Molecular Mechanism of Antioxidant and Anti-Inflammatory Effects of Omega-3 Fatty Acids in Perilla Seed Oil and Rosmarinic Acid Rich Fraction Extracted from Perilla Seed Meal on TNF-α Induced A549 Lung Adenocarcinoma Cells.

Payungsak Tantipaiboonwong,Sirichat Kaowinn,Maitree Suttajit,Chakkrit Khanaree,Wittaya Chaiwangyen,Napapan Kangwan,Komsak Pintha,Wanisa Punfa

doi:10.3390/molecules26226757

Abstract

Industrially, after the removal of oil from perilla seeds (PS) by screw-type compression, the large quantities of residual perilla seed meal (PSM) becomes non-valuable waste. Therefore, to increase the health value and price of PS and PSM, we focused on the biological effects of perilla seed oil (PSO) and rosmarinic acid-rich fraction (RA-RF) extracted from PSM for their role in preventing oxidative stress and inflammation caused by TNF-α exposure in an A549 lung adenocarcinoma culture model. The A549 cells were pretreated with PSO or RA-RF and followed by TNF-α treatment. We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells. Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line. The mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF. The Western blot indicated that the expression of MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment. The results demonstrated that PSO and RA-RF act as antioxidants to scavenge TNF-α induced ROS levels, resulting in decreased the expression of MnSOD, FOXO1, NF-κB and JNK signaling pathway in a human lung cell culture exposed to TNF-α.

Highlights

Perilla frutescens L., Nga-mon in Thai, is an edible food and medicinal herb grown in parts of certain Asian countries, including Thailand, China, