Salvia miltiorrhiza Burge (Danshen) is an eminent medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries. Accumulating evidence suggests that Danshen and its components prevent vascular diseases, in particular, atherosclerosis and cardiac diseases, including myocardial infarction, myocardial ischemia/reperfusion injury, arrhythmia, cardiac hypertrophy and cardiac fibrosis. The published literature indicates that lipophilic constituents (tanshinone I, tanshinone IIa, tanshinone IIb, cryptotanshinone, dihydrotanshinone, etc) as well as hydrophilic constituents (danshensu, salvianolic acid A and B, protocatechuic aldehyde, etc) contribute to the cardiovascular protective actions of Danshen, suggesting a potential synergism among these constituents. Herein, we provide a systematic up-to-date review on the cardiovascular actions and therapeutic potential of major pharmacologically active constituents of Danshen. These bioactive compounds will serve as excellent drug candidates in small-molecule cardiovascular drug discovery. This article also provides a scientific rationale for understanding the traditional use of Danshen in cardiovascular therapeutics.

/pdf/salvia-miltiorrhizaburge-danshen-a-golden-herbal-medicine-in-44a11r5kxf.pdf

Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics.

Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic and pathologic roles have not been well defined for this pathway. The capacity to isolate immunochemically human plasma neuron-derived exosomes (NDEs), containing neuron-specific cargo, has permitted characterization of CNS-derived exosomes in living humans. Constituents of the amyloid β-peptide (Aβ)42-generating system now are examined in 2 distinct sets of human neural cells by quantification in astrocyte-derived exosomes (ADEs) and NDEs, enriched separately from plasmas of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD) and matched cognitively normal controls. ADE levels of β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1), γ-secretase, soluble Aβ42, soluble amyloid precursor protein (sAPP)β, sAPPα, glial-derived neurotrophic factor (GDNF), P-T181-tau, and P-S396-tau were significantly (3- to 20-fold) higher than levels in NDEs for patients and controls. BACE-1 levels also were a mean of 7-fold higher in ADEs than in NDEs from cultured rat type-specific neural cells. Levels of BACE-1 and sAPPβ were significantly higher and of GDNF significantly lower in ADEs of patients with AD than in those of controls, but not significantly different in patients with FTD than in controls. Abundant proteins of the Aβ42 peptide-generating system in ADEs may sustain levels in neurons. ADE cargo proteins may be useful for studies of mechanisms of cellular interactions and effects of BACE-1 inhibitors in AD.-Goetzl, E. J., Mustapic, M., Kapogiannis, D., Eitan, E., Lobach, I. V., Goetzl, L., Schwartz, J. B., Miller, B. L. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.

Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.

Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions

Alzheimer’s disease (AD) is one of the most well-known neurodegenerative diseases and explains 50–60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects ≥ 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepezil. New therapeutic agents that can block the disease-inducing mechanisms are essential. Diverse efforts have been made to discover anti-AD agents from natural sources. In this review article, we describe some representative terpenoids such as ginsenosides, gingkolides, and canabinoids as potential anti-AD agents. These compounds exhibit promising in vitro and in vivo biological activities, but are still waiting clinical trials. Additionally, we also discuss some terpenoids including cornel iridoid glycoside, oleanolic acid, tenuifolin, cryptotanshinone, and ursolic acid, which are under investigation for their in vitro and in vivo animal studies.

/pdf/terpenoids-as-potential-anti-alzheimer-s-disease-2eqrotjtwh.pdf

Terpenoids as potential anti-Alzheimer's disease therapeutics.

Salvia is one of the largest genera of the family Lamiaceae. It is widely distributed in the temperate, subtropical, and tropical regions all over the world. Besides its ethnobotanical importance, some species such as S. officinalis (sage, common sage), S. sclarea (clary sage), S. lavandulifolia (Spanish sage), S. miltiorrhiza (danshen), and S. hispanica (chia) are traded on the market as a food and because of the interest in their essential oils and/or popularity in traditional medicine. The high diversity of the Salvia genus and phytochemical richness generate great interest for discovering new biological active compounds, including those found in essential oils. Salvia plant essential oils exhibit broad-spectrum pharmacological activities and represent great interest for food preservation as potential natural products. Thus, this review describes the phytochemical composition of essential oils from different Salvia spp. according to the geographic regions, plant organ, and phenological stage. Moreover, the cultivation and growing conditions of Salvia plants have been also revised. Finally, the interest on Salvia plants for food and pharmaceutical applications has been covered, through reporting their biological properties, including as antioxidant, antimicrobial, anti-alzheimer, hypotensive, anti-hyperglycemia, anti-hyperlipidemia, anti-cancer, and skin curative agents.

Salvia spp. plants-from farm to food applications and phytopharmacotherapy

Cryptotanshinione upregulates α-secretase by activation PI3K pathway in cortical neurons

Deposition of amyloid β (Aβ) to form neuritic plaques in the brain is the pathological hallmark of Alzheimer’s disease (AD). Aβ is generated from sequential cleavages of the β-amyloid precursor protein (APP) by the β- and γ-secretases, and β-site APP-cleaving enzyme 1 (BACE1) is the essential β-secretase for Aβ generation. Vulnerable regions in AD brains show increased BACE1 protein levels. However, the underlying mechanism how BACE1 is regulated remains to be further illustrated. Nuclear Factor of Activated T-cells (NFAT) has been implicated in AD pathogenesis. Despite the increasing appreciation for the importance of NFAT-dependent transcription in the nervous system, the regulation and function of specific NFAT isoforms in neurons is poorly understood. In this report we found that both BACE1 and NFAT3 levels were significantly increased in the brains of APP/PS1 transgenic mice. We found that overexpression of NFAT3 resulted in increase of BACE1 promoter activity and BACE1 transcription, while disruption of NFAT3 expression decreased BACE1 gene transcription and protein expression in SAS1 cells. In a addition, overexpression of NFAT3 leads to increase levels of Aβ production. Chromatin immunoprecipitation analysis revealed direct binding of NFAT3 to specific DNA sequences within BACE1 promoter region. Taken together, our results indicate that NFAT is a BACE1 transcription factor. Our study suggests that inhibition of NFAT-mediated BACE1 expression may be a valuable drug target for AD therapy.

Transcriptional regulation of BACE1 by NFAT3 leads to enhanced amyloidogenic processing.

Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N-acetylcysteine is the FDA-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, we developed a carrier-free and bilirubin dotted nanoparticle (B/BG@N), which was formed using bilirubin (an endogenous metabolite of the body) and 18β-Glycyrrhetinic acid (a metabolic component of glycyrrhiza acid in vivo), and bovine serum albumin (BSA) was then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. In addition, BSA modification could also improve the stability and biocompatibility of the formed nanoparticles. Our results demonstrate that B/BG@N could effectively reduce the production of NAPQI and ROS. Moreover, B/BG@N nanoparticles exhibited antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signal axis, decreasing ROS, and reducing the production of inflammatory factors. In vivo study showed that B/BG@N can effectively improve the clinical symptom of the mice model by histological and blood biochemical tests. Our study suggested that B/BG@N own increased circulation half-life, improved accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment. This article is protected by copyright. All rights reserved.

A Biomimetic Nanoparticle Exerting Protection Against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS.

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Cryptotanshinione upregulates α-secretase by activation PI3K pathway in cortical neurons

Transcriptional regulation of BACE1 by NFAT3 leads to enhanced amyloidogenic processing.

A Biomimetic Nanoparticle Exerting Protection Against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS.