Close-up views:

| Last updated: January 2023 |

In the Plants of the World Online website, the accepted botanical name of this plant is Scleromitrion diffusum while both Oldenlandia diffusa and Hedyotis diffusa are treated as synonyms. In the 2019 Flora of Singapore publication on Rubiaceae, the accepted name was indicated as Hedyotis diffusa. There were some pictures of this plant in page 120 of this publication that resembled the pictures above.

According to a 2021 publication [1], when the name Hedyotis diffusa was first published in 1798, the author was not clear in his description of the flower arrangement (i.e. whether he was referring to "a solitary flower or an inflorescence"). As a result, there were different interpretations along the years and the name was moved around among different plants which is rather confusing even up till this point. The assignment of this plant to the genus Scleromitrion seemed to take place in 2013 [2]. This 2013 system was adopted in a 2017 Taiwan publication as well [3].

A search done in the PubMed website on 5 November 2022 resulted in 3 publications that mentioned Scleromitrion diffusum; one each in 2020, 2021 and 2022. On the other hand, Hedyotis diffusa and Oldenlandia diffusa were mentioned in 184 and 79 publications respectively with their first mentioned in a publication were in 1979 and 1964 respectively (see image on the right). It appeared that the uptake of the accepted name Scleromitrion diffusum was uncommon among researchers.

In the iNaturalist website viewed on 29 January 2023, there were 4 records of Scleromitrion diffusum from Singapore with the earliest one dated in February 2021. Both Oldenlandia diffusa and Hedyotis diffusa are treated as synonyms in this website.

In NPark's Flora & Fauna Web viewed on 29 January 2023, pictures of a slightly different-looking Hedyotis diffusa was displayed. It had flower stalks (pedicels) that were very short or almost non-existence. According to the Flora of China website, the flower stalk of Oldenlandia diffusa should have a length of 4-20 millimetres. It looked more like Scleromitrion brachypodum or maybe another species.

Reference:

[1] Siu TY, Yik MHY, Boufford DE, Shaw PC, Lau DTW. (2813) Proposal to conserve the name Hedyotis diffusa (Oldenlandia diffusa, Scleromitrion diffusum) (Rubiaceae) with a conserved type. TAXON 2021;70(2):443-444. | Read article |

[2] Guo X, Wang RJ, Simmons MP, But PPH, Yu J. 2013. Phylogeny of the Asian Hedyotis-Oldenlandia complex (Spermacoceae, Rubiaceae): Evidence for high levels of polyphyly and the parallel evolution of diplophragmous capsules. Molec Phylogen Evol 2013;67(1):110-122. | Read abstract |

[3] Hsu TC, Chen ZH. Scleromitrion sirayanum (Rubiaceae: Spermacoceae), a new species of the Hedyotis-Oldenlandia complex in Taiwan. Taiwania 2017;62(2):151-156. | Read article |

| Plants of the World Online | Flora of China | Global Biodiversity Information Facility (GBIF) |

[2023] Deng H, Jiang J, Zhang S, Wu L, Zhang Q, Sun W. Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis. Sci Rep 2023;13(1):1425. | Read article |

[2023] Han CH, Ma JY, Zou W, Qu JL, Du Y, Li N, Liu Y, Jin G, Leng AJ, Liu J. 3D microfluidic system for evaluating inhibitory effect of Chinese herbal medicine Oldenlandia diffusa on human malignant glioma invasion combined with network pharmacology analysis. Chin J Integr Med 2023;29(1):52-60. | Read abstract |

[2023] Lv Y, Wang Y. Chemical constituents from Oldenlandia diffusa and their cytotoxic effects on human cancer cell lines. Nat Prod Res 2023;37(3):397-403. | Read abstract |

[2023] Wu H, Zhang L, Wang C, Li F, Qi L, Xiao L, Zhang M, Zhang H, Zhang G, Qin Y. Network pharmacology Aaalysis and experimental verification on antiangiogenesis mechanism of Hedyotis diffusa Willd in liver cancer. Evid Based Complement Alternat Med 2023;2023:1416841. | Read article |

[2023] Wang P, Wang Y, Feng T, Yan Z, Zhu D, Lin H, Iqbal M, Deng D, Kulyar MF, Shen Y. Hedyotis diffusa alleviate aflatoxin B1-induced liver injury in ducks by mediating Nrf2 signaling pathway. Ecotoxicol Environ Saf 2023;249:114339. | Read article |

[2022] Cheng YY, Tuzo ET, Dalley JW, Tsai TH. Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen. Biomed Pharmacother 2022;145:112466. | Read article |

[2022] Dai Y, Jiang D, Wang X, Wu D, Dong W, Fu Q, Jin Y, Liang X. Rapid fingerprint analysis based on supercritical fluid chromatography for quality evaluation of Hedyotis diffusa. J Pharm Biomed Anal 2022;218:114864. | Read abstract |

[2022] Huang F, Pang J, Xu L, Niu W, Zhang Y, Li S, Li X. Hedyotis diffusa injection induces ferroptosis via the Bax/Bcl2/VDAC2/3 axis in lung adenocarcinoma. Phytomedicine 2022;104:154319. | Read article |

[2022] Hung HY, Cheng KC, Kuo PC, Chen IT, Li YC, Hwang TL, Lam SH, Wu TS. Chemical constituents of Hedyotis diffusa and their anti-inflammatory bioactivities. Antioxidants (Basel) 2022;11(2):335. | Read article |

[2022] Li J, Liu D, Li D, Guo Y, Du H, Cao Y. Phytochemical composition and anti-aging activity of butanol extract of Hedyotis diffusa in caenorhabditis elegans. Chem Biodivers 2022;19(2):e202100685. | Read abstract |

