Ulasiman-kalat is a slender, spreading or ascending,
smooth, more or less branched, annual herb, reaching a length or 50 centimeters
or less. Leaves are linear and 1 to 3 centimeters long. Flowers are white, 3 millimeters long and occurring singly in the
axils of the leaves. Pedicels are about as long as the calyx. Corolla
lobes are entire. Ovary is 2-celled. Fruits are capsules, loculicidal, ovoid, about 4 millimeters long
and do not protrude beyond the calyx segments.
- A common weed in and about towns and in waste places, gardens and open lands throughout the Philippines.
- Also occurs in India to Japan and Malaya.
· Entire plant.
· Harvest the entire plant from April to September.
· Wash and sun-dry.
- Yield flavones, anthraquinones, polysaccharides.
- Study yielded a four anthraquinones, triterpenoids (ursolic acid and oleanolic acid).
- Study of chemical constituents yielded anthraquinones, terpenoids, flavonoids, steroid alcohols, alkanes, organic acids, polysaccharides, coumarin and alkaloids.
- Bioassay-guided study for neuroprotective compounds from a methanol extract of whole plants of H. diffusa yielded five flavonol glycosides, kaempferol 3-O-[2-O-(6-O-E-feruloyl)-β-d-glucopyranosyl]-β-d-galactopyranoside (1), quercetin 3-O-[2-O-(6-O-E-feruloyl)-β-d-glucopyranosyl]-β-d-galactopyranoside (2), quercetin 3-O-[2-O-(6-O-E-feruloyl)-β-d-glucopyranosyl]-β-d-glucopyranoside (3), kaempferol 3-O-(2-O-β-d-glucopyranosyl)-β-d-galactopyranoside (4), and quercetin 3-O-(2-O-β-d-glucopyranosyl)-β-d-galactopyranoside (5), and four O-acylated iridoid glycosides (6−9). (see study below) (1)
- Study yielded nine compounds: 2, 6-dihydroxy-1-methoxy-3-methylanthraquinone, 2-hydroxy-1-methoxy-3-methylanthraquinone, 2-hydroxy-3-methylanthraquinone, quercetin-3-O-[2-O-(6-O-E-sinapoyl)-beta-D-glucopyranosyl]-beta-glucopyranoside, quercetin-3-O-[2-O-(6-O-E-feruloyl)-beta-D-glucopyranosyl]-beta-glucopyranoside, kaempferol-3-O-[2-O-(6-O-E-feruloyl)-beta-D-glucopyranosyl]-beta-galactopyranoside, quercetin-3-O-(2-O-beta-D-glucop-yranosyl)-beta-D-glucopyranoside, rutin, and quercertin.
- Studies have yielded 171 compounds including iridoids, flavonoids anthraquinones, phenolic acids and their derivatives, sterolds, triterpenes, polysaccharides, cyclotides, coumarins, alkaloids, and volatile oils. (see study below) (27)
- A n-butanol fraction of methanol extract of aerial parts isolated an iridoid glycoside, oldenlandoside III (5), along with six other previously characterized iridoid glycosides viz., geniposidic acid (1), scandoside (2), feretoside (3), 10-O-benzoylscandoside methyl ester (4), asperulosidic acid (6), and deacetylasperulosidic acid (7). (see study below) (45)
- GC-MS analysis for essential oil
yielded 43 components with 11 alkaloids, 7 alkenes, 5 ketones, 7 aldehydes, 6 acid substances, 2 esters, and 5 other substances. Main components of the oil were hexadecanoic acid (48.89%) followed by pentadecanoic acid (6.11%), D-limonene (5.74%), and fatty acid. (47)
- Sweet tasting, cooling in effect.
- Considered alterative, antibacterial, antidote, analgesic, anti-inflammatory,
antitumor, diuretic, febrifuge and sedative.
- Studies have shown anticancer, immunomodulatory, neuroprotective, radical scavenging, hepatoprotective, anti-inflammatory activities.
· For any kind of inflammation,
e.g., tonsillitis, laryngitis, and appendicitis: use dried preparation
30 to 60 gms (or fresh material 120 to 240 gms) boil to decoction and
· Used for jaundice and hepatitis, malignant tumors.
· Poultice of plant material used for external bruises or blood
congestions, boils, and abscesses.
· Plant decoction used for biliousness, fever and gonorrhea.
· Used for fevers, cough, asthma.
· In Chinese folk
medicine, used in hepatitis and malignant tumors of the liver, lung
and stomach. Also used for carbuncles, skin sores and ulcerations, tonsillitis, painful
swollen throats, appendicitis, urethral affections, gynecologic infections, and snake bites.
