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- Phyllanthaceae, commonly known as the leaf flower family, a family of lowering plants in the order Malpighiales, consisting of about 60 genera and 2,000 species of herbs, shrubs, trees, and rarely climbers or aquatics, predominantly pantropical with highest diversity in the tropics.
- Taxonomy:
The name Phyllanthaceae was first validly published by Ivan Ivanovich Martynov in 1820 in a Russian book Tekhno-botanico Slovar.
- Many plants now in Phyllanthaceae were one placed in the large and heterogeneous family Euphorbiaceae. Since 1993, phylogenetic analyses have shown Euphorbiaceae consisted of several lineages that did not together form a clade in the order of Malpighiales. Euphorbiaceae was dismantled into a much smaller family, and Phyllanthaceae, among others, were removed from it.
- Phyllanthus urinaria is a species of flowering plant in the family Phyllanthaceae, native to Asia and introduced in tropical and subtropical areas worldwide.
-
Etymology: The genus name means "leaf-flower" from Greek words phyllon (leaf) and anthos (flower), referring to flowers that appear to grow directly from edges of leaves. The species name urinaria derived from Latin for urine or its relationship to the urinary tract and to its long history of folkloric
use and benefit in the treatment of kidney and gallbladder stones; and
hence, its common names of shatterstone or stonebreaker.
 Botany
• Ibaiba-an is an erect, branched, slender, glabrous or nearly glabrous herb,
10 to 40 centimeters high, with angled branches. Leaves are distichous, imbricate, alternate, pale beneath, sessile,
elliptic-oblong to oblong, thin, 5 to 10 millimeters long, obtuse or apiculate,
base slightly oblique, stipules lanceolate. Flowers are unisexual, very small, 5-merous, axillary, about 1
millimeter in diameter, sessile or very shortly pedicelled. Sepal are greenish,
stamens 3, filaments united below; anthers erect, the slit vertical. Fruits are capsules, about 2 millimeters in diameter, muricate or smooth,
of 3 dehiscent.
• Phyllanthus urinaria is a summer annual and germinates from early summer to early fall, requiring warm soil and light. It grows to a height of about 60 centimetres (2 feet), has small alternate leaves resembling those of the genus Mimosa, disposed in two ranges. It is suffruticose, woody at the base and herbaceous above. The leaves are large at the tip and smaller towards the petiole. Leaves are closed at night and are open in the day. Flowers are greenish white, minute and appear in the leaf axils, hanging on short petioles below the leaves. Numerous small green-red fruits, round and smooth, are found along the underside of the stems, which are erect and red. It reproduces by seeds, which are found in the green, wart-like fruit attached to the underside of the branch.
Distribution
- Native to the Philippines. (13)
-
A weed in open spaces at low and medium altitude.
- In waste places throughout the Philippines.
- Also native to Andaman Is., Assam, Bangladesh, Borneo, Cambodia, Caroline Is., China North-Central, China South-Central, China Southeast, East Himalaya, Hainan, India, Japan, Jawa, Korea, Laccadive Is., Laos, Lesser Sunda Is., Malaya, Maldives, Marianas, Myanmar, Nansei-shoto, New Guinea, Nicobar Is., Northern Territory, Ogasawara-shoto, Pakistan, Queensland, South China Sea, Sri Lanka, Sulawesi, Sumatera, Taiwan, Thailand, Tibet, Vietnam, West Himalaya, Western Australia. (13)
 Constituents
- Contains alkaloids, tannins.
- Study isolated 14 compounds, seven were identified as: corilagin, rutin,
brevifolincarboxylic acid, isostrictiniin, geraniin, gallic acid and
ellagic acid. (10)
- Study isolated two new phenolic compounds, crystal VI (methyl brevifolincarboxylate) and crystal IX (trimethyl ester dehydrochebulic acid) together with 8 known compounds elucidated as n-octadecane(I), beta-sitosterol(III), ellagic acid(IV), daucosterol(V), kaempferol(VII), quercetin(VIII), gallic acid(X) and rutin(XI).
