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Family Selaginellaceae
Pakong-tulog
Selaginella tamariscina (Beauv.) Spring.
RESURRECTION FERN
Juan Pai

Scientific Names Common Names
Lycopodioides tamariscina (P, Beauv.) H. S. Kung Kaim-kum (Ilk.) 
Lycopodium tamariscinum (P.Beauv.) Desv. ex Poir. Kayumkom (Tag,)
Selaginella tamariscina (Beauv.) Spring. Keoun Back (Korea) 
Selaginella veitchii W.R.McNab Pakaunkung (Ilk.)  
Stachygynandrum tamariscinum P.Beauv. Pakong-sipres (Tag.) 
  Pakong-tulog (Tag.)  
  Little club moss (Engl.)
  Resurrection fern (Engl.) 
  Spike moss (Engl.)
Pako and its variations is a local name shared by many medicinal plants: (1) Pako - Athyrium esculentum (2) Pakong-alagdan - Blechnum orientale (3) Pakong-anuanag, pako, buhok-virgin, dila-dila - Onychium siliculosum (4) Pakong-gubat, pakong kalabao, Pityrogramma calomelanos (5) Pakong-parang - Pteris ensiformis (6) Pakong-roman - Ceratopteris thalictroides. (7) Pakong-tulog, pakong-cipres, Selaginella tamariscina (8) Pakong buwaya - Cyathea contaminans.
Selaginella tamariscina (P.Beauv.) Spring is an accepted name. KEW: Plants of the World Online

Other vernacular names
CHINESE: Wan nian qing, Juan bai, Chuan Pai.
JAPANESE: Iwa hiba, Iwa matsu.
KOREAN: Keoun back.
THAI: Dok hin.
VIETNAMEE: Mong lung rong.


Gen info
- The plant family Selaginellaceae has only one genus, Selaginella.  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. (40)

Botany
Pakong-tulog is an evergreen, perennial fern with densely tufted stems, 4 to 15 centimeters long, branched nearly to the base. Leaves of the lower plane are crowded, ovate, with a distinct cusp, bright green, rigid, serrulate on both margins. Leaves of the upper plane are nearly as long, ovate lanceolate, cuspidate. Sporophylls are keeled.

Distribution
• Native to the Philippines.
• Reported in Cagayan, Ilocos Norte, Bontoc, Zambales, Pampanga, Rizal, Batangas, and Laguna, Quezon.
• Also native to Amur, China, Hainan, Inner Mongolia, Japan, Jawa, Khabarovsk, Korea, Lesser Sunda Is., Manchuria, Nansei-shoto, Ogasawara-shoto, Primorye, Qinghai, Sulawesi, Taiwan, Thailand, Vietnam.
• The whole plant may be collected throughout the year. Wash thoroughly, cut off the roots and sun-dry. This may also be processed into charcoal form by heating it with small glow until it turns black, sprinkle with some clean water and re-dry under the sun. Rhizome or the trunk-like portion of the main axis used for propagation. Preferably transplant collected living plants.

Constituents
Study yielded flavonoids as main compounds, including amentoflavone, hinokiflavone, sotetsuflavone and apogenin.
Study isolated four compounds from the n-BuOH fraction of water extracts: 1-hydroxy-2-[2-hydroxy-3-methoxy-5-(1-hydroxyethyl)-phenyl]-3-(4-hydroxy-3,5-dimethoxy)-propane-1-O-beta-D-glucopyranoside (tamariscinoside B) (1), adenosine (2), guanosine (3) and arbutin (4). (8)
Study isolated five compounds elucidated as: carnaubic acid, Selaginellin, 5,7,4',5'',7'',4'''-hexahydroxy-3',8''-Biflavone, β-D-fructofuranose-(2-1)-α-D-Glucopyr-anoside, α-D-mannopyranose-(1-1)-α-D-Mannopyranoside.

Study isolated a new selaginellin named selaginellin O (1), along with three other known selaginellins (2-4). (see study below) (16)
• Study on amentoflavone content yielded 11.46 mg/g. (30)
• Study for cytotoxic constituents yielded three selaginellins and seven biflavones from the whole plant: selaginellin (1), selaginellin A (2), selaginellin B (3), amentoflavone (4), sequoiaflavone (5), bilobetin (6), ginkgetin (7), isoginkgetin (8), hinokiflavone (9), and isocryptomerin (10). (see study below) (31)
• Study isolated two new selaginellin derivatives, selaginellins K (1) and L (2) and characterized as 2-formyl-4,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene and 4,4'-dihydroxy-2-methyl-3[(4-hydroxyphenyl)ethynyl]biphene. (41)
• Study isolated two new compounds, selaginellins I (1) and J (2) and characterized as (R,S)-4-((2'4'-dihydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene) cyclohexa-2,5-dione (1) and (R,S)-4-((3-((3,4-dihydroxyphenyl)ethynyl)-4'-hydroxy-4-(hydroxymethyl)
biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2-5-dione (2). (42)
• Study isolated a new diarylbenzophenone, selagibenzophenone C (1), along with 1,3-di-p-hydroxyphenyl-4-penten-1-one (2) and unciflavone E (3). (47)
• Study isolated two new unusual natural pigments from the whole herbs of Selaginella tamariscina, selaginellin A and B, along with four known biflavonoids, amentoflavone (3), hinokiflavone (4), heveaflavone (5) and 7"-O-methylamentoflavone (6). (48)
• Study isolated three new sterols, 3ß,16α-dihydroxy-5α,17ß-cholestan-21-carboxylic acid (1), 3ß-(3-hydroxybutyroxy)-16α-hydroxy-5α,17ß-cholestan-21-carboxylic acid (2) and 3ß-(3-hydroxybutyroxy)-16α-hydroxy-5α,17ß-cholestan-21-carboxylic acid (3).  (see study below) (50)

Properties
• When dry, the fronds, particularly the young one, contract or roll up like the claws of a bird or like a miniature Cypress tree. Yellowish-brown, when moistened they spread out again and become green.
• The plant never dies, hence the name Resurrection Fern, and considered life-prolonging.
• Considered astringent and hemostatic.

