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Family Rubiaceae

Ulasiman-kalat
Oldenlandia diffusa (Willd.) Roxb.
SNAKE NEEDLE GRASS
Ding jing cao

Scientific names  Common names 
Hedyotis brachypoda R.Br. ex Wall. [Invalid] Daniri (Bis.) 
Hedyotis diffusa Willd. Ulasiman-kalat (Tag.) 
Hedyotis extensa R.Br. ex Wall. [Invalid] Snake needle grass (Engl.) 
Oldenladia brachypoda G.Don. [Illegitimate] Snake tongue grass (Engl.) 
Oldenladia diffusa (Willd.) Roxb. Spreading hedyotis (Engl.)
Oldenladia paucifloraRoxb. ex. Wight & Am.  
Hedyotis diffusa Willd. is a synonym of Oldenlandia diffusa (Willd.) Roxb. The Plant List
Oldenlandia diffusa (Willd.) Roxb. is an accepted name. The Plant List

Other vernacular names
ASSAMESE: Bonjaluk.
CHINESE: Ding jing cao, Bai hua she she cao, She she cao, Mu mu shang zhu cao, Liao Ge Li, Qian da Chui, Yang xu cao, She zong guan, He she cao, Xi ye liu zi, Lung tu zhu, Zhu zhai cao.

Botany
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.

Distribution
- 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.

Parts utilized
· Entire plant.
· Harvest the entire plant from April to September.
· Wash and sun-dry.

Constituents
- 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 (69). (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)

Properties
- 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.

Uses
Folkloric
· 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 drink.
· 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)

Studies
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)
• Anticancer / 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)

Availability
- Wild-crafted.
- Extracts, tinctures, supplements in the cybermarket.  

Updated April 2019 / March 2017 / June 2014

Photos © Godofredo Stuart / StuartXchange

Additional Sources and Suggested Readings
(1)
Neuroprotective Constituents from Hideouts diffuse
/ Youngleem Kim, Eun Jung Park, Jinwoong Kim, Yang-Bae Kim, So Ra Kim, and Young Choong Kim / J. Nat. Prod., 2001; 64 (1): pp 75–78 / DOI: 10.1021/np000327d

(2)
A comparable, chemical and pharmacological analysis of the traditional Chinese medicinal herbs Oldenlandia diffusa and O. corymbosa and a new valuation of their biological potential / Phytomedicine, Volume 15, Issue 4, Pages 259-267
(3)
Comparative study on the immunocompetent activity of three different kinds of Peh-Hue-Juwa-Chi-Cao, Hedyotis diffusa, H. corymbosa and Mollugo pentaphylla after sublethal whole body x-irradiation / PTR. Phytotherapy research / 1997, vol. 11, no6, pp. 428-432
(4)
Antioxidant activity of extracts of Peh-Hue-Juwa-Chi-Cao in a cell free system./ American Journal of Chinese Medicine

