscle tissues was used to study the mechanism of total flavonoids of S. tamariscina.
Antioxidant: Total flavonoids of S. tamariscina mitigate oxidative stress through activation of the heme oxygenase-1 (HO-1) signaling pathway mediated by nuclear factor erythroid 2-related factor 2 (Nrf2).
Anti-inflammatory: Amentoflavone and sumaflavone isolated from S. tamariscina have demonstrated anti-inflammatory activities.
Autophagic cell death (cancer): The total bioflavonoid extract of S. doederleinii, especially delicaflavone, can induce ROS-mediated apoptosis via caspase-dependent pathway accompanying cell cycle arrest and inhibition of MAPK signaling cascades. In addition, delicaflavone can induce autophagy cell death by inhibiting the Akt/mTOR/p70S6K signaling pathway.

4. Scientific Evidence by Area of Use

The overwhelming majority of research on Selaginella is preclinical — consisting of in vitro cell-culture studies and in vivo rodent models. As of the time of writing, there are no published large-scale, randomized, controlled clinical trials (RCTs) in humans for any Selaginella species used as a standalone supplement. This limitation must be stated prominently: all evidence summaries below describe preclinical findings only unless otherwise explicitly noted.

4.1 Anticancer and Antiproliferative Activity

In vitro evidence (cell lines):

HPLC analysis revealed two major common peaks identified as amentoflavone and robustaflavone. S. labordei, S. tamariscina, and S. uncinata had relatively stronger activities on Bel-7402 and HeLa cells, and S. moellendorffii had moderate antiproliferation activities, but S. remotifolia and S. pulvinata had almost no inhibitory activities. The main active components were in the ethyl acetate extracts which had abundant biflavonoids.

Compounds from S. doederleinii were evaluated for antiproliferative activities by the MTT assay on three human cancer cell lines: colon cancer (HT-29), cervical cancer (HeLa), and lung cancer (A549). Compound 7 exhibited the best activity on the three cancer cell lines by inhibiting the rate of growth of the cancer cells in a dose-dependent manner with IC50 values of 27.97, 35.47, and 20.71 µM, respectively.

Biflavonoids isolated from S. doederleinii significantly inhibited the proliferation of non-small cell lung cancer (NSCLC) cells (IC50 = 2.3–8.4 μM) with low toxicity to non-cancer MRC-5 cells. The most active compound suppressed XIAP and survivin expression, promoted upregulation of caspase-3/cleaved-caspase-3, and induced cell apoptosis and cycle arrest in A549 cells.

The mechanisms of tumorigenesis and cell apoptosis induced by S. doederleinii extracts may be associated with decreasing the ratio of bcl-2 and bax mRNA level, activating caspase-3, suppressing survivin, and decreasing the gene expression of COX-2, 5-LOX, FLAP, and 12-LOX mRNA. The main active component in S. doederleinii extracts is biflavonoids, and some exhibited strong interactions with COX-2, 5-LOX, 12-LOX, and 15-LOX. These results offer evidence of possible mechanisms by which SD extracts suppress cell proliferation and promote apoptosis.

Selaginella tamariscina has been identified as a potential chemopreventive agent against various human cancer cell lines, such as gastric cancer, lung cancer, breast cancer, and cervical cancer.

In vivo (animal) evidence:

Selaginella tamariscina extract and amentoflavone were tested for synergistic anti-tumor effects combined with doxorubicin hydrochloride in a nude mouse xenograft model of A549 human lung cancer cells. In the experiment, S. tamariscina extract and amentoflavone were administered orally, and doxorubicin hydrochloride was injected intraperitoneally. There was no statistical difference between the single treatment of doxorubicin and the combinatorial treatment of these phytochemicals and doxorubicin.

Traditional clinical application (observational, not RCT):

In clinical application in China, S. doederleinii is commonly used in several antitumor prescriptions (such as TCM Yiqi Yangyin for treatment of lung cancer), or has been prepared into tablets (mainly consisting of SD alcohol extract) for the treatment of digestive tract cancer, nasopharynx cancer, and lung cancer. This represents observational clinical use, not controlled trial evidence.

Evidence strength: Preliminary. Evidence is predominantly from in vitro cell-culture models and rodent xenograft studies. No RCTs have been published. The documented clinical use in Chinese medicine provides context but not controlled efficacy evidence.

4.2 Anti-Inflammatory Activity

S. tamariscina pharmacological studies have reported its anti-inflammatory, antibacterial, anti-hypertensive, and anti-hyperglycemic activities.

