 Gen info
- Picria fel-terrae is a species of flowering plant belong to the family Linderniaceae. It is the sole species in the genus Picria. (21)
Botany
• Sagai-uak is a smooth, prostrate herb. Branches are slender, straggling, 60 to 90 centimeters long, rooting at the lower nodes. Leaves are ovate, 3 to 6 centimeters long, 2 to 3 centimeters wide, pointed at both ends, and toothed at the margins. Flowers are crowded on short axillary and terminal racemes. Calyx in the flower is about 6 millimeters long, double that length in the fruit; its outer sepals are broadly ovate and heart-shaped. Corolla is dark reddish brown. Fruit is a capsules, ovate, flattened, 3 to 4 millimeters long, bivalved with several seeds. Spherical seeds are about 0.6 millimeter in diameter, with 8 oblong hollows.
 • Stems up to 40 cm, often rooting at the nodes, densely minutely pubescent. Leaves chartaceous; petioles 2–15 mm; blades ovate, 2–5 by 1.5–3 cm, subacute at apex, cuneate to rounded at base, many crenate-serrate, minutely pubescent on both surfaces. Inflorescences 2–6 cm long. Pedicels 4–7 mm, minutely pubescent. Calyx with 4 sepals; upper one 7–9 by 6–8 mm in flower, 12–14 by 8–10 mm , in fruit, minutely pubescent; lateral two sepals 2–3 by 0.5 mm; flower one 5–6 by 4–5 mm in flower, 7–9 by 6–7 mm in fruit, minutely pubescent. Corolla red-brown, 8 mm long, tube externally glabrous, internally with two antero-lateral ridges densely covered by short glandular hairs; upper lip 2–3 mm long and wide; flower lip 25–3.5 by 4–5 mm, undulate on margin. Stamens ca 1 mm. Capsule 4 by 3 mm. Seeds ca 0.6 mm long and wide. (Flora of Thailand)
Distribution
- Native to the Philippines.
- Found in Cagayan, Kalinga and Laguna Provinces in Luzon and in Zamboanga, Mindanao.
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On forested slopes at low altitudes, ascending to 400 meters, rather rare and local.
- Also native to Assam, Bangladesh, Caroline Is., China South-Central, China Southeast, East Himalaya, Laos, Malaya, Philippines, Thailand, Vietnam. (9)
 Constituents
- Plant yields an amorphous bitter glucoside, curangin, which is either nonpoisonous or only very slightly poisonous.
- Study isolated two triterpenoids: (1) picfeltarraenone I (3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5,23-diene) and (2) picfeltarraenin XI (3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5, 23-diene-2beta-O-beta-D-glucopyranoside). (11)
- Study isolated seven compounds: apigenin (1), apigenin-7-O-β-D-glucuronide (2), apigenin-7-O-α-L- rhamnopyranosyl(1→2)-β-D-glucuronide (3), rosmarinic acid (4), picfeltarraegenin Ⅳ (5), picfeltarraegenin X (6), and acteoside (7). (12)
- Study isolated three flavonoid glucoronides viz., 7-O-β-glucuronide, luteolin 7-O-β-glucuronide and apigenin 7-O-β-(2″-O-α-rhamnosyl)glucuronide. (2)
- Study of whole plant isolated a new cucurbitacin, picfeltarraenone II (1), along with four known cucurbitacins, picfeltarraegenin I (2), picfeltarraenin IA (3), picfeltarraenin IB (4), and picfeltarraenin IV (5). (17)
- Phytochemical screening of ethanol extract of leaves yielded
secondary metabolites of alkaloids, flavonoids, glycosides, tannins, saponins, triterpenoids, and steroids. (see study below) (18)
Properties
- Plant, especially the fresh leaves, is very bitter.
- Considered aperient, febrifuge, diuretic, emmenagogue, sudorific.
- Curangine, an alkaloid derived from the plant, reported to have a marked febrifuge property.
- Studies suggest antimicrobial, antidiabetic, and complement inhibiting, immunomodulatory, relaxation, anti-inflammatory, complement inhibiting, anthelmintic, acetylcholinesterase inhibitory, antidiabetic, diuretic, antiproliferative, teratogenic, cytoprotective, antiproliferative, apoptosis-inducing, antioxidant, hepatoprotective, antibacterial properties.
Parts used
Whole plant, leaves.
 Uses
Folkloric
- In the Philippines, decoction of the plant is used as febrifuge, especially for malaria.
- The plant, masticated, decocted or infused, is used as stomachic and for irregular menstruation.