Uses
Nutrition
- Edible: leaves; young shoots (cooked).
Folkloric
- Decoction use for the treatment of traumatic bleeding, hemoptysis, gastrointestinal bleeding, metrorrhagia, hematuria, persistent post-partum lochia, rectal prolapse and leucorrhea.
- Used to stop external bleed of any cause: powder or dress the wound with granulated drug materials.
- Selaginella plus Thuja: For hematochezia due to a boil in the anal region (patient cannot sit) or for an extra-menstrual bleeding uterus. Selaginella preparation plus Thuja leaf preparation: Grind into powder, add warm water. Drink the resulting infusion.
- In China, used for tracheitis and tumors; also, for amenorrhea and bowel hemorrhage. Also used for fever, detoxification and mobilization of blood circulation. (•) In Chinese traditional medicine, used to promote blood circulation, stimulate menstrual discharge, treat hemoptysis, abnormal uterine bleeding, hematochezia, and prolapse of the rectum.
(38)
- In Vietnam, whole plant used for treatment of burns, hepatitis, jaundice, and as concoction for hemorrhoids and various respiratory diseases.
- In Germany, a "beauty tea" prepared from S. tamariscina is drunk for treatment of fragile and brittle finger nails. (49)

Studies
Biflavonoids: Methanol extract significantly inhibited UV irradiation induced activity of MMP-1 in primary fibroblasts from human skin. Of the five biflavonoids isolated, sumaflavone and amentoflavone showed significant MMP-1 inhibitory activity. (1)
Anti-mutagenic / Tumoricidal: Called Keon in Korea, S tamariscina is a traditional medicinal plant for therapy of advanced cancer patients in the Orient. It is thought to modify gene expression and cytokine production. It also lowers blood sugar and lipid peroxide levels. The biflavones isolated from related Selaginella species exert both tumoricidal effects against human tumor cell lines and anti-mutagenic activity. There is ongoing study for its chemopreventive effects in stomach cancers.
Isocryptomerin / Anti-fungal:
Study isolated isocryptomerin, a biflavoinoid, which exerted antifungal activity in an energy-independent manner without hemolytic effects. The antifungal activity may be through a membrane-disruption mechanism. (2)
Amentoflavone / Anti-fungal:
Study isolated amentoflavone from the ethyl acetate extract of the whole plant. It exhibited potent antifungal activity against several pathogenic fungal strains presenting a great potential to be a lead compound for the development of antifungal agents. (9)
Antimetastatic:
Study investigated the effects of S. tamariscina extracts on the invasion and motility of highly metastatic A549 cells and Lewis lung carcinoma (LLC) cells. Results showed STE treatment decreased (p<0.05) the expression of matrix metalloproteinase (MMP)-2, -0 and urokinase plasminogen activator (u-PA) in a dose-dependent manner in the A549 and LLC cell. Results demonstrated that Selaginella tamariscina extract could be a candidate antimetastatic agent against lung cancer. (3)
Cell apoptosis: Cell apoptosis is important in cellular homeostasis and anticarcinogenesis. Study suggests oxidative stress may be involved in the cytotoxicity of ST and that ST-induced apoptosis of HL-60 cells is primarily mediated by the caspase activation pathway. (4)
Vasorelaxation: Study yielded an active biflavonoid, amentoflavone and results suggest it relaxes smooth muscle via endothelium-dependent nitric oxide-cGMP signaling, with possible involvement of K and Ca channels. (5)
Anti-gastric cancer: Study results suggest that Selaginella tamariscina could be a candidate chemopreventive agent against gastric cancer. (6)
Amentoflavone / Anti-Cancer: Amentoflavone and the extracts from S. tamariscina were screened against five cancer cells. Assays in vitro showed inhibition of the proliferation of HL-60 (human leukemia cells), MCF-7 (human breast cancer cells), HeLa (human cervical carcinoma cells), human hepatoma carcinoma cells, and PANC-1 (human pancreatic cancer cells).
Candidiasis: S-Phase Accumulation of Candida albicans by Anticandidal Effect of Amentoflavone Isolated from Selaginella tamariscina: Study suggests amentoflavone has a potential for treatment of candidiasis.
(7)
Chemical Constituents / Liganoside: Study isolated a new liganoside, tamariscinoside C, together with D-mannitol, tyrosine and shikimic acid.
Inhibitory Effects on Immediate Allergic Reactions: Study of the ethanol extract of ST for anti-allergic effects. Results showed it could inhibit mouse systemic anaphylactic shock and dose-dependently block passive cutaneous anaphylaxis and skin reactions caused by exogenous histamine and serotonin. Activity may be mediated by reducing the release of vasoactive amines such as histamine from mass cells via stabilization of the cell membrane and weakening the inflammatory action of these amines. One of its active flavonoids may be useful as a potential remedy for allergic rhinitis and other allergy-related diseases. (10)