[2022] Li J, Yang G, Shi W, Fang X, Han L, Cao Y. Anti-Alzheimer's disease active components screened out and identified from Hedyotis diffusa combining bioaffinity ultrafiltration LC-MS with acetylcholinesterase. J Ethnopharmacol 2022;296:115460. | Read abstract |

[2022] Ling JY, Wang QL, Liang HN, Liu QB, Yin DH, Lin L. Flavonoid-rich extract of Oldenlandia diffusa (Willd.) Roxb. inhibits gastric cancer by activation of caspase-dependent mitochondrial apoptosis. Chin J Integr Med 2022 Aug 31. | Read abstract |

[2022] Li Y, Ding T, Chen J, Ji J, Wang W, Ding B, Ge W, Fan Y, Xu L. The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice. Front Immunol. 2022;13:943827. | Read article |

[2022] Mao ZQ, Minakawa N, Moi ML. Novel antiviral efficacy of Hedyotis diffusa and Artemisia capillaris extracts against dengue virus, Japanese encephalitis virus, and zika virus infection and immunoregulatory cytokine signatures. Plants (Basel) 2022;11(19):2589. | Read article |

[2022] Ning W, Xu N, Zhou C, Zou L, Quan J, Yang H, Lu Z, Cao H, Liu J. Ethyl acetate fraction of Hedyotis diffusa Willd induces apoptosis via JNK/Nur77 pathway in hepatocellular carcinoma cells. Evid Based Complement Alternat Med 2022;2022:1932777. | Read article |

[2022] Wang X, Zhao J, Zhang R, Liu X, Ma C, Cao G, Wei Y, Yang P. Protective effect of Hedyotis diffusa Willd. ethanol extract on isoniazid-induced liver injury in the zebrafish model. Drug Des Devel Ther 2022;16:1995-2015. | Read article |

[2022] Wu J, Ye ZJ, Yu LJ, Chen XQ. Two new iridoid glycosides from Hedyotis diffusa. J Asian Nat Prod Res 2022:1-9. | Read abstract |

[2022] Wu K, Wu X, Liang Y, Wang T, Wu D, Li L, Wang Z. Inhibitory effects of total triterpenoids isolated from the Hedyotis diffusa willd on H1975 cells. Front Pharmacol 2022;13:922477. | Read article |

[2022] Wu Z, Yin B, You F. Molecular mechanism of anti-colorectal cancer effect of Hedyotis diffusa Willd and its extracts. Front Pharmacol 2022;13:820474. | Read article |

[2022] Xiao Q, Deng B, Akbari A, Liu Q, Zhu B. The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis. J Food Biochem 2022;46(12):e14407. | Read abstract |

[2022] Xu L, Li Y, Ji J, Lai Y, Chen J, Ding T, Li H, Ding B, Ge W. The anti-inflammatory effects of Hedyotis diffusa Willd on SLE with STAT3 as a key target. J Ethnopharmacol 2022;298:115597. | Read article |

[2022] Yang Z, Lu S, Tang H, Qu J, Wang B, Wang Y, Pan G, Rao B. Molecular targets and mechanisms of Hedyotis diffusa-Scutellaria barbata herb pair for the treatment of colorectal cancer based on network pharmacology and molecular docking. Evid Based Complement Alternat Med 2022;2022:6186662. | Read article |

[2022] Zhang J, Huo J, Zhao Z, Lu Y, Hong Z, Li H, Chen D. An anticomplement homogeneous polysaccharide from Hedyotis diffusa attenuates lipopolysaccharide-induced acute lung injury and inhibits neutrophil extracellular trap formation. Phytomedicine 2022;107:154453. | Read abstract |

[2022] Zhang Y, Hu H, Luo J. Diffusosides C and D, two new iridoid glucosides from Oldenlandia diffusa. Nat Prod Res 2022;36(9):2300-2305. | Read abstract |

[2022] Zhu H, Xiong XG, Lu Y, Wu HC, Zhang ZH, Sun MJ. The mechanism of the anti-inflammatory effect of Oldenlandia diffusa on arthritis model rats: a quantitative proteomic and network pharmacologic study. Ann Transl Med 2022;10(20):1098. | Read article |

[2021] DanQing L, YuJie G, ChengPeng Z, HongZhi D, Yi H, BiSheng H, Yan C. N-butanol extract of Hedyotis diffusa protects transgenic Caenorhabditis elegans from Aβ-induced toxicity. Phytother Res 2021;35(2):1048-1061. | Read abstract |

[2021] Huang L, Xu H, Wu T, Li G. Hedyotis diffusa Willd. suppresses hepatocellular carcinoma via downregulating AKT/mTOR pathways. Evid Based Complement Alternat Med 2021;2021:5210152. | Read article |

[2021] Lv YX, Pan HR, Song XY, Chang QQ, Zhang DD. Hedyotis diffusa plus Scutellaria barbata suppress the growth of non-small-cell lung cancer via NLRP3/NF-κB/MAPK signaling pathways. Evid Based Complement Alternat Med 2021;2021:6666499. | Read article |

[2021] Qian K, Fu D, Jiang B, Wang Y, Tian F, Song L, Li L. Mechanism of Hedyotis diffusa in the treatment of cervical cancer. Front Pharmacol 2021;12:808144. | Read article |

[2021] Shi F, Tong C, He C, Shi S, Cao Y, Wei Q. Diagnostic ion filtering targeted screening and isolation of anti-inflammatory iridoid glycosides from Hedyotis diffusa. J Sep Sci 2021;44(13):2612-2619. | Read abstract |

[2021] Ting CT, Cheng YY, Tsai TH. Preclinical pharmacokinetic interaction and histopathological analyses of Hedyotis diffusa on sorafenib in rats. ACS Omega 2021;6(4):3060-3067. | Read article |

