Ginsenosides for cardiovascular diseases; update on pre-clinical and clinical evidence, pharmacological effects and the mechanisms of action.

Cardiovascular disease (CVD) remains the major cause of death worldwide, accounting for almost 31% of the global mortality annually. Several preclinical studies have indicated that ginseng and the major bioactive ingredient (ginsenosides) can modulate several CVDs through diverse mechanisms. However, there is paucity in the translation of such experiments into clinical arena for cardiovascular ailments due to lack of conclusive specific pathways through which these activities are initiated and lack of larger, long-term well-structured clinical trials. Therefore, this review elaborates on current pharmacological effects of ginseng and ginsenosides in the cardiovascular system and provides some insights into the safety, toxicity, and synergistic effects in human trials. The review concludes that before ginseng, ginsenosides and their preparations could be utilized in the clinical treatment of CVDs, there should be more preclinical studies in larger animals (like the guinea pig, rabbit, dog, and monkey) to find the specific dosages, address the toxicity, safety and synergistic effects with other conventional drugs. This could lead to the initiation of large-scale, long-term well-structured randomized, and placebo-controlled clinical trials to test whether treatment is effective for a longer period and test the efficacy against other conventional therapies.

Macrophage Activities in Myocardial Infarction and Heart Failure.

Heart diseases remain the major cause of death worldwide. Advances in pharmacological and biomedical management have resulted in an increasing proportion of patients surviving acute heart failure (HF). However, many survivors of HF in the early stages end up increasing the disease to chronic HF (CHF). HF is an established frequent complication of myocardial infarction (MI), and numerous influences including persistent myocardial ischemia, shocked myocardium, ventricular remodeling, infarct size, and mechanical impairments, as well as hibernating myocardium trigger the development of left ventricular systolic dysfunction following MI. Macrophage population is active in inflammatory process, yet the clear understanding of the causative roles for these macrophage cells in HF development and progression is actually incomplete. Long ago, it was thought that macrophages are of importance in the heart after MI. Also, though inflammation is as a result of adverse HF in patients, but despite the fact that broad immunosuppression therapeutic target has been used in various clinical trials, no positive results have showed up, but rather, the focus on proinflammatory cytokines has proved more benefits in patients with HF. Therefore, in this review, we discuss the recent findings and new development about macrophage activations in HF, its role in the healthy heart, and some therapeutic targets for myocardial repair. We have a strong believe that there is a need to give maximum attention to cardiac resident macrophages due to the fact that they perform various tasks in wound healing, self-renewal of the heart, and tissue remodeling. Currently, it has been discovered that the study of macrophages goes far beyond its phagocytotic roles. If researchers in future confirm that macrophages play a vital role in the heart, they can be therapeutically targeted for cardiac healing.

Biomarkers in heart failure: the past, current and future.

Despite the enhanced knowledge of the pathophysiology of heart failure (HF), it still remains a serious syndrome with substantial morbidity, mortality, and frequent hospitalizations. These are due to the current improvements in other cardiovascular diseases (like myocardial infarction), the aging population, and growing prevalence of comorbidities. Biomarker-guided management has brought a new dimension in prognostication, diagnosis, and therapy options. Following the recommendation of natriuretic peptides (B-type natriuretic peptide and N-terminal-proBNP), many other biomarkers have been thoroughly studied to reflect different pathophysiological processes (such as fibrosis, inflammation, myocardial injury, and remodeling) in HF and some of them (like cardiac troponins, soluble suppression of tumorigenesis-2, and galectin 3) have subsequently been recommended to aid in the diagnosis and prognostication in HF. Consequently, multi-marker approach has also been approved owing to the varied nature of HF syndrome. In this review, we discussed the guidelines available for HF biomarkers, procedures for evaluating novel markers, and the utilities of both emerging and established biomarkers for risk stratification, diagnosis, and management of HF in the clinics. We later looked at how the rapidly emerging field-OMICs, can help transform HF biomarkers discoveries and establishment.

Polygonum multiflorum Thunb suppress bile acid synthesis by activating Fxr-Fgf15 signaling in the intestine.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb (Heshouwu, HSW) is commonly used in clinical medicine, while the hepatotoxicities of HSW are reported increasingly in recent years. Currently, researchers have demonstrated an essential role of Bile Acids (BAs) in liver diseases. The occurrence of hepatotoxicity cases linked to HSW are characterized by jaundice and cholestasis, suggesting an interaction that between BAs and HSW AIM OF THE STUDY: This study was designed to investigate the HSW-induced liver functional and histological changes in mice and the role of HSW on bile acid synthesis, metabolism, clearance and intestinal absorption. MATERIALS AND METHODS: The mice were intragastrically (i.g.) given HSW at doses of 1.275 and 3.825 g/kg (Crude extracts /body weight) once a day for seven days. Liver function was evaluated by measuring the serum levels of enzymes and analyzing the liver histology. The LC/MS analysis was performed to quantify BAs from liver, ileum and serum. Moreover, the expression of bile metabolic-related transporters and metabolic enzymes at both protein and mRNA levels were observed to elucidate the underlying mechanisms. RESULTS: Oral administration of HSW for 7 days could not cause liver damage. A significant change was observed for the concentrations of liver and serum BAs in treatment groups compared with normal control. The mRNA expression levels of bile acid excretory transporter (Bsep) and basolateral uptake transporter (Ntcp) were increased with the development of HSW. The concentrations of unconjugated BAs increased in mice intestines after the administration of HSW. Western blot and qRT-PCR analyses showed that HSW upregulated the protein and mRNA expression of Shp and Fgf15 in the ileum of the mice. CONCLUSION: HSW treatment for 7days did not cause liver damage. HSW accelerated bile acid enterohepatic circulation and changed the composition of intestinal BAs, leding to the activation of Fxr-Fgf15 signal in intestines, and further inhibited the expression of Cyp7a1 in the liver.