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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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Over the past decade there has been a renewed interest in research and development of both dietary and nutritional supplements. Significant advancements have been made in the scientific assessment of the quality, safety, and efficacy of these products because of the strong interest in and financial support of these projects. As research in both fields continues to advance, opportunities to use new and innovative research technologies and methodologies, such as proteomics and metabolomics, are critical for the future progress of the science. The purpose of the symposium was to begin the process of communicating new innovative proteomic and metabolomic methodologies that may be applied by researchers in both the nutrition and the natural product communities. This symposium highlighted 2 proteomic approaches, protein fingerprinting in complex mixtures with peptoid microarrays and top-down mass spectrometry for annotation of gene products. Likewise, an overview of the methodologies used in metabolomic profiling of natural products was presented, and an illustration of an integrated metabolomics approach in nutrition research was highlighted.

Over the past decade, herbal medicine has become a topic of increasing global importance, with both medical and economic implications. In developing countries, as much as 80% of the indigenous populations depends on traditional systems of medicine and medicinal plants as their primary source of healthcare. Within the European Community, herbal medicines represent an important share of the pharmaceutical market, with annual sales in the range of US$7 billion. In the United States, the sale of herbal products has skyrocketed from $200 million in 1988 to >$3.3 billion in 1997. Such widespread use of botanicals throughout the world has raised serious questions concerning the quality, safety and efficacy of these products. Thus, accurate scientific assessment of herbal medicine is a prerequisite for global harmonization of herbal health claims. In 1995, as part of its overall global strategy of "Health for All" and due to numerous requests from the member states, the Traditional Medicine Program of the WHO began the extensive task of reviewing the world's scientific literature of commonly used herbal medicines and publishing this information in monographs. The WHO monographs are technical reviews of the quality, safety and efficacy of commonly used herbal medicines and are intended primarily to harmonize the proper use of herbal medicines throughout the world.

We have previously reported that elicitor-induced benzophenanthridine alkaloid biosynthesis in suspension-cell cultures of Sanguinaria canadensis L. (SCP-GM) is mediated by a signal transduction system that involves calcium and possibly protein kinase(s). In this work, a number of exogenous agents were employed to further investigate the components of the signal transduction pathway involved in the induction of alkaloid biosynthesis by a fungal elicitor and abscisic acid (ABA). SCP-GM suspension-cells were treated with compounds that modify protein kinase activity, including phorbol esters, and 1-oleoyl-2-acetyl-rac-glycerol (OAG), a synthetic diacylglycerol analogue. Phorbol-12-myristate-13-acetate induced alkaloid accumulation by as much as 65-fold over control values, while the negative control, phorbol-13-monoacetate, had no effect. OAG also increased alkaloid production by approximately 25-fold as compared to controls. Likewise, pretreatment of the suspension-cell cultures with H-7 or staurosporine, significantly suppressed ABA- or fungal-induction of benzophenanthridine alkaloid biosynthesis. Modulators of GTP-binding protein activity were also active in this system. Treatment of the suspension-cells with cholera toxin (CHX) induced alkaloid accumulation by 25-fold, which increased to 34-fold when CHX was combined with a fungal elicitor derived from Penicillium expansum (PE), and 32-fold when CHX was combined with ABA. Treatment of SCP-GM cells with CHX also enhanced the activities of two N-methyltransferases in the benzophenanthridine biosynthetic pathway namely, tetrahydroberberine-N-methyltransferase and tetrahydrocoptisine-N-methyltransferase, by six and seven fold, respectively. Furthermore, benzophenanthridine alkaloid biosynthesis was induced by treating the suspension-cells with the G-protein activators, mastoparan, mas-7 or melittin, while the inactive homologue, mas-17, did not. Suppression of alkaloid accumulation occurred when the suspension-cells were treated with GDP beta S or pertussis toxin prior to treatment of the SCP-GM cells with either PE or ABA. The results support the hypothesis that one or more protein kinases, and putative G proteins are involved in the signal transduction pathway that mediates ABA and fungal-induced benzophenanthridine alkaloid biosynthesis.