Background Chinese medicine often targets more than one system and as such comprises several compounds, often in non-purified form, with treatments therefore consisting of whole extracts of herbs rather than isolated compounds. The additive and synergistic effects of the phytochemicals in OMN54, a novel mixture of extracts from three commonly used Chinese medicine components; Ganoderma lucidum, Salvia miltiorrhiza and Scutellaria barbata, were previously demonstrated to have potent anti-cancer activity. This study aims to test whether this heterogeneous, multifunctional and multitargeted agent has an acceptable toxicity profile. Methods We conducted preliminary and formal preclinical tolerability determination of OMN54 in Sprague-Dawley rats. In the preliminary study rats were given OMN54 by oral feeding daily for 14 days at doses of 1000mg/kg, 1750mg/kg, 2500mg/kg or 3000mg/kg per day. A subsequent daily dosing (x 28, 60, 120 or 180) formal toxicology study was conducted in male and female Sprague-Dawley rats at a dose of single dose of 2000mg/kg/day. Results Significant body weight loss was noted in one of the rats treated at 3000mg/kg/day, with decline beginning study day 11. This animal experienced mild GI toxicity in the form of diarrhoea. Gross observation indicated kidney damage (pale kidneys) in both this group and in one rat treated at 2500mg/kg/day. For the later studies, no body weight loss was noted over the course of the study. Blood counts and chemistry were not substantially altered following administration of OMN54, nor were there any findings on histological assessment of organs. Conclusion OMN54 was found to be well tolerated in rat models. OMN54 did not cause any microscopic, anatomic or pathologic changes in exposed animals at the concentrations and under the conditions employed in this study.

Chinese Medicine 2009, 4:22doi:10.1186/1749-8546-4-22

In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du-Tang (HLJDT), Gui-Zhi-Fu-Ling-Wan (GZFLW), and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1^- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria radix showed strong growth inhibition and induction of apoptosis in comparison with baicalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1^- immature myeloma cells rather than MPC-1⁺ myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB-, which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria radix have an antiproliferative effect on myeloma cells, especially MPC-1^- immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria radix by blocking IkB- degradation. (Blood. 2005;105:3312-3318)

Zi Ma, Ken-ichiro Otsuyama, Shangqin Liu, Saeid Abroun, Hideaki Ishikawa, Naohiro Tsuyama, Masanori Obata, Fu-Jun Li, Xu Zheng, Yasuko Maki, Koji Miyamoto, and Michio M. Kawano

From the Department of Bio-Signal Analysis, Applied Medical Engineering Science (AMES), Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan; and Department of Kampo Medicine, Molecular Science, and Applied Medicine, Yamaguchi University School of Medicine, Yamaguchi University, Yamaguchi, Japan.

Toxicology. 2009 Oct 7.

Burns JJ, Zhao L, Taylor EW, Spelman K.

Pinnacle Integrative Medicine, Phoenix, AZ, USA.

ScienceDaily (Nov. 5, 2009) — Green tea extract has shown promise as cancer prevention agent for oral cancer in patients with a pre-malignant condition known as oral leukoplakia, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, published online in Cancer Prevention Research, is the first to examine green tea as a chemopreventative agent in this high-risk patient population. The researchers found that more than half of the oral leukoplakia patients who took the extract had a clinical response.

Long investigated in laboratory, epidemiological and clinical settings for several cancer types, green tea is rich in polyphenols, which have been known to inhibit carcinogenesis in preclinical models. Still, clinical results have been mixed.

“While still very early, and not definitive proof that green tea is an effective preventive agent, these results certainly encourage more study for patients at highest risk for oral cancer,” said Vassiliki Papadimitrakopoulou, M.D., professor in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology, and the study’s senior author. “The extract’s lack of toxicity is attractive — in prevention trials, it’s very important to remember that these are otherwise healthy individuals and we need to ensure that agents studied produce no harm.”

In the Phase II dose-finding study, 41 M. D. Anderson oral leukoplakia patients were randomized between August 2002 and March 2008 to receive either green tea extract or placebo. Participants took the extract, an oral agent, for three months at one of three doses — 500 per meter squared of body mass (mg/m2); 750 mg/m2 or 1,000 mg/m2 — three times daily. To best assess biomarkers, participants also underwent a baseline and 12-week biopsy, an important component in the design of the study, the researchers say.

“Collecting oral tissue biopsies was essential in that it allowed us to learn that not only did the green tea extract appear to have benefit for some patients, but we pointed to anti-angiogenic effects as a potential mechanism of action,” said Anne Tsao, M.D., assistant professor in the Department of Thoracic/Head and Neck Medical Oncology, and the study’s first author. “While preliminary because our patient population was so small, this gives us direction for further study.”

