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Review
. 2022 Jul 8;27(14):4396.
doi: 10.3390/molecules27144396.

Antiaging Mechanism of Natural Compounds: Effects on Autophagy and Oxidative Stress

Affiliations
Review

Antiaging Mechanism of Natural Compounds: Effects on Autophagy and Oxidative Stress

Elizabeth Taylor et al. Molecules. .

Abstract

Aging is a natural biological process that manifests as the progressive loss of function in cells, tissues, and organs. Because mechanisms that are meant to promote cellular longevity tend to decrease in effectiveness with age, it is no surprise that aging presents as a major risk factor for many diseases such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. Oxidative stress, an imbalance between the intracellular antioxidant and overproduction of reactive oxygen species, is known to promote the aging process. Autophagy, a major pathway for protein turnover, is considered as one of the hallmarks of aging. Given the progressive physiologic degeneration and increased risk for disease that accompanies aging, many studies have attempted to discover new compounds that may aid in the reversal of the aging process. Here, we summarize the antiaging mechanism of natural or naturally derived synthetic compounds involving oxidative stress and autophagy. These compounds include: 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) derivatives (synthetic triterpenoids derived from naturally occurring oleanolic acid), caffeic acid phenethyl ester (CAPE, the active ingredient in honey bee propolis), xanthohumol (a prenylated flavonoid identified in the hops plant), guggulsterone (a plant steroid found in the resin of the guggul plant), resveratrol (a natural phenol abundantly found in grape), and sulforaphane (a sulfur-containing compound found in cruciferous vegetables).

Keywords: CAPE; CDDO derivatives; aging; autophagy; guggulsterone; oxidative stress; resveratrol; sulforaphane; xanthohumol.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of antioxidant phytochemicals with potential effects on autophagy and oxidative stress.
Figure 2
Figure 2
Regulation of autophagy by phytochemicals. Activation of AMPK signaling pathway promotes autophagy through the activation of multiple signaling molecules and transcription factors, including but not limited to SIRT1 and PGC1-a and the inhibition of mTOR [188]. mTOR further phosphorylates and inactivates TFEB, an important regulator of autophagy. Inhibitors of mTOR and its upstream pathway, Akt signaling, can promote autophagy [189]. Similarly, inhibitors of NF-κB have the potential to enhance the completion of autophagy process [190]. Nrf2, when bound to Keap1, a major regulator of Nrf2, is quickly degraded but under oxidative stress, it gets released from Keap1 to regulate autophagic process by getting translocated into the nucleus to activate the transcription of target genes [191]. Phytochemicals reviewed in this manuscript activate or inhibit multiple pathways to modulate autophagy.
Figure 3
Figure 3
Phytochemicals inhibit OS-induced aging. Imbalance between the free radicals and antioxidants seen under inflammatory conditions leads to OS contributing to the process of aging. Several environmental factors and components of lifestyle play a significant role in increasing ROS levels, leading to oxidative stress-induced aging.

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