[2021] Wazir J, Ullah R, Khongorzul P, Hossain MA, Khan MW, Aktar N, Cui X, Zhou X. The effectiveness of Hedyotis diffusa Willd extract in a mouse model of experimental autoimmune prostatitis. Andrologia 2021;53(1):e13913. | Read abstract |

[2021] Xu X, Chen F, Zhang L, Liu L, Zhang C, Zhang Z, Li W. Exploring the mechanisms of anti-ovarian cancer of Hedyotis diffusa Willd and Scutellaria barbata D. Don through focal adhesion pathway. J Ethnopharmacol 2021;279:114343. | Read abstract |

[2021] Yang PW, Chen TT, Zhao WX, Liu GW, Feng XJ, Wang SM, Pan YC, Wang Q, Zhang SH. Scutellaria barbata D.Don and Oldenlandia diffusa (Willd.) Roxb crude extracts inhibit hepatitis-B-virus-associated hepatocellular carcinoma growth through regulating circRNA expression. J Ethnopharmacol 2021;275:114110. | Read abstract |

[2021] Yik MH, Kong BL, Siu TY, Lau DT, Cao H, Shaw PC. Differentiation of Hedyotis diffusa and common adulterants based on chloroplast genome sequencing and DNA barcoding markers. Plants (Basel) 2021;10(1):161. | Read article |

[2021] Zhang R, Ma C, Wei Y, Wang X, Jia J, Li J, Li K, Cao G, Yang P. Isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides: A review. Int J Biol Macromol 2021;183:119-131. | Read abstract |

[2021] Zhao L, Deng J, Xu ZJ, Zhang WP, Khalil MM, Karrow NA, Sun LH. Mitigation of aflatoxin B1 hepatoxicity by dietary Hedyotis diffusa is associated with activation of NRF2/ARE aignaling in chicks. Antioxidants (Basel) 2021;10(6):878. | Read article |

[2021] Zou W, Dong Y, Yang S, Gong L, Zhang Y, Shi B, La L, Tang L, Liu M. Imperatae rhizoma-Hedyotis diffusa Willd. herbal pair alleviates nephrotic syndrome by integrating anti-inflammatory and hypolipidaemic effects. Phytomedicine 2021;90:153644. | Read abstract |

[2020] Chen X, Zhao B, Zhang M, Dong M, Li Y, Li Q. Application of HPLC-Q/orbitrap MS in the detection and identification of anticancer constituents in ethyl acetate components from Hedyotis diffusa. Anal Methods 2020;12(32):4037-4047. | Read abstract |

[2020] Fang T, Yan YX, Yang Y, Lv YX, Chang QQ, Zhang DD. Ethyl acetate fraction from Hedyotis diffusa plus Scutellaria barbata suppresses migration of bone-metastatic breast cancer cells via OPN-FAK/ERK/NF-κB axis. Evid Based Complement Alternat Med 2020;2020:3573240. | Read article |

[2020] Han X, Zhang X, Wang Q, Wang L, Yu S. Antitumor potential of Hedyotis diffusa Willd: A systematic review of bioactive constituents and underlying molecular mechanisms. Biomed Pharmacother 2020;130:110735. | Read article |

[2020] Huo J, Lu Y, Jiao Y, Chen D. Structural characterization and anticomplement activity of an acidic polysaccharide from Hedyotis diffusa. Int J Biol Macromol 2020;155:1553-1560. | Read abstract |

[2020] Li YL, Chen X, Niu SQ, Zhou HY, Li QS. Protective antioxidant effects of amentoflavone and total flavonoids from Hedyotis diffusa on H2 O2 -induced HL-O2 cells through ASK1/p38 MAPK pathway. Chem Biodivers 2020;17(7):e2000251. | Read abstract |

[2020] Lu L, Zhan S, Liu X, Zhao X, Lin X, Xu H. Antitumor Effects and the Compatibility mechanisms of herb pair Scleromitrion diffusum (Willd.) R. J. Wang-Sculellaria barbata D. Don. Front Pharmacol 2020;11:292. | Read article |

[2020] Ma TT, Zhang GL, Dai CF, Zhang BR, Cao KX, Wang CG, Yang GW, Wang XM. Scutellaria barbata and Hedyotis diffusa herb pair for breast cancer treatment: Potential mechanism based on network pharmacology. J Ethnopharmacol 2020;259:112929. | Read abstract |

[2020] Park JH, Whang WK. Bioassay-guided isolation of anti-alzheimer active components from the aerial parts of Hedyotis diffusa and simultaneous analysis for marker compounds. Molecules 2020;25(24):5867. | Read article |

[2020] Yang Y, Fang T, Cao YL, Lv YX, Chang QQ, Zhang DD. Ethyl acetate fraction from Hedyotis diffusa plus Scutellaria barbata exerts anti-breast cancer effect via miR-200c-PDE7B/PD-L1-AKT/MAPK axis. Evid Based Complement Alternat Med 2020;2020:3587095. | Read article |

[2019] Hu CJ, He J, Li GZ, Fang PP, Xie JD, Ding YW, Mao YQ, Hu KF. Analyzing Hedyotis diffusa mechanisms of action from the genomics perspective. Comput Methods Programs Biomed 2019;174:1-8. | Read abstract |

[2019] Li H, Lai Z, Yang H, Peng J, Chen Y, Lin J. Hedyotis diffusa Willd. inhibits VEGF‑C‑mediated lymphangiogenesis in colorectal cancer via multiple signaling pathways. Oncol Rep 2019;42(3):1225-1236. | Read abstract |

[2019] Lin L, Cheng K, Xie Z, Chen C, Chen L, Huang Y, Liang Z. Purification and characterization a polysaccharide from Hedyotis diffusa and its apoptosis inducing activity toward human lung cancer cell line A549. Int J Biol Macromol 2019;122:64-71. | Read abstract |

