Dicaffeoylquinic Acid
Also known as: Dicaffeoylquinic acids, DCQA, dicaffeoylquinic acid isomers, 3,5-DCQA, 4,5-DCQA, 3,4-DCQA, Dicaffeoylquinic Acid
Overview
Dicaffeoylquinic acids (DCQAs) are naturally occurring polyphenolic compounds, specifically esters of quinic acid with two caffeic acid moieties. They are classified as chlorogenic acid derivatives and potent natural phenolic antioxidants. DCQAs are found in various plants, including *Ilex* species (e.g., *Ilex kudingcha*, *Ilex kaushue*) and coffee. These compounds are biosynthesized through the shikimic acid and phenylpropanoid pathways. Research indicates that DCQAs possess significant antioxidant activity, inhibit various enzymes like elastase and acetylcholinesterase, and modulate inflammatory pathways. They are being investigated for a range of potential health benefits, including anti-inflammatory, antioxidant, chondroprotective, respiratory protective, antiobesity, and antimicrobial effects. While promising, the research on DCQAs is still emerging, with most evidence derived from in vitro and in vivo animal studies, and limited human clinical data available.
Benefits
Dicaffeoylquinic acids (DCQAs) have demonstrated several potential benefits, primarily in preclinical models. One significant effect is **chondroprotection**, where 4,5-DCQA was shown to reduce cartilage degradation and suppress catabolic activity in a rat osteoarthritis model, leading to histological improvement after two weeks of oral administration. DCQAs also exhibit strong **anti-inflammatory and respiratory protective** effects; for instance, 3,5-DCQA inhibited human neutrophil elastase and attenuated inflammatory signaling in vitro, and protected against lipopolysaccharide-induced acute lung injury in mice. Furthermore, DCQAs have shown **antiobesity and microbiota-modulating** properties, with extracts from *Ilex kudingcha* decreasing adipose tissue mass, serum inflammatory markers, and hepatic lipid synthesis gene expression in high-fat diet mice, while also increasing beneficial gut bacteria like *Bifidobacterium* and *Akkermansia*. Secondary effects observed in reviews include antioxidant, hepatoprotective, neuroprotective, antibacterial, antiviral, and hypoglycemic properties. While these effects are significant in animal models, human clinical relevance and specific population benefits are yet to be established through randomized controlled trials.
How it works
Dicaffeoylquinic acids (DCQAs) exert their effects through multiple biological pathways. Their primary mechanism involves potent **antioxidant activity** via radical scavenging, which helps mitigate oxidative stress. DCQAs also act as **enzyme inhibitors**, notably targeting human neutrophil elastase, an enzyme involved in inflammatory processes, and acetylcholinesterase. They modulate **inflammatory signaling pathways**, such as those involving Src family kinases/Vav, thereby reducing pro-inflammatory responses. In the context of metabolic health, DCQAs regulate **lipid metabolism genes** and can positively influence **gut microbiota composition**, leading to beneficial changes in the gut environment. These actions allow DCQAs to interact with various body systems, including the musculoskeletal system (cartilage protection), respiratory system (lung inflammation reduction), metabolic system (lipid metabolism regulation), and immune system (inflammation modulation).
Side effects
The overall safety assessment of Dicaffeoylquinic Acids (DCQAs) is primarily based on preclinical toxicology studies, which indicate a low acute toxicity profile for both dermal and oral administration, and low neurotoxicity. In silico analyses have not raised concerns regarding mutagenicity or carcinogenicity. Sub-chronic toxicity studies conducted in animal models have also shown no major safety concerns. To date, common, uncommon, or rare side effects have not been reported in animal studies. Specific drug interactions have not been studied, but given their enzyme inhibitory properties, potential interactions with other medications are theoretically possible and warrant further investigation. There are no established contraindications for DCQAs. However, a significant limitation is the lack of human safety data, including reproductive toxicity and teratogenicity data. Therefore, caution is advised, especially for pregnant or breastfeeding individuals, and in the absence of comprehensive human clinical trials, the full safety profile in humans remains to be fully elucidated.
Dosage
Currently, there are no established dosage guidelines for Dicaffeoylquinic Acids (DCQAs) in humans, as human clinical trials are lacking. Animal studies have utilized various oral doses, with effects observed even with intermittent dosing, such as every two days for 4,5-DCQA in rat osteoarthritis models. However, these dosages cannot be directly extrapolated to humans. The minimum effective dose, optimal dosage ranges, and maximum safe dose for human consumption remain undefined. DCQAs have been studied both as isolated compounds and as components within plant extracts. Absorption and bioavailability are factors that may influence efficacy, as DCQAs are polyphenols with moderate bioavailability, and their metabolism can be influenced by gut microbiota. No specific cofactors have been identified as necessary for their action. Until human safety and efficacy trials are conducted, any human use of DCQAs should be approached with caution and under professional guidance.
FAQs
Is DCQA safe for human consumption?
Preclinical data suggest low toxicity, but comprehensive human safety data are currently lacking. More research is needed to confirm safety in humans.
Can DCQA be used for osteoarthritis?
Animal models show promising chondroprotective effects, but human randomized controlled trials are needed to confirm efficacy for osteoarthritis in people.
Does DCQA help with respiratory inflammation?
Animal and in vitro studies indicate anti-inflammatory effects in lung injury models, suggesting potential for respiratory protection, but human data are absent.
How quickly do benefits appear?
In animal models, effects have been observed within 1 to 2 weeks of administration. The time course in humans is unknown.
Are there known drug interactions?
No specific drug interaction data are available. Due to potential enzyme inhibition, caution is advised, and interactions are possible but unstudied.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8944529/ – This study investigated the chondroprotective effects of 4,5-dicaffeoylquinic acid (4,5-DCQA) in a rat model of osteoarthritis. The findings indicated that 4,5-DCQA significantly reduced cartilage degradation and suppressed catabolic activity, leading to histological improvements in the affected joints after two weeks of oral administration. This research highlights the potential of 4,5-DCQA as a therapeutic agent for osteoarthritis.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11374715/ – This systematic review summarized the pharmacological and toxicological profiles of dicaffeoylquinic acids (DCQAs). It highlighted their anti-inflammatory, antioxidant, and respiratory protective benefits observed primarily in preclinical studies, while also noting their low toxicity. The review emphasized the current lack of human randomized controlled trials, indicating that most evidence is derived from preclinical data.
- https://www.nature.com/articles/srep34243 – This research explored the anti-inflammatory and respiratory protective effects of 3,5-dicaffeoylquinic acid (3,5-DCQA). In vitro, 3,5-DCQA inhibited human neutrophil elastase and reduced oxidative burst, while in mice, it protected against lipopolysaccharide-induced acute lung injury. The study provides strong mechanistic and animal evidence for 3,5-DCQA's potential in mitigating inflammatory lung conditions.
- https://pubs.acs.org/doi/abs/10.1021/acs.jafc.8b05444 – This study investigated the antiobesity effects of dicaffeoylquinic acids (DCQAs) from *Ilex kudingcha* in a mouse model of diet-induced obesity. The results showed that DCQAs reduced adipose tissue mass, lowered serum inflammatory markers, and decreased hepatic lipid synthesis gene expression. Furthermore, DCQAs modulated gut microbiota composition, increasing beneficial bacteria like *Bifidobacterium* and *Akkermansia* in a dose-dependent manner.