Of those taking green tea at the two highest doses, 58.8 percent had a clinical response, compared with 36.4 percent in the lowest extract dose and 18.2 percent in the placebo arm. At an extended follow-up with a mean of 27.5 months, 15 participants had developed oral cancer, with a median time to disease development of 46.4 months.

Although not statistically significant, the green tea extract also improved histology and trended towards an improvement in a number of biomarkers that may play a vital role in predicting cancer development.

Another important finding, say the researchers, was that that the extract was well tolerated. Side effects, including insomnia and nervousness, were mostly seen in the high-dose group but produced no significant toxicity.

“While these are encouraging findings, much more research must be done before we can conclude that green tea may prevent oral or any other type of cancer. It’s also important to remind people that this trial enrolled very few participants who, at the highest dose levels took the equivalent of eight cups of green tea three times a day,” said Papadimitrakopoulo. “We need to further understand if green tea offers longer-term prevention effects for patients.”

Papadimitrakopoulo and Tsao think that future studies with green tea in this high-risk population should focus on participants being exposed to the supplement for a longer time period. The researchers also stressed that the green tea extract studied in this trial was never sold over-the-counter and/or the Internet, both of which are not highly regulated. Rather, the compound was exclusively developed as a pharmaceutical.

According to the American Cancer Society, more than 35,720 are expected to be diagnosed with oral and/or pharynx cancer and the five year survival rate is less than 50 percent.

The study was funded by Ito En, the company that produced the green tea extract.

In addition to Papadimitrakopoulou and Tsao, other M. D. Anderson authors on the study include: Waun Ki Hong, M.D., professor and chair of the Division of Cancer Medicine; Jack Martin, D.D.S., professor in the Department of Dental Oncology; Li Mao, M.D., adjunct professor and Xi Ming Tang, M.D., Ph.D. research scientist, both of the Department of Thoracic/Head and Neck Medical Oncology; Adel El-Naggar, M.D., Ph.D., professor in the Department of Pathology; Iganacio Wistuba, M.D., professor in the Department of Pathology-Research; Kirk Culotta, Phar M.D., Department of Pharmacy Pharmacology Research; Ann Gillenwater, M.D., professor in the Department of Head and Neck Surgery; J. Jack Lee, Ph.D., professor and Diane Liu, both of the Department of Biostatistics. Other authors include Yuko Sagesaka of Ito En, Ltd.

ScienceDaily (Oct. 26, 2009) — Antioxidant extracts of the leaves of the Gingko biloba tree may protect cells from radiation damage, according to a study published in the International Journal of Low Radiation. The discovery may one day be used to help reduce side effects in cancer patients undergoing radiotherapy.

Chang-Mo Kang of the Korea Institute of Radiological and Medical Sciences in Taegu and colleagues are interested in the protective effects of well-known herbal remedies of which Gingko biloba is one. G. biloba is a unique tree species with no close living relatives and extracts of its leaves contain antioxidant compounds including glycosides and terpenoids known as ginkgolides and bilobalides.

These compounds are thought to protect cells from damage by free radicals and other reactive oxidizing species found in the body. These are generated continuously by the body’s normal metabolism, and in excess in some diseases or after exposure to pollution or radiation. They damage proteins, DNA and other biomolecules and left unchecked can kill cells.

As such, extracts of certain plants that contain antioxidants, including G. biloba, have attracted interest for their pharmacological activity. G. biloba is currently sold as a herbal supplement and there are numerous claims for health benefits, including the possibility of preventing the onset of dementia or Alzheimer’s disease.

Kang and colleagues have now collected human white blood cells, lymphocytes, from healthy donors aged 18 to 50 years. They treated half of these cells with commercially available G. biloba extract in the laboratory and doused the other half with salt solution as an experimental control. They then compared the effects of gamma radiation from radioactive cesium on the white blood cells compared to the untreated control samples.

The team uses a light microscope to look for lymphocytes undergoing programmed cell death, or apoptosis, as a result of radiation exposure. They found that there was a significant increase in apoptosis in the untreated cells compared with those treated with G. biloba extract. Almost a third of the untreated cells underwent apoptosis compared with approximately one in twenty of the treated cells. Parallel studies with laboratory mice also demonstrated a similar protective effect against radiation poisoning.

The results suggest that the extracts can neutralize the free-radicals and oxidizing agents produced in the cells by the radiation and so prevent them from undergoing apoptosis.

1. Shin et al. Protective effect of Gingko biloba against radiation-induced cellular damage in human peripheral lymphocytes and murine spleen cells. International Journal of Low Radiation, 2009; 6 (3): 209 DOI: 10.1504/IJLR.2009.028889