· In traditional Chinese medicine, used in the treatment of breast cancer. (25)
· In Taiwan popularly used as anticancer medicine. (27)
• Neuroprotective Constituents:
Bioassay-guided study for neuroprotective compounds from a methanol extract of whole plants of H. diffusa yielded five flavonol glycosides and four O-acylated iridoid glycosides.
All nine compounds exhibited significant neuroprotective activity in primary cultures of
rat cortical cells damaged by L-glutamate. (see constituents above) (1)
• Antitumor: Although
used in folk medicine for malignant tumors of the liver, lung and stomach,
study showed no antiproliferative or antiangiogenic effects to support
its folkloric antitumor use.
• Increased Immunocompetent Activity:
Study showed H diffusa improved the leukopenia and splenic cellular
decrease caused by irradiation and increased the immunocompetence of
splenic cells after mitogenic stimulation. Study suggests H diffusa
may be effective in preventing hematopoietic damage in combination use
with radiotherapy. (3)
• Antioxidant / Radical Scavenging: In
a study of H diffusa, H corymbosa and M pentaphylla, all three showed
varying levels of antioxidant and radical scavenging activities. (•) Study evaluated the radical scavenging activity of a dried sampled of H. diffusa extracted by 85% ethanol using Nitric Oxide assay. The plant showed maximal activity of 72.28% at 1000 µg/ml concentration with IC50 value of quercetin and herb at 10.24 µg/ml and 104.18 µg/ml respectively. (34)
• Phytochemicals: Study isolated five flavonoids from H diffusa: kaempferol, kaempferl 3-O-beta-D-glucopyranoside, kaempferol 3-O-(6"-O--L-rhamnosyl)-beta-D glucopyranoside, quercetin 3-O-(2"-O-beta-D-glucopyranosyl)-beta-D-glygopyranoside.
• Anticancer: Study evaluated O. diffusa water extract extract against eight cancer cell lines and one normal cell line. Results showed strong antiproliferative activity against all cancer cell lines and induced significant increase of apoptosis. The extract showed limited cytotoxicity on normal pancreatic cells. Also, there was significant inhibition of lung metastases in the animal model without noticeable side effects. Results suggest a potential for an anticancer agent. (6)
• Methylanthraquinone / Anticancer: Study yielded methylanthraquinone from Hedyotis diffusa which exhibited potent anticancer activity. In a study in human breast cancer cells, results suggested that methylantrhaquinone induced MCF-7 cells apoptosis via Ca2+/calpain/caspase-4-pathway. (7 )
• Antitumor / Phytotoxic: Study of leaf methanol extract of Oldenlandia diffusa showed tumor inhibition on potato disc and significant phytotoxicity. Results suggest Oldenlandia diffusa might be a potential source of antitumor agent for use in the treatment of tumors in human. (8)
• Oleanolic Acid / Fibroblast Inhibition / Chemopreventive / Chemotherapeutic: Study showed oleanolic acid inhibited the growth of ras oncogene-transformed R6 cells at doses not toxic to normal fibroblasts. Results demonstrate oleanolic acid possess both cancer therapeutic and chemopreventive activities and presenting a great potential as a novel anti-cancer drug. (9)
• Cytotoxicity / Ursolic/Oleanolic Acid: Study sought to identify the most cytotoxic constituents of a water extract. Results suggest certain constituents, possibly including ursolic/oleanolic acid, may be bioavailable and at sufficient concentration induces apoptosis in cancer cells through mechanisms including the cleavage of PARP. (12)
• Corymbosa Vs Diffusa: A systematic survey showed O. corymbosa to be used indiscriminately as O. diffusa. Study showed the oleanolic acid and ursolic acid contents in O. diffusa were lower than O. corymbosa. (13)
• Evidence- Based Perspective For Cancer: About 15% of anticancer herbal concoctions used in China contain H. diffusa. Preclinical and clinical studies have established safety and efficacy for certain cancers. It can inhibit growth of some cancer cells, induce apoptosis in vitro and in vivo, exhibit selective cytotoxicity. It has immune modulation functions against cancer, and enhances natural killer cells and macrophage activities. (14)
• Cancer Cell Apoptosis / Burst-Mediated Caspase Activation: Study of ethanol extract showed dose-dependent inhibition of cancer cell growth in MTT assay. The cancer cell apoptosis was probably through burst-mediated caspase activation. (15)
• Ulcerative Colitis: Study investigated the protective effect of Oldenlandia diffusa in dextran sulfate sodium (DSS)-induced colitis. OD attenuated clinical signs and suppressed levels of interleukin IL-6, IL-1ß and expression of COX-2 in DSS-treated colon tissues. Results suggest a potential experimental medicine for patients with ulcerative colitis. (16)