- Leaves are aperient; a stimulant to the intestines, sudorific, diuretic and emmenagogue.
- Leaves are used in the early stages of dropsy, in intermittent fevers, amenorrhea, arrested lochia, colic and lumbar pains.
- Sap or decoction of plant used as vermifuge in children.
- In the Moluccas, used as vermifuge, for tertian fever, as liver and bile stimulant. Also used for colic.
- Malays used it for its bitterness to whet the appetite.
- Juice given to provoke nausea.
- In Vietnam, whole plant used for treatment of herpes infections, fever, and tumors.
In India, leaves used in early stages of dropsy, for intermittent fever, amenorrhea, colic, and lumbar pains. (32)
- Decoction of leaves used for stomachache.
- Plant decoction used to increase appetite.
- Leaves applied to the head in cases of headache; cooling the head and allaying the pain.
- In Chinese medicine used as folk medicine for the treatment of herpes, infections, cancer, and inflammation. (14)
Studies
• Flavonoid Glucoronides: Study of a n-butanol extract yielded three flavonoid glucoronides: apigenin 7-O-β-glucuronide, luteolin 7-O-β-glucuronide and a new compound, apigenin 7-O-β-(2″-O-α-rhamnosyl)glucuronide, the latter one being a new compound. (2)
• New Cucurbitacin: Study yielded a new compound, 11, 24-dioxo-5, 21-diene-cucurbit-3alpha-O-beta-D-xylopyranosyl-16alpha-O-alpha-L-rhamnopyranoside (dehydrobryogenin glycoside). Hexanorcucurbitacin F, was obtained for the first time from Picria fel-terrae. (3)
• New Phenylethanoid Glycosides: Study searching for bioactive compounds from the whole plant yielded three new phenylethanoid glycosides, picreosides A-C, along with five known phenylethanoid glycosides: wiedemannioside, acteoside, acteoside isomer, cis-acteoside isomer, and cis-acteoside. (4)
• Complement-Inhibiting Cucurbitacin Glycosides: Study isolated four cucurbitacin glycosides: Picfeltarraenins 1A and 1B, picfeltarraenin IV, and a new compound picfeltarraenin VI. All showed activity as inhibitors of both the classical and alternative pathways of the complement system. (5)
• ß- Sitosterol / Anti-Diabetic Effect / Leaves: Study isolated ß-sitosterol from an n-hexane extract of leaves of Picria fel-terrae. The extract showed good antidiabetic effect, indicated by significant blood glucose lowering in alloxan induced diabetic mice. (7)
• Antimicrobial /Stem and Leaves: An in vitro study of a crude stem with leaf extract showed against five human pathogenic microorganisms showed effective activity against E. coli, Bacillus subtilis, Klebsiella sp., Staphylococcus aureus and Candida albicans. (8)
• Anthelmintic / Leaves: Study investigated the anthelmintic activity of leaf extract of Curanga fel-terrae against Pheretima posthuma. Results showed anthelmintic activity significantly more potent compared to standard albendazole. (13) Study evaluated the anthelmintic activity of subfractions (SF1-4) from n-hexane fraction of P. fel-terrae leaves on Pheretima posthuma. Activity was measured by paralysis and death times of worms. Pyrantel 0.1% was used as positive control. Results suggest the SFs from the n-hexane fraction possess anthelmintic activity, with the SF4 showing strongest activity compared to the other SFs and pyrantel. (35)
• Acetylcholinesterase Inhibitors: Study reports on the isolation of bioactive principles isolated from P. fel-terrae. An AChE inhibitory bioassay coupled HPLX of an EA extract yielded six compounds: picfeltarraenin IA (1), picfeltarraenin IB (2), picfeltarraenin IV (3), picfeltarraenin X (4), picfeltarraenin XI (5), and one unknown compound. (14)
• Anthelmintic: Study isolated fractions of plant extract against free-living nematode Caenorhabditis elegans and parasitic nematode Haemonchus contortus. Results showed a single fraction enriched for nematocidal activity killed ≥ 90% of C. elegans adults and inhibited motility of exsheathed L3 of H. contortus. (15)
• Diuretic / Leaves: Study evaluated the diuretic activity of various solvent extracts of leaves of Picria fel-terrae. An n-hexane extract showed better diuretic effect compared with other extracts with significant increase in urine volume at dose of 800 mg/kbw. There was increased sodium excretion by all extracts. (16)
• Antioxidant / Antiproliferative / T47D Cell Line: Study evaluated an ethyl acetate fraction of Picria fel-terrae for antioxidant activity and cytotoxicity effects in T47D cell line. The EAF showed anti-proliferative activity IC50 of 62.98 µg/ml. Antioxidant evaluation by DPPH assay showed an IC50 of 166.90 ± 0.10 µg/ml. (18)