Antibacterial / Streptomycin / Synergism with Cefotaxime: Study of the novel antibacterial isocryptomerin isolated from S. tamariscina against Gram-positive and Gram-negative bacterial strains including MRSA showed the isocryptomerin had considerable synergistic activity in combination with cefotaxime. (12)
Hyoglycemic: Study in rats showed both EtOH and H2O extracts were able to ameliorate the fasting blood glucose and improved OGTT. Total cholesterol, LDL and fatty acids were also lowered. Compared with the water extract, the EtOH extract effects were more marked. (13)
Anti-Fatigue: Study in mice of a polysaccharide from S. tamariscina showed an anti-fatigue effect with prolonged swimming time of loaded mice, decrease in BUN and blood lactic acid after swimming. (14)
Selaginellins / Cytotoxic / Antioxidant: Study yielded a new selaginellin named selaginellin O, along with three other known selaginellins, 2-4. Selaginellins 1, 2, and 3 exhibited cytotoxic activity against cultured HeLa cells (human cervical carcinoma cells) as well as antioxidant activity. (16)
Bone Disease Benefits / Anti-Osteoclastogenesis and Anti-Osteoclastic Activities: Study evaluated the inhibitory effect of S. tamariscina on osteoclast differentiation. Results showed a water extract to have beneficial effects on bone disease by inhibiting osteoclastogenesis and osteoclastic activity. (17)
Hypolipidemic / Hepatoprotective / Amentoflavone: Amentoflavone isolated from S. tamariscina showed strong lipid lowering effect and favorable hepatoprotective effect in vivo. (19)
Anti-Metastatic / Inhibition of MMP-9 in Human Nasopharyngeal Ca HONE-1 Cells: Study evaluated the anti-metastatic properties of ST extract in human nasopharyngeal carcinoma HONE-1 cells in vitro. The ST extract inhibited MMP-9 expression and HONE-1 cell metastasis. The inhibitory effects may involve the Src/FAK/ERK 1/2 pathway. Results suggest a potential of being an anti-metastatic agent against nasopharyngeal carcinoma (21)
Attenuation of Metastasis / Oral Cancer: Study investigated the mechanism by which S. tamariscina inhibits the invasiveness of human oral squamous cell carcinoma (OSCC) HSC-3 cells. Results showed ST attenuated HSC-3 cell migration and invasion in a dose-dependent manner, at least, partially, through down-regulation of matrix metalloproteinases. Study suggests a potential as adjuvant therapeutic agent in the prevention of oral cancer. (22)
Antidiabetic / Antioxidant / Antihyperlipidemic / Flavonoids: Study investigated the antidiabetic, antihyperlipidemic, and antioxidant activity of total flavonoids of ST in a mouse model of diabetes. Results showed an excellent effect in high blood glucose reduction, however, with no effect on normal blood glucose level. The antidiabetic effect may be explained by its antioxidant activity and antihyperlipidemic effect which could have elevated the insulin sensitivity of the liver. (24)
Estrogenic Activity: Study evaluated the estrogenic activity of ten kinds of Selaginella tamariscina from ten different places of origin. Results showed S. tamariscina exerts estrogenic effect by activating gene transcription mediated by ERα. (25)
Insulin-Mimetic Selaginellins: Study of methanol extract isolated three new selaginellins (2,4, and 5) together with two known selaginellin derivatives (1 and 3). All isolates showed strong glucose uptake stimulatory effects in 3T3-L1 adipocyte cells. They also showed inhibitory effects on PTP1B enzyme activity. Results suggest potential for these selaginellin derivatives as lead compounds for development of agents for T2DM. (26)
Toxicity / Anticancer: Study evaluated the toxicity and antitumor effect of ethanol extract of S. tamariscina in a mice model. In a single-dose acute toxicity text, an oral administration of 10,000 mg/kg did not cause any lethality. The STE could not prevent tumor formation but provided strong inhibition of tumor growth. (27)
Tyrosine Phosphatase 1B inhibitory Activity / Selaginellin / Antidiabetic: Study isolated six selaginelline derivatives (1-6), comprising four new compounds (selariscinas A-D). The compounds exhibited inhibitory effect on PTP1B enzyme activity with IC50 ranging from 5.5 ± 0.1 to 21.6 ± 1.5 µM. Compound 2 showed greatest potency with IC50 of 5.5±0.1 µM. Results suggest a potential of the lead molecules for the development of antidiabetic agents. (28)
Phytoremediation / Formaldehyde: In a study of 86 species of plants representing five general classes (ferns, woody and herbaceous foliage plants, Korean native plants and herbs), Selaginella tamariscina was one of nine plants that showed the highest formaldehyde removal efficiency. Phytoremediation potential was assessed by exposing the plants to gaseous formaldehyde in airtight chambers. (29)
• Cytotoxicity / Anticancer: Selaginella tamariscina is considered the most powerful and useful plant Selaginella in the world, which can inhibit various cancer growths such as lung, leukemia, gastric and breast. It has shown antimetastatic activity in osteosarcoma. Ethyl acetate extracts of S. tamariscina showed significantly decreased viability of HeLa cells in a dose-dependent manner. (30)