[2019] Lin L, Cheng K, He Z, Lin Q, Huang Y, Chen C, Xie Z, Chen L, Liang Z. A polysaccharide from Hedyotis diffusa interrupts metastatic potential of lung adenocarcinoma A549 cells by inhibiting EMT via EGFR/Akt/ERK signaling pathways. Int J Biol Macromol 2019;129:706-714. | Read abstract |

[2019] Ma C, Wei Y, Liu Q, Xin Y, Cao G, Wang X, Yang P. Polysaccharides from Hedyotis diffusa enhance the antitumor activities of cytokine-induced killer cells. Biomed Pharmacother 2019;117:109167. | Read article |

[2019] Song Y, Wang H, Pan Y, Liu T. Investigating the multi-target pharmacological mechanism of Hedyotis diffusa Willd acting on prostate cancer: A network pharmacology approach. Biomolecules 2019;9(10):591. | Read article |

[2019] Su X, Li Y, Jiang M, Zhu J, Zheng C, Chen X, Zhou J, Li Y, Xiao W, Wang Y. Systems pharmacology uncover the mechanism of anti-non-small cell lung cancer for Hedyotis diffusa Willd. Biomed Pharmacother 2019;109:969-984. | Read article |

[2019] Yang B, Wang N, Wang S, Li X, Zheng Y, Li M, Song J, Zhang F, Mei W, Lin Y, Wang Z. Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis. Biomed Pharmacother 2019;112:108607. | Read article |

[2018] Chen X, Zhu P, Liu B, Wei L, Xu Y. Simultaneous determination of fourteen compounds of Hedyotis diffusa Willd extract in rats by UHPLC-MS/MS method: Application to pharmacokinetics and tissue distribution study. J Pharm Biomed Anal 2018;159:490-512. | Read abstract |

[2018] Lee JE, Song HS, Park MN, Kim SH, Shim BS, Kim B. Lee, J.E. et al. Ethanol extract of Oldenlandia diffusa herba attenuates scopolamine-induced cognitive impairments in mice via activation of BDNF, P-CREB and inhibition of acetylcholinesterase. Int J Mol Sci 2018;19(4):996. | Read article |

[2018] Lee JE, Song HS, Park MN, Kim SH, Shim BS, Kim B. Ethanol extract of Oldenlandia diffusa herba attenuates scopolamine-induced cognitive impairments in mice via activation of BDNF, P-CREB and inhibition of acetylcholinesterase. Int J Mol Sci 2018;19(2):363. | Read article |

[2018] Lin Y, Wei Y, Hu X, Wu M, Ying X, Ding M. Influences of Oldenlandia diffusa on the CYP450 activities in rats Using a cocktail method by UHPLC-MS/MS. Biochem Res Int 2018;2018:1467143. | Read article |

[2018] Liu R, Wang P, Wu C, Chen J, Li C, Xie Y, Wang Q, Liu J, He H, Zhu J. Therapeutic effects of Hedyotis diffusa Willd in a COPD mouse model challenged with LPS and smoke. Exp Ther Med 2018;15(4):3385-3391. | Read article |

[2018] Liu X, Wu J, Zhang D, Wang K, Duan X, Meng Z, Zhang X. Network pharmacology-based approach to investigate the mechanisms of Hedyotis diffusa Willd. in the treatment of gastric cancer. Evid Based Complement Alternat Med 2018;2018:7802639. | Read article |

[2018] Liu X, Wu J, Zhang D, Wang K, Duan X, Zhang X. A network pharmacology approach to uncover the multiple mechanisms of Hedyotis diffusa Willd. on colorectal cancer. Evid Based Complement Alternat Med 2018;2018:6517034. | Read article |

[2018] Tan J, Li L, Shi W, Sun D, Xu C, Miao Y, Fan H, Liu J, Cheng H, Wu M, Shen W. Protective effect of 2-hydroxymethyl anthraquinone from Hedyotis diffusa Willd in lipopolysaccharide-induced acute lung injury mediated by TLR4-NF-κB pathway. Inflammation 2018;41(6):2136-2148. | Read abstract |

[2018] Wang Y, Wang C, Lin H, Liu Y, Li Y, Zhao Y, Li P, Liu J. Discovery of the potential biomarkers for discrimination between Hedyotis diffusa and Hedyotis corymbosa by UPLC-QTOF/MS metabolome analysis. Molecules 2018;23(7):1525. | Read article |

[2018] Wang Z, Gao K, Xu C, Gao J, Yan Y, Wang Y, Li Z, Chen J. Metabolic effects of Hedyotis diffusa on rats bearing Walker 256 tumor revealed by NMR-based metabolomics. Magn Reson Chem 2018;56(1):5-17. | Read abstract |

[2018] Xu Y, Chen XX, Jiang YX, Zhang DD. Ethyl acetate fraction from Hedyotis diffusa plus Scutellaria barbata exerts anti-inflammatory effects by regulating miR-155 expression and JNK signaling pathway. Evid Based Complement Alternat Med. 2018;2018:3593408. | Read article |

[2018] Yang W, He S, Xiao N, Qiao Y, Sui H, Liang L, Chen J, Li W, Zhang L. Simultaneous determination of 15 flavonoids in Scutellaria barbata-Hedyotis diffusa herb pair by HPLC Q-TOF MS. J AOAC Int 2018;102(1):75-80. | Read article |

[2018] Zhu H, Liang QH, Xiong XG, Wang Y, Zhang ZH, Sun MJ, Lu X, Wu D. Anti-inflammatory effects of p-coumaric acid, a natural compound of Oldenlandia diffusa, on arthritis model rats. Evid Based Complement Alternat Med 2018;2018:5198594. | Read article |

[2017] Chung TW, Choi H, Lee JM, Ha SH, Kwak CH, Abekura F, Park JY, Chang YC, Ha KT, Cho SH, Chang HW, Lee YC, Kim CH. Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells. J Ethnopharmacol 2017;195:309-317. | Read abstract |