• Relaxation Effect / Serotonin Contracted Rat Ileum / Leaves: Study of an ethanolic extract of P. fel-terrae leaves showed a relaxation effect on isolated rat ileum contracted by serotonin (5-HT). (see constituents above) (18)
•
Effect on Adrenoreceptors, Histamine, and ACh Receptors / Leaves:Study evaluated the effect of an ethanolic extract of P. fel-terrae leaves on ß2-adrenoreceptors, histamine, and muscarinic-3 acetylcholine receptors in isolated guinea pig trachea. Results showed ethanolic extracts of leaves of P. fel-terrae possess stimulatory effect on ß2-adrenoreceptors, inhibitory effect on histamine and a relaxation effect on M3-ACh receptors. (19)
• Picfeltarraenin IA / Anti-Inflammatory / Airway Inflammation: Picfeltarraenin IA is extracted from the plant and has been used in traditional Chinese medicine as an acetylcholinesterase inhibitor. Study evaluated the effect of picfeltarraenin IA on respiratory inflammation via its effect on interleukin (IL)-8 and prostaglandin E2 (PGE2) production. The expression of COX2 in human pulmonary adenocarcinoma epithelial A549 cells in culture was also examined. Results showed IA downregulated LPS-induced COX2 expression, and inhibits IL-8 and PGE2 production in pulmonary epithelial cells. Results indicate IA regulates LPS-induced cytokine release in A549 cells via NF-kB pathway. (20)
• Immunomodulatory Against Inflammatory Markers: Study evaluated the immunomodulatory activities of P. fel-terrae herbs extract against inflammatory biomarker using cell culture experiments. Herbs were dried and extracted with n-hexane, ethyl acetate, and 96% ethanol. Cell viability was assessed by MTT assay. Phytochemical screening revealed steroids in the n-hexane extract and flavonoids, glycosides, saponins, tannins in the ethyl acetate and ethanol extracts. Viability of RAW 264.7 cell showed no toxicity effects. At the gene level, extracts decreased gene expression of TNF-α, IL-6, IL-1ß, iNOS, and COX-2 which induced with LPS. Results suggest the extracts possess immuno-modulatory activity via inhibition of selected inflammatory biomarkers at the gene levels in LPS-induced macrophages. (22)
• Inhibitory on Nitric Oxide Production Toward RAW 264.7 Cells / Anti-Inflammatory: Inhibition of NO production in LPA-stimulated RAW264.7 cells is one of the ways to screen various anti-inflammatory drugs. Study of P. fel-terrae herbs showed reduction of NO production toward RAW 264.7 cells induced by lipopolysaccharide. The n-hexane extracts showed high potential to reduce NO compared to ethyl acetate and ethanol extracts. (23)
• Teratogenic Effect / Leaves: Study evaluated an ethanol extract of P. fel-terrae leaves for phytochemical constituents and teratogenic effect toward the fetus. Extract doses of 125, 500, and 1000 mg/kg were used. Gabapentin 50 mg/kg was used as control. Treatment was done during organogenesis period. Observations included reproductive and uterus performance and external malformations. Phytochemical screening revealed flavonoids, tannins, glycosides, saponins, and steroids/triterpenoids. The extract showed significant effect on weight loss, fetal body length, number of dead fetuses, resorption and hemorrhages compared to healthy control (p<0.05). Uterus abnormality was found in group treated with extract dose of 500 and 1000 mg/kg. All groups showed external malformations. Results conclude all doses of ethanol extract of leaves had teratogenic effect during organogenesis period, and the ethanol extract should not be used during pregnancy. (24)
• Subchronic Toxicity Evaluation / Leaves: Study evaluated the subchronic toxic effect of P. fel-terrae leaf extract by OECD (Organization for Economic Cooperation and Development) guidelines. Doses of 125, 250, 500, 1000 mg/kbw orally to test animals for 90 days. Signs of toxicity, mortality, macroscopic and microscopic changes, along with increased biochemical parameters, were observed after treatment with extract doses of 500 and 1000 mg/kbw. However, the abnormal biochemical parameters returned to normal when treatment was stopped. There was no hematological effect at all extract doses. The toxic effect of 500 and 1000 mg/kbw was reversible. (25)