(15)
- Aqueous and chloroform plant extracts yielded tannins, saponins, flavonoids, cardenolides, phlobatannins, cardiac glycosides, and phenolic compounds. Specific bioactive compounds were methylene chloride (1),
2-(3- Oxo- 1,3-Dihydroisobenzenefuran-1- ylmethyl) Benzoic acid (2), Carissanol dimethyl ether (3), Phenethylamine, 2-Methoxy α,-Methyl-4,5-( Methylenedioxy) (4), 16 - Heptadecanal (5), Cyclohexane, 1-(1,5- Dimethylhexyl)-4-(4- Methylpentyl) (6). (see study below) (18)
- Study of ethanolic extract of plant isolated 9 compounds: phyllanthin (1), phyltetralin (2), trimethyl-3,4-dehydrochebulate (3), methylgallate (4), and rhamnocitrin (5), methyl brevifolincarboxylate (6), β-sitosterol-3-O-β-d-glucopyranoside (7), quercitrin (8), and rutin (9). (see study below) (26)
- Study of P. urinaria extracts yielded polyphenols including gallic acid, methyl gallate, epicatechin, epigallocatechin-3-gallate, gallocatechin-3-gallate, rutin, epicatechin-3-gallate, and naringin. (see study below) (28)
- UPLC/MS identified key compounds: gallic acid, proline, choline, betaine and malic acid. (see study below) (37)
Properties
- Considered a competitive weed in some areas because of its numerous seeds, high shade tolerance, and extensive root system.
(25)
-
Considered abortifacient, demulcent, diuretic, ecbolic, febrifuge, antihepatotoxic, antiviral,
antibacterial and hypoglycemic.
- Studies have suggested anticancer, antidiabetic, antioxidant, antiviral, cardioprotective, anti-inflammatory, anti-angiogenic, anti-telomerase, α-amylase inhibitory, antimetastatic, nephroprotective properties.
Parts
utilized
· Entire plant.
 Uses
Edibility
· Not used as standard food or vegetable; however, dried or fresh leaves and aerial parts are used in the traditional preparations of herbal tea and medicinal infusions. Caution is advised: consuming large amounts can cause adverse toxic effects or stomach irritation. (see others below)
Folkloric
· Used in folk medicine for Infantile convulsions, hepatitis, jaundice, diabetes, malaria, nephritic edema, urinary infection, lithiasis, enteritis-diarrhea, dysentery,
· Used for reddening and swelling pains of the eye.
· Dosage: use 15 to 30 gms of dried material or 30 to 60 gms
of fresh material in decoction.
· In Ayurveda, used to treat jaundice,
dysentery, diabetes, skin ulcers, itching.
· In China, traditionally used to eliminate gallstones and kidney stones; for liver disease and as immune stimulation.
· In Taiwan, traditionally used to reduce heat, remove food stagnancy, improve eyesight, relieve inflammation, calm the liver, suppress yang hyperactivity of the liver, detoxify body poisons and increase the flow of urine. Decoction used as tea for treatment of inflammatory diseases. (26)
· In Thailand, P. urinaria is traditionally used as an adjuvant or alternative medicine for cancer patients, including liver cancer. (38)
· Plant ash in water applied as ear drops for treatment of earache. Crush plant parts or infusion applied for treatment of ulcers, sores, and tumors. Paste of fresh crushed leaves and kaolin in water is drunk and applied to the body to treat convulsions, colic, constipation, urethral discharges. Bitter leaves are used for treatment of hiccups and cough. Also used as bitter tonic, for treatment of fevers, including malaria. (39)
Others
· Fish poison: Bruised or crushed plant parts used as fish poison, thrown into streams and ponds to stun or kill fish for catching.
Studies
• Ellagic Acid / Anti-Angiogenic Activity: Study evaluated the anti-angiogenic effect of a water extract of P. urinaria in chorioallantoic membrane in chicken embryo and human vascular endothelial cells. Results suggest that Ellagic Acid is the active component of P urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 (matrix metalloproteinase-2) protein from HUVECs (human vascular endothelial cells). (11)
• Anti-viral / Anti-HSV2: (1)
Acetone, ethanol and methanol extracts of Phyllanthus urinaria inhibit
HSV-2 infection in vitro: Study showed the extracts likely inhibited
HSV-2 infection by decreasing virus infectivity and disturbing the early
stage of infection. (2) Study yielded excoecarianin with possible
entry-inhibitor activity against HSV2 and presents a potential for combinational
drug treatment in the management of HSV-2 infection.
