Stress Buffering and Longevity Effects of Amber Extract on Caenorhabditis elegans (C. elegans).

Amber is a fossilized tree resin historically used in wound healing and stress relief. Unfortunately, there is no concrete scientific evidence supporting such efficacy. Here, the stress buffering and longevity effect of Amber extract (AE) in Caenorhabditis elegans (C. elegans) was investigated. Survival assays, health span assays, Enzyme-Linked Immunosorbent Assay (ELISA), Stress biomarker detection assays, Green Fluorescence Proteins (GFP), Real Time quantitative PCR (RT-qPCR) and C. elegans mutants were employed to investigate the stress buffering and longevity effect of AE. In the study, it was observed that AE supplementation improved health span and survival in both normal and stressed worms. Additionally, AE positively regulated stress hormones (cortisol, oxytocin, and dopamine) and decreased fat and reactive oxygen species (ROS) accumulation. Through the Insulin/IGF-1 signaling (IIS) pathway, AE enhanced the nuclear localization of DAF-16 and the expression of heat shock proteins and antioxidant genes in GFP-tagged worms and at messenger RNA levels. Finally, AE failed to increase the survival of daf-16, daf-2, skn-1 and hsf-1 loss-of-function mutants, confirming the involvement of the IIS pathway. Evidently, AE supplementation relieves stress and enhances longevity. Thus, amber may be a potent nutraceutical for stress relief.

Protective Effect of Amber Extract on Human Dopaminergic Cells against 6-Hydroxydopamine-Induced Neurotoxicity.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, after Alzheimer's disease. In our previous study, we found that amber-a fossilized plant resin-can protect cells from apoptosis by decreasing the generation of reactive oxygen species (ROS). In this study, we focused on the effect of amber on 6-hydroxydopamine-induced cell apoptosis in the human neuroblastoma cell line SHSY5Y (one model for PD). Initially, we determined the protective effect of amber on the PD model. We found that amber extract has a protective effect against 6-hydroxydopamine-induced cell apoptosis. The decrease in ROS, cleaved caspase-3, pERK, and extracellular signal-regulated kinase (ERK) protein levels confirmed that amber extract decreases apoptosis via the ROS-mediated ERK signaling pathway. Furthermore, we determined the effects of amber extract on autophagy. The results showed that amber extract increased the levels of LC3II and Beclin-1, suggesting that amber extract can protect neuronal cells against 6-hydroxydopamine-induced cell apoptosis by promoting autophagy.

Amber Extract Reduces Lipid Content in Mature 3T3-L1 Adipocytes by Activating the Lipolysis Pathway.

Amber-the fossilized resin of trees-is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. Mature adipocytes are used to evaluate the effect of amber extract on lipolysis by measuring the triglyceride content, glucose uptake, glycerol release, and lipolysis-related gene expression. Our results show that the amount of triacylglycerol, which is stored in lipid droplets in mature adipocytes, decreases following 96 h of treatment with different concentrations of amber extract. Amber extract treatment also decreases glucose uptake and increases the release of glycerol from the cells. Moreover, amber extract increases the expression of lipolysis-related genes encoding perilipin and hormone-sensitive lipase (HSL) and promotes the activity of HSL (by increasing HSL phosphorylation). Amber extract treatment also regulates the expression of other adipocytokines in mature adipocytes, such as adiponectin and leptin. Overall, our results indicate that amber extract increases the expression of lipolysis-related genes to induce lipolysis in 3T3-L1 cells, highlighting its potential for treating various obesity-related diseases.

Role of amber extract in protecting SHSY5Y cells against amyloid ß1-42-induced neurotoxicity.

Alzheimer disease (AD) is an irreversible, progressive brain disease. Amyloid ß plays a critical role in AD development. Some Chinese traditional medicines, such as the fossilized plant resin, amber, have been applied as mental stabilizers. However, the effects of amber on AD pathogenesis remain unknown. Therefore, we aimed to determine the potential of amber extract for treating AD by evaluating its effects on amyloid-ß (1-42) (Aß (1-42))-induced neuronal cell death. We measured levels of ROS, Bcl-2, and Bax mRNA, and found that amber extract decreased Aß (1-42)-induced cell apoptosis via the reactive oxygen species (ROS)-mediated mitochondrial pathway. Amber extract also decreased ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) and increased microtubule-associated proteins 1A/1B light chain 3B (LC3II) and Beclin 1. These findings suggested that amber extract protects neuronal cells against Aß (1-42)-induced cell apoptosis by upregulating autophagy and downregulating BACE1.

Isolation of yeast Ca2+ signal transduction inhibitors from the Early Cretaceous Burmese amber.

Two kinds of biologically active compounds were isolated from the MeOH extract of the Early Cretaceous Burmese amber [99 million years ago (Ma)], which is older than the K-Pg boundary (65 Ma). These compounds had inhibitory activity against the hypersensitive mutant yeast strain (zds1∆ erg3∆ pdr1∆ pdr3∆) with respect to Ca2+ signal transduction. They were identified as 16,17-bisnordehydroabietic acid (1) and 16,17-bisnorcallitrisic acid (2), respectively, on the basis of spectral analyses including HREIMS, 1D, and 2D NMR. Both have faint growth restoring activities around the clear inhibition zone against the mutant yeast on the 0.31-0.16 µg/spot. This is the first report of direct structural elucidation of 1 and 2 and the biologically active compounds derived from Burmese amber.

Exploratory Cortex Metabolic Profiling Revealed the Sedative Effect of Amber in Pentylenetetrazole-Induced Epilepsy-Like Mice.

Epilepsy is a common clinical syndrome characterized by sudden and recurrent attacks and temporary central nervous system dysfunction caused by excessive discharge of neurons in the brain. Amber, a fossilized organic substance formed by the resins of conifers and leguminous plants, was prescribed to tranquilize the mind in China. In this paper, the antiepileptic effect of amber was evaluated by a pentylenetetrazole (PTZ)-induced epileptic model. An untargeted metabolomics approach was applied to investigate metabolic changes in the epileptic model, which was based on HILIC-UHPLC-MS/MS multivariate statistical analysis and metabolism network analysis. The outcome of this study suggested that 35 endogenous metabolites showed marked perturbations. Moreover, four metabolism pathways were mainly involved in epilepsy. After treatment by amber, the endogenous metabolites had a marked tendency to revert back to the situation of the control group which was consistent with phenobarbital. This study characterized the pentylenetetrazole-induced epileptic model and provided new evidence for the sedative effect of amber.

Ca2+-Signal Transduction Inhibitors, Kujiol A and Kujigamberol B, Isolated from Kuji Amber Using a Mutant Yeast.

A podocarpatriene and a labdatriene derivative, named kujiol A [13-methyl-8,11,13-podocarpatrien-19-ol (1)] and kujigamberol B [15,20-dinor-5,7,9-labdatrien-13-ol (2)], respectively, were isolated from Kuji amber through detection with the aid of their growth-restoring activity against a mutant yeast strain ( zds1Δ erg3Δ pdr1Δ pdr3Δ), which is known to be hypersensitive with respect to Ca2+-signal transduction. The structures were elucidated by spectroscopic data analysis. Compounds 1 and 2 are rare organic compounds from Late Cretaceous amber, and the mutant yeast used seems useful for elucidating a variety of new compounds from Kuji amber specimens, produced before the K-Pg boundary.