(5)
Study on flavonoids from Hedyotis diffusa Willd / Zhang, Jaijuan et al / Journal of Chinese medicinal materials (Zhong Yao Cai) / 2005-May; vol 28 (issue 5) : pp 385-7
(6)
Anticancer Activities of Oldenlandia diffusa / Salin Gupta et al / Journal of Herbal Pharmacotherapy, 2004; Vol. 4 No 1: pp 21-33 / PMID: 15273074
(7)
Methylanthraquinone from Hedyotis diffusa WILLD induces Ca2+-mediated apoptosis in human breast cancer cells / Zhdeng Liu et al / Toxicology in Vitro • Volume 24, Issue 1, February 2010, Pages 142-147 / doi:10.1016/j.tiv.2009.08.002
(8)
Antitumor and Phytotoxic Activities of Leaf Methanol Extract of Oldenlandia diffusa (Willd.) Roxb / M Soriful Islam et al / Global Journal of Pharmacology, 2009; 3(2): pp 99-106
(9)
Oleanolic acid isolated from Oldenlandia diffusa exhibits a unique growth inhibitory effect against ras-transformed fibroblasts / Pui Kei Wu et al / Life Sciences • Volume 85, Issues 3-4, 15 July 2009, Pages 113-121 / doi:10.1016/j.lfs.2009.04.025
(10)
Hedyotis diffusa Willd. / Catalogue of Life, China 2010
(11)
Studies on constituents of Oldenlandia diffusa
/ Zhou YJ, Wu KS, Zeng GY, Tan JB, Xu KP, Li FS, Tan GS. / Zhongguo Zhong Yao Za Zhi. 2007 Apr;32(7):590-3
(12)
Cytotoxicity and bioavailability studies on a decoction of Oldenlandia diffusa and its fractions separated by HPLC. / Ganbold M, Barker J, Ma R, Jones L, Carew M. / J Ethnopharmacol. 2010 Sep 15;131(2):396-403. Epub 2010 Jul 13.
(13)
Determination of Oleanolic Acid and Ursolic Acid in Oldenlandia diffusa and Its Substitute Using High Performance Liquid Chromatography / ZHITAO LIANG, ZHIHONG JIANG, DAVID WANGFUN FONG AND ZHONGZHEN ZHAO / Journal of Food and Drug Analysis, Vol. 17, No. 2, 2009, Pages 69-77
(14)
An Evidence-based Perspective of Hedyotis Diffusa or Oldenlandia Diffusa (Spreading Hedyotis) for Cancer Patients / Jun Shao, Guoqing Gong and Louis Trombetta / EVIDENCE-BASED ANTICANCER MATERIA MEDICA / Evidence-based Anticancer Complementary and Alternative Medicine, 2011, 179-192, DOI: 10.1007/978-94-007-0526-5_9
(15)
Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide burst and caspase activation. / Yadav SK, Lee SC. / Zhong Xi Yi Jie He Xue Bao. 2006 Sep; 4(5): pp 485-489 / PMID: 16965742
(16)
Oldenlandia diffusa Ameliorates Dextran Sulphate Sodium-Induced Colitis Through Inhibition of NF-κB Activation / Su-Jin Kim et al, Am. J. Chin. Med. 39, 957 (2011).
(17)
Oldenlandia diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERα/Sp1-mediated p53 activation / Guowei Gu, Ines Barone, Stefania Catalano and Sebastiano Andò et al / Journal of Cellular Physiology, Vol 227, No 10, pages 3363–3372, October 2011 / DOI: 10.1002/jcp.24035
(18)
Tumor inhibition by several components extracted from Hedyotis corymbosa and Hedyotis diffusa / H Y Hsu / PhD / Cancer Detection and Prevention 1998; 22(Supplement 1).
(19)
Anti-Inflammatory and Hepatoprotective Activity of Peh-Hue-Juwa-Chi-Cao in Male Rats / Chun-Ching Lin, Lean-Teik Ng, Jenq-Jer Yang, Yu-Fang Hsu / Chun-Ching Lin et al, Am. J. Chin. Med., 2002; 30(2-3): pp 225-234 / DOI: 10.1142/S0192415X02000405
(20)
Protective effect of Hedyotis diffusa on lipopolysaccharide (LPS)-induced liver damage / Min-Jung Kang and Jung-In Kim / The FASEB Journal. 2013;27:1155.5

(21)
Effect of Hedyotis Diffusa Willd extract on tumor angiogenesis. / Lin J, Wei L, Xu W, Hong Z, Liu X, Peng J / Molecular Medicine Reports [2011, 4(6):1283-1288
(22)
Hedyotis diffusa Combined with Scutellaria barbata Are the Core Treatment of Chinese Herbal Medicine Used for Breast Cancer Patients: A Population-Based Study / Yuan-Chieh Yeh Hsing-Yu Chen, Sien-Hung Yang, Yi-Hsien Lin, Jen-Hwey Chiu, Yi-Hsuan Lin, and Jiun-Liang Chen / Evidence-Based Complementary and Alternative Medicine, Volume 2014 (2014) / http://dx.doi.org/10.1155/2014/202378
(23)
Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular / Y. Yoshida, M.Q. Wang, J.N. Liu, B.E. Shan, U. Yamashita / International Journal of Immunopharmacolo, July 1997;
Volume 19, Issue 7: pp 359-370 / https://doi.org/10.1016/S0192-0561(97)00076-3
(24)
Hedyotis diffusa Willd Inhibits Colorectal Cancer Growth in Vivo via Inhibition of STAT3 Signaling Pathway / Qiaoyan Cai, Jiumao Lin, Lihui Wei, Ling Zhang, Lili Wang, Youzhi Zhan, Jianwei Zeng, Wei Xu , Aling Shen, Zhenfeng Hong, and Jun Peng* / Int. J. Mol. Sci. 2012, 13(5) / doi:10.3390/ijms13056117
(25)
Hedyotis diffusa Combined with Scutellaria barbata Are the Core Treatment of Chinese Herbal Medicine Used for Breast Cancer Patients: A Population-Based Study / Yuan-Chieh Yeh, Hsing-Yu Chen, Sien-Hung Yang, Yi-Hsien Lin, Jen-Hwey Chiu, Yi-Hsuan Lin, and Jiun-Liang Chen / Evidence-Based Complementary and Alternative Medicine, Volume 2014 (2014) / http://dx.doi.org/10.1155/2014/202378
(26)
The Study of the Effect of Hedyotis diffusa on the Proliferation and the Apoptosis of the Cervical Tumor in Nude Mouse Model. / Zhang P, Zhang B, Gu J, Hao L, Hu F, Han C. / Cell Biochem Biophys. 2015 Jul; 72(3): 783-9. / doi: 10.1007/s12013-015-0532-9.
(27)
The Hedyotis diffusa Willd. (Rubiaceae): A Review on Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics / Rui Chen, Jingyu He, Xueli Tong, Lan Tang and Menghua Liu * / Molecules 2016, 21, 710 / doi:10.3390/molecules21060710 www.mdpi.com/journal/molecules
(28)
Oldenlandia diffusa / Synonyms / The Plant List
(29)
Chinese names: Hedyotis diffusa /Asian Anti-Cancer Materia Database
(30)
Inhibitory effects of Hedyotis diffusa Willd. on colorectal cancer stem cells / Guodong Sun Lihui Wei Jianyu Feng Jiumao Lin Jun Peng / Oncology Letters, April 13, 2016: pp 3875-3881 / DOI: 10.3892/ol.2016.4431
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Hedyotis diffusa Willd extract inhibits HT‐29 cell proliferation via cell cycle arrest / MINGHE LIN, JIUMAO LIN, LIHUI WEI, WEI XU, ZHENFENG HONG, QIAOYAN CAI, JUN PENG, and DEZENG ZHU / EXPERIMENTAL AND THERAPEUTIC MEDICINE 4: 307-310, 2012 / DOI: 10.3892/etm.2012.599
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HPLC determination of oleanolic acid content in Hedyotis diffusa Willd. and its anti-HepG-2 cell activity. / Lin Sun, Jeushi Liu, Hua Xiang / Biomedical Research, 2015; 26 (4): pp 710-714
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Anticancer Activity of Oldenlandia Diffusa & Viola Philippica Car / Wen Deng, Bo Hu, Chun-Ling Dai, Yi-Jun Wang, Hai-Fan Chen, S. William Zito, Li-Wu Fu and Zhe-Sheng Chen* / Journal of Cancer Research Updates, 2013; 2: pp 87-94
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A study of the in vitro free radical-scavenging property of Hedyotis diffusa using nitric oxide assay / Napolean Kagoo, Chellathai Darling / International Journal of Pharmacologic Research, Vol 4, No 3 (2014)
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Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2 / Qiongyu Li, Xiangfeng Wang, Aling Shen, Yuchen Zhang, Youqin Chen, Thomas J. Sferra, Jiumao Lin, Jun Peng / Experimental and Therapeutic Medicine, Nov 2015
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Ethanol Extract of Oldenlandia diffusa – an Effective Chemotherapeutic for the Treatment of Colorectal Cancer in Humans--Anti-Cancer Effects of Oldenlandia diffusa / Soojin Lee, Ji Hwan Shim, Huijin Gim, Hyun Soo Park, and Byung Joo Kim / J. Pharmacopuncture., 2016 Mar; 19(1): pp 51-58 / doi: 10.3831/KPI.2016.19.007
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Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat Hepatocellular Carcinoma with Liver Cirrhosis / Yun-Young Sunwoo, Jin-Hee Lee, Ho Yong Jung, Yu Jin Jungn et al / Evidence-Based Complementary and Alternative Medicine, Volume 2015 / http://dx.doi.org/10.1155/2015/501508
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Oldenlandia diffusa Extracts Exert Anti-Tumor Effects on Human Ovarian Cancer Cells Via an Epigenetic Regulator, KDM1B / Yeon Kyu Lee, Jin Yeong Lim, Jong Cheon Joo, Soo Jung Park, and Yoon Jung Park / The FASEB Journal, April 2017; 31(1), Supplement
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An Evidence-based Perspective of Hedyotis Diffusa or Oldenlandia Diffusa (Spreading Hedyotis) for Cancer Patients / Jun Shao, Guoqing Gond, Louis Trombetta / BooK: Evidence-based Anticancer Materia Medica, March 2011 / DOI: 10.1007/978-94-007-0526-5_9
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Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS‑activated macrophages via suppression of the NF‑κB and MAPK signaling pathways / Yunlong Chen, Yanyan Lin, Yachan Li, Candong Li / Experimental and Therapeutic Medicine, March 2016; 11(3) / https://doi.org/10.3892/etm.2015.2963
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Influences of Oldenlandia diffusa on the CYP450 Activities in Rats Using a Cocktail Method by UHPLC-MS/MS / Yiping Lin, Yanli Wei, Xiaoxia Hu, Meilling Wu, Xiaoqian Ying, and Mingxing Ding / Biochem Res Int., 2018; 2018: 1467143. / doi: 10.1155/2018/1467143 / PMID: 29850248
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Antitumour effects of ursolic acid isolated from Oldenlandia diffusa / Sung Hoon Kim, Byung-Zun Ahn, Shi Yong Ryu / Phytotherapy Research, Dec 1998; 12(8): pp 553-556 / https://doi.org/10.1002/(SICI)1099-1573(199812)12:8<553::AID-PTR359>3.0.CO;2-W
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Oldenlandia diffusa Extract Inhibits Biofilm Formation by Haemophilus influenzae Clinical Isolates / Takeaki Wajima, Yui Anzai, Tetsuya Yamada, Hideaki Ikoshi, Norihisa Noguchi  / PLOS|One, Nov 2916 / https://doi.org/10.1371/journal.pone.0167335
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Extract of Hedyotis diffusa Willd Influences Murine Leukemia WEHI-3 Cells In Vivo as well as Promoting T- and B-Cell Proliferation in Leukemic Mice / Chin-Chung Lin, Chao-Lin Kuo, Mau-Hva Lee, Shu-Chun Hsu, An-Chen Huang, Nou-Ying Tang et al / in vivo: International Journal of Experimental and Clinical Pathphysiology and Drug Research, July-August 2011; 25(4): pp 633-640
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Iridoid glycosides isolated fromOldenlandia diffusa inhibit LDL-oxidation / Dong-Hyun Kim, Hyo-Jung Lee, Young-Jun Oh. Min-Jung Kim, Sung-Hoon Kim, Tae-Sook Jeong / Archives of Pharmacal Research, Oct 2005; 28(10): pp 1156-1160
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Apoptotic Effects of Stearic Acid, an Active Compound Isolated from Oldenlandia diffusa, on Human Hepatoma Cells / Patrick Ming-Kuen Tang, Linda Dong-Mei Zhang, Judy Yuet-Wa Chan, et al / Research Journal of Medical Sciences, 2007; 1(1): pp 30-38
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Comparative Chemical Composition of the Essential Oils from Hedyotis Diffusa WILLD and Its Adulterants Hedyotis Corymbosa Lam by GC-MS / Wu Jian, Yang Tairan, Xu Ying, Xiang Zheng / 2016 8th International Conference on Information Technology in Medicine and Education (ITME) / DOI:  10.1109/ITME.2016.0034
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SR: A pilot study of lung cancer following chemotherapy and traditional medicine: report of 12 cases / George Zhu, Fabio Musumeci, Peter Byrne, Deepil Gupta, Ekta Gupta, John Baer / DOI: 10.15761/LBJ.1000115
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Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study / Yi-Ting Kuo MD, Hou-Hsun Liao MD, Jen-Huai Chiang MS et al / Integrative Cancer Therapies / https://doi.org/10.1177/1534735417722224
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Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings / Pei-Hua Lu, Min-Bin Chen, Chao Ji, Wen-Ting Li, Mu-Xin Wei, Mian-Hua Wu / Oncotarget, 2016; 7: pp 45889-45900 / https://doi.org/10.18632/oncotarget.9969


 

       



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