• Chronic Hepatitis B: Study
of aqueous extracts of dried herbs of PU did not show cytotoxicity in
uninfected normal cells while protecting MDBK cells from viral infection.
Results support other clinical studies that suggests the herbal supplement
may be beneficial for chronic hepatitis B patients.
• Hippomanin / Anti-Herpes: Hippomanin
A from Acetone Extract of Phyllanthus urinaria inhibited HSV-2 but not
HSV-1 Infection In Vitro: Results shows hippomanin A impeded HSV-2 but
not HSV1. (2)
• Antioxidant / Cardioprotective:
Antioxidative and Cardioprotective
Effects of Phyllanthus urinaria L. on Doxorubicin-Induced Cardiotoxicity:
Study showed the PU's cardioprotection was mediated through multiple
pathways, and suggests this plant may be an alternative source of antioxidants
for the prevention of DOX cardiotoxicity. (3)
• Antioxidants: Study isolated a series of 15 phenolic compounds, including ellagitannins 1-7, flavonoids 8-10, and simple hydoxylated aromatic acides 11-15. Results demonstrated considerable
radical-scavenging activity. (4)
• Hepatoprotective: Study
of alcohol extract of Phyllanthus urinaria showed hepatoprotective effects
by inducing the activity of the liver enzyme system. (5) Study concludes that P urinaria is effective in attenuating the acetaminophen-induced hepatotoxicity. The therapeutic mechanism may involve the inhibition of cytochrome P450 CYP2E1 enzyme. (12)
• Anti-Telomerase Activity /
Anti-Cancer: Study investigated
the effect of P urinaria on telomerase activity and apoptotic pathways
in the human nasopharyngeal carcinoma lines. Study yielded 5 major compounds:
gallic acid, brevifolin carboxylic acid, corilagin, phyllanthusiin C
and ellagic acid. Results showed PU induces death of NPC-BM1 cells in
vitro through apoptosis induction and telomerase inhibition.
(6)
• Anticancer: Water
extract of P urinaria was tested for anticancer effect on human myeloid
leukemia cells. P urinaria induced apoptosis of HL-60 cells probably
mediated through a ceramide-related pathway.
• Anticancer Effects and Mechanisms: Study reports the anticancer effects of P. urinaria both in vivo and in vitro, together with relevant mechanisms. Study suggests the anticancer activity of the water extract is mainly due to induced apoptosis of cancer cells as demonstrated by DNA fragmentation and increased caspase-3-activity through both intrinsic and extrinsic pathways. Decrease in viability might be partly due to down-regulation of telomerase activation and induction of the apoptotic process. (16)
• Apoptosis in Human Osteosarcoma 143B Cells: Study demonstrated that P. urinaria inhibited human osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate Fas receptor/ligand expression. Study offers evidence that mitochondria are essential for the anticancer mechanism induced by P. urinaria through both intrinsic and extrinsic pathways. (17)
• Anti-Diabetic: Study evaluated the antidiabetic properties of bioactive compounds extracted from P. urinaria. Chloroform and aqueous extracts both yielded bioactive compounds, with the aqueous extract showing to be richer in phytochemicals than the chloroform extract. The phytochemicals showed better efficiency in lowering blood glucose level as compared to metformin. (see constituents above) (18)
• Antagonistic Antimicrobial Activity with P. tectorius and L. rhamnosus: Study evaluated the bioactivity of P. urinaria leaf extract before and after it was combined with Pandanus tectorius fruit extract and Lactobacillus rhamnosus extract. In combination the extracts showed weaker activities. Results showed the antagonistic characteristics of P. urinaria and P. tectorius and L. rhamnosus on Staphylococcus aureus and Pseudomonas aeruginosa. (19)
• Amelioration of Nutritional Steatohepatitis: Study evaluated the effects of P. urinaria on nutritional steatohepatitis both in vitro and in vivo. Phyllanthus prevented MCD (methionine-and-cholie-deficient)-induced hepatic fat accumulation and steatohepatitis in mice, probably by dampening oxidative stress, ameliorating inflammation, and decreasing lipid accumulation. (20)