• Antiproliferative / Apoptotic / Breast Cancer: Study showed OD and its bioactive compounds exert antiproliferative and apoptotic effects selectively in ERa-positive breast cancer cells, suggesting a potential for preventive or therapeutic use. (17)
• Tumor Inhibition: Study evaluated the key components exhibiting anti-tumor activities in the two herbs, Hedyotis corymbosa and H. diffusa using plant components ursolic acid, oleanolic acid, and geniposidic acid. Results showed ursolic acid and oleanolic acid to inhibit the growth of cultured hep-2B cells and enlargement of subcutaneous tumor. (18)
• Anti-Inflammatory / Hepatoprotective / Peh-Hue-Juwa-Chi-Cao: Study in rats evaluated Peh-Hue-Juwa-Chi-Cao, containing extracts of Hedyotis diffusa, H. corymbosa or Mollugo pentaphylla. Results showed all three possess anti-inflammatory activity and hepatoprotective properties, reducing acute elevation of SGOT and SGPT after intraperitoneal administration of hepatotoxins. (19)
• Hepatoprotective / LPS-Induced Liver Damage: Study evaluated the hepatoprotective effects of HD against lipopolysaccharide-induced liver damage in Sprague-Dawley rats. Results showed hepatoprotective activity attributed, in part, to its antioxidant activity. (20)
• Tumor Angiogenesis: Study evaluated the angiogenic effects of an ethanolic extract of H. diffusa. Results showed in vivo inhibition of angiogenesis in chick embryo chorioallantoic membrane and dose-time-dependent inhibition of proliferation of human umbilical vein endothelial cells by blocking of cell cycle progression. EEHDW also down regulated the mRNA and protein expression levels of VEGF-A in HT029 human colon carcinoma and HUVECs. Results suggest inhibition of tumor angiogenesis is one of the mechanisms by which H. diffusa is involved in cancer therapy. (21)
• Immunomodulating: In vitro study evaluated the effect of eight Chinese medicinal herbs on lymphocytes using murine spleen cells. Oldenlandia diffusa and Astralagus membranaceous markedly stimulated murine spleen cells to proliferate. Study suggested the active component of O. diffusa was glycoprotein in nature. Results suggest immunomodulating activity that can be clinically used for the modulation of immune responses. (23)
• Inhibition of Colorectal Cancer Growth in Vivo Via Inhibition of Signaling Pathway: Signal Transducer and Activator of Transcription 3 (STAT3) is a common oncogenic mediator in many types of human cancers. Hedyotis diffusa is a common anticancer component in many Chinese medicine formulas. This study evaluated the effect of an ethanol extract on tumor growth in vivo in mice. Results showed reduced tumor volume and tumor weight without apparent adverse effect. Treatment also altered the expression pattern of several target genes of STAT3 signaling pathway. Results suggest the STAT3 suppression may be one the mechanisms of its effect in colorectal treatment. (24)
• Effect on Apoptosis and Proliferation of Cervical Tumor: Study evaluated the inhibitory effect of Hedyotis diffusa on cervical cancer in human cervical carcinoma nude mice xenograft. Results showed an inhibitory effect on cervical cancer cells and induced apoptosis of HeLa cells, with significantly decreased expression of K1-67 protein. (26)
• Phytochemistry Review: Phytochemical studies have reported one hundred and seventy-one compounds including iridoids, flavonoids anthraquinones, phenolic acids and their derivatives, sterolds, triterpenes, polysaccharides, cyclotides, coumarins, alkaloids, and volatile oils. Of these, iridoids, flavonoids, and anthraquinones are three main ingredients which may play a roles in its activities. (27)
• Inhibitory Effects on
Colorectal Cancer Stem Cells: Cancer stem cells (CSCs) have been proposed to have close correlation with the development and progression of tumors, as well as chemo- and radioresistance. Study isolated stem-like side population (SP) from colorectal cancer HT-29 cells. An ethanol extract of Hedyotis diffusa exerted inhibitory effects on cancer stem cells (CSCs). (30)
• Inhibition of HT-29 Human Colorectacl Cancer Cell Proliferation Via Cell Cycle Arrest: Study evaluated the mechanism of H. diffusa ethanol extract on proliferation of HT-29 human colon carcinoma cells. Results showed a reduction in HT-29 cell viability and survival in a dose- and time-dependent manner. Treatment also blocked cell cycle, preventing progression of B1 to S, reduced mRNA expression of pro-proliferative PCNA, Cycin D1 and CDK4, while increasing anti-proliferative p21. Results suggest potential treatment for colorectal cancer via suppression of cancer cell apoptosis. (31)
