Epigenetic regulation of bone remodeling by natural compounds.

Osteoporosis and osteopenia impact more than 54 million Americans, resulting in significant morbidity and mortality. Alterations in bone remodeling are the hallmarks for osteoporosis, and thus the development of novel treatments that will prevent or treat bone diseases would be clinically significant, and improve the quality of life for these patients. Bone remodeling involves the removal of old bone by osteoclasts and the formation of new bone by osteoblasts. This process is tightly coupled, and is essential for the maintenance of bone strength and integrity. Since the osteoclast is the only cell capable of bone resorption, the development of drugs to treat bone disorders has primarily focused on reducing osteoclast differentiation, maturation, and bone resorption mechanisms, and there are few treatments that actually increase bone formation. Evidence from observational, experimental, and clinical studies demonstrate a positive link between naturally occurring compounds and improved indices of bone health. While many natural extracts and compounds are reported to have beneficial effects on bone, only resveratrol, sulforaphane, specific phenolic acids and anthocyanins, have been shown to both increase bone formation and reduce resorption through their effects on the bone epigenome. Each of these compounds alters specific aspects of the bone epigenome to improve osteoblast differentiation, reduce osteoblast apoptosis, improve bone mineralization, and reduce osteoclast differentiation and function. This review focuses on these specific natural compounds and their epigenetic regulation of bone remodeling.

Ginsenoside Re: Its chemistry, metabolism and pharmacokinetics.

Ginsenosides, the bioactive components of ginseng, can be divided into two major groups, namely 20(S)-protopanaxatriol (e.g. Re, Rg1, Rg2, and Rb3) and 20(S)-protopanaxadiol (e.g. Rb1, Rb2, Rc, and Rd). Biological and environmental factors may affect the content of ginsenosides in different parts of ginseng plant. Evidence from pharmacokinetic and metabolic studies of Re demonstrated that (1) the absorption of Re is fast in gastrointestinal tract; (2) Re may be metabolized mainly to Rh1 and F1 by intestinal microflora before absorption into blood; and (3) Re is quickly cleared from the body.

Ginsenoside Re: pharmacological effects on cardiovascular system.

Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs to the panaxatriol group. Many reports demonstrated that G-Re possesses the multifaceted beneficial pharmacological effects on cardiovascular system. G-Re has negative effect on cardiac contractility and autorhythmicity. It causes alternations in cardiac electrophysiological properties, which may account for its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and induces angiogenic regeneration. In this review, we first outline the chemistry and the pharmacological effects of G-Re on the cardiovascular system.

Chemical and pharmacological studies of saponins with a focus on American ginseng.

Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L.) are the two most recognized ginseng botanicals. It is believed that the ginseng saponins called ginsenosides are the major active constituents in both ginsengs. Although American ginseng is not as extensively studied as Asian ginseng, it is one of the best selling herbs in the U.S., and has garnered increasing attention from scientists in recent years. In this article, after a brief introduction of the distribution and cultivation of American ginseng, we discuss chemical analysis of saponins from these two ginsengs, i.e., their similarities and differences. Subsequently, we review pharmacological effects of the saponins, including the effects on the cardiovascular system, immune system, and central nervous system as well as the antidiabetes and anti-cancer effects. These investigations were mainly derived from American ginseng studies. We also discuss evidence suggesting that chemical modifications of ginseng saponins would be a valuable approach to develop novel compounds in drug discovery.

Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial.

Ganoderma lucidum is a herbal medicine commonly used in oriental countries as a remedy for treating various medical conditions. In this controlled study, we evaluated the safety and tolerance of oral administration of Ganoderma lucidum in 16 human volunteers who received 2 grams of the extract or placebo twice daily for 10 consecutive days. During the study, information from subjective questionnaires were obtained, electrocardiograms, complete blood counts, blood chemistry analysis and urinalysis were performed. In addition, blood tests reflecting immunity were done. Our data showed that compared to placebo group, no adverse effects were observed after the extract intake. Although there were no obvious changes in CD4, CD8, and CD19 levels after the extract, CD56 cell count increased during the study and returned to baseline 10 days after the herbal intake. However, due to relatively high variability and small sample size, this CD56 increase did not achieve statistical significance, and remains to be re-evaluated in the future. It appears that an additional long-term safety and tolerance trial with herbal dose-escalating design is warranted.