• Cytotoxic Constituents Against Human Cancer Cell Lines: Study yielded three selaginellins and seven biflavones from whole plant of S. tamariscina. Compounds 1, 4, 7, 9, and 9 showed selective cytotoxic activity against tested human cell lines. (see constituents above) (31)
• Fatty Acid Synthase Inhibition by Amentoflavone / Anticancer: Date of evidence suggests that amentoflavone isolated from Selaginella tamariscina induced breast cancer apotheosis ad antiproliferation of human breast cancer cells through blockade of fatty acid synthesis. (32)
• Amentoflavone /Anti-Cancer Mechanisms / MCF-7 Breast Cancer Cells: Study investigated the anticancer mechanism(s) of amentoflavone in MCF-7 cells. Results showed amentoflavone induces apoptosis of MCF-7 breast cancer cells that is closely related to mitochondrial dysfunction. (33)
• Amentoflavone: Amentoflavone is a polyphenolic compound present in various plants like Ginkgo biloba, Chamaecyparis obtusa, Hypericum perforatum, and Xerophyta plicata. Amentoflavone has shown various molecular mechanisms i.e., phosphodiesterase inhibition, muscular strength, inhibition of PTP1B, acetylcholinesterase inhibition, weak vasodilation, and inhibition of fatty acid synthase. Studies have shown the compound to be a potent antimicrobial, antifungal, antiviral, antidepressant, anti-inflammatory, antioxidant, antiulcerogenic, antiangiogenic, radioprotective and cytotoxic. (34)
• Anti-Inflammatory / Antioxidant / HO-1 Induction: Study investigated the anti-inflammatory and antioxidant activities of ethanol extract of S. tamariscina against lipopolysaccharide ILPS)-induced inflammatory responses The STE dose-dependently inhibited the production of inflammatory mediators (NO and PGE2) and pro-inflammatory cytokines (IL-1ß and IL-6) in LPS-stimulated RAW 264.7 cells. The STE also showed good free radical scavenging activity and inhibited ROS generation by LPS. The mechanisms may involve the MAPK, NF-kB, and Nrf2/H)-1 signaling pathways. (35)
• Effect of Stir-Frying on Coagulation Activity: ST has been widely used for improving blood circulation. However, its processed product, S. tamariscina carbonisatus (STC), has opposite haemostatic activity. Study evaluated the activity of ST and STC on the coagulation system of rats. While ST with its amentoflavone content can shorten APTT and TT and decrease fibrinogen (FIB) content, STC with its increased dihydrocaffeic acid showed hemostatic activity by promoting platelet aggregation and reducing APTT and PT. Two active compounds, dihydrocaffeic acid and amentoflavone, may be partly responsible for the haemostatic and anticoagulant activity of STC and ST, respectively. (36)
• Amentoflavone / Effect on Malignant Glioma: Malignant glioma is the most common type of brain tumor with poor clinical outcome and survival. Study investigated the role of amentoflavone (AF), an active flavonoid component of S. tamariscina in glioma cells. Results showed significant down-regulation of miR-124-3p expression in glioma tissues relative to normal brain tissue. AF decreased cell viability and triggered apoptosis in both glioma cell lines in a dose-dependent manner. AF could induce apoptosis and inhibited glycolysis in glioma cells via miR-124-3p. Results proved preliminary experimental data for further investigation. (37)
• KR1B10-Inhibitory / Amentoflavone / A549 Human Lung Cancer Cells: Study evaluated the inhibitory activity of S. tamariscina extract and its major compound, amentoflavone, on human aldo-keto reductase family 1B10 (AKR1B10), a detoxification enzyme, and evaluated the anticancer effects and potential as adjuvant for doxorubicin cancer chemotherapy. Results showed STE and amentoflavone potently inhibited human AKA1B10 and synergistically increased the doxorubicin anti-profliferative effect in A549 and NCI-H460 human lung cancer cells. (39)
• Potential as Functional Food / Antimicrobial / Nutritional and Biochemical Analysis / Powder: Study reports on the nutritional components of S. tamariscina. Iron nutrient content was 0.94 ± 0.06 mg/100 g powder; selenium was present in small amount, which showed strong antioxidant power. Total phenolic content was 8.65-11.61 mg GAE/g. Antioxidant activity was shown in ABTS and DPPH radical scavenging assays. Ferric reducing power was higher in the ethanol extract. Also, the EA exhibited antimicrobial activity against Bacillus subtilis KCTC 2189. Level of HDL cholesterol was significantly higher in the HF20% + S. tamariscina 20% group. Study suggests the plant possesses antimicrobial, antioxidant, and anticytotoxic activities and has potential as functional food. (43)
• Antioxidant / Anti-Inflammatory / Wound Healing / Leaves: Study evaluated the antioxidant, anti-inflammatory, and wound healing activities of hot-water extract (STW) and 80% ethanol extract (STE). Polyphenol content of STW and STE were 38.108 mg/g and 17.927 mg/g, respectively. DPPH and ABTS radical scavenging activities  showed IC50s of the STQW were over 2 times lower than STE. In MTT assay, RAW264.7 cell viability of the two extracts decreased by about 6% at 1 mg/mL. HaCaT cell viability increased by 18% at 50 µg/mL. Both suppressed production of NO, TNF-α, COX-2 and PGE2 in LPS-induced RAW264.7 cells. The STE showed wound healing via promotion of skin cell migration in TNF-α stimulated human keratinocytes. Results indicate potential as new cosmetic ingredients in skin care. (44)