• Oleanolic Acid Content / Anti-HepG-2 Cell Activity: HPLC method established the determination of oleanolic acid content of H. diffusa, which showed good linearity within the experimental concentration range, good stability, and reliability. Results showed H. diffusa can effectively inhibit the proliferation of human hepatoma HepG2-cells. (32)
• Anticancer Activity
of Oldenlandia diffusa & Viola philippica: Study evaluated the in vitro cytotoxic activities of ethanol extract of two herbs viz., O. diffusa and V. philippica on four cancer cell lines and two non-cancer cell lines using MTT cytotoxicity assay. Both ethanol extracts effectively inhibited the growth of all the cancer cell lines, particularly MiaPacA-2 cancer cells. (33)
Potential in Drug Resistant Colorectal Carcinoma: Study evaluated the efficacy and potency of ethanol extracts of H. diffusa on a multidrug resistant CRC HCT-8/5-FU cell line. Results showed significant reduction in cell viability of HCT-8/5-FU cells in a dose- and time-dependent manner. Treatment with HD also inhibited ABCG2-mediated drug resistance by down-regulating the expression of ABCG2 and P-gp. Results suggest a potential application as alternative approach in the treatment of drug-resistant CRC. (35)
/ Colorectal Cancer Cell Line: Study evaluated the anti-cancer effects of an ethanol extract of Oldenlandia diffusa on HT-29 human adenocarcinoma cells. EOD inhibited the proliferation of HT-29 cells, increased the number of cells in sub-G1 peak in a dose-dependent manner, elevated mitochondrial membrane depolarization, significantly increased ROS generation. A combination of EOC and chemotherapeutic agents noticeably suppressed the growth of HT-29 cancer cells. (36)
• Antiproliferative and Apoptotic / Hepatocellular Carcinoma with Liver Cirrhosis: Liver cirrhosis is a risk for hepatocellular carcinoma (HCC). Study evaluated the therapeutic effect of Oldenlandia diffusa (OD) in in-vitro and chemically-induced HCC model in rats. Results suggest OD may have antiproliferative activity, inhibitory effect on metastasis, and apoptotic effects in chemically induced HCC model, with potential clinical application as an herbal anticancer drug. (37)
• Anti-Tumor Effects Via Epigenetic Regulator / Human Ovarian Cancer Cells: Ovarian cancer is the most fatal gynecologic malignancy among women with a high risk of late diagnosis and recurrence. Cisplatin, a platinum-based anti-tumor drug, is widely used against ovarian cancer. However, acquired chemo- resistance is common after treatment. Study evaluated the antitumor effects of OD extracts and/or cisplatin on ovarian cancer cells. Consistently, treatment of methanol extract on A2780cis cells significantly reduced KDM1B mRNA expression in a dose-dependent manner. Results showed the OD extract may promote cell death in the resistance cells under cisplatin through modulation of KDM1B. (38)
• Evidence-Based Perspective for Cancer Patients: Oldenlandia diffusa is one of the most commonly used anticancer herbs. About 15% of Chinese anticancer herbal formulas contain O. diffusa. Pre-clinical and clinical studies have established efficacy and safety in the treatment of various cancers. It has shown inhibition of various cancer cell growth and in-vivo and in-vitro induction of apoptosis, selective cytotoxicity, suppression of some oncogenes and up-regulation of anti-oncogenes, immune modulation functions against cancer, and enhancement of efficacies and reduction of adverse effects of conventional chemotherapies. The commonly used clinical doses of 30-60mg/day have not shown to cause considerable adverse effects. (39)
• Anti-Inflammatory in LPS-Activated Macrophages / Suppression of NF-lB and MAPK Signaling Pathways: Nuclear factor kB (NF-kB) and mitogen-activated protein kinase (MAPK) signaling pathways play a central role in inflammatory responses. Total flavonoids of H. diffusa Willd (TFHDW) are active compounds of Hedyotis diffusa used in traditional Chinese medicine for treatment of inflammatory conditions, including bronchitis and ulcerative colitis. This study evaluated the anti-inflammatory effect of TFHDW and its molecular mechanisms in an in vitro anti-inflammatory model using LPS-stimulated RAW 264.7 cells. Results suggested TFHDW negatively modulated the production of NO and cytokines in a concentration dependent manner. TFHDW exerted anti-inflammatory activity via suppression of NF-kB and MAPK signaling pathways. (40)
