Potential therapeutic compounds from traditional Chinese medicine targeting endoplasmic reticulum stress to alleviate rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which affects about 0.5-1% of people with symptoms that significantly impact a sufferer's lifestyle. The cells involved in propagating RA tend to display pro-inflammatory and cancer-like characteristics. Medical drug treatment is currently the main avenue of RA therapy. However, drug options are limited due to severe side effects, high costs, insufficient disease retardation in a majority of patients, and therapeutic effects possibly subsiding over time. Thus there is a need for new drug therapies. Endoplasmic reticulum (ER) stress, a condition due to accumulation of misfolded proteins in the ER, and subsequent cellular responses have been found to be involved in cancer and inflammatory pathologies, including RA. ER stress protein markers and their modulation have therefore been suggested as therapeutic targets, such as GRP78 and CHOP, among others. Some current RA therapeutic drugs have been found to have ER stress-modulating properties. Traditional Chinese Medicines (TCMs) frequently use natural products that affect multiple body and cellular targets, and several medicines and/or their isolated compounds have been found to also have ER stress-modulating capabilities, including TCMs used in RA treatment by Chinese Medicine practitioners. This review encourages, in light of the available information, the study of these RA-treating, ER stress-modulating TCMs as potential new pharmaceutical drugs for use in clinical RA therapy, along with providing a list of other ER stress-modulating TCMs utilized in treatment of cancers, inflammatory diseases and other diseases, that have potential use in RA treatment given similar ER stress-modulating capacity.

Hypocretins, Neural Systems, Physiology, and Psychiatric Disorders.

The hypocretins (Hcrts), also known as orexins, have been among the most intensely studied neuropeptide systems since their discovery about two decades ago. Anatomical evidence shows that the hypothalamic neurons that produce hypocretins/orexins project widely throughout the entire brain, innervating the noradrenergic locus coeruleus, the cholinergic basal forebrain, the dopaminergic ventral tegmental area, the serotonergic raphe nuclei, the histaminergic tuberomammillary nucleus, and many other brain regions. By interacting with other neural systems, the Hcrt system profoundly modulates versatile physiological processes including arousal, food intake, emotion, attention, and reward. Importantly, interruption of the interactions between these systems has the potential to cause neurological and psychiatric diseases. Here, we review the modulation of diverse neural systems by Hcrts and summarize potential therapeutic strategies based on our understanding of the Hcrt system's role in physiology and pathophysiological processes.