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Family Rubiaceae

Hedyotis diffusa Willd.
Ding jing cao

Scientific names  Common names 
Hedyotis diffusa Willd. Daniri (Bis.) 
Hedyotis media Cav. Ulasiman-kalat (Tag.) 
Hedyotis diffusa Willd. Snake needle grass (Engl.) 
Oldenladia brachypoda DC. Snake tongue grass (Engl.) 
Oldenladia diffusa (Willd.) Roxb.  
Oldenladia capensis Blanco  
Bai hua she she cao (Chin.)  

Other vernacular names
CHINESE: Ding jing cao.

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.

Parts utilized
· 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 alchols, alkanes, organic acids, polysaccharides, coumarin and alkaloids.
- Study of 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.

- Sweet tasting, cooling in effect.
- Considered alterative, antibacterial, antidote, analgesic, antiinflammatory, antitumor, diuretic, febrifuge and sedative.

· 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.

Neuroprotective: Study yielded five flavonol glycosides and four O-acylated iridoid glycosides. All nine compounds exhibited neuroprotective activity in cultures of damaged rat cortical cells.
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.
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: In a study of H diffusa, H corymbosa and M pentaphylla, all three showed varying levels of antioxidant and radical scavenging activities.

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 of OD extract against eight cancer cell lines showed strong antiproliferative activity against all cancer cell lines and induced significant increase of apoptosis. Also, there was significant inhibition of lung metastases in the animal model without noticeable side effects. Results suggest a potential for an anticancer agent.
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: 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)
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 esxpression 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)

Extracts in the cyber market.  

Last Update June 2014

Photos ©Godofredo Stuart / Scrutinised

Additional Sources and Suggested Readings
Neuropsychiatry Constituents from Hideouts diffuse
/ Young le em Kim et al / J. Nat. Prod., 2001, 64 (1), pp 75–78 / DOI: 10.1021/np000327d
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
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
Antioxidant activity of extracts of Peh-Hue-Juwa-Chi-Cao in a cell free system./ American Journal of Chinese Medicine

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
Anticancer Activities of Oldenlandia diffusa / Salin Gupta et al / Summary Journal of Herbal Pharmacotherapy • 2004, Vol. 4, No. 1, Pages 21-33
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
Antitumor and Phytotoxic Activities of Leaf Methanol Extract of Oldenlandia diffusa (Willd.) Roxb / M Soriful Islam et al / Global Journal of Pharmacology, 3 (2): 99-106, 2009
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
Hedyotis diffusa Willd. / Catalogue of Life, China 2010
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
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.
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
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
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):485-9. /
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).
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
Tumor inhibition by several components extracted from Hedyotis corymbosa and Hedyotis diffusa / H Y Hsu / PhD / Cancer Detection and Prevention 1998; 22(Supplement 1).
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. 30, 225 (2002). DOI: 10.1142/S0192415X02000405
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

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
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

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