Functions and mechanisms of green tea catechins in regulating bone remodeling.

Osteoporosis is caused by an imbalance in bone remodeling, a process involving bone-building osteoblasts and bone-resorptive osteoclasts. Excessive reactive oxygen species and inflammatory responses have been shown to stimulate differentiation and function of osteoclasts while inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation via extracellular signal-regulated kinases (ERK), ERK-dependent nuclear factor-κB and Wnt/ß-catenin signaling pathways. The anti-oxidant and anti-inflammatory green tea catechins (GTC) have been shown to promote osteoblastogenesis, suppress osteoclastogenesis and stimulate the differentiation of mesenchymal stem cells into osteoblasts rather than adipocytes by modulating the signaling pathways. This paper reviews the pharmacokinetics and metabolism of GTC, their bone-protective activities evidenced in in vitro and in vivo studies, and the limited clinical studies supporting these preclinical findings. In light of the physical, economical, and social burdens due to osteoporosis, easily accessible and affordable preventive measures such as GTC deserves further clinical studies prior to its clinical application.

Bioactive compounds and phenolic-linked functionality of powdered tropical fruit residues.

Tropical fruit residues consisting of seeds, peels and residual pulp generated as by-products of fruit processing industry were investigated for bioactive compounds, the in vitro antioxidant capacity as well as alpha-glucosidase and alpha-amylase inhibitory activities. Cyanidin, quercetin, ellagic acid (EA) and proanthocyanidins were found in acerola, jambolan, pitanga and cajá-umbu residue powders. Acerola powder had the highest phenolic content (8839.33 mg catechin equivalents (CE)/100 g) and also high-ascorbic acid (AA) concentration (2748.03 mg/100 g), followed by jambolan and pitanga. The greatest 1,1-Diphenyl-2-picrylhydrazyl (DPPH) inhibition was observed for jambolan (436.76 mmol Trolox eq/g) followed by pitanga (206.68 mmol Trolox eq/g) and acerola (192.60 mmol Trolox eq/g), while acerola had the highest ferric reducing antioxidant power (FRAP) assay result (7.87 mmol Trolox eq/g). All fruit powders exhibited enzymatic inhibition against alpha-amylase (IC50 ranging from 3.40 to 49.5 mg CE/mL) and alpha-glucosidase (IC50 ranging from 1.15 to 2.37 mg CE/mL). Therefore, acerola, jambolan and pitanga dried residues are promising natural ingredients for food and nutraceutical manufacturers, due to their rich bioactive compound content.

The evaluation of catechins that contain a galloyl moiety as potential HIV-1 integrase inhibitors.

Four catechins with the galloyl moiety, including catechin gallate (CG), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), and epicatechin gallate (ECG), were found to inhibit HIV-1 integrase effectively as determined by our ELISA method. In our docking study, it is proposed that when the HIV-1 integrase does not combine with virus DNA, the four catechins may bind to Tyr143 and Gln148, thus altering the flexibility of the loop (Gly140-Gly149), which could lead to an inhibition of HIV-1 integrase activity. In addition, after combining HIV-1 integrase with virus DNA, the four catechins may bind between the integrase and virus DNA, consequently, disrupt this interaction. Thus, the four catechins may reduce the activity of HIV-1 integrase by disrupting its interaction with virus DNA. The four catechins have a highly cooperative inhibitory effect (IC50=0.1 µmol/L). Our study suggests that catechins with the galloyl moiety could be a novel and effective class of HIV-1 integrase inhibitors.

Cost analysis of flavocoxid compared to naproxen for management of mild to moderate OA.

OBJECTIVE: Flavocoxid is a medical food used for the clinical dietary management of osteoarthritis (OA). The acquisition cost of flavocoxid is higher than most traditional, generic NSAIDs. However, flavocoxid may have more favorable gastrointestinal (GI) toxicity resulting in lower overall costs. These costs have not been previously examined. This study provides a decision analytic model to assess the net costs of using flavocoxid for OA from a Medicare perspective. RESEARCH DESIGN AND METHODS: A decision model was developed to estimate the total costs associated with flavocoxid versus naproxen for the management of Medicare patients with mild to moderate OA. Probabilities were obtained from literature and expert opinion, and costs were obtained from Medicare. Sensitivity analyses were conducted by varying probabilities and costs within clinically relevant ranges. RESULTS: The base case resulted in flavocoxid having lower total annual costs ($1482 per patient) compared to naproxen ($1592). Flavocoxid remained the lowest cost option when the cost inputs were varied by 25% (above and below the base case), and when the probability of GI events with flavocoxid were varied by 25%. However, when GI rates from the literature and implied relative risks from the expert panel were used, or if the cost of PPIs was $0, then naproxen was the less costly alternative, though saving less than the annual cost of flavocoxid. Key limitations were the limited outcomes in the model (only GI events), lack of consideration of adherence or combination therapy, and the reliance on expert opinion due to a lack of data for flavocoxid. CONCLUSIONS: In patients over 65 years of age who suffer from mild to moderate OA, flavocoxid may result in lower overall costs, despite a higher acquisition cost. Managed care organizations should consider total health care costs in the decision to include flavocoxid as a covered benefit.

A cost-effectiveness analysis of sinecatechins in the treatment of external genital warts.

OBJECTIVE: To evaluate the cost-effectiveness and treatment-cost impact of sinecatechins (Veregen) as first-line therapy against its principal comparator, imiquimod (Aldara), in the treatment of external genital warts (EGWs). METHOD: A two-stage decision model is proposed to compare sinecatechins with its principal comparator, imiquimod, as a first-line topical therapy in the treatment of EGWs. The model utilizes estimates of sustained clearance from two pivotal sinecatechins trials and from a systematic literature review for imiquimod. Resource inputs are: (1) trial-based estimates of average drug utilization and (2) CPT (Current Procedural Terminology) codes describing anticipated office visits and utilization of second-line ablative procedures. The analysis considers: (1) comparative costs of achieving a successful outcome with sinecatechins versus imiquimod, and (2) comparative cost-consequences of sinecatechins versus imiquimod. As a modeled approach to evaluating comparative product effectiveness, the claims made reflect the structure of the model, which focuses on topical products as first-line therapy in EGW interventions and in its reliance on estimates of sustained clearance from pivotal randomized clinical trials (RCTs). Sustained clearance in this context being defined as the proportion of patients who report initial wart clearance over the RCT period corrected for subsequent recurrence. RESULTS: As first-line therapy, sinecatechins dominates imiquimod as a lower cost treatment with a higher sustained clearance rate (51.9 vs. 40.6%). First-line average cost of treatment with sinecatechins is $774 compared to imiquimod at $930. Cost per successful outcome with sinecatechins is $1,492, which is lower than $2,289 for imiquimod. Taking account of patients failing first-line therapy moving to a second-line ablative therapy yields an average cost of treatment for patients initiated to sinecatechins of $943 and $1,138 for those initiated to imiquimod. A sensitivity assessment confirmed the position of sinecatechins within the decision-model framework. CONCLUSION: Sinecatechins yields a lower cost of treatment compared to imiquimod in the treatment of EGW. It also offers cost savings to healthcare systems. This conclusion should be qualified by the limitations of the decision framework within which the assessment has been made. The model focuses on topical preparations as first-line therapies, with estimates of sustained clearance taken from pivotal RCTs. Treatment cost estimates are generated independently, but reflect current product and ancillary costs.