• Acute Toxicity Study / Leaves: Study evaluated the acute toxicity of ethanolic leaf extract of P. fel-terrae on Artemia salina and male mice, by invivo and invitro methods; in vitro, by exposing nauplii to extract concentrations of 10, 100, 200, 500, and 1000 mg/ml for 48 hours; in vivo, on male mice treated with sodium carboxymethyl cellulose 0.5% and extract doses of 1000, 2000, and 5000 mg/kbw. Results showed the leaf extract to be weakly toxic on A. salina with LC509 of 768.07 mg/mL. In vivo, extract doses of 2,000 and 5,000 mg/kbw produced changes on alanine aminotransferase level, with histological changes on heart, liver, and kidney. Results showed the ethanolic extract was weakly toxic on A. salina and at high doses, caused histological changes on male mice organs. (26)
• Cytoprotective / Toxicity Study / Leaves: Study evaluated the cytoprotective activity of ethyl acetate fraction (EAF) of P. fel-terrae by MTT assay and flow cytometry assay on Vero cells induced with H2O2 0.8 mM. The EAF showed cytoprotective effect with highest viability (88.83%) and ROS expression (66.75%) on Vero cells. (27)
• Silver Nanoparticles / Antibacterial / Leaves: Study reports on the green synthesis of silver nanoparticles. The AgNPs showed antibacterial activity against Staphylococcus epidermis. The OD value at 10 mg/mL (0.367) showed biofilm inhibition of 23.77, indicating the greater the extract concentration, the smaller the biofilm formation of the S. epidermis bacteria. (28)
• Effect on Procalcitonin Level / Acute Bacterial Rhinosinusitis / Leaves: Acute rhinosinusitis (AR) is of viral etiology, only 0.5%-2% develop into acute bacterial rhinosinusitis. Study evaluated the effect of ethanol extract of leaves on procalcitonin level and amount of bacteria in an acute bacterial rhinosinusitis mice model. There was a statistically significant decrease in procalcitonin level (p<0.001) and amount of bacteria colony, showing an anti-inflammatory and antibacterial effect. (30)
• Immunomodulatory Effect of Combined P. fel-terrae and Curcuma mangga: Study evaluated the modulatory effects of combined ethanol extracts of Picria fel-terrae leaves and Curcuma mangga rhizomes on cellular- and humoral-mediated immunity in macrophages and Wistar rats and mice models. Doses of 25, 50, and 100 mg/kbw orally administered for 7 days and carbon clearance was used to investigated phagocytosis activity. The combined extracts at 1:1 ratio demonstrated dose-dependent stimulation of both cellular- and humoral-mediated immunity in both animal models. Strongest DTH response and phagocytosis activity was observed at 100 mg/kbw, which was comparable to positive control, levimasole. The combined extracts' demonstrated strong stimulatory activities suggest potential as a nutraceutical for modulation of immune responses. (31)
• Cytotoxicity Against 4T1 and MCF-7 Breast Cancer Cells / Herb Powder: Study evaluated the cytotoxicity of P. fel-terrae herb fractions toward 4T1 and MCF-7 breast cancer cell lines. Herb powder was extracted by maceration with n-hexane, ethyl acetate, and ethanol solvents. Results showed IC50s of 234.10, 50.49, and 212.53 µg/mL for 4T1, and 84.62, 56.79, and 235.51 µg/mL for NCF-7 cell lines, respectively. Results suggest the herb fractions provide anticancer effect. Further studies were suggested for ethyl acetate fraction in inhibiting angiogenesis and metastasis in breast cancer. (33)
• Modulation of TCD4+ and TCD8+ in Doxorubicin-Induced Immuno-Suppressed Rats: Study evaluated the immunomodulatory effects of ethanol extract of puguntano on TCD4 and TCD8 cells doxorubicin-induced Sprague Dawley rats. Treatment of 300 mg/kbw of ethanol extract resulted in reduction of side effect of doxorubicin evidenced by increase in TCD4+ and TCD8+ blood level. (34)
• Effect of Ethanol Percentage on Antioxidant Activity: Study evaluated the antioxidant activity, total phenolic content and total flavonoid content in ethanol extract of P. fel-terrae. Best antioxidant activity was shown by extract with 100% ethanol solvent with DPPH IC50 10.68 µg/mL, FRAP 18.15 µg/mL, and high level of TPC 279.11 mg GAE/g, high TFC of 31.90 mg QE/g. Results suggest potential for development as antioxidant and functional food. (36)
• Antiproliferative / Apoptotic on T47D Cell Line: Study evaluated the cytotoxic, antiproliferative and apoptotic induction activities of n-hexane fraction (nHF) of P. fel-terrae herbs. Cytotoxic activity by MTT assay showed an IC 50 of 75.87 µg/mL. The nHF at 15 µg/mL caused accumulation in G2-M (37.47%) and S phase accumulation (19.41%) and increase early (24.25%) and late apoptosis (4.26%). Results suggest nHF possess antiproliferative and apoptotic induction activities. (37)
