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Review
. 2017 Dec 1;8(6):760-777.
doi: 10.14336/AD.2016.0620. eCollection 2017 Dec.

Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation

Zhifang Xu  1   2 , Wei Feng  3 , Qian Shen  4 , Nannan Yu  1 , Kun Yu  1 , Shenjun Wang  1   2 , Zhigang Chen  4 , Seiji Shioda  5 , Yi Guo  1   2
Affiliations
Review

Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation

Zhifang Xu et al. Aging Dis. .

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.

Keywords: AMPK; Rhizoma coptidis; aging; aging-related diseases; anti-oxidation; berberine.

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Conflict of interest statement

Conflict of Interests The authors have no conflict of interests in this paper.

Figures

Figure 1.
Figure 1.
The photographs of RC dried root and rhizome.
Figure 2.
Figure 2.
The structures of berberine and other key protoberberine-type alkaloids contained in RC.
Figure 3.
Figure 3.. Schematic illustration of the molecular mechanisms and pathways of RC/berberine anti-aging and aging-related diseases
(1) RC/berberine could activate AMPK signaling pathway in the cellular mitochondria. (2) The activation of AMPK by RC/berberine inhibits the oxidative stress in mitochondria via down-regulating ROS production and up-regulating anti-oxidative enzymes. (3) The downstream targets of the AMPK signaling regulated by RC/berberine include the activation of mitochondrial biogenesis, SIRT1/FOXO and Nrf2 signaling, and inhibition mTOR/S6K, NADPH and NF-??B pathways. (4) Via regulating the downstream productions of the signaling pathways mentioned above, RC/berberine could activate cellular autophagy which finally inhibits cellular senescence, aging process and the pathological process of aging-related diseases.
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