Objectives Macrophages are determinant cells for atherosclerotic lesion formation. The objectives of this study were to incorporate macrophage target ligands on the surface of biocompatible and biodegradable epigallocatechin gallate (EGCG)‐loaded nanoparticles (Enano), to evaluate their target specificity to macrophages and anti‐atherogenic effects in vitro and in vivo. Method The target specificity to macrophages (in vitro) and to atherosclerotic lesions in low density lipoprotein receptor knockout (LDLr‐/‐) mice was measured using a fluorescence microscopy and IVIS® in vivo imaging system, respectively. Macrophage cholesterol content was determined using a HPLC method, and macrophage monocyte chemoattractant protein 1 (MCP‐1) release was measured using an ELISA kit. After treating LDLr‐/‐ mice with EGCG, untargeted Enano, targeted Enano, void untargeted nano, void targeted nano, or saline via weekly intravenous injection for 20 weeks, atherosclerotic lesion area and inflammatory response were determined. Results As compared to untargeted Enano, targeted Enano significantly increased their binding affinity to THP‐1 macrophages, increased macrophage EGCG content and decreased macrophage cholesterol content and macrophage release of MCP‐1 The targeted Enano improved the target specificity to atherosclerotic lesions, and decreased atherosclerotic lesion area and inflammatory response in LDLr‐/‐ mice Conclusions Targeted nanoparticles represent a potential breakthrough in molecular imaging of atherosclerosis and have a potential for the prevention and treatment of atherosclerosis.

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/β-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.

The present work evaluates chronic safety in middle-aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. The experiment used 6-month-old sham (n=39) and ovariectomized (OVX, n=143) female rats. All sham (n=39) and 39 of the OVX animals received no GTP treatment and their samples were collected for outcome measures at baseline, 3 months, and 6 months (n=13 per group for each). The remaining OVX animals were randomized into 4 groups receiving 0.15%, 0.5%, 1%, and 1.5% (n=26 for each) of GTP (wt/vol), respectively, in drinking water for 3 and 6 months. No mortality or abnormal treatment-related findings in clinical observations or ophthalmologic examinations were noted. No treatment-related macroscopic or microscopic findings were noted for animals administered 1.5% GTP supplementation. Throughout the study, there was no difference in the body weight among all OVX groups. In all OVX groups, feed intake and water consumption significantly decreased with GTP dose throughout the study period. At 6 months, GTP intake did not affect hematology, clinical chemistry, and urinalysis, except for phosphorus and blood urea nitrogen (increased), total cholesterol, lactate dehydrogenase, and urine pH (decreased). This study reveals that the no-observed-adverse-effect level (NOAEL) of GTP is 1.5% (wt/vol) in drinking water, the highest dose used in the present study.

The project is to evaluate chronic toxicity and safety in middle‐aged ovariectomized rats supplemented with different dosages of green tea polyphenols (GTP) in drinking water. 182 SD were sham (n=39) or ovariectomized (OVX, n=143). Both sham and OVX‐control animals receiving no GTP were assigned for sample collection at baseline, 3, and 6 months. The remaining OVX animals were randomized into 0.15%, 0.5%, 1%, and 1.5% (wt/vol) GTP for 3 and 6 months. Routinely clinical observation was performed. Ophthalmologic examination (control, 1% and 1.5% GTP groups), blood for hematology and clinical chemistry, urine analysis were assessed at baseline, 3, and 6 months. Histologic examination was performed on all tissues from animals in both control and high dose groups at baseline and the end of study. No mortality or abnormal treatment‐related findings in clinical observations or ophthalmologic examinations were noted. No treatment‐related macroscopic or microscopic findings were noted for animals administered 1.5% GTP. There was no difference in baseline body weight among all OVX‐treated treatment groups. The OVX+1.5% GTP group had the smallest body weight of the OVX‐treated groups. No difference in food intake among all treatment groups. In all OVX‐treated groups, GTP supplementation decreased water consumption of rats in a dose‐dependent pattern. At 6 months, GTP intake did not affect complete hematology, clinical chemistry, and urinalysis, except for PO4 and BUN (increased); total cholesterol, BUN, LDH, and urine pH (decreased).This study reveals that the No‐Observed‐Effect Level (NOEL) of GTP is 1.5%, the highest dose used. Supported by NIH/NCCAM AT006691.