Inhibition of Autophagy Aggravates Arachis hypogaea L. Skin Extracts-Induced Apoptosis in Cancer Cells.

The skin of Arachis hypogaea L. (peanut or groundnut) is a rich source of polyphenols, which have been shown to exhibit a wider spectrum of noteworthy biological activities, including anticancer effects. However, the anticancer activity of peanut skin extracts against melanoma and colorectal cancer (CRC) cells remains elusive. In this study, we systematically investigated the cytotoxic, antiproliferative, pro-apoptotic, and anti-migration effects of peanut skin ethanolic extract and its fractions on melanoma and CRC cells. Cell viability results showed that the ethyl acetate fraction (AHE) of peanut skin ethanolic crude extract and one of the methanolic fractions (AHE-2) from ethyl acetate extraction exhibited the highest cytotoxicity against melanoma and CRC cells but not in nonmalignant human skin fibroblasts. AHE and AHE-2 effectively modulated the cell cycle-related proteins, including the suppression of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6), phosphorylation of Retinoblastoma (p-Rb), E2F1, Cyclin A, and activation of tumor suppressor p53, which was associated with cell cycle arrest and paralleled their antiproliferative efficacies. AHE and AHE-2 could also induce caspase-dependent apoptosis and inhibit migration activities in melanoma and CRC cells. Moreover, it is noteworthy that autophagy, manifested by microtubule-associated protein light chain 3B (LC3B) conversion and the aggregation of GFP-LC3, was detected after AHE and AHE-2 treatment and provided protective responses in cancer cells. Significantly, inhibition of autophagy enhanced AHE- and AHE-2-induced cytotoxicity and apoptosis. Together, these findings not only elucidate the anticancer potential of peanut skin extracts against melanoma and CRC cells but also provide a new insight into autophagy implicated in peanut skin extracts-induced cancer cell death.

Development of a traditional Chinese medicine-based agent for the treatment of cancer cachexia.

BACKGROUND: Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need. METHODS: We developed an integrated, multi-tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)-based anti-cachectic agents. In the initial screening, we used inflammatory cytokine-induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age-related reduction of mobility and contractility, followed by the C-26 colon adenocarcinoma mouse model of cachexia to confirm the anti-muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL-6). Transcriptome analysis, quantitative real-time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour-induced muscle atrophy. RESULTS: Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis-à-vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age-associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P < 0.0001 and <0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C-26 mouse model. MDP at 1000 mg/kg (MDP-H) was effective in protecting body weight loss (P < 0.05) in C-26 tumour-bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P < 0.0001) and the forelimb grip strength (P < 0.05). MDP-treated C-26-tumour-bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL-6 levels (P = 0.06) relative to vehicle control. This decreased serum IL-6 was associated with the in vitro suppressive effect of MDP (25 and 50 µg/mL) on IL-6 secretion into culture medium by C26 cells. RNA-seq analysis, followed by quantitative real-time polymerase chain reaction and/or immunoblotting, shows that MDP's anti-cachectic effect was attributable to its ability to reverse the C-26 tumour-induced re-programming of muscle homoeostasis-associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin-1), in skeletal muscles. CONCLUSIONS: All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.

Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study.

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1-4 weeks, 6-9 weeks, and 13-16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs.

A review of potential harmful interactions between anticoagulant/antiplatelet agents and Chinese herbal medicines.

BACKGROUND: The risks attributed to drug-herb interactions, even when known, are often ignored or underestimated, especially for those involving anti-clotting drugs and Chinese medicines. The aim of this study was to structurally search and evaluate the existing evidence-based data associated with potential drug interactions between anticoagulant/antiplatelet drugs and Chinese herbal medicines (CHMs) and evaluate the documented mechanisms, consequences, and/or severity of interactions. METHODOLOGY AND FINDINGS: Information related to anticoagulant/antiplatelet drug-CHM interactions was retrieved from eight interaction-based textbooks, four web resources and available primary biomedical literature. The primary literature searches were conducted in English and/or Chinese from January 2000 through December 2011 using the secondary databases (e.g., PubMed, Airiti Library, China Journal full-text database). The search terms included the corresponding medical subject headings and key words. Herbs or natural products not used as a single entity CHM or in Chinese Medicinal Prescriptions were excluded from further review. The corresponding mechanisms and severity ratings of interactions were retrieved using MicroMedex®, Lexicomp® and Natural Medicines Comprehensive Database®. Finally, we found 90 single entity CHMs contributed to 306 documented drug-CHM interactions. A total of 194 (63.4%) interactions were verified for its evidence describing possible mechanisms and severity. Of them, 155 interactions (79.9%) were attributable to pharmacodynamic interactions, and almost all were rated as moderate to severe interactions. The major consequences of these interactions were increased bleeding risks due to the additive anticoagulant or antiplatelet effects of the CHMs, specifically danshen, dong quai, ginger, ginkgo, licorice, and turmeric. CONCLUSIONS/SIGNIFICANCE: Conventional anticoagulants and antiplatelet drugs were documented to have harmful interactions with some commonly used single entity CHMs. For those patients who are taking conventional anti-clotting medications with CHMs for cardiovascular or cerebrovascular diseases, the potential risks of increased bleeding due to drug-CHM interactions should not be ignored.

Concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese medications: a population-based cohort study.

PURPOSE: We examined the extent of concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese medications (CMs) and identified its associated factors. METHODS: A retrospective cohort study was conducted using one million random samples from the Longitudinal Health Insurance Database 2005 in Taiwan. High-risk Western medications (HRWMs) focused on in this study were antiplatelets (aspirin, clopidogrel, dipyridamole, ticlopidine), anticoagulants (heparin, warfarin), and digoxin. Concurrent use was described as having an overlapping use period of HRWM with CMs any time in 2005. Baseline demographics, comorbidities, and health service utilizations between patients with and without concurrent HRWM-CM use were compared. Logistic regression analyses were performed to identify factors associated with incident concurrent use. RESULTS: Of the 70,698 eligible HRWM users, 13.2 % used CMs concurrently for an average duration of 26.7 ± 43 days. The incidence of concurrent HRWM-CM use, which excluded prior CM use within 6 months preceding the first CM use, was 6.3 %. Warfarin or ticlopidine users were more likely to be prescribed with CMs than were the other HRWM users. Factors associated with an increasing incidence of concurrent HRWM-CM use included female sex, age 45-54 years, middle monthly income, higher number of outpatient visits or distinct prescribed medications, and a previous diagnosis of heart diseases, stroke, or hypertension. In contrast, age ≥ 65 years and higher medical expenditure were associated with a lower incidence of concurrent use. CONCLUSIONS: In the Taiwanese population, approximately one in eight HRWM users were concomitantly prescribed CMs. Whether such concurrent use is associated with adverse clinical outcomes warrants further investigations.

Use of Chinese medicine among survivors of nasopharyngeal carcinoma in Taiwan: a population-based study.

UNLABELLED: Hypotheses. The authors hypothesized that the use of alternative medicine, in the form of Chinese medicine (CM), among patients in the continuing care phase of nasopharyngeal carcinoma (NPC) in Taiwan is higher than the use in a matched control group of noncancer individuals. STUDY DESIGN: This was a case-control study. METHODS: Using a population-based claim database, the authors identified 181 long-term survivors of NPC and 905 matched controls. They obtained information on CM use and associated cost as outcome measures. Descriptive analysis and regression models were applied to examine the association between NPC and the outcome measures. RESULTS: The unadjusted CM initiation (34% vs 32%; P = .54), intensity of use (2.15 vs 1.73 visits; P = .37), and cost (US$79 vs US$58; P = .16) were higher for patients in the NPC group than for those in the control group. Regression analyses suggested that the NPC group had significantly more CM visits (1.01; 95% confidence interval = 0.07-1.96), and more than 50% of these visits were related to cancer. CONCLUSION: The authors confirmed their hypotheses that the use of CM in the continuing care phase by patients with NPC in Taiwan was higher than the use in their matched, noncancer counterparts. These findings suggest that current clinical surveillance strategies for NPC might not meet patients' physical and emotional needs.

An instrument to evaluate pharmacists' patient counseling on herbal and dietary supplements.

OBJECTIVE: To develop a measure of pharmacists' patient counseling on herbal and dietary supplements. METHODS: A systematic process was used for item generation, testing, and validation of a measure of pharmacists counseling on herbal and dietary supplements. Because a pharmacist-patient encounter may or may not identify an indication for taking an herb or dietary supplement, the instrument was bifurcated into 2 distinct components: (1) patient counseling in general; and (2) patient counseling related to herbal and dietary supplements. RESULTS: The instrument demonstrated high reliability and desirable construct validity. After adjusting for item difficulty, we found that pharmacists tended to provide more general patient counseling than counseling related to herbal and dietary supplements. CONCLUSION: This instrument can be applied to assess the quality of counseling provided by pharmacists and pharmacy students, and the outcomes of pharmacist and pharmacy student education on herbal and dietary supplements.

Conceptual development of a measure to assess pharmacists' knowledge of herbal and dietary supplements.

OBJECTIVES: To describe the conceptual development of a measure for assessing pharmacist knowledge of herbal and dietary supplements. METHODS: A standardized approach to constructing a multiple-choice competency examination following 8 pre-specified criteria (eg, specifying the target spectrum of herbal and dietary supplements) was used to create an item bank. The quality of each item was evaluated by 5 herbal and dietary supplement content experts based on specific criteria in 3 rounds of review. RESULTS: From 122 initial items, 56 items were retained for the item bank representing 4 content areas: efficacy/effectiveness, safety, drug-supplement interactions, and regulation. The experts tended to agree that the constructed items represented a wide range of difficulty. CONCLUSION: The initial development of a conceptually based item bank/measure of pharmacist herbal and dietary supplement knowledge lays the groundwork for a large-scale validation study. The measure should be useful as a standalone tool and as a component of a knowledge, attitude, and behavior survey for the assessment of pharmacist traits related to herbal and dietary supplements.