This weight loss effect has been attributed to a natural phytochemical, Chlorogenic Acid, found in generous amounts in green coffee beans. An earlier in vitro study in rat brain demonstrated that 5‐CQA exerts its neuroprotective effects against AD by inhibiting the activity of two key enzymes, namely acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE), as well as by suppressing oxidative stress‐induced neuronal damage (Oboh et al., 2013). Many factors affect your mug's CGA content—everything including your roast, brew, sweetener, and … According to results from clinical trials and animal studies, 5‐CQA bioavailability supports, at least in part, the association between 5‐CQA intake and health benefits. Besides, an efficient method for the preparative separation and purification of 5‐CQA, phenolics, and phlorizin from thinned young apples was developed using X‐5 resin and polyamide resins (Sun, Guo, Fu, Li, & Li, 2013). Recently, discrepant results have been reported about the effects of 5‐CQA on the expression of NFE2L2‐regulated genes, particularly HMOX1 (Bao et al., 2018; Chen et al., 2018; Domitrović et al., 2014; Salomone et al., 2017; Shi et al., 2016). Additionally, a recent in vitro study indicated that 5‐CQA could be beneficial to host health by significantly inducing the growth of Bifidobacterium spp. And let’s keep in mind too that historically diet pills have brought a plethora of side effects (ever heard of Fen-Phen?) Some earlier long‐term follow‐up studies indicated that components of decaffeinated coffee (mostly 5‐CQA) lower the risk of NDDs such as ischemic stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) (Larsson et al., 2011; Lopez‐Garcia et al., 2009; Mikami & Yamazawa, 2015; Oboh, Agunloye, Akinyemi, Ademiluyi, & Adefegha, 2013; Teraoka et al., 2012). Recently, Nabavi et al. I mention them because they are rich in chlorogenic acid, too. The possible mechanism by which 5‐CQA disrupted the membrane barrier might involve the perturbation of the membrane lipid bilayer, resulting in cell leakage and dissipation of the membrane electrical potential. (2010a) reported that either 5‐CQA alone or coadministered with tetrahydrocurcumin (THC) improved lipid abnormalities by decreasing LDL, very LDL (VLDL), and increasing high‐density lipoprotein cholesterol (HDL‐C) in type 2 diabetic rats. As discussed above, various mechanisms have been proposed to explain how 5‐CQA exerts its beneficial effects on various physiological processes or tissues including neuroprotective, cardiovascular protective, hepatoprotective, renoprotective, gastrointestinal protective, and anticarcinogenic effects. Also, after coffee consumption, CA, 5‐CQA, DHCA, gallic acid (GA), FA, isoFA, DHFA, vanillic acid (VA), sinapic acid, p‐hydroxybenzonic acid, p‐CoA, etc. In rat primary hippocampal neuronal cells, treatment with 5‐CQA was shown to protect neurons against aluminum chloride (AI)‐induced oxidative stress by upregulating nuclear factor, erythroid 2 like 2 (NFE2L2; also known as NRF2) and phase 2 enzymes (Wang et al., 2017). The preclinical protective benefits of 5‐CQA against stroke either in mouse or rat model may be attributed to the inhibition of neuronal cell death and protection against cortical neurons injury by preventing the glutamate‐induced increase in intracellular Ca2+ concentration and maintaining intracellular redox homeostasis, but 5‐CQA has little effect on NO‐induced neuronal cell death, which is downstream of ischemia‐induced neuronal cell death (Mikami & Yamazawa, 2015; Rebai et al., 2017). Thus, these studies suggest that at least two mechanisms are involved in 5‐CQA bioavailability (Clifford et al., 2020; Liang & Kitts, 2016; Madrigal et al., 2001; Stefanello et al., 2019). Accordingly, the remarkable hepatoprotective effects of 5‐CQA on liver injury may be related to its antioxidative and anti‐inflammatory activities. Also, Bao et al. Moreover, 5‐CQA may be beneficial to the host by selectively modulating the colonic microbiota and functions as a possible “prebiotic” in the large intestine (Mills et al., 2015). It is known that chlorogenic acid can modulate or suppress the immune response, though it’s not yet clear how. All authors read the manuscript and agreed on the final version. Another recent study suggested that 5‐CQA supplementation can reduce intestinal permeability and partly mitigate colonic epithelial barrier injury by inhibiting the myosin light chain kinase (MYLK, also known as MLCK) pathway and modulating the dynamic distribution and localization of TJPs in colitis rats (Ruan et al., 2016). Furthermore, in vitro and in vivo evidence indicated that 5‐CQA reduced glucose absorption in the small intestine through direct and/or indirect inhibition of glucose transport across sodium/glucose cotransporters 1 (SLC5A1, also known as SGLT1) (Tunnicliffe et al., 2015). Zhichang Liu corrected portions of the manuscript. In addition, 5‐CQA was also found to reduce chronic inflammation in obese mice by decreasing mRNA expression levels of macrophage marker genes, including adhesion G protein‐coupled receptor E1 (Adgre1; also known as Emr1, F4/80), integrin alpha M (Itgam, also known as Cd11b), integrin alpha X (Itgax, also known as Cd11c), and macrosialin (Cd68), and inhibiting proinflammatory mediator genes such as Tnf, C‐C motif chemokine 2 (Ccl2, also known as Mcp‐1), and C‐C chemokine receptor type 2 (Ccr2) (Ma et al., 2015). Recently, a growing body of evidence has suggested that consumption of polyphenol‐rich foods could be beneficial against CVDs (Chen, Costa, & Carolo dos Santos, 2019; Manach, Mazur, & Scalbert, 2005). Remarkably, Zheng, Sheng, Lu, and Ji (2015) demonstrated that 5‐CQA exerted a therapeutic detoxification effect against AP‐induced mouse hepatic damage through the TLR3/4 and NF‐κB inflammation signaling pathway. In weaned rats, 5‐CQA attenuated LPS‐mediated intestinal barrier dysfunction by increasing tight junction protein 1 (TJP1; also known as ZO‐1) and occludin (OCLN) (Ruan et al., 2014). Thus, despite the increasing evidence showing that long‐term coffee intake, high in 5‐CQA can attenuate neurodegeneration, the molecular mechanisms of the protective effects of 5‐CQA against neurodegeneration are complex and thus additional, formal, well‐controlled preclinical and clinical studies are needed to elucidate such mechanisms. Moreover, evidence from the recovery tests in human plasma showed that small amounts of 5‐CQA (∼7%) were hydrolyzed into CA, which might be due to the hydrolysis of 5‐CQA during metabolism in human body and/or analytical artifacts. Raw Foods: Losing Weight and Feeling Great, Stop Overeating! Quercetin-3-rutinoside was metabolized mainly to phenylacetic acids, i.e., 3-hydroxyphenylacetic acid (36%), 3-methoxy-4-hydroxyphenylacetic acid (8%) and 3,4-dihydroxyphenylacetic acid (5%). (2018) reported that pretreatment with 5‐CQA attenuates diabetic renal damage and prevent diabetic nephropathy by increasing the expression level of HMOX1 and promoting the nuclear translocation of NFE2L2. SKIN CARE BOOKS & E-BOOKS HAIR CARE DENTAL CARE BEAUTY DEVICES SPECIALS. Available compelling evidence indicates that consumed 5‐CQA can promote a broad range of health benefits and multidirectional biological effects in various tissues and organs including the nervous system, cardiovascular system, gastrointestinal tract, kidney, liver, muscle, and pancreas (Figure 5).