In a published in vitro study (PMC, 2018), HO-1 induction by S. tamariscina extract was shown to inhibit inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages — a standard preclinical model for acute inflammation. Crude extracts from Selaginella tamariscina have inhibited human mesangial cell proliferation, and have decreased interleukin-1beta and tumor necrosis factor-alpha production.

Total flavonoids of S. tamariscina mitigate oxidative stress through the activation of the heme oxygenase-1 (HO-1) signaling pathway mediated by nuclear factor erythroid 2-related factor 2 (Nrf2), thereby ameliorating acute lung injury induced by diabetes in murine models.

Evidence strength: Preliminary. All anti-inflammatory evidence is from cell culture or animal studies. No human clinical trials have been published.

4.3 Antidiabetic Activity

To evaluate the anti-diabetic effects of the total flavonoids of S. tamariscina (TFST), high fat diet and STZ (35 mg/kg) induced diabetic rats were administered with TFST at graded oral doses (100, 200, and 400 mg/kg/day) for 8 weeks. A range of parameters including blood glucose and lipid, serum insulin and glucagon, glucose tolerance were tested. The protein expression of PPAR-γ in adipose tissue and insulin receptor substrate 1 (IRS-1) in hepatic and skeletal muscle tissues was used to study the mechanism.

TFST possessed anti-diabetic activities as shown by decreased serum levels of fasting blood glucose (FBG), glycosylated hemoglobin A1C (HbA1c), triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA).

Biflavonoids from S. doederleinii are naturally occurring dimers that have demonstrated good antioxidant, hypoglycemic, antitumor, and anti-inflammatory pharmacological effects.

There are robust experimental data, based on in vitro and in vivo models, documenting the use of S. tamariscina extract to treat type 2 diabetes, several inflammatory diseases, and some cancers (in combination with standard chemotherapy). However, it must be emphasized these data come from animal models, not clinical trials.

Evidence strength: Preliminary to moderate (preclinical). The antidiabetic activity is one of the more consistently demonstrated effects across multiple independent animal studies, but no human trials exist.

4.4 Antioxidant Activity

All tested species demonstrated antioxidant activity using the oxygen radical absorption capacity (ORAC) assay, which showed that MeOH extracts had higher antioxidant capacity, with the EC50 ranging from 12 ± 1 (S. myosuroides) to 124 ± 2 (S. cupressina) mg/L.

S. tamariscina powder contains a total phenolic content of 8.65–11.61 mg gallic acid equivalents/g. S. tamariscina showed antioxidant activity in ABTS and DPPH radical scavenging assays.

Amentoflavone has a DPPH radical scavenging IC50 of 5.73 ± 0.08 µg/mL, as reported by Frota et al.

Evidence strength: Consistent across multiple in vitro assays and species, but in vitro antioxidant capacity does not directly translate to clinical benefit in humans.

4.5 Antimicrobial Activity

S. repanda, which is a rich source of potent natural bioactive compounds, showed promising antibacterial activity against tested pathogenic bacteria (S. aureus, P. aeruginosa, E. coli, and S. flexneri). The crude extract displayed favorable antioxidant activity against DPPH (IC50 = 231.6 μg/mL) and H2O2 (IC50 = 288.3 μg/mL).

The inhibition of Helicobacter pylori, a human pathogen associated with gastric cancer, by methanolic extracts obtained from dried S. lepidophylla plants indicates the potential of this species in medicine.

Ethanol extract of S. tamariscina demonstrated antimicrobial activity against Bacillus subtilis KCTC 2189.

Evidence strength: Preliminary. All antimicrobial data are from in vitro assays. No clinical evidence exists.

4.6 Hemostasis

A specific carbonized extract (S. tamariscina carbonisatus) has shown hemostatic effects, whereas standard STE can promote blood circulation. This differential effect based on preparation method is noteworthy from a traditional pharmacology perspective and is consistent with classical TCM doctrine that holds that carbonized herbs act differently from raw preparations. No controlled human trials have been conducted to evaluate this effect.

Evidence strength: Preclinical and historical/observational. The hemostatic use is one of the oldest documented applications but lacks controlled human evidence.

4.7 Longevity and Anti-Aging (Model Organism Research)

A study collected 23 Selaginella samples from 13 different provinces across China to assess their geographical influence. Two representative methanol extracts, S4 (high in amentoflavone) and S16 (low in amentoflavone), were selected for in-depth evaluation using the Caenorhabditis elegans model. Lifespan assays, stress resistance tests, and comparative transcriptomics were employed to analyze the effects on longevity and pathway modulation.

S. rossii has been shown to confer protection against skin aging and UVB-induced wrinkling via its antioxidant activity.

Evidence strength: Very preliminary. Longevity studies are restricted to invertebrate models (C. elegans) and in vitro systems. No human data exist.