• Haemostatic Nanoparticles / Carbonisata: High-temperature carbonisation is used to prepare many traditional Chinese medicine charcoal drugs. Study reports on the synthesis of nanoparticles from Selaginella pulvinate Carbonisata (STC) for the first time. The STC-NPs displayed low toxicity against mouse monocyte macrophage RAW 264.7 cells by CCK-8 assay. STC-NP treatment significantly shortened bleeding time in rat and mouse models. Coagulation assays showed the haemostatic effects of STC-NPs were related to improvement of fibrinogen and platelet contents, along with decreasing of prothrombin time that resulted from stimulation of extrinsic blood coagulaion and activation of the fibrinogen system. The novel evaluation supports the material basis of STC us in traditional Chinese medicine. (45)
• Antimetastatic on Human Osteosarcoma Cells: Study evaluated the effect of S. tamariscina on metastasis of osteosarcoma. S. tamariscina at range of concentrations (from 0-50 µg/mL), concentration-dependently inhibited the migration/invasion capacities of three osteosarcoma cell lines without cytotoxic effects. ST inhibited the matrix metalloproteinase (MMP)-2 and MMP-9 enzyme activity as well as protein expression. Western blot analysis showed inhibition of phosphorylation of p38 and Akt. Results suggest ST possesses antimetastatic activity in osteosarcoma cells and has great potential for development as a preventive agent for osteosarcoma metastasis. (46)
• Potential Role in Prevention of Modern Chronic Diseases / Review: Review discussed the evidence-based ethnomedicinal and ethnopharmacological uses, phytochemicals and bioactive potential of Selaginella species and its potential role in the prevention of modern chronic diseases. (49)
• Antiproliferative Activity in Leukemia Cells / Sterols: Study isolated three new sterols, 3ß,16α-dihydroxy-5α,17ß-cholestan-21-carboxylic acid (1), 3ß-(3-hydroxybutyroxy)-16α-hydroxy-5α,17ß-cholestan-21-carboxylic acid (2) and 3ß-(3-hydroxybutyroxy)-16α-hydroxy-5α,17ß-cholestan-21-carboxylic acid (3). The compounds were evaluated for growth inhibitory effects and differentiation induction abilities in human leukemia HL-60 cells.  Compound 1 was more effective than 2 and 3 in inhibiting cell growth, but compound 3 was more effective in enhancing induction of all-trans-retinoic acid differentiation. (50)
• Amentoflavone / Inhibition of TGF-ß-Induced Metastasis of Human Cancer Cells:  Epithelial mesenchymal transition (EMT) is an important step in metastasis and can be a key target in cancer treatment. Study evaluated the EMT inhibitory effects of S. tamariscina and its active component, amentoflavone (AF). Results showed aqueous extracts of STE and AF inhibited EMT in human cancer cells. At non toxic levels, they exerted remarkable inhibitory effects on migration (wound healing assay) and invasion (Tanswell assay) in TNF-ß-treated cancer cells. Results suggest STE and AF are promising EMT inhibitors and have potential as antitumor agents. (51)
• New Triarylindanone and Isobenzofuranone  / Cytotoxicity:  Study isolated a new triarylindanone, selagindanone A (1), and a new isobenzofuranone (2). Compound 2 showed weak cytotoxicity against human hepatocellular carcinoma SMMC-7721 and HepG2 cell lines.  (52)
• Natural Phosphodiesterase-4 Inhibitors:  Recent studies have reported some selaginellin analogues have potent phosphodiesterase-2 (PDE4) inhibitory activity. Study isolated two unusual selaginellin analogues, selariscin A (1) and B (2), along with eight new diarylfluorene derivatives, selaginpulvilins
M-T (3-10), and five known analogues, 11-15. Compounds 1 and 3-10 showed PDE4 inhibitory activity with IC50s range of 2.8-33.8 µM. (53)
• Cytotoxicity:  Study isolated two new anthraquinone derivatives, Selaginones A and B (1 and 2), and one new triarylbenzophenone analog, selagibenzophenone B (3). Compound 3 showed moderate activity against SMCC-7721 and MHCC97-H cell lines with IC50s of 39.8 and 51.5 µM respectively. (54)
• Hypoglycemic Flavonoids / Involvenflavones:  Study isolated six flavonoids: three undescribed biflavonoids, one undescribed 8-aryl flavonoid, and two known compou8nds. The compounds were evaluated for hypoglycemic activity in HepG2 cells. Involvenflavone H, I, and J significantly increased glucose consumption in both normal and i9nsulin-resistant HepG2 cells. The three compounds can effectively upregulate the protein expression of glucokinase (GCK) and adenylate cyclases (ADCYs). Results suggest the involvenflavone, especially J, may have potent hypoglycemic activity, which provide promising molecular targets for treatment of diabetes. (55)
• Inhibition of Enterovirus Replication / Polysaccharides:  Study evaluated the inhibitory effect of polysaccharides from S. tamariscina on Enterovirus 71 (EV71) replication in vitro. Cellular model was established by infecting RD cells with EV71.  The CC50 of 30% and 50% alcohol precipitated polysaccharides on RD cells were 396 and 142 mg/L respectively. Additionally, two polysaccharides significantly reduced viral RNA copies in EV71-infected RD cells. Results showed Selaginella tamariscina together with its 30% and 50% alcohol precipitated polysaccharides can be developed as potential new anti-EV71 drugs. (56)

