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Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a TCM compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice. Gong C, Qian L, Yang H, Ji LL, Wei H, Zhou WB, Qi C, Wang CH. BMC Complement Altern Med. 2015 Aug 18;15:283. doi: 10.1186/s12906-015-0799-9. Institute of Chinese Materia Medica, Shanghai Univ of TCM, Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of TCM Complex Prescription, 1200 Cailun Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, PRC. wchcxm@hotmail.com
BACKGROUND: Cisplatin is a highly effective chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. Zengmian Yiliu Granule (ZMYL), a compound preparation of TCMs, has been used in clinic as a complementary and alternative medicine for attenuating Cisplatin-induced toxicities and enhancing the tumor therapeutic effect of Cisplatin. The aim of the present study is to investigate hepaprotective effect of ZMYL against Cisplatin-induced hepatotoxicity. Further, the pharmacokinetic characteristics of Cisplatin in SKOV-3-bearing nude mice were observed.
METHODS: The ICR mice were dosed orally with ZMYL for 7 days and then Cisplatin was injected intraperitoneally at a dose of 45 mg/kg body weight. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate the liver function. The total glutathione (T-GSH), reduced glutathione (GSH) and glutathione S-transferase (GST) levels were determined to evaluate the oxidant damage in liver homogenates. Tissue pathological change in liver was conducted by light microscopy analysis. The pharmacokinetic and tissue distribution of free and total platinum (Pt) after dosing of Cisplatin alone and combination with ZMYL were determined in SKOV-3-bearing nude mice by ICP-MS.
RESULTS: Oral administration of ZMYL prior to the Cisplatin treatment could prevent the Cisplatin-induced in lifting of ALT and AST, reduction of T-GSH, R-GSH and GST, and some histopathological alterations in ICR mice. Some differences in pharmacokinetic parameters between the two groups have been observed in higher CL and decreased MRT of free platinum (Pt) in plasma and total Pt in spleen in Cisplatin co-administration with ZMYL group. It indicated Cisplatin was cleared more quickly from blood and spleen, and could reduce the accumulation and toxic possibility of Cisplatin in combination with ZMYL.
CONCLUSIONS: Zengmian Yiliu Granule attenuated Cisplatin-induced hepatotoxicity during Cisplatin chemotherapy and did not disturb the pharmacokinetics fate of Cisplatin significantly. PMCID: PMC4538754 PMID: 26283082 [PubMed - in process]
Traditional herbal medicine as adjunctive therapy for breast cancer: A systematic review. Kim W, Lee WB, Lee JW, Min BI, Baek SK, Lee HS, Cho SH. Complement Ther Med. 2015 Aug;23(4):626-32. doi: 10.1016/j.ctim.2015.03.011. Epub 2015 Apr 16. Dept of East-West Medicine, Graduate School, Kyung Hee Univ, Seoul 130-701, South Korea. chosh@khu.ac.kr OBJECTIVES: To assess the effectiveness of traditional herbal medicine (THM) as adjunctive therapy for breast cancer as evidenced by randomized controlled trials (RCTs).
METHODS: Five electronic English and Chinese databases were systematically searched up to February, 2014. All RCTs involving THM in combination with conventional cancer therapy for breast cancer were included. RESULTS: Eight RCTs involving 798 breast cancer patients were systematically reviewed. Three studies reported a significant difference in the improvement of QoL compared to the control group. Two studies reported an increase in the white blood cell count after treatment. Data on hot flashes and sleep quality were evaluated. However, no significant differences in immediate tumor response were observed.
CONCLUSION: THM combined with conventional therapy in the treatment of breast cancer is efficacious in improving QoL and in decreasing the number of hot flashes / day. More research and well-designed, rigorous, large clinical trials are necessary to further address these issues. Copyright © 2015. Published by Elsevier Ltd. PMID: 26275657 [PubMed - in process]
Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC. Singh TD, Meitei HT, Sharma AL, Robinson A, Singh LS, Singh TR. Biol Res. 2015 Aug 20;48:46. doi: 10.1186/s40659-015-0037-4.
BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE) induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin). This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs.
RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP) cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK) pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase (JNK). Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE.
CONCLUSION: Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment. PMID: 26290043 [PubMed - in process] PMCID: PMC4545984
Double-Blind, Placebo-Controlled Pilot Study of Processed Ultra Emu Oil Versus Placebo in the Prevention of Radiation Dermatitis. Rollmann DC, Novotny PJ, Petersen IA, Garces YI, Bauer HJ, Yan ES, Wahner-Roedler D, Vincent A, Sloan JA, Issa Laack NN. Int J Radiat Oncol Biol Phys. 2015 Jul 1;92(3):650-8. doi: 10.1016/j.ijrobp.2015.02.028. Epub 2015 Apr 28.
PURPOSE: The purpose of this single-institution pilot study was to evaluate the feasibility and safety of an oil-based skin agent, Ultra Emu Oil, on skin-related toxicity in patients undergoing radiation therapy to the breast or chest wall.
METHODS AND MATERIALS: Patients were randomized 2:1 in a double-blind fashion and were instructed to apply processed Ultra Emu Oil or placebo (cottonseed oil) twice daily during the course of radiation therapy. The oils were applied before the third fraction and continued for 6 weeks after completion of treatment. The primary endpoint was the area under the curve (AUC) of Skindex-16 scale scores over time. Secondary outcomes included maximum grade of radiation dermatitis using the Common Terminology Criteria (CTC) for Adverse Events (CTCAE 3.0), the Skin Toxicity Assessment Tool, quality of life (QOL) measured by Linear Analogue Self-Assessment, and a symptom experience diary (SED).