4.8 Antigout Properties

Antidiabetic and antigout properties of the ultrasound-assisted extraction of total biflavonoids from Selaginella doederleinii were revealed by in vitro and in silico studies (published 2024). The relevant mechanisms involve inhibition of xanthine oxidase (the enzyme targeted by the standard gout drug allopurinol), but this evidence remains at the preclinical stage.

Evidence strength: Very preliminary. In vitro and computational only.

5. Body Systems and Health Areas Associated with Selaginella

Oncology / Cell Biology: Antiproliferative and pro-apoptotic effects across multiple cancer cell lines (lung, colon, cervical, breast, liver, nasopharyngeal). Modern pharmacological investigations confirmed that the antitumor activity of S. doederleinii extract could effectively inhibit the proliferation of human breast cancer MCF-7 cells, human lung cancer A549 cells, and human nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro.
Endocrine / Metabolic: Antidiabetic activity through PPAR-γ and IRS-1 pathways; effects on blood glucose, HbA1c, and lipid parameters in animal models.
Cardiovascular: S. doederleinii has been traditionally used in folk medicine to treat inflammation, cardiovascular disease, and malignant tumors.
Immunological / Inflammatory: Inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in cell models; HO-1/Nrf2 pathway activation.
Hematological: Hemostatic effects (carbonized preparation); promotion of blood circulation (standard preparation) per TCM tradition.
Dermatological / Cosmetic: Plant extracts are used in cosmetics, as anti-inflammatory agents, and skin protectors.
Hepatic: Traditional use in hepatitis, jaundice, and liver disorders documented across Asian and Indonesian ethnomedicine.
Respiratory: Traditional use in asthma, bronchial disease, cough, and lung conditions in Chinese folk medicine.
Renal / Urinary: Diuretic use recorded in Mexican folk medicine; traditional use in renal calculi and disorders of urination.
Reproductive: Traditional applications in menstrual disorders, dysmenorrhea, amenorrhea, and metrorrhagia across multiple traditions.
Neurology (preliminary): Ginkgetin and amentoflavone inhibit ERK1/2 activation and/or preserve antioxidant enzyme activity, shielding HT22 neurons from glutamate-induced oxidative damage. Inhibition of acetylcholinesterase (AChE) was discerned in DCM extracts and exhibited in S. myosuroides, S. cupressina, S. biformis, and S. apoda extracts, with IC50 in the range of 19 ± 3 to 62 ± 1 mg/L.

6. Dosage Forms and Dosages Reported in Studies

The following dosages are reported from published preclinical research only. No standardized clinical dosages for human use have been established through controlled trials.

Animal antidiabetic model (S. tamariscina total flavonoids): High fat diet and STZ-induced diabetic rats were administered total flavonoids of S. tamariscina at graded oral doses of 100, 200, and 400 mg/kg/day for 8 weeks.
Animal anticancer xenograft model (S. tamariscina extract): S. tamariscina extract and amentoflavone were administered orally and doxorubicin hydrochloride was injected intraperitoneally in a nude mouse xenograft model. Published data indicate STE was used at 1,000 mg/kg in that model.
Pharmacokinetic study (S. doederleinii total bioflavonoid extract): Rats were administered a single dose of TBESD at 600 mg/kg intragastrically; tissue distribution and excretion were determined.
In vitro anticancer (biflavonoids, S. doederleinii): Biflavonoids significantly inhibited the proliferation of NSCLC cells with IC50 values of 2.3–8.4 μM.
In vitro antiproliferative, S. doederleinii compounds: IC50 values of 27.97, 35.47, and 20.71 µM against colon (HT-29), cervical (HeLa), and lung cancer (A549) cell lines, respectively.
Antioxidant (amentoflavone): DPPH radical scavenging IC50 of 5.73 ± 0.08 µg/mL.
Traditional infusion (S. lepidophylla): An infusion is made by steeping a tablespoon of dried material in hot water.
Tablet form (S. doederleinii in TCM): Tablets have been prepared mainly consisting of SD alcohol extract for use in digestive tract cancer, nasopharynx cancer, and lung cancer; specific tablet dosages have not been standardized in the published literature reviewed.

Pharmacokinetic studies on delicaflavone and total bioflavonoid extract from S. doederleinii have indicated that when administered as single oral (30–60 and 300–600 mg/kg, respectively) or intravenous (4 and 5–15 mg/kg, respectively) doses, amentoflavone, delicaflavone, robustaflavone, 2″,3″-dihydro-3′,3‴-biapigenin, and 3′,3‴-binaringenin have a short in vivo half-life and oral bioavailability below 3.5%. This very low oral bioavailability is a significant pharmacokinetic limitation that affects translation of in vitro findings to clinical use.