• Antiviral / Herpes Simplex Viruses: Study evaluated the antiviral activity of aqueous extracts of four Phyllanthus species against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells. P. urinaria exhibited the strongest antiviral activity against HSV-1 and HSV-2, with S1>33.6. (21)
• Anti-Inflammatory / Adjuvant-Induced Arthritis: Study evaluated the preventive effects of PU extract on paw edema in adjuvant-induced arthritis in rats. Results indicate the PU extract is effective as anti-inflammatory agent in adjuvant-induced arthritis in rats, an activity probably markedly influenced by the inhibition of neutrophil migration into inflamed tissue. (22)
• Antiviral / Corilagin: Study evaluated the antiviral effect of P. urinaria and corilagin, a major component, on EV71 (human enterovirus 71) and CA16 (coxsackie virus A16) infection in vitro. Results showed corilagin reduced the cytotoxicity induced by EV71 and CA16 on Vero cells with an !C50 value of 5.6 and 32.33 µg/ml, respectively. (23)
• Anti-Inflammatory / Antioxidant: Study of ethanolic extract of plant isolated 9 compounds, and evaluated for antioxidant and anti-inflammatory activities in vitro. In antioxidant assay, isolates 3, 4, and 6 exhibited significant DPPH radical scavenging activity with IC50-s of 9.4, 9.8 and 8.9 µM, respectively. In inflammatory mediators growth inhibitory assay from LPS/interferon (IFN)-γ activated peritoneal macrophages, all isolates except for 7, significantly and dose-dependently inhibited the enhanced production of NO radicals - a modulation closely associated with inhibition of TNF-
α and IL-6. At 30 µM, isolates 3 and 6, and 50 µM of 4, significantly arrested the mitogen-stimulated spleen cells in G0/G1 stage. Study suggests the isolates have potential for treatment of cell-mediated immune diseases. (see constituents above) (26)
• α-Amylase Inhibition / Leaves: Study evaluated herbs by in vitro enzyme assay for inhibitory activity against porcine pancreatic amylase (PPA). Phyllanthus urinaria and three other herbs showed potent inhibitory activity. Liquid chromatography of fractions from 50% aqueous methanol-soluble extract of leaves isolated gallic acid, corilagin, and macatannin B, and showed mild activity against PPA (activity in 1 mmol L-1 concentration: 23%, 21%, 33%, respectively). Results suggest further exploration and potential for management of borderline diabetes. (27)
• Antimetastatic on A549 and Lewis Lung Carcinoma Cells: Study reports on the molecular evidence associated with antimetastatic effects of P. urinaria extract (PUE) showing marked inhibition on invasion (p<0.001) and migration (p<0.001) of highly metastatic A549 and Lewis lung carcinoma (LLC) cells. PUE treatments may decrease expressions of matrix metalloproteinase-2, urokinase plasminogen activator, and their endogenous inhibitors. PUE showed inhibitory effects on metastasis and growth of LLC cells. Results suggest potential for PUE as antimetastatic agent. (see constituents above) (28)
• Anticancer / Apoptosis Induction via Mitochondria-Associated Intrinsic Pathway: Study evaluated the anticancer effect of water extract of P. urinaria. The extract significantly reduced the number of Lewis lung carcinoma cells in a dose- and time-dependent manner by MTT assay. The extract did not exert cytotoxic effect on normal cells i.e., endothelial and liver cells. Flow cytometry study showed dose-dependent increase of dead cells 24 hours after treating Lewis lung carcinoma cells. The anticancer activity was due to apoptosis induced in Lewis lung carcinoma cells. Apoptosis was associated with down-regulation of Bcl-2 gene expression. The apoptosis of Lewis lung carcinoma cells, at least in part, may be through a mitochondria-associated intrinsic pathway. (29)
• Inhibitory Effects on Phagocytic Activity: Study sought to correlate the prevalent constituents of the herbs and their inhibitory effects on phagocytic activity of human neutrophils. RP-HPLC of Phyllanthus urinaria and P. amarus identified gallic acid, ellagic acid, corilagin, geraniin, phyllanthin and hypophyllan-
thin.