[2017] Dai M, Wang F, Zou Z, Xiao G, Chen H, Yang H. Metabolic regulations of a decoction of Hedyotis diffusa in acute liver injury of mouse models. Chin Med 2017;12:35. | Read article |

[2017] Feng J, Jin Y, Peng J, Wei L, Cai Q, Yan Z, Lai Z, Lin J. Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways. Oncol Lett 2017;14(6):8197-8205. | Read article |

[2017] Jiang J, Wang B, Li J, Ye B, Lin S, Qian W, Shan L, Efferth T. Total coumarins of Hedyotis diffusa induces apoptosis of myelodysplastic syndrome SKM-1 cells by activation of caspases and inhibition of PI3K/Akt pathway proteins. J Ethnopharmacol 2017;196:253-260. | Read abstract |

[2017] Ji S, Fattahi A, Raffel N, Hoffmann I, Beckmann MW, Dittrich R, Schrauder M. Antioxidant effect of aqueous extract of four plants with therapeutic potential on gynecological diseases; Semen persicae, Leonurus cardiaca, Hedyotis diffusa, and Curcuma zedoaria. Eur J Med Res 2017;22(1):50. | Read article |

[2017] Kuo YJ, Liu YJ, Way TD, Chiang SY, Lin JG, Chung JG. Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo. Exp Ther Med 2017;13(6):3388-3396. | Read article |

[2017] Lai Z, Yan Z, Chen W, Peng J, Feng J, Li Q, Jin Y, Lin J. Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway. Mol Med Rep 2017;16(5):7752-7758. | Read abstract |

[2017] Li Q, Lai Z, Yan Z, Peng J, Jin Y, Wei L, Lin J. Hedyotis diffusa Willd inhibits proliferation and induces apoptosis of 5‑FU resistant colorectal cancer cells by regulating the PI3K/AKT signaling pathway. Mol Med Rep 2018;17(1):358-365. | Read abstract |

[2017] Wang C, Zhou X, Wang Y, Wei D, Deng C, Xu X, Xin P, Sun S. The antitumor constituents from Hedyotis diffusa Willd. Molecules 2017;22(12):2101. | Read article |

[2017] Wu C, Luo H, Ma W, Ren X, Lu C, Li N, Wang Z. Polysaccharides isolated from Hedyotis diffusa inhibits the aggressive phenotypes of laryngeal squamous carcinoma cells via inhibition of Bcl-2, MMP-2, and μPA. Gene 2017;637:124-129. | Read abstract |

[2017] Wang C, Xin P, Wang Y, Zhou X, Wei D, Deng C, Sun S. Iridoids and sfingolipids from Hedyotis diffusa. Fitoterapia 2018;124:152-159. | Read abstract |

[2017] Yan Z, Feng J, Peng J, Lai Z, Zhang L, Jin Y, Yang H, Chen W, Lin J. Chloroform extract of Hedyotis diffusa Willd inhibits viability of human colorectal cancer cells via suppression of AKT and ERK signaling pathways. Oncol Lett 2017;14(6):7923-7930. | Read article |

[2016] Chen R, He J, Tong X, Tang L, Liu M. The Hedyotis diffusa Willd. (Rubiaceae): A review on phytochemistry, pharmacology, quality control and pharmacokinetics. Molecules 2016;21(6):710. | Read article |

[2016] Chen Y, Lin Y, Li Y, Li C. Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS-activated macrophages via suppression of the NF-κB and MAPK signaling pathways. Exp Ther Med 2016;11(3):1116-1122. | Read article |

[2016] Gao X, Li C, Tang YL, Zhang H, Chan SW. Effect of Hedyotis diffusa water extract on protecting human hepatocyte cells (LO2) from H2O2-induced cytotoxicity. Pharm Biol 2016;54(7):1148-1155. | Read abstract |

[2016] Lee S, Shim JH, Gim H, Park HS, Kim BJ. Ethanol extract of Oldenlandia diffusa - an effective chemotherapeutic for the treatment of colorectal cancer in humans: -anti-cancer effects of Oldenlandia diffusa. J Pharmacopuncture 2016;19(1):51-58. | Read article |

[2016] Li YL, Zhang J, Min D, Hongyan Z, Lin N, Li QS. Anticancer effects of 1,3-dihydroxy-2-methylanthraquinone and the ethyl acetate fraction of Hedyotis diffusa Willd against HepG2 carcinoma cells mediated via apoptosis. PLoS One 2016;11(4):e0151502. | Read article |

[2016] Lu PH, Chen MB, Ji C, Li WT, Wei MX, Wu MH. Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings. Oncotarget 2016;7(29):45889-45900. | Read article |

[2016] Pan LT, Sheung Y, Guo WP, Rong ZB, Cai ZM. Hedyotis diffusa plus Scutellaria barbata induce bladder cancer cell apoptosis by inhibiting Akt signaling pathway through downregulating miR-155 expression. Evid Based Complement Alternat Med 2016;2016:9174903. | Read article |

[2016] Pu F, Chen F, Lin S, Chen S, Zhang Z, Wang B, Shao Z. The synergistic anticancer effect of cisplatin combined with Oldenlandia diffusa in osteosarcoma MG-63 cell line in vitro. Onco Targets Ther 2016;9:255-263. | Read article |

[2016] Sun G, Wei L, Feng J, Lin J, Peng J. Inhibitory effects of Hedyotis diffusa Willd. on colorectal cancer stem cells. Oncol Lett 2016;11(6):3875-3881. | Read article |

[2016] Wajima T, Anzai Y, Yamada T, Ikoshi H, Noguchi N. Oldenlandia diffusa extract inhibits biofilm formation by Haemophilus influenzae clinical isolates. PLoS One 2016;11(11):e0167335. | Read article |