7. Safety Considerations and Interactions

Acute Toxicity Data

In the single-dose acute toxicity test, an oral administration of 10,000 mg/kg of S. tamariscina extract did not cause any lethality. The sub-acute toxicity study showed that treatment by 250, 1,000, and 3,000 mg/kg/day for 30 continuous days did not produce significant toxic effects. These are rodent data and cannot be directly extrapolated to human safety profiles.

Clinical Toxicology Data Gap

No relevant studies on acute and subacute toxicity of S. uncinata have been found by searching databases such as Web of Science, PubMed, Elsevier, and Wiley. However, there have been no cases of toxicity in the treatment of diseases in clinical practice.

Cytochrome P450 Enzyme Interactions — A Significant Safety Concern

This is the most thoroughly documented safety-relevant finding across Selaginella research and warrants particular attention for individuals taking prescription medications.

The ethyl acetate extract from S. doederleinii (SDEA) showed strong inhibitory effect on CYP2C9 and CYP2C8 (IC50 ≈ 1 μg/ml) and moderate inhibitory effect against CYP2C19, CYP2E1, and CYP3A (IC50 < 10 μg/ml).

CYP2C8, CYP2C9, and CYP2J2 metabolize approximately 4.7%, 12.8%, and 3% of clinically used drugs, respectively. UGT1A1 also metabolizes approximately 17.3% of drugs which have glucuronidation as a clearance mechanism. The inhibitory effect of selaginellins might be important for producing potential herb–drug interactions with drugs which undergo CYP2C8, CYP2C9, CYP2J2, and UGT1A1-mediated biotransformation; such drugs include glipizide, irinotecan, losartan, paclitaxel, tolbutamide, and warfarin.

To predict herb-drug interaction and lay the groundwork for further clinical trials, the inhibitory effect of SDEA and its four constituents (amentoflavone, palmatine, apigenin, delicaflavone) on seven CYP450 isoforms were investigated.

When people take herbal products and drugs at the same time, potential herb-drug interaction should be considered. In the past 20 years, more and more studies have shown that there are significant CYP450 enzyme interactions between herbal products and prescription medicines, which will increase patients' risk of unnecessary and unintended adverse effects.

Pharmacokinetic Considerations

The excretion of bioflavonoids from S. doederleinii occurred mostly via the intestinal tract and constituted 30% of the administered dose up to 48 hours. The finding that oral bioavailability of key biflavonoids is below 3.5% means that even at high doses, systemic exposure is inherently limited — a fact that complicates dose estimation and may explain discrepancies between in vitro activity and in vivo efficacy.

Absence of Adequate Human Safety Data

Crude extract and different bioactive compounds of Selaginella have revealed various in vitro bioactivities such as antimicrobial, antiviral, anti-diabetic, anti-mutagenic, anti-inflammatory, anti-nociceptive, anti-spasmodic, anticancer and anti-Alzheimer activity. However, more studies into the pharmacological activities are needed, since none of the professed bioactivity of this plant have ever been fully evaluated.

Despite documented therapeutic effects, a systematic evaluation of the lifespan-extending potential of Selaginella species and the underlying molecular mechanisms remains lacking. This gap highlights the need for comprehensive investigations.

Notable Interactions Summary

Warfarin and anticoagulants: CYP2C9 inhibition by Selaginella extracts may theoretically increase exposure to warfarin (a CYP2C9 substrate), potentially elevating bleeding risk. This is in vitro evidence only.
Paclitaxel and chemotherapy drugs: Drugs undergoing CYP2C8, CYP2C9, CYP2J2, and UGT1A1-mediated biotransformation — including irinotecan, paclitaxel, and tolbutamide — may be subject to altered plasma levels if co-administered with Selaginella extracts.
Antidiabetic medications: Glipizide and tolbutamide, which undergo CYP2C9 metabolism, may be affected. Additionally, the antidiabetic activity of Selaginella flavonoids could produce additive hypoglycemic effects when combined with insulin or oral antidiabetics.
Losartan: As a CYP2C9-metabolized antihypertensive, theoretical interaction with Selaginella extracts may alter drug pharmacokinetics.

All CYP450-related interaction data cited above derive from in vitro microsomal assays; clinical significance in humans has not been established, but the findings were published specifically as a preclinical warning and basis for future clinical trial design.

References

Health Conditions

Health conditions that Selaginella may help support.

No conditions available.

Body Systems

Body systems that Selaginella may help support.

No body systems available.