Dicaffeoylquinic Acid
Also known as: DCQAs, dicaffeoylquinic acid isomers, chlorogenic acid derivatives, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, Dicaffeoylquinic Acid
Overview
Dicaffeoylquinic acids (DCQAs) are naturally occurring polyphenolic compounds, specifically esters of quinic acid with two caffeic acid moieties. Common isomers include 3,5-, 4,5-, and 3,4-dicaffeoylquinic acid. They are found in various plants such as *Ilex* species (e.g., *Ilex kudingcha*, *Ilex kaushue*), coffee, and certain medicinal herbs. DCQAs are classified as plant-derived bioactive phytochemicals and are being investigated for a wide range of potential therapeutic effects, including anti-inflammatory, antioxidant, chondroprotective, antiobesity, and respiratory protective properties. Research into DCQAs is currently in an emerging phase, with most evidence derived from in vitro and animal model studies, and limited human clinical trials.
Benefits
DCQAs have demonstrated several promising benefits primarily in preclinical studies. 4,5-DCQA showed a significant chondroprotective effect in a rat osteoarthritis model, reducing cartilage degradation comparable to diclofenac after oral administration every two days for two weeks. 3,5-DCQA exhibited anti-inflammatory and respiratory protective effects by inhibiting human neutrophil elastase and attenuating inflammatory signaling, protecting against lipopolysaccharide-induced acute lung injury in mice. DCQAs from *Ilex kudingcha* also demonstrated antiobesity effects in high-fat diet mice, reducing liver and adipose tissue mass, lowering serum inflammatory markers, and positively altering gut microbiota. Secondary effects suggested by pharmacological reviews include antibacterial, antiviral, hepatoprotective, neuroprotective, and cardiovascular protective properties, though these are mostly based on preclinical data. While these findings are significant in animal models, human clinical data are currently lacking, and the clinical relevance and effect sizes for human populations are yet to be established through large-scale randomized controlled trials.
How it works
Dicaffeoylquinic acids exert their biological effects through multiple mechanisms. They primarily act as potent antioxidants, reducing reactive oxygen species and mitigating oxidative stress. DCQAs are known to inhibit various enzymes, including human neutrophil elastase, which plays a role in inflammatory processes, and acetylcholinesterase. They also modulate inflammatory signaling pathways, such as those involving Src family kinases and Vav. In metabolic contexts, DCQAs can influence lipid metabolism gene expression and alter the composition of gut microbiota, contributing to their antiobesity effects. Their interaction with body systems includes modulating the immune system (anti-inflammatory), musculoskeletal system (chondroprotection), respiratory system (lung protection), and metabolic system (lipid metabolism). As polyphenols, their bioavailability is moderate and their metabolism likely involves gut microbiota and hepatic conjugation.
Side effects
The overall safety assessment for Dicaffeoylquinic Acids is primarily based on preclinical data, which indicate low acute toxicity and neurotoxicity. In silico analyses have not raised concerns regarding mutagenicity or carcinogenicity. Sub-chronic toxicity studies involving DCQAs and related chlorogenic acids in animals have not reported any significant safety concerns. However, human data on side effects are largely absent. Common, uncommon, and rare side effects in humans are currently unknown due to the lack of clinical trials. Drug interactions are not well-studied, and potential interactions with anti-inflammatory or metabolic medications would require further evaluation. Contraindications for DCQAs have not been established. Furthermore, data regarding reproductive and teratogenic toxicity are lacking, so caution is advised for pregnant or breastfeeding individuals and those in special populations until more comprehensive safety data become available.
Dosage
Optimal dosage ranges for Dicaffeoylquinic Acids in humans have not been defined due to the limited number of human clinical trials. Preclinical animal studies have utilized various doses, with some showing effects with oral administration every two days (e.g., 4,5-DCQA in rats for osteoarthritis). However, exact human equivalent doses are not established. The maximum safe dose is also unknown, although sub-chronic animal studies have not reported adverse effects. Timing considerations are not well-understood for humans, though intermittent dosing showed efficacy in animal models. For supplementation, pure compounds or plant extracts standardized for DCQA content would be recommended. As polyphenols, their absorption and bioavailability can be influenced by gut microbiota and individual metabolism, which should be considered when assessing efficacy. No specific cofactors are identified as required for their action.
FAQs
Is DCQA safe for human use?
Preclinical data suggest low toxicity, but human safety data are insufficient to confirm overall safety for widespread human use.
Can DCQA be used for osteoarthritis or respiratory diseases?
Animal studies show promise for these conditions, but high-quality human randomized controlled trials are needed to confirm efficacy.
How long before effects are seen?
Animal studies indicate that anti-inflammatory and chondroprotective effects can be observed within 1-2 weeks.
Are there known drug interactions?
Drug interactions with DCQAs are not well-studied, so caution is advised, especially if taking other medications.
Is DCQA the same as chlorogenic acid?
No, chlorogenic acid is a monocaffeoylquinic acid, while DCQAs have two caffeic acid groups attached to quinic acid.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8944529/ – This animal study investigated the chondroprotective effects of 4,5-dicaffeoylquinic acid (4,5-DCQA) in a rat model of osteoarthritis. Researchers found that oral administration of 4,5-DCQA every two days significantly reduced cartilage degradation and improved histological scores, demonstrating an effect comparable to diclofenac. The study suggests 4,5-DCQA as a potential therapeutic agent for osteoarthritis.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11374715/ – This systematic review synthesizes the pharmacological profiles of dicaffeoylquinic acids (DCQAs), highlighting their antioxidative, anti-inflammatory, and respiratory protective effects observed in preclinical studies. The review also discusses the low toxicity reported in animal models, but emphasizes the current lack of human clinical trials to confirm efficacy and safety in humans.
- https://www.nature.com/articles/srep34243 – This study explored the anti-inflammatory and respiratory protective properties of 3,5-dicaffeoylquinic acid (3,5-DCQA). In vitro, it inhibited human neutrophil elastase and reduced oxidative stress in human neutrophils. In vivo, 3,5-DCQA protected mice against lipopolysaccharide-induced acute lung injury, suggesting its potential as a therapeutic agent for inflammatory lung conditions.
- https://pubs.acs.org/doi/abs/10.1021/acs.jafc.8b05444 – This animal study investigated the antiobesity effects of dicaffeoylquinic acids (DCQAs) extracted from *Ilex kudingcha* in high-fat diet-fed mice. The findings showed that DCQAs significantly decreased liver and adipose tissue mass, reduced serum inflammatory markers, modulated lipid metabolism gene expression, and positively altered gut microbiota composition, indicating their potential in managing obesity.