Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF‐α–induced injury via inhibiting NF‐κB and JNK signals

Abstract

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos , chlorogenic acid (CGA) has been reported to possess anti‐inflammatory, anti‐oxidant and anti‐apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)‐induced heart failure mouse model, through mitigating the TNF‐α–induced toxicity. We further used TNF‐α‐induced cardiac injury in human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) to elucidate the underlying mechanisms. CGA pre‐treatment could reverse TNF‐α–induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF‐κB/p65 and major mitogen‐activated protein kinases (MAPKs) signalling pathways involved in TNF‐α–induced apoptosis of hiPSC‐CMs. Importantly, CGA can directly inhibit NF‐κB signal by suppressing the phosphorylation of NF‐κB/p65. As for the MAPKs, CGA suppressed the activity of only c‐Jun N‐terminal kinase (JNK), but enhanced extracellular signal‐regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF‐κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure.

Protective Role of Polyphenols in Heart Failure: Molecular Targets and Cellular Mechanisms Underlying Their Therapeutic Potential

“…Similar protective effects were observed in cardiomyocytes pretreated with chlorogenic acid (1 µmol/L for 12 h) followed by TNF-α treatment (40 ng/mL for 24 h) [154]. While TNF-α alone increased mPTP and protein expression of cleaved caspase-3 (activated), chlorogenic acid pretreatment completely blunted these effects, which corresponded to a significant attenuation in TNF-α-induced apoptosis.…”

“…Further illustrating the multiple targets of phenolic acids, cardiomyocytes treated with TNF-α alone (40 ng/mL) for 24 h were apoptotic compared to control. Nonetheless, these apoptotic effects were completely blunted by pretreatment with chlorogenic acid (1 µmol/L) for 12 h [154]. Further, NF-κB phosphorylation was increased due to TNF-α treatment; however, chlorogenic acid reduced NF-κB phosphorylation to control levels.…”

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

“…Furthermore, Kang et al (28) revealed that CGA derived from coffee impaired colorectal cancer cell metastasis by suppressing NF-κB, MEK and T-LAK cell-originated protein kinase. Additional studies indicated that CGA could attenuate LPS-induced acute kidney injury, protect cardiomyocytes and ameliorate lead-induced renal damage via suppressing the NF-κB signaling pathway (29)(30)(31). Considering the important role of NF-κB in breast cancer, it was hypothesized that CGA, a potent NF-κB signaling inhibitor, may be a potential drug for clinical therapy of breast cancer.…”

Implication of dietary phenolic acids on inflammation in cardiovascular disease

“…Later in 2019, it was reported that chlorogenic acid improved NO bioavailability and eventually improved blood pressure in cyclosporine induced hypertensive rats (Agunloye et al, 2019). Besides, chlorogenic acid also protects cardiomyocytes from TNF-α-induced injury via inhibition of NF-κB and JNK signals (Tian et al, 2019). Chlorogenic acid supplementation in high-carbohydrate, high-fat diet-fed rats resulted in reduced visceral fat, especially abdominal circumference and retroperitoneal fat.…”