Abstract
Aging is the greatest risk factor for human diseases, as it results in cellular growth arrest, impaired tissue function and metabolism, ultimately impacting life span. Two different mechanisms are thought to be primary causes of aging. One is cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK) and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive component of natural Chinese medicine rhizoma coptidis (RC), berberine has recently been reported to expand life span in Drosophila melanogaster, and attenuate premature cellular senescence. Most components of RC including berberine, coptisine, palmatine, and jatrorrhizine have been found to have beneficial effects on hyperlipidemia, hyperglycemia and hypertension aging-related diseases. The mechanism of these effects involves multiple cellular kinase and signaling pathways, including anti-oxidation, activation of AMPK signaling and its downstream targets, including mTOR/rpS6, Sirtuin1/ forkhead box transcription factor O3 (FOXO3), nuclear factor erythroid-2 related factor-2 (Nrf2), nicotinamide adenine dinucleotide (NAD+) and nuclear factor-κB (NF-κB) pathways. Most of these mechanisms converge on AMPK regulation on mitochondrial oxidative stress. Therefore, such evidence supports the possibility that rhizoma coptidis, in particular berberine, is a promising anti-aging natural product, and has pharmaceutical potential in combating aging-related diseases via anti-oxidation and AMPK cellular kinase activation.
Highlights
Introduction ofrhizoma coptidis (RC) and its main components.RC is the dried root and rhizome of three Coptis species: Coptis chinensis Franch, Coptis deltoidea C
This study demonstrated that RC extract may have more therapeutic effects than berberine alone, which may be due to the synergistic actions of other components in RC
Drosophila melanogaster is a valuable model for preclinical testing of drugs with therapeutic potential for aging, and aging-associated medical and psychiatric disorders (AAMPD) because of its small genomic size, short generation time, and short mean life span compared to both mice and humans with similar vulnerability to agerelate decline
Summary
Blood concentrations of RC alkaloids are extremely low after oral administration, but can be higher in some pathological conditions. The alkaloids exert systemic effects through generated metabolites or by directly modulating effectors in the gut [31]. Berberine is present at a very low level in blood due to its poor aqueous solubility and dissolution [33], but the pharmacological effect of berberine is correlated with its high tissue distribution. Several formulations have been devised to improve its bioavailability by a noral berberine-loaded micro-emulsion [36]. An anhydrous reverse micelle system of berberine prepared via lyophilization of water-in-oil emulsions was reported to show enhanced anti-diabetic efficacy attributed to higher bioavailability [37]. Wang et al examined berberine’s after intravenous administration in rats: half-life: 0.22 h, maximum thalamus concentration: 272 ng/g, time to peak concentration: 3.67 h and elimination half-life:12.0 h [35]
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