Pharmacokinetics and brain penetration study of chlorogenic acid in rats

Abstract

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles-Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path. 2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10 mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method. 3. The study observes that CGA is rapidly absorbed in plasma with t of 1 min similar to IV route after IN administration. The peak plasma concentration and AUC are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route. 4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360 min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.

Effect of Chlorogenic Acid Supplementation in MPTP-Intoxicated Mouse

“…Also, the usage of anti-inflammatory drugs to suppress neuroinflammation to alleviate DA neurodegeneration has been seen in different models of PD ( Choi et al, 2005 ). Researchers have particularly focused to study the antioxidant properties of CGA as it crosses the blood–brain barrier whether in its pure form or as its metabolite ( Ito et al, 2008 ; Chu et al, 2009 ; Kumar et al, 2018 ). Throughout our study, we tried to suggest the novel role of CGA by inhibiting the neuroinflammation by decreasing the production of ROS and release of pro-inflammatory cytokines and suppressing the activation of astrocytes by downregulating the expression of NF-κB.…”

Attenuation of Palmitic Acid–Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes

“…As expected, CGA displayed strong DPPH free radical quenching ability with IC50 values less than 45 µg mL −1 . After oral administration of 1.2 g kg −1 CGA to mice or intravenous administration of 10 mg kg −1 CGA to rat, the maximum plasma concentration of CGA reaches 82.6 µg mL or 442.498 µg mL, indicating its high bioavailability . Therefore, it is tempting to speculate that CGA, by inhibiting ROS generation and oxidative stress, protects cell from lipotoxicity under a physiologically achievable concentration.…”

Chlorogenic acid: A comprehensive review of the dietary sources, processing effects, bioavailability, beneficial properties, mechanisms of action, and future directions

“…It is well known that NDDs are highly correlated with inflammation and accumulation of oxidative stress‐induced damage (Kim & Lee, 2015). The phenolic compound 5‐CQA is thought to be a strong antioxidant and anti‐inflammatory agent, which can cross the blood–brain barrier (BBB) to act directly and/or indirectly on the central nervous system (Heitman & Ingram, 2017; Kumar, Paliwal, et al., 2019). 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).…”