Sandra S. Appiah

Antiinflammatory and hepatoprotective medicinal herbs as potential substitutes for bear bile

Practitioners of traditional Chinese medicine (TCM) commonly prescribe medicinal formulations relying on the purported synergism of a combination of plant species, sometimes incorporating animal parts and minerals. Bear bile, obtained from either wild or farmed bears, is a commonly used constituent of traditional medicine formulations. With several bear species now listed under Convention on International Trade in Endangered Species of Wild Fauna and Flora as threatened with extinction and with bear farming being actively campaigned against on ethical grounds, it is important to seek and promote alternatives to the use of bear bile as medicine. This chapter describes and evaluates the scientific data relating to the efficacy of bear bile and potential alternatives to its use, including the use of bile from other animal species, the use of synthetic chemical alternatives, and the use of herbal substitutes. Scientific studies have confirmed the efficacy of bear bile as an antiinflammatory and a hepatoprotective agent. Ursodeoxycholic acid (UDCA), the active component of bear bile is used in a synthetic form in Western medicine and can serve as an alternative to bear bile in the treatment and management of certain cholestatic liver conditions. In TCM practice, bile from domesticated animal species (such as cattle, chicken, and pig) has been used as a substitute for bear bile. Following evaluation of TCM literature and pharmacological/clinical data, the authors propose six plant species, either as single herbs or in combination, Gardenia jasminoides (zhī zi; ), Scutellaria baicalensis (huáng qín; ), Coptis chinensis (huáng lián, ), Phellodendron amurense (huáng băi; ), Andrographis paniculata (chuan xin lian; ), and Rheum palmatum (dà huang; ), two medicinal Kampo formulations, Orengedokuto, Dia-Orengedokuto (which originated from traditional Chinese herbal formula Huanglian Jiedu Tang, ), and two individual phytochemicals (berberine and andrographolide) as alternatives to bear bile. The proposed herbal alternatives are frequently found listed in traditional formulations also containing bear bile, usually with different therapeutic roles ascribed to them. The existing evidence base for the effectiveness of herbal alternatives is sufficiently strong for TCM practitioners and consumers to consider using these without the addition of bear bile. This consideration is driven by the imperative to protect populations of bears from overexploitation in the wild and when farmed. However, for the identified alternatives to be accepted by users, it is essential that researchers and TCM practitioners collaborate effectively to initiate consumer behavior change.

Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

Baicalein (BL), a potential cancer chemopreventative flavone, has been reported to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest in various human cancer cell models. Delivery of BL via nanoliposomes has been shown to improve its oral bioavailability and long-circulating property in vivo. However, the role of BL in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms has yet to be elucidated. In the present study, BL was formulated into liposomes with different sizes to improve its solubility and stability. The cytotoxic and pro-apoptotic effects of free BL and liposomal BL were also evaluated. The results demonstrated that 100 nm liposomes were the most stable formulation when compared with 200 and 400 nm liposomes. Liposomal BL inhibited K562 cell growth as efficiently as free BL (prepared in DMSO), indicating that the liposome may be a potential vehicle to deliver BL for the treatment of CML. Flow cytometry analysis showed that there was significant (P<0.005) cell cycle arrest in the sub-G1 phase (compared with vehicle control), indicating cell apoptosis following 20 µM liposomal BL or free BL treatment of K562 cells for 48 h. The induction of cell apoptosis by all BL preparations was further confirmed through the staining of treated cells with Annexin V-fluorescein isothiocyanate/propidium iodide. A significant increase in reactive oxygen species (ROS) generation was observed in free BL and liposomal BL treated cells, with a higher level of ROS produced from those treated with free BL. This indicated that cell apoptosis induced by BL may be via ROS generation and liposome delivery may further extend the effect through its long-circulating property.

Evidence for the outcomes and impact of clinical pharmacy: context of UK hospital pharmacy practice

Objectives The role of clinical pharmacists in hospitals has evolved and continues to expand. In the UK, outside of a few national policy drivers, there are no agreed priorities, measures or defined outcomes for hospital clinical pharmacy (CP). This paper aims to (1) highlight the need to identify and prioritise specific CP roles, responsibilities and practices that will bring the greatest benefit to patients and health systems and (2) describe systematic weaknesses in current research methodologies for evaluating CP services and propose a different approach. Method Published reviews of CP services are discussed using the Economic, Clinical and Humanistic Outcomes framework. Recurring themes regarding study methodologies, measurements and outcomes are used to highlight current weaknesses in studies evaluating CP. Results Published studies aiming to demonstrate the economic, clinical or humanistic outcomes of CP often suffer from poor research design and inconsistencies in interventions, measurements and outcomes. This has caused difficulties in drawing meaningful conclusions regarding CP’s definitive contribution to patient outcomes. Conclusion There is a need for more research work in National Health Service (NHS) hospitals, employing a different paradigm to address some of the weaknesses of existing research on CP practice. We propose a mixed-methods approach, including qualitative research designs, and with emphasis on cost-consequence analyses for economic evaluations. This approach will provide more meaningful data to inform policy and demonstrate the contribution of hospital CP activities to patient care and the NHS.

Abstract LB-271: Inulin inhibits free radical species in HCT 116 adenoma carcinoma and normal human HK (keratinocyte) cell line

Background: Bile acids have been implicated in oxidative damage via stimulation of reactive species including superoxide and nitric oxide. Superoxide and nitric oxide production are associated with inflammation. NF-κB up- regulation provides a critical link between inflammation and cancer. It has also been shown that there is a possible correlation between total activity of nitric oxide synthase and p53 mutation frequency in lung adenocarcinoma. Inulin is an oligosaccharide, classified as a prebiotic, and shown to improve gut health when used in combination with probiotics. However, there is paucity of data on how prebiotics alone affect gut health and by which mechanism of action. Objectives: To evaluate the potential of inulin in reduction of reactive species and its mechanism of inhibiting cancer cells. Methods: HCT116 adenocarcinoma cells were treated with inulin at different concentrations and stopped at various time ranges (30 minutes - 24 hours). Modified Greiss reagent was used in the study of reactive nitrogen species (RNS). Nitro blue tetrazolium (NBT) assay (Modified), was used in the investigation of superoxide production (SOP) in HCT116 in the presence of deoxycholic acids (DC); a secondary bile acids. Inulin (5%-40%) significantly inhibited DC (100μM-500 μM), generated RNS in HCT 116 cell lines (p DC150μM. 30% Inulin enhanced cell death of morphologically changed cells in the presence of DC >150μM, with complete cell death occurring at DC300μM.Inulin inhibits proliferation of HCT 116 cancer cells. Inulin inhibits nitric oxide induced by DC p Conclusions: Peroxynitrite is formed by nitric oxide and superoxide; and considered to be cytotoxic, causing DNA damage and leading to carcinogenesis via inactivation of tumour suppressor oncoprotein p53. Possible mechanism of action by which inulin could exert protective effect on colon cells could be via its antioxidant effect. Further work is underway investigating the effect of inulin and bile-acid on NF-κB, p53 and apoptosis in adenocarcinoma and normal dermal HK epithelial cells. Citation Format: Bene Akromaa Ekine-Afolabi, Sandra Appiah, Azra Pachenari, Lucy Ghali. Inulin inhibits free radical species in HCT 116 adenoma carcinoma and normal human HK (keratinocyte) cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-271. doi:10.1158/1538-7445.AM2015-LB-271

Abstract B01: Impacts of inulin on bile acids induced colon cancer

Bile acids are normal components of the luminal contents of gastrointestinal tract but have been reported to cause oxidative damage by stimulating the generation of free oxygen radicals from the mitochondria. Several studies have demonstrated the contribution of reactive species to mutagenesis, carcinogenesis and tumor promotion. There is accumulating evidence to show that some carbohydrates and carbohydrate-containing molecules possess antioxidant ability by inhibiting the production of reactive species. Prebiotics are complex carbohydrates which have been shown to improve gut health when used in combination with probiotics. However, there is paucity of data on how prebiotics alone affect gut health and by which mechanism of action. The reactive oxygen scavenging ability of inulin, a prebiotic, has been shown in vitro in non-cell based system and in mice. The anti-inflammatory effect, through production of short chain fatty acids by fermentable inulin has also been shown. However, the mechanism of inulin in the amelioration of bile acid induced cancer remains unknown. Methods: Three different cell-lines (colon stem cells, human colon carcinoma cells-HCT-116 and control normal colon epithelial cells) will be examined. Cells will be treated separately with secondary bile acids, primary bile acids and prebiotics. Cells will also be treated with microorganisms9 filtrate such as probiotics (bifidobacteria) in conjunction with secondary bile acids, primary bile acids or prebiotics. Production of free radicals will be measured using nitro blue tetrazolium chloride assay (NBT) and inflammatory proteins will be measured using RT-PCR. DNA damage will be assessed using Endonuclease 111 enzyme modified Comet assay. In addition, C1 Single-Cell auto pep system will be used for mRNA sequencing of individual cells within the well plate. This study hypothesized that normal cells exposed to secondary bile acids in the presence of inulin may be protected from transformation to cancer cells and this may correlate with decrease in production of reactive radicals and pro-inflammatory proteins. The anti inflammatory ability of short chain fatty acid and antioxidant ability of inulin may possibly be associated with AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (P13-K), NF-κB signaling pathways. Thus inulin and their fermentation/breakdown products may not only stimulate beneficial bacteria in the colon but may directly interfere with absorption and cellular metabolism processes in the colon. Citation Format: Bene Akromaa Afolabi, Sandra Appiah, Azra Pachenari, Lucy Ghali. Impacts of inulin on bile acids induced colon cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B01.