[2016] Zhang L, Zhang J, Qi B, Jiang G, Liu J, Zhang P, Ma Y, Li W. The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells. J Ethnopharmacol 2016;192:132-139. | Read abstract |

[2015] Hu E, Wang D, Chen J, Tao X. Novel cyclotides from Hedyotis diffusa induce apoptosis and inhibit proliferation and migration of prostate cancer cells. Int J Clin Exp Med 2015;8(3):4059-4065. | Read article |

[2015] Kuo YJ, Lin JP, Hsiao YT, Chou GL, Tsai YH, Chiang SY, Lin JG, Chung JG. Ethanol extract of Hedyotis diffusa Willd affects immune responses in normal Balb/c mice in vivo. In Vivo 2015;29(4):453-60. | Read abstract |

[2015] Kuo YJ, Yang JS, Lu CC, Chiang SY, Lin JG, Chung JG. Ethanol extract of Hedyotis diffusa willd upregulates G0/G1 phase arrest and induces apoptosis in human leukemia cells by modulating caspase cascade signaling and altering associated genes expression was assayed by cDNA microarray. Environ Toxicol 2015;30(10):1162-1177. | Read abstract |

[2015] Li D, Schmitz OJ. Comprehensive two-dimensional liquid chromatography tandem diode array detector (DAD) and accurate mass QTOF-MS for the analysis of flavonoids and iridoid glycosides in Hedyotis diffusa. Anal Bioanal Chem 2015;407(1):231-240. | Read abstract |

[2015] Lin J, Li Q, Chen H, Lin H, Lai Z, Peng J. Hedyotis diffusa Willd. extract suppresses proliferation and induces apoptosis via IL-6-inducible STAT3 pathway inactivation in human colorectal cancer cells. Oncol Lett 2015;9(4):1962-1970. | Read article |

[2015] Li Q, Wang X, Shen A, Zhang Y, Chen Y, Sferra TJ, Lin J, Peng J. 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. Exp Ther Med 2015;10(5):1845-1850. | Read article |

[2015] Sunwoo YY, Lee JH, Jung HY, Jung YJ, Park MS, Chung YA, Maeng LS, Han YM, Shin HS, Lee J, Park SI. Oldenlandia diffusa promotes antiproliferative and apoptotic Effects in a rat hepatocellular carcinoma with liver cirrhosis. Evid Based Complement Alternat Med 2015;2015:501508. | Read article |

[2015] Wei MC, Yang YC, Hong SJ. Determination of oleanolic and ursolic acids in Hedyotis diffusa using hyphenated ultrasound-assisted supercritical carbon dioxide extraction and chromatography. Evid Based Complement Alternat Med 2015;2015:450547. | Read article |

[2015] Ye JH, Liu MH, Zhang XL, He JY. Chemical profiles and protective effect of Hedyotis diffusa Willd in lipopolysaccharide-induced renal inflammation mice. Int J Mol Sci 2015;16(11):27252-27269. | Read article |

[2015] Zhang P, Zhang B, Gu J, Hao L, Hu F, Han C. The study of the effect of Hedyotis diffusa on the proliferation and the apoptosis of the cervical tumor in nude mouse model. Cell Biochem Biophys 2015;72(3):783-789. | Read abstract |

[2014] Dong Q, Ling B, Gao B, Maley J, Sammynaiken R, Yang J. Hedyotis diffusa water extract diminished the cytotoxic effects of chemotherapy drugs against human breast cancer MCF7 cells. Nat Prod Commun 2014;9(5):699-700. | Read abstract |

[2014] Li C, Zhao Y, Guo Z, Zhang X, Xue X, Liang X. Effective 2D-RPLC/RPLC enrichment and separation of micro-components from Hedyotis diffusa Willd. and characterization by using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. J Pharm Biomed Anal 2014;99:35-44. | Read abstract |

[2014] Yeh YC, Chen HY, Yang SH, Lin YH, Chiu JH, Lin YH, Chen JL. Hedyotis diffusa combined with Scutellaria barbata are the core treatment of Chinese herbal medicine used for breast cancer patients: A population-based study. Evid Based Complement Alternat Med 2014;2014:202378. | Read article |

[2014] Zhang Y, Xie RF, Xiao QG, Li R, Shen XL, Zhu XG. Hedyotis diffusa Willd extract inhibits the growth of human glioblastoma cells by inducing mitochondrial apoptosis via AKT/ERK pathways. J Ethnopharmacol 2014;158 Pt A:404-11. | Read abstract |

[2014] Zhu H, Liang QH, Xiong XG, Chen J, Wu D, Wang Y, Yang B, Zhang Y, Zhang Y, Huang X. Anti-inflammatory effects of the bioactive compound ferulic acid contained in Oldenlandia diffusa on collagen-induced arthritis in rats. Evid Based Complement Alternat Med 2014;2014:573801. | Read article |

[2013] Li M, Wong YL, Jiang LL, Wong KL, Wong YT, Lau CB, Shaw PC. Application of novel loop-mediated isothermal amplification (LAMP) for rapid authentication of the herbal tea ingredient Hedyotis diffusa Willd. Food Chem 2013;141(3):2522-5. | Read abstract |

[2013] Lin J, Wei L, Shen A, Cai Q, Xu W, Li H, Zhan Y, Hong Z, Peng J. Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis. Int J Oncol 2013;42(2):651-656. | Read abstract |

[2013] Niu Y, Meng QX. Chemical and preclinical studies on Hedyotis diffusa with anticancer potential. J Asian Nat Prod Res 2013;15(5):550-65. | Read abstract |