All plant extracts strongly inhibited migration of phagocytes. Strong inhibitory effects of extracts on phagocytic activity of neutrophils was attributed to the compounds, which were able to modulate the innate response of phagocytes at different steps. (30)
• Nephroprotective in Cisplatin-Induced Acute Kidney Injury: Study evaluated the therapeutic potential of P. urinaria (PU) against AKI (acute kidney injury) triggered by cisplatin administration. Results showed PU may mitigate cisplatin's structural damage to renal tissue. Post-treatment with PU showed significant reduction in pro-inflammatory cytokines IL-1ßm UK-6, and TNF-α. Reduced oxidative stress markers MDA and SOD activity suggest reduction in oxidative damage. PU also countered cisplatin-induced downregulation of NRF2 and NqO1, highlighting its restorative effect on antioxidant pathways. Results showed PU's protective capability against cisplatin-induced AKI, suggesting therapeutic potential in counteracting cisplatin's nephrotoxicity. (31)
• No Anti-Viral Effect on Hepatitis B / Clinical Trial: Double-blind placebo-controlled study evaluated the anti-viral effect of Phyllanthus urinaria in chronic hepatitis B patients with +HBeAg, HBV DNA > 500 copies/mL and elevated ALT. P- urinaria treatment for 6 months showed no demonstrable anti-viral effect in chronic hepatitis B. (32)
• Inhibitory Effect on Replication of Lamivudine-Resistant Hepatitis B Virus: Phyllanthus urinaria extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating cells harboring HBV wild-type and LMV-resistant mutants, probably by inducing expression of IFN-ß, COX-2, and IL-6. Study suggests P. urinaria extract has potential as alternative therapeutic agent for treatment of drug-resistant CHB patients. (33)
• Anti-Tumor / Anti-Angiogenic in Lewis Lung Carcinoma: Study evaluated the antitumor activity of P. urinaria extract in C57BL/6J mice implanted with Lewis lung carcinoma cells. Oral administration of P. urinaria in mice caused significant inhibition of tumor development with lower occurrence rate and markedly reduced tumor size. TUNEL assay showed increase of apoptosis in tumor sections. Tumor neovascularization was inhibited, which suggested potential anti-angiogenic effect. (34)
• Increase Apoptosis and Decreased Telomerase Activity in Human Nasopharyngeal Carcinoma Cells: Study evaluated the effect of P. urinaria on telomerase activity and apoptotic pathways in human nasopharyngeal carcinoma cell line (NPC-BM1). HPLC/MS identified 5 major compounds: gallic acid, brevifolin carboxylic acid, corilagin, phyllanthusin C and ellagic acid. MTT assay demonstrated gallic acid and ellagic acid reduce cell viability. Apoptosis features showed DNA fragmentation and increased caspase-3 (proliferating cell nuclear antigen) in NPC-BM1 treated cells. Treatment also led to inhibition of hTERT (human telomerase reverse transcriptase), hTP1 (human telomerase-associated protein. Results suggest P. urinaria induced death of NPC-BM1 cells in vitro via induction of apoptosis and inhibition of telomerase activity. (35)
• Chemopreventive on DMBA-induced Skin Carcinogenesis: Study evaluated the tumor inhibition by hydroalcoholic extract of whole plant of P. urinaria in female albino mice on two-stage process of skin carcinogenesis induced by repeated application of croton oil. Results showed significant reduction in tumor incidence and number of papillomas. Results suggest possible chemopreventive property against DMBA-induced skin papillomagenesis in mice. (36)
• Amelioration of Lipid Accumulation in Fatty Liver Syndrome: Fatty liver syndrome (FLS) is a common metabolic disease in laying hens, causing reduced egg production and sudden death. Study showed PU improves FLS by reducing plasma TG and serum TBARS levels, body fats and inflammation while enhancing ß-oxidation. PU has potential as dietary supplement and treatment for fatty liver disease in humans and chickens. (see constituents above) (37)
• Effect on HepG2 Cell Viability and Oxidative Phosphorylation: Study evaluated the cytotoxic effect of 50% methanolic extract of P. urinaria on human hepatocellular carcinoma HepG2 cells and the effect on oxidative phosphorylation by isolated rat liver mitochondria. Results showed the hydromethanolic extract induced cell death death of HepG2 cells in a dose-dependent fashion. IC50 by trypan blue exclusion and MTT assay were 431 µg/ml and 445 µg/ml, respectively. The extract impairs energy metabolism via inhibition of oxidative phosphorylation and as weak mitochondrial uncoupler. The mito-
chondrial effects may play a role in the cytotoxic action on HepG2 cells. Results suggest potential as adjunctive medicinal potential for treatment of the deadly disease. (38)
Availability
• Wild-crafted.
• Dried herbs, capsules, powders, and live plants in the cybermarket. |