Availability
- Wild-crafted. 
- Extracts in the cybermarket.

Updated September 2022 / March 2019 / August 2017 / August 2016

PHOTOS / ILLUSTRATIONS
Photo © Godofredo Stuart / StuartXchange
OTHER IMAGE SOURCE: File:004 Selaginella tamariscina iwahiba.jpg / 1925 . Michio Murakoshi / Public Domain / Wikimedia Commons
OTHER IMAGE SOURCE: Selaginella tamariscina (Photo) / Permission granted to use under GFDL by Kurt Stueber. Source: www.biolib.de / GNU Free Documentation License / click on image to go to source page / alterVISTA

Additional Sources and Suggested Readings
(1)
Biflavonoids isolated from Selaginella tamariscina regulate the expression of matrix metalloproteinase in human skin fibroblasts / Chan-Woo Lee, Hyun-Jung Choi et al /
Bioorganic & Medicinal Chemistry, Vol 16, Issue 2, 15 January 2008, Pages 732-738 / doi:10.1016/j.bmc.2007.10.036
(2)
Isocryptomerin, a novel membrane-active antifungal compound from Selaginella tamariscina / Lee Juneyoung et al / Biochemical and biophysical research communications • 2009, vol. 379, no3, pp. 676-680 /
(3)
Antimetastatic activities of Selaginella tamariscina (Beauv.) on lung cancer cells in vitro and in vivo / Shun Fa Yang et al / Journal of Ethnopharmacology, 4 April 2007; Volume 110, Issue 3: pp 483-489 /
DOI: 10.1016/j.jep.2006.10.010
(4)
Selaginella tamariscina Induces Apoptosis via a Caspase-3-Mediated Mechanism in Human Promyelocytic Leukemia Cells / Seong-Hun Ahn et al / Journal of Medicinal Food, Summer 2006; 9(2): pp 138-144 / DOI: 10.1089/jmf.2006.9.138
(5)
Vasorelaxation by amentoflavone isolated from Selaginella tamariscina / Dae Gill Kang et al / lanta Med 2004; 70:  pp 718-722 / DOI: 10.1055/s-2004-82720
(6)
Effects of Selaginella tamariscina on in vitro tumor cell growth, p53 expression, G1 arrest and in vivo gastric cell proliferation / I Lee / Cancer Letters, 1999; Volume 144, Issue 1: pp 93-99 /
DOI: 10.1016/S0304-3835(99)00202-5
(7)
S-Phase Accumulation of Candida albicans by Anticandidal Effect of Amentoflavone Isolated from Selaginella tamariscina

(8)
Study on the chemical constituents of Selaginella tamariscina (Beauv.) Spring / Zheng X K et al / Acta Pharmaceutica Sinica, Apr 2004; 39(4): pp 266-268 /
PubMed ID 15303655
(9)
Antifungal effect of amentoflavone derived fromSelaginella tamariscina / Hyun Jun Jung et al / Archives of Pharmacal Research • Volume 29, Number 9 / September, 2006 / DOI 10.1007/BF02974074