[2013] Wang N, Li DY, Niu HY, Zhang Y, He P, Wang JH. 2-hydroxy-3-methylanthraquinone from Hedyotis diffusa Willd induces apoptosis in human leukemic U937 cells through modulation of MAPK pathways. Arch Pharm Res 2013;36(6):752-758. | Read abstract |

[2013] Yang YC, Wei MC, Chiu HF, Huang TC. Development and validation of a modified ultrasound-assisted extraction method and a HPLC method for the quantitative determination of two triterpenic acids in Hedyotis diffusa. Nat Prod Commun 2013;8(12):1683-1686. | Read abstract |

[2012] Cai Q, Lin J, Wei L, Zhang L, Wang L, Zhan Y, Zeng J, Xu W, Shen A, Hong Z, Peng J. Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of STAT3 signaling pathway. Int J Mol Sci 2012;13(5):6117-6128. | Read article |

[2012] Chen XZ, Cao ZY, Chen TS, Zhang YQ, Liu ZZ, Su YT, Liao LM, Du J. Water extract of Hedyotis diffusa Willd suppresses proliferation of human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by inhibiting the CDK2-E2F1 pathway. Oncol Rep 2012;28(2):742-748. | Read abstract |

[2012] Gu G, Barone I, Gelsomino L, Giordano C, Bonofiglio D, Statti G, Menichini F, Catalano S, Andò S. Oldenlandia diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERα/Sp1-mediated p53 activation. J Cell Physiol 2012;227(10):3363-3372. | Read abstract |

[2012] Lau CB, Cheng L, Cheng BW, Yue GG, Wong EC, Lau CP, Leung PC, Fung KP. Development of a simple chromatographic method for distinguishing between two easily confused species, Hedyotis diffusa and Hedyotis diffusa. Nat Prod Res 2012;26(15):1446-1450. | Read abstract |

[2012] Lin M, Lin J, Wei L, Xu W, Hong Z, Cai Q, Peng J, Zhu D. Hedyotis diffusa Willd extract inhibits HT-29 cell proliferation via cell cycle arrest. Exp Ther Med 2012;4(2):307-310. | Read article |

[2012] Li N, Liu C, Mi S, Wang N, Zheng X, Li Y, Huang X, He S, Chen H, Xu X. Simultaneous determination of oleanolic acid, p-coumaric acid, ferulic acid, kaemperol and quercetin in rat plasma by LC-MS-MS and application to a pharmacokinetic study of Oldenlandia diffusa extract in rats. J Chromatogr Sci 2012;50(10):885-892. | Read abstract |

[2012] Liu EH, Zhou T, Li GB, Li J, Huang XN, Pan F, Gao N. Characterization and identification of iridoid glucosides, flavonoids and anthraquinones in Hedyotis diffusa by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. J Sep Sci 2012;35(2):263-272. | Read abstract |

[2012] Song YH, Jeong SJ, Kwon HY, Kim B, Kim SH, Yoo DY. Ursolic acid from Oldenlandia diffusa induces apoptosis via activation of caspases and phosphorylation of glycogen synthase kinase 3 beta in SK-OV-3 ovarian cancer cells. Biol Pharm Bull 2012;35(7):1022-1028. | Read article |

[2012] Wang X, Cheng W, Yao X, Guo X. Qualitative analysis of the chemical constituents in Hedyotis diffusa by HPLC-TOF-MS. Nat Prod Res 2012;26(2):167-172. | Read abstract |

[2011] Kim SJ, Chung WS, Kim SS, Ko SG, Um JY. Antiinflammatory effect of Oldenlandia diffusa and its constituent, hentriacontane, through suppression of caspase-1 activation in mouse peritoneal macrophages. Phytother Res 2011;25(10):1537-1546. | Read abstract |

[2011] Kim SJ, Kim YG, Kim DS, Jeon YD, Kim MC, Kim HL, Kim SY, Jang HJ, Lee BC, Hong SH, Um JY. Oldenlandia diffusa ameliorates dextran sulphate sodium-induced colitis through inhibition of NF-κB activation. Am J Chin Med 2011;39(5):957-969. | Read abstract |

[2011] Lee HZ, Bau DT, Kuo CL, Tsai RY, Chen YC, Chang YH. Clarification of the phenotypic characteristics and anti-tumor activity of Hedyotis diffusa. Am J Chin Med 2011;39(1):201-213. | Read abstract |

[2011] Lin CC, Kuo CL, Lee MH, Hsu SC, Huang AC, Tang NY, Lin JP, Yang JS, Lu CC, Chiang JH, Chueh FS, Chung JG. 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. In Vivo 2011;25(4):633-640. | Read abstract |

[2011] Lin J, Wei L, Xu W, Hong Z, Liu X, Peng J. Effect of Hedyotis diffusa Willd extract on tumor angiogenesis. Mol Med Rep 2011;4(6):1283-1288. | Read abstract |

[2011] Wang JH, Shu LH, Yang LL, Zhang M, He P. 2-Hydroxy-3-methylanthraquinone from Hedyotis diffusa WILLD induces apoptosis via alteration of Fas/FasL and activation of caspase-8 in human leukemic THP-1 cells. Arch Med Res 2011;42(7):577-83. | Read abstract |

[2011] Zhu T, Row KH. Preparation of amino-modified active carbon cartridges and their use in the extraction of quercetin from Oldenlandia diffusa. J Pharm Biomed Anal 2011;56(4):713-720. | Read abstract |

[2010] Ganbold M, Barker J, Ma R, Jones L, Carew M. Cytotoxicity and bioavailability studies on a decoction of Oldenlandia diffusa and its fractions separated by HPLC. J Ethnopharmacol 2010;131(2):396-403. | Read abstract |

[2010] Lin J, Chen Y, Wei L, Chen X, Xu W, Hong Z, Sferra TJ, Peng J. Hedyotis diffusa Willd extract induces apoptosis via activation of the mitochondrion-dependent pathway in human colon carcinoma cells. Int J Oncol 2010;37(5):1331-1338. | Read abstract |