• Cardioprotective Against Doxorubicin Cardiomyopathy: Study evaluated an ethyl acetate extract of Picria fel-terrae leaves (EEP) for cardioprotective effect against doxorubicin-induced cardiomyopathy in rats. Phytochemical screening of extract revealed flavonoids, tannins, glycosides, and saponins. DOX significantly raised biomarkers troponin T (cTnT), CK-MB levels (p<0.05), which decreased after administration of vitamin E, rutin, and extract. Histopathological exam of rat's heart tissue showed myocytolysis with congestion of blood vessels, pyknosis, cytoplasmic vacuolization and fragmentation. Concomitant treatment revealed normal muscle fiber. Results suggest the EEP has cardioprotective effect. (38)
• Hypoglycemic Effect / Meta-Analysis: Systematic review and meta-analysis reviewed the effect of Poguntano extract in lowering plasma glucose levels. The effect size was pooled using a random effect model. Two animal studies were included. Results showed a significant difference in plasma glucose level between diabetic control and diabetic rats treated with poguntano extract, with mean reduction of 26.77 mg/dL. In diabetic patients, the extract was associated with lower fasting blood glucose and HbA1c compared to control. Re safety profile, even at doses as high as 10,000 mg/kbw, there were no deaths. Results suggest Poguntano extract is safe in the animal models studied. (39)
• Effect of Combination of Poguntano Leaves Extract with Doxorubicin on MCF-7 Breast Cancer Cells: Study evaluated the cytotoxicity and effect of combination of n-hexane extract with doxorubicin using MTT assay. The IC50 value of n-hexane extract was 119.906 µg/ml and the combination showed higher inhibitory effect compared with single treatment. (40)
• Effect on Metabolic and Inflammatory Profile of Newly Diagnosed T2DM: Study compared the effect of metformin and dhawalsan-1 (Curanga fel-terrae) extract on metabolic and inflammatory characteristics in patients with newly diagnosed type-2 diabetes. Preliminary study indicated C. fel-terrae extract was effective in improving metabolic characteristics and significantly increased adiponectin levels in newly diagnosed T2DM. Improvement was comparable with metformin. (41)
• Effect on hs-CRP Level on Newly Diagnosed T2DM / Clinical Trial: A randomized controlled clinical trial on 24 newly diagnosed T2DM patients evaluated the effect of Puguntano extract on hs-CRP level in newly diagnosed T2DM patients. Metformin was used as control. Results showed lowering of hs-CRP by 1.41 (p=0.06) in the Puguntano group and decrease of 0.58 (p=0.695) in the metformin group. Results showed lowering effect on HbA1c and hs-CRP levels, although it was not statistically significant. (42)
• Capsule Formulation as Hepatoprotective Drug: Puguntano extract has been studied for effect as hepatoprotector. Use of extract has limitation due to unpleasant taste and odor. Study reports on the formulation of ethanol extract of puguntano as granule mass in a capsule dosage form. Excipients used were lactose granules, corn starch (5, 7.5 and 10%m / F1,2,3), talcum, magnesium stearate, methyl-paraben, and propylparaben. All the formulae showed good flowability and free-flowing properties. Results suggest the extract formula can be formulated into granule mass for capsule dosage form. (43)
• Hepatoprotective / Leaves: Study evaluated the hepatoprotective effect of ethanol extract of Curanga fel-terrae leaves in preventing paracetamol-induced liver damage. High dose paracetamol dose of 2.5 g/kbw can cause liver damage evidenced by elevation of AST and ALT. Extract doses of 125, 250 and 500 mg/kg were used. Catechin 2 mg/kg was used as positive control. Results showed hepatoprotective effect evidenced by prevention of AST and ALT elevation, along with histopathology support. (44)
• Antibacterial: Study for chemical constituents isolated six compounds and identified by NMO as follows: 28-O-acetylbetula (1), stigmasterol (2), betula platyphylol (3), picfeltarraenin IA (4), picfeltarraenone I (5), and picria fel-terrae aglycone IV (6). Compound 4 showed good antibacterial activity against Staphylococcus aureus and Bacillus dysteriae. (45)
Availability
Wild-crafted.
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