Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials

Abstract

Chlorogenic acid (CGA) is a type of polyphenol compound found in rich concentrations in many plants such as green coffee beans. As an active natural substance, CGA exerts diverse therapeutic effects in response to a variety of pathological challenges, particularly conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional functions, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders, skin diseases, diabetes mellitus, liver and kidney injuries, and anti-tumor activities. Mechanistically, its integrative functions act through the modulation of anti-inflammation/oxidation and metabolic homeostasis. It can thwart inflammatory constituents at multiple levels such as curtailing NF-kB pathways to neutralize primitive inflammatory factors, hindering inflammatory propagation, and alleviating inflammation-related tissue injury. It concurrently raises pivotal antioxidants by activating the Nrf2 pathway, thus scavenging excessive cellular free radicals. It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids. Additionally, CGA shows functions of neuromodulation by targeting neuroreceptors and ion channels. In this review, we systematically recapitulate CGA's pharmacological activities, medicinal properties, and mechanistic actions as a potential therapeutic agent. Further studies for defining its specific targeting molecules, improving its bioavailability, and validating its clinical efficacy are required to corroborate the therapeutic effects of CGA.

Keywords: AMPK; NF-kB; chlorogenic acid; chronic metabolic diseases; inflammation; metabolic homeostasis; neuromodulation; oxidation.

Figure 1

A summary of therapeutic effects of CGA on multiorgan. CGA shows various beneficial roles in many pathological conditions. It can (A) mitigate inflammatory response and oxidative stress; (B) modulate glucose and lipid homeostasis and alleviate DMs; (C–E) protect cardiovascular system, kidneys, and liver; (F) facilitate the recovery from neurological impairments such as neurodegenerative disorders and diabetic peripheral neuropathy; (G) inhibit tumor cell proliferation and migration; (H) ameliorate skin pathologies; (I) execute anti-pathogen effects, and (J) exert antiaging effects. ↑, increasing; ↓, decreasing. The graph was created with Biorender.com.

Figure 2

The potential mechanistic actions of CGA on multi-targets. CGA can potentially (A) target NF-kB, MPAKs, and JAK pathways to mitigate inflammation; (B) activate Nrf2-dependent and independent pathways to execute antioxidation function; (C) regulate lipid metabolism through increasing lipolysis and fatty acid oxidation and suppressing synthesis of cholesterol and fatty acids; (D) modulate glucose metabolism through increasing glycolysis and suppressing glucose uptake and glucose synthesis; and (E) exhibit neuromodulation through targeting multiple neuroreceptors and ion channels. The graph was created with Biorender.com.