[2010] Liu Z, Liu M, Liu M, Li J. Methylanthraquinone from Hedyotis diffusa WILLD induces Ca(2+)-mediated apoptosis in human breast cancer cells. Toxicol In Vitro 2010;24(1):142-147. | Read abstract |

[2010] Xu GH, Kim YH, Chi SW, Choo SJ, Ryoo IJ, Ahn JS, Yoo ID. Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett 2010;20(2):513-515. | Read abstract |

[2010] Zhang Y, Chen Y, Fan C, Ye W, Luo J. Two new iridoid glucosides from Hedyotis diffusa. Fitoterapia 2010;81(6):515-517. | Read abstract |

[2009] Wu PK, Chi Shing Tai W, Liang ZT, Zhao ZZ, Hsiao WL. Oleanolic acid isolated from Oldenlandia diffusa exhibits a unique growth inhibitory effect against ras-transformed fibroblasts. Life Sci 2009;85(3-4):113-121. | Read abstract |

[2008] Huang WH, Yu SH, Li YB, Jiang JQ. Four anthraquinones from Hedyotis diffusa. J Asian Nat Prod Res 2008;10(9-10):887-889. | Read abstract |

[2008] Kang XD, Li X, Zhao CC, Mao Y. Two new anthraquinones from Hedyotis diffusa W. J Asian Nat Prod Res 2008;10(1-2):193-197. | Read abstract |

[2008] Li C, Xue X, Zhou D, Zhang F, Xu Q, Ren L, Liang X. Analysis of iridoid glucosides in Hedyotis diffusa by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal 2008;48(1):205-211. | Read abstract |

[2008] Shi Y, Wang CH, Gong XG. Apoptosis-inducing effects of two anthraquinones from Hedyotis diffusa WILLD. Biol Pharm Bull 2008;31(6):1075-1078. | Read article |

[2008] Yang T, Yang YH, Yang JY, Chen BM, Duan JP, Yu SY, Ouyang HT, Cheng JP, Chen YX. Fingerprint of Hedyotis diffusa Willd. by HPLC-MS. Phytochem Anal 2008;19(6):487-492. | Read abstract |

[2007] Liang Z, Jiang Z, Ho H, Zhao Z. Comparative analysis of Oldenlandia diffusa and its substitutes by high performance liquid chromatographic fingerprint and mass spectrometric analysis. Planta Med 2007;73(14):1502-1508. | Read abstract |

[2007] Willimott S, Barker J, Jones LA, Opara EI. Apoptotic effect of Oldenlandia diffusa on the leukaemic cell line HL60 and human lymphocytes. J Ethnopharmacol 2007;114(3):290-299. | Read abstract |

[2006] Cheung HY, Cheung SH, Law ML, Lai WP. Simultaneous determination of key bioactive components in Hedyotis diffusa by capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 2006;834(1-2):195-198. | Read abstract |

[2006] Cui J, Wang SC, Shi SS, Wang ZT. Structural characterization of a glucan isolated from Hedyotis diffusa Willd. Zhong Yao Cai 2006;29(9):912-915. | Read abstract |

[2006] Liang ZT, Jiang ZH, Leung KS, Peng Y, Zhao ZZ. Distinguishing the medicinal herb Oldenlandia diffusa from similar species of the same genus using fluorescence microscopy. Microsc Res Tech 2006;69(4):277-282. | Read abstract |

[2006] Yadav SK, Lee SC. Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide burst and caspase activation. Zhong Xi Yi Jie He Xue Bao 2006;4(5):485-489. | Read abstract |

[2005] Kim DH, Lee HJ, Oh YJ, Kim MJ, Kim SH, Jeong TS, Baek NI. Iridoid glycosides isolated from Oldenlandia diffusa inhibit LDL-oxidation. Arch Pharm Res 2005;28(10):1156-1160. | Read abstract |

[2004] Gupta S, Zhang D, Yi J, Shao J. Anticancer activities of Oldenlandia diffusa. J Herb Pharmacother 2004;4(1):21-33. | Read abstract |

[2002] Chung HS, Jeong HJ, Hong SH, Kim MS, Kim SJ, Song BK, Jeong IS, Lee EJ, Ahn JW, Baek SH, Kim HM. Induction of nitric oxide synthase by Oldenlandia diffusa in mouse peritoneal macrophages. Biol Pharm Bull 2002;25(9):1142-1146. | Read article |

[2001] Kim Y, Park EJ, Kim J, Kim Y, Kim SR, Kim YY. Neuroprotective constituents from Hedyotis diffusa. J Nat Prod 2001;64(1):75-78. | Read abstract |

[2000] Lu CM, Yang JJ, Wang PY, Lin CC. A new acylated flavonol glycoside and antioxidant effects of Hedyotis diffusa. Planta Med 2000;66(4):374-377. | Read abstract |

[1997] Yoshida Y, Wang MQ, Liu JN, Shan BE, Yamashita U. Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular. Int J Immunopharmacol 1997;19(7):359-370. | Read abstract |

[1996] Wong BY, Lau BH, Jia TY, Wan CP. Oldenlandia diffusa and Scutellaria barbata augment macrophage oxidative burst and inhibit tumor growth. Cancer Biother Radiopharm 1996;11(1):51-56. | Read abstract |

[1981] Nishihama Y, Masuda K, Yamaki M, Takagi S, Sakina K. Three new iridoid glucosides from Hedyotis diffusa. Planta Med 1981;43(1):28-33. | Read abstract |

[1979] Liao LL, Chen CH, Chen GC. Formosan medicinal herb, Hedyotis diffusa Willd, as an antitumor agent. Taiwan Yi Xue Hui Za Zhi 1979;78(7):658-660.