• Influence on CYP450 Activities: Cytochrome P450, a drug metabolic enzyme, may be influence by herbal medicine and various drug-drug interactions. Study evaluated the potential influences of O. diffusa on CYP450 activities in rats using a cocktail method using five specific probe drugs i.e., phenacetin, omeprazole, tolbutamide, metoprolol, and midazolam according to pharmacokinetic parameters changes. No statistically significant difference (p<0.05) in pharmacokinetic behaviors were observed in the five probe drugs. Results provide potential guidance on clinical drug combination with OD. (41)
• Ursolic Acid / Antitumor Effects: Cytotoxicity-guided fractionation of methanol extract of O. diffusa isolated ursolic acid (UA) as an active principle. Ursolic acid demonstrated significant inhibition of the proliferation of cultured tumor cells, i.e., A549 (human lung), SK-OV-3 (ovary), SK-MEL-2 (skin), XF498 (brain), HCT-15 (colon), SNU-1 (stomach), L1210 (murine leukemia), and B16-Fo (murine melanoma). Results suggest the cytotoxicity or apoptotic effect on tumor cells might be related to the activation of endonucleolytic enzyme and subsequent activation of poly(ADP-ribose) polymerase in tumor cells which may eventually lead to cell lysis. (42)
• Inhibition of Biofilm Formation by Hemophilus influenzae: Study evaluated the clinical utility, antimicrobial and biolfim inhibitory activities of O. diffusa extract against clinical isolates of Haemophilus influenzae, a major respiratory and sensory organ pathogen. Results showed inhibitory activity against luxS-dependent biofilm formation but no antimicrobial activity against planktonic cells of H. influenza. (43)
• Effect on Murine Leukemia WEHI-3 Cells In Vivo and Promotion of T- and B-Cell Proliferation: Study established murine WEHI-3 leukemia in BALB/c mice and hypothesized the antileukemic effects of an aqueous extract on leukemic animals in vivo. The extract increased the percentage of CD3 (T-cell) and CD19 (B-cell) markers. The isolated splenocytes from extract-treated leukemic mice showed an increase in T- and B-cell proliferation in vivo. Results suggest the extract has antileukemic activity in WEHI-3 cell-induced leukemia in vivo. (44)
• Iridoid Glycoside / Oldenlandoside III / Inhibition of LDL-Oxidation / Aerial Parts: Study isolated an iridoid glycoside, oldenlandoside III from a n-butanol fraction of methanol extract of aerial parts, along with six other known iridoid glycosides. Compounds 1, 2, and 7 inhibited LDL-oxidation, with 63.3, 62.2 and 63.8% inhibition, respectively. (see constituents above) (45)
• Stearic Acid / Apoptotic Effects on Human Hepatoma Cells: Bioassay guided study isolated stearic acid. SA showed significant inhibitory effects on the growth of human hepatoma cell lines, HepG2 and Hep3B, but not on human normal liver cell line. Results showed induction of apoptosis on both HepG2 and Hep3B cells with induction of sub-G1 population, DNA fragmentation, changing of mitochondrial transmembrane potential and activation of caspase precursors. Results suggest an active component with potential for hepatoma treatment. (46)
• Inhibition of Tumor Growth / Augmentation of Macrophage Oxidative Burst: Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung, and rectal tumors. Study showed a dose-dependent augmentation of oxidative burst with both OD and SB. Oral feeding with either OD and SB significantly inhibited growth of murine renal cell carcinoma in mice. Results showed both OD and SB can enhance macrophage function in vitro and inhibit tumor growth in vivo. (48)
• Complementary Chinese Herbal Medicine / Improved Survival in Pancreatic Cancer: Pancreatic cancer is a difficult cancer to treat, late in presentation, with a poor prognosis. This study investigated the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. The nationwide population-based cohort study included 386 CHM users and 386 non-CHM users. According to the Cox hazard ration model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity and treatments, the CHM users showed a lower hazard ration of mortality risk, with higher survival probability. Bai-hua-she-she-cao (Herba oldenlandia: Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum combination) were the most frequently used single herb and Chinese herbal formula. Study suggests Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trials are warranted. (50)
• Inhibition of Colorectal Cancer Cells Via Activation of AMP-Activated Kinase Signalings: Study evaluated the anti-cancer activity of aqueous extracts of O. diffusa in colorectal cancer (CRC) cells. Results showed potent anti-proliferative, cytotoxic, and pre-apoptotic activities against a panel of CRC lines (HCT-116, DLD-1, HT-29, and Lovo)and primary (patient-derived) human CRC cells. Results showed inhibition of CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings. (51)
- Extracts, tinctures, supplements in the cybermarket.