Herba Hedyotis Diffusa (Bai Hua She She Cao)
Herba Hedyotis Diffusa (synonym: Oldenlandia diffusa (OD)) as an annual herb has a wide range of pharmacological effects, including antioxidant, anticancer and immune regulation. It is one of the most well-known Chinese herbs for its anticancer effect. Chemical analysis has revealed that bioactive compounds including vanillic acid, 2-hydroxy-3-methyl-anthraquinone, 2-hydroxy-7-methyl-3methoxyanthraquinone, and 1-formaldehyde-4-hydroxyl anthraquinone are the main anticancer components of OD.[1] Vanoxalic acid and 2-hydroxy-3-methyl-anthraquinone are good tyrosinase inhibitors which have been used clinically to fight cancer. For clinical use, the ethanol-extracted OD had better efficacy.
OD and its active components can effectively induce apoptosis of prostate cancer, colorectal cancer, cervical cancer, gastric cancer, and other tumor cells.[2] It can reduce the proliferation and metastasis of liver cancer cells by inhibiting the expression of chemokine receptors such as CXCR1, CXCR2, and CXCR4 and induce apoptosis through caspase 3 pathway.[3] Chung et al. found that OD inhibits the expression of MMP-9 to inhibit the invasion of breast cancer cells and regulates the expression level of apoptosis-related proteins to induce apoptosis of cancer cells.[4] In addition, the water extract of OD leads to the apoptosis of lung cancer cells by inhibiting the MAPK pathway.[5]
The expressions of apoptosis-related proteins Fas, caspase 3, and caspase 7 were significantly increased, and the expression of Fas L protein was inhibited in the kidney cancer model mice with the treatment of OD.[6] It can also induce apoptosis and inhibit the proliferation of bladder cancer T24 cells through the JAK2/STAT3 pathway.[7] In vivo experiments showed that total flavonoids of OD could significantly inhibit the tumor growth of cervical cancer in mice. The mechanism may be related to the increase of serum TNF-α, IFN-γ, and IL-2 levels.[8] Furthermore, the clinical application has proved that the herb can also achieve the effect of cancer control by enhancing body immunity.[9]
As an anticancer drug, OD has a long history of clinical use with a good inhibitory effect on a variety of cancers, but it is often used in combination with other drugs to enhance its anticancer effects, most commonly in combination with Scutellaria barbata. It can be the best herb for antitumor therapy.[10]
Anticancer activities of Oldenlandia diffusa
The water extract of the raw herb Oldenlandia diffusa was used in this study. The in vitro anti-proliferative activities of the extract were tested against eight cancer cell lines (A5-49 Human Lung Epithelial Carcinoma, C-33A Human Cervix Carcinoma, MCF-7 Human Breast Adenocarcinoma, Ln-Cap Human Prostate Carcinoma, Tsu-Pr1 Human Prostate Carcinoma, MDA-MB-453 Human Breast Carcinoma, DU-145 Human Prostate Carcinoma, normal Pancreatic Cell & B16-F10 Murine Melanoma) and one normal cell line. Microscopic examination and DNA ladder analysis were carried out to determine the pro-apoptotic effect of the extract. The extract exhibited a strong anti-proliferative activity against all cancer cell lines tested. The concentrations of growth inhibition at 50% (IC(50)) ranged from 7 to 25 mg raw material/ml after 48-hour treatment. The extract had a very limited cytotoxicity (10% inhibition) on the normal pancreatic cells even at the concentration of 50 mg/mL. Oral administration of the herbal extract effectively reduced B16-F10 cell (melanoma).
Oldenlandia diffusa extract effectively inhibited the growth of all the eight cancer cell lines and induced significant increase of apoptosis. The extract exhibited minimum toxic effect on normal pancreatic cells. Furthermore, there was a significant inhibition of lung metastases in the animal model with no noticeable adverse effects. The herb extract could be a potential anticancer agent.[11]
References
[1] Zeng YC, Liang SY, Wu JH. Chemical constituents from hedyotis diffusa and their antitumor activities," Chinese Traditional Patent Medicine, vol. 40, Article ID 17681772, 2018.
[2] Che HW, Yang HN, Tan XC. Research progress on the tumour cell inhibition activities of different extraction of Oldenlandia diffusa. Asia-Pacific Traditional Medicine. 2019;15:191–193.
[3] Sunwoo YY, Lee JH, Jung HY, et al. Oldenlandia diffusa promotes antiproliferative and apoptotic effects in a rat hepatocellular carcinoma with liver cirrhosis. Evidence-Based Complementary and Alternative Medicine. 2015;2015:11. doi: 10.1155/2015/501508.501508
[4] Chung TW, Choi H, Lee JM, et al. 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. Journal of Ethnopharmacology. 2017;195:309–317. doi: 10.1016/j.jep.2016.11.036.
[5] Guo HM, Zhao D, Cao L. Hedyotis diffusa Willd promotes the apoptosis of lung cancer cells by inhibiting MAPK pathway. Pharmaceutical and Clinical Research. 2019;27:5–9
[6] Zhou J, Zhao P. Effect of hedyotis diffusa on expressions of apoptosis related protein Fas, caspase3 and caspase7 in Renca renal cell carcinoma of model mice. Chinese Journal of Biochemical Pharmaceutics. 2016;36:37–45. doi: 10.3969/j.issn.1005-1678.2016.12.009.
[7] Nan XH, Yu F, Tian H. Herba hedyotis diffusae induces human bladder cancer T24 cells apoptosis through inhibiting JAK2/STAT3 signalling pathways. Journal of China Prescription Drug. 2018;16:31–32
[8] Li M, Zhang HY, Shao HO. Effects of total flavonoids of Oldenlandia diffusa on immune and antioxidant capacity of cervical cancer U14 tumour-bearing mice. Journal of Chinese Medicinal Materials. 2019;6:1417–1420.
[9] Zhao YL. Application of hedyotis diffusa in tumor treatment. Gansu Science and Technology. 2018;34:141–142.
[10] Liu W, Yang B, Yang L , et al. Therapeutic Effects of Ten Commonly Used Chinese Herbs and Their Bioactive Compounds on Cancers. Evid Based Complement Alternat Med. 2019; 2019: 6057837. doi: 10.1155/2019/6057837
[11] Gupta S, Zhang D, Yi J, Shao J. Anticancer activities of Oldenlandia diffusa. J Herb Pharmacother. 2004;4(1):21-33.