(10)
Inhibitory Effects of Selaginella tamariscina on Immediate Allergic Reactions / Yue Dai / The American Journal of Chinese Medicine, 2005; 33(6): pp 957-966 / DOI: 10.1142/S0192415X05003442
(11)
Amentoflavone and the extracts from Selaginella tamariscina and their anticancer activity
/ Yiing Jing, Guogang Zhang et al / School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
(12)
Antibacterial and Synergistic Activity of Isocryptomerin Isolated from Selaginella tamariscina / Lee, Juneyoung, Yunjung Choi et al / J. Microbiol. Biotechnol., 2009; 19(2): pp 204–207 /
DOI: 10.4014/jmb.0810.566
(13)
Antihyperglycemic activity of Selaginella tamariscina (Beauv.) Spring / Xiao-ke Zheng, Yu-Jie Li et al /
Journal of Ethnopharmacology, Vol 133, Issue 2, 27 January 2011, Pages 531-537 /
DOI: 10.1016/j.jep.2010.10.028
(14)
Study on Anti-fatigue Biological Effect of Polysaccharide fromSelaginella Tamariscina / Liu Juan, Wang Chun-ying et al / DOI CNKI:SUN:JMDB.0.2009-04-053
(15)
The isolation and identification of a new lignanoside from Selaginella tamariscina (Beauv.) Spring. / Zheng XK, Shi SP et al / Yao Xue Xue Bao. 2004 Sep;39(9):719-21.
(16)
Bioactive selaginellins from Selaginella tamariscina (Beauv.) Spring / Chao Yang, Yutian Shao, Kang Li and Wujiong Xia / Beilstein J. Org. Chem. 2012, 8, 1884–1889. doi:10.3762/bjoc.8.217
(17)
Selaginella tamariscina water extract inhibits receptor activator for the nuclear factor-κB ligand-induced osteoclast differentiation by blocking mitogen-activated protein kinase and NF-κB signaling / Ki-Shuk Shim, Ju-Seop Kang, Min-Ho Lee, Jin Yeul Ma / Pharmacognosy Magazine, 2012; Vol 8, No 31: pp 184-191
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Studies on the Chemical Constituents and of Selaginella Tamariscina / China Papers
(19)
Lowering blood lipid and hepatoprotective activity of amentoflavone from Selaginella tamariscina in vivo
/ Shu-Mei Yue and Wen-Yi Kang* / Journal of Medicinal Plants Research, 2011; 5(14): pp 3007-3014 /
ISSN: 1996-0875
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Selaginella tamariscina / KEW: Plants of the World Online
(21)
Selaginella tamariscina extract suppresses TPA-induced invasion and metastasis through inhibition of MMP-9 in human nasopharyngeal carcinoma HONE-1 cells / Chung-Han Hsin, Buor-Chang Wu, Chun-Yi Chuang, Shun-Fa Yang, Yi-Hsien Hsieh, Hsin-Yu Ho, Huang-Pin Lin, Mu-Kuan Chen and Chiao-Wen / BMC Complement Altern Med., 2013; 13: 234. / doi: 10.1186/1472-6882-13-234
(22)
Selaginella tamariscina Attenuates Metastasis via Akt Pathways in Oral Cancer Cells / Jia-Sin Yang , Chiao-Wen Lin , Chung-Han Hsin, Ming-Ju Hsieh, Yu-Chao Chang / PLoS ONE 8(6): e68035. /
DOI: 10.1371/journal.pone.0068035
(23)
Natural products from resurrection plants: Potential for medical applications
/ Tsanko S. Gechev, Jacques Hille, Herman J. Woerdenbag, Maria Benina, Nikolay Mehterov, Valentina Toneva, Alisdair R. Fernie, Bernd Mueller-Roeber / Biotechnology Advances, Vol 32, Issue 6, 1 Nov 2014, Pp 1091–1101
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Antihyperlipidaemic and antioxidant effect of the total flavonoids in Selaginella tamariscina (Beauv.) Spring in diabetic mice / Xiao-ke Zheng, Wei-wei Wang, Li Zhang, Cheng-fu Su, Yong-yong Wu, Ying-ying Ke, Qing-wei Hou, Zhao-yan Liu, Ai-she Gao, Wei-sheng Feng / Journal of Pharmacy and Pharmacology, Vol 65, Issue 5, May 2013, pp 757-766 / DOI: 10.1111/jphp.12035
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Experimental study on estrogenic activity of ten kinds of Selaginella tamariscina from ten different place of origin / ZHENG Xiao-ke; JIANG Yun; PEI Su-juan; WANG Xiao-lan; ZHANG Na; KE Ying-ying; ZHAI Ying-ying; FENG Wei-sheng / China Journal of Traditional Chinese Medicine and Pharmacy, 2015-01
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Insulin-Mimetic Selaginellins from Selaginella tamariscina with Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity / Phi-Hung Nguyen, Bing-Tian Zhao, Md Yousof Ali, Jae-Sue Choi, Dong-Young Rhyu, Byung-Sun Min, and Mi-Hee Woo* / J. Nat. Prod., 2015; 78 (1): pp 34–42 / DOI: 10.1021/np5005856
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Toxicity and anticancer effects of an extract from Selaginella tamariscina on a mice model / Le Minh Ha*, Do Thi Thao, Hoang Thanh Huong, Chau Van Minh & Nguyen Tien Dat* / Natural Product Research: Formerly Natural Product Letters, Volume 26, Issue 12, 2012 / DOI:10.1080/14786419.2011.560847
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Six selaginellin derivatives with protein tyrosine phosphatase 1B inhibitory activity from Selaginella tamariscina / BT Zhao, DH Nguyen, JS Choi, MH Woo / Planta Med 2015; 81 - PX45
DOI: 10.1055/s-0035-1556489
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Study of phytoremediation benefits of 86 indoor plants published; Japanese royal fern tops list for formaldehyde removal effectiveness / Science Daily: June 24, 2011
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Comparison of cytotoxic activities of extracts from Selaginella species / Juan Li, Xiang Lei, and Ke-li Chen / Pharmacogn Mag. 2014 Oct-Dec; 10(40): 529–535.  / doi:  10.4103/0973-1296.141794
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Cytotoxic Constituents from Selaginella tamariscina. / Cao Yuan; Wu Yong-ping; Wen Xiao-zhou; Weng Yan; Wang Qiang / Natural Product Research & Development, Feb 2012, Vol. 24 Issue 2, p150-154
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Fatty Acid Synthase Inhibition by Amentoflavone Induces Apoptosis and Antiproliferation in Human Breast Cancer Cells / Jin Sun Lee, Myung Sun Lee, Won Keun Oh, Ji Young Sul / Biological and Pharmaceutical Bulletin, Vol 32, No 8 (2009) pp 1427-1432 / http://doi.org/10.1248/bpb.32.1427
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Amentoflavone Induces Cell-cycle Arrest and Apoptosis in MCF-7 Human Breast Cancer Cells viaMitochondria-dependent Pathway / Jen-Shen Pei, Chia-Chi Liu, Yuan-Nian Hsu, Li-Ling Lin, Shou-Cheng Wang, Jing-Gung Chung, Da-Tian Bau, Song-Shei Lin / In Vivo, September 2016, 30 (5): pp 605-610
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Review on Chemistry and Pharmacological Potential of Amentoflavone / Souravh Bais and Naveena Abrol / Current Research in Neuroscience, 6: 16-22. / DOI: 10.3923/crn.2016.16.22
