Modern concepts and biomarkers of blood stasis in cardio- and cerebrovascular diseases from the perspectives of Eastern and Western medicine: a scoping review protocol.

OBJECTIVE: The objective of this review is to provide a modern definition and identify potential biomarkers of blood stasis in cardio- and cerebrovascular diseases by mapping, comparing, and combining Eastern and Western concepts. INTRODUCTION: Blood stasis is a pathological concept found in both Eastern and Western medical literature. In traditional East Asian medicine, blood stasis is a differential syndrome characterized by stagnant blood flow in various parts of the body. Similarly, in Western medicine, various diseases, especially cardio- and cerebrovascular diseases, are known to be accompanied by blood stasis. Numerous scientific studies on blood stasis have been conducted over the last decade, and there is a need to synthesize those results. INCLUSION CRITERIA: We will use the keywords "blood stasis," "blood stagnation," "blood stagnant," and "blood congestion" in 3 electronic databases: PubMed, Cochrane CENTRAL, and Google Scholar. In addition, we will use the keywords "어혈" and "혈어" in 4 Korean electronic databases (ie, NDSL, OASIS, KISS, and DBpia). Peer-reviewed articles published from 2010 to the present that focus on blood stasis in cardio- and cerebrovascular diseases in human subjects according to the International Classification of Diseases 11 th revision categories BA00-BE2Z, 8B00-8B2Z, 8E64, and 8E65 will be included. Reviews, opinion articles, in vivo, in vitro, and in silico preclinical studies will be excluded. METHODS: We will follow the frameworks by Arksey and O'Malley and Levac et al. as well as JBI guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Two reviewers will independently search and screen titles and abstracts followed by full-text screening of eligible studies. If there are discrepancies between the 2 reviewers, a third reviewer will be consulted to make the final decision. We will use descriptive narrative, tabular, and graphical displays, and content analysis to present the results. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/gv4ym.

Pharmacological Properties of Jaeumgeonbi-Tang on Redox System and Stress-Related Hormones in Chronic Subjective Dizziness: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial.

Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.

Pharmacological Effects of Gami-Yukmijihwang-Tang on the Lipopolysaccharide-Induced Hippocampus Oxidation and Inflammation via Regulation of Sirt6.

Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced neuroinflammation in the hippocampus regions. C57BL/6J male mice (16-24 weeks old) were divided into six groups: (1) the control group (DW with 0.9% saline injection), (2) LPS group (DW with LPS injection), YJT groups ((3) 100, (4) 200, or (5) 400 mg/kg of YJT with LPS injection), and (6) glutathione (GSH) group (100 mg/kg of GSH with LPS injection), respectively. Mice were orally administrated with various doses of YJT or glutathione (GSH) for the first five days. Neuroinflammation in the hippocampus region was induced by repeated injection of LPS during the last three days. As predicted, LPS not only increased oxidative stress-related markers including malondialdehyde, 4-hydroxynonenal, nitrotryptophan, and hydrogen peroxide, but also drastically enhanced inflammatory reactions including nitric oxide, inducible nitric oxide synthase, p65, and toll-like receptor 4, respectively. YJT administration, on the other hand, notably decreased the above pathological alterations by enhancement of antioxidant capacities such as superoxide dismutase and catalase activities. To explain the underlying pharmacological actions of YJT, we focused on a representative epigenetic regulator, a nicotinamide adenine dinucleotide + (NAD+)-dependent chromatin enzyme, Sirtuin 6 (Sirt6). Neuroinflammation in hippocampus regions depleted Sirt6 at the protein level and this alteration directly affected the nuclear factor erythroid 2-related factor (Nrf2)/hemeoxygenase (HO)-1 signaling pathway in the LPS group; however, YJT significantly recovered the Sirt6 protein levels, and it could recover the abnormal status of Nrf2/HO-1 signaling pathways in the hippocampus regions. Additionally, Sirt6 led to the up-regulation of GSH sub-enzymes of mRNA expression and protein levels of total GSH content. These findings suggest that YJT can protect against LPS-induced neuroinflammation and oxidative stress by regulating the Sirt6-related pathways and normalizing the GSH redox cycle.