RESULTS: In all, 42 of 45 patients completed the study and were evaluable. The median times to peak rash, skin redness, peeling, and skin swelling were weeks 6, 6, 7, and 7, respectively as measured by the SED. The Skindex AUC scores tended to be lower in emu oil patients than in placebo patients (mean total AUC 7.2 vs 10.4, respectively). This trend was also seen in all the Skindex subdomains. The overall QOL was slightly better in the emu oil group but remained stable throughout the study for both arms. Peak CTC toxicity occurred at week 6. Patients using emu oil appeared slightly worse on maximum CTC grade, but the difference was not significant. CONCLUSIONS: This pilot study confirmed the safety of oil-based skin treatments during radiation therapy and suggests a trend for reduced skin toxicity for patients receiving emu oil. A larger study is needed to evaluate the efficacy of emu oil in reducing radiation dermatitis in patients receiving breast radiation. PMID: 25936812 [PubMed - indexed for MEDLINE]
Saussurea involucrata: A review of the botany, phytochemistry and ethnopharmacology of a rare traditional herbal medicine. Chik WI, Zhu L, Fan LL, Yi T, Zhu GY, Gou XJ, Tang YN, Xu J, Yeung WP, Zhao ZZ, Yu ZL, Chen HB. J Ethnopharmacol. 2015 Aug 22;172:44-60. doi: 10.1016/j.jep.2015.06.033. Epub 2015 Jun 23.
ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucratais an endangered species of the Asteraceae family, growing in the high mountains of central Asia. It is widely used in traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as Tianshan Snow Lotus (Tianshan Xuelianhua). In traditional medical theory, it can promote blood circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates cold and dampness from the body, diminishes inflammation, invigorates, and strengthens Yin and Yang. It has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in Uyghur and Chinese medicine.
AIM OF THE REVIEW: To summarize the miscellaneous research that has been done regarding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. involucrata.
METHOD: An extensive review of the literature was carried out. Apart from different electronic databases including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced for information, abstracts, full-text articles and books written in English and Chinese, including those traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal records in Uyghur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for pertinent information.
RESULTS: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70 compounds have been isolated and identified; they include phenylpropanoids, flavonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientific studies on the biological activity of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-inflammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and immunomodulating effects. Many have shown correlations to the traditional clinical applications in Traditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth, adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting expression of tumor suppressor genes. Dosage efficacy is found to be generally concentration- and time-dependent. However, studies on the correlation between particular chemical constituents and specific bioactivities are limited.
CONCLUSION: In this review, we have documented the existing traditional uses of S. involucrata and summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the traditional uses have been validated by phytochemical and modern pharmacological studies but there are still some areas where the current knowledge could be improved. Although studies have confirmed that S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules and the mechanism of action are expected. Whether we should use this herb independently or in combination deserves to be clarified. The exact quality control as well as the toxicology studies is necessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S. involucrata and provides some directions for the future development of this plant. PMID: 26113182 [PubMed - in process]
Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine. He X, Fang J, Huang L, Wang J, Huang X. J Ethnopharmacol. 2015 Aug 22;172:10-29. doi: 10.1016/j.jep.2015.06.010. Epub 2015 Jun 16.
ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens (Fabaceae), also known as Kushen (Chinese: ), has been an important species in Chinese medicine since the Qin and Han dynasties. The root of Sophora flavescens has a long history in the traditional medicine of many countries, including China, Japan, Korea, India and some countries in Europe. In traditional Chinese medicine (TCM), Sophora flavescens has been used extensively, mainly in combination with other medicinal plants in prescriptions to treat fever, dysentery, hematochezia, jaundice, oliguria, vulvar swelling, asthma, eczema, inflammatory disorders, ulcers and diseases associated with skin burns. The aim of this review is to provide updated and comprehensive information regarding the botany, ethnopharmacology, phytochemistry, biological activities and toxicology of Sophora flavescens and to discuss possible trends and opportunities for further research on Sophora flavescens.
MATERIALS AND METHODS: We systematically searched major scientific databases (PubMed, Elsevier, SpringerLink, Google Scholar, Medline Plus, ACS, "Da Yi Yi Xue Sou Suo (http://www.dayi100.com/login.jsp)", China Knowledge Resource Integrated (CNKI) and Web of Science) for information published between 1958 and 2015 on Sophora flavescens. Information was also acquired from local classic herbal literature, conference papers, government reports, and PhD and MSc dissertations.
RESULTS: The broad spectrum of biological activities associated with Sophora flavescens has been considered a valuable resource in both traditional and modern medicine. Extracts are taken either orally or by injection. More than 200 compounds have been isolated from Sophora flavescens, and the major components have been identified as flavonoids and alkaloids. Recent in vitro and in vivo studies indicate that at least 50 pure compounds and crude extracts from Sophora flavescens possess wide-ranging antitumor, antimicrobial, antipyretic, antinociceptive, and anti-inflammatory pharmacological abilities. The anticancer and anti-infection abilities of these components are especially attractive areas for research.
CONCLUSIONS: Sophora flavescens is a promising traditional medicine, but there is a need for more precise studies to test the safety and clinical value of its main active crude extracts and pure compounds and to clarify their mechanisms of action. Moreover, some existing studies have lacked systematic methods and integration with the existing literature, and some of the experiments were isolated, used small sample sizes and were unreliable. More validated data are therefore required. PMID: 26087234 [PubMed - in process]