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HO-1 Induction by Selaginella tamariscina Extract Inhibits Inflammatory Response in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages / An-Na Won, Sun Ah Kim, Jugn Yun Ahn, Jae-Hyun Han, Chang-Hyun Kim, Ju-Hee Lee, and Dong-Il Kim / Evidence-Based Complementary and Alternative Medicine,
Volume 2018 / https://doi.org/10.1155/2018/7816923
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Comparing coagulation activity of Selaginella tamariscina before and after stir-frying process and determining the possible active constituents based on compositional variation / Qian Zhang, Ya-Li Wang, Die Gao, Liang Cai, Yi-Yao Yang, Yuan-Jia Hu / Pharmaceutical Biology, 2018; 56(1) / https://doi.org/10.1080/13880209.2017.1421673
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Amentoflavone induces apoptosis and suppresses glycolysis in glioma cells by targeting miR-124-3p.
/ Zhaohui W, Yingli N, Hongli L, Haijing W et al / Neurosci Lett., Nov 2018; 686: pp 1-9 / doi: 10.1016/j.neulet.2018.08.032.
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Selaginella tamariscina / Epilepsy Naturopedics
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AKR1B10-inhibitory Selaginella tamariscina extract and amentoflavone decrease the growth of A549 human lung cancer cells in vitro and in vivo / Yu Jin Jung, Eun Ha Lee, Chang Gun Lee, Kijong Rhee, Woo Suk Jung, Yongsoo Choi, Cheol Ho Pan, Kyungsu Kang / Journal of Ethnopharmacology, 2017; 202: pp 78-84 / https://doi.org/10.1016/j.jep.2017.03.010
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The traditional and modern uses of Selaginella tamariscina (P.Beauv.) Spring in medicine and cosmetic: Applications and bioactive ingredients / Christian Bailly / Journal of Ethnopharmacology, Nov 2021; Vol 280: 114444 / DOI: 10.1016/j.jep.2021.11444
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Two new selaginellin derivatives from Selaginella tamariscina (Beauv.) Spring / Kang-Ping Xu, Hui Zou, Hong-Pin Long et al / Journal of Asian Natural Products Research, 2011; 13(4): pp 356-360 /
DOI: 10.1080/10286020.2011.558840
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Selaginellins I and J, two new alkynyl phenols from Selaginella tamariscina (Beauv.) Spring / Kang-Ping Xu. Hui Zou et al / Journal of Asian Natural Products Research, 2011, 13(2): pp 93-96 /
DOI: 10.1080/10286020.2010.536535
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A study on the nutritional and biochemical analysis of Selaginella tamariscina powder / Hyo-Jeong Hwang, Jeong-Yeon Kim and Kyung-Ok Shin / Food and Science and Biotechnology, 2021; 30: pp 1445-1454 /
DOI: 10.1007/s10068-021-00991-z
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Anti-oxidant, Anti-inflammatory, and Wound Healing Activities of Selaginella tamariscina Leaf Extract / Yu-Jin Kim, Ji-An Lee / Journal of Convergence for Information Technology, 2021; 11(4): pp 194-202 / eISSN: 2586-4440 / DOI: 10.22156/CS4SMB.2021.11.04.194
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Haemostatic Nanoparticles-Derived Bioactivity from Selaginella tamariscina Carbonisata /
Yusheng Zhao, Yue Zhang, Hui Kong et al /  Molecules, 25(3) / DOI: 10.3390/molecules25030446
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Selaginella tamariscina (Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways /  Jia-Sin Yang, Chiao-Wen Lin, Ko-Hsiu Lu et al / Food and Chemical Toxicology, 2013; Vol 59: pp 801-807 /
DOI: 10.1016/j.fct.2013.06.028
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A New Diarylbenzophenone from Selaginella tamariscina / Wanling Chen, Yujie Peng, Wanxia Huang et al / Rec Nat Product, 2020 / DOI: 10.25135/mp.182.20.03.1586
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Selaginellin A and B, Two Novel Natural Pigments Isolated from Selaginella tamariscina / Xian-Long Cheng, Shuang-Cheng Ma, Jian-Dong Yu et al / Chemical and Pharmaceutical Bulletin, 2008; 56(7) /
eISSN: 1347-5223 / pISSN: 0009-2363 / DOI: 10.1248/cpb.56.982
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Evidence-Based Medicinal Potential and Possible Role of Selaginella in the Prevention of Modern Chronic Diseases: Ethnopharmacological and Ethnobotanical Perspective / Mohd Adnan, Arif Jamal Siddiqui et al / Rec Nat Prod. 2021; 15(5): pp 330-355
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Three Novel Sterols Isolated from Selaginella tamariscina with Antiproliferative Activity in Leukemia Cells /
Liang-liang Gao, Shi-liang Yin, Hui-ming Hua et al / Planta Med, 2007; 73(10): pp 1112-1115 /
DOI: 10.1055/s-2007-981562, 2021 /
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Amentoflavone, active compound of Selaginella tamariscina, inhibits in vitro and in vivo TGF-ß-induced metastasis of human cancer cells / Gye Lin Kim, Eun Hyang Jang, Jong-Ho Kim et al / Archives of Biochemistry and Biophysics, July 2020; Vol 687: 108384 / DOI: 10.1016/j.abb.2020.108384
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A new triarylindanone and a new isobenzofuranone derivative from Selaginella tamariscina
/ Yu-Jiee Peng, Dan Zhang, Wan-Ling Chen, Si-Yi Wang, Yao Zhang, Hui Zou / Natural Product Research, 2021 /
DOI: 10.1080/14786419.2021,1938042
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Molecular Networking Reveals the Chemical Diversity of Selaginellin Derivatives, Natural Phosphodiesterase-4 Inhibitors from Selaginella tamariscina / Sunmin Woo, Kyo Bin Kang, Jinwoong Kim, Sang Hyun Sung / J Nat Prod, 2019; 82(7): pp 1820-1830 / DOI: 10.1021/acs.jnatprod.9b00049
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Two new anthraquinone derivatives and one new triarylbenzophenone analog from Selaginella tamariscina / Rui Liu, Hui Zou Ping-Sheng Wu et al / Natural Product Research, 2020; 34(19): pp 2709-2714 / DOI: 10.1080/14786419.2018.1452008
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Hypoglycemic flavonoids from Selaginella atamariscina (P.Beauv.) Spring / Hong-Ping Long, Jian Liu, Gui-Shan Tan et al / Phytochemistry, 2022, Vol 195: 113073 / DOI: 10.1016/j.phytochem.2021.113073
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Inhibition of EV71 replication in vitro to polysaccharides from Selaginella tamariscina /
Ming-Ming Han / Journal of International Pharmaceutical Research, 2013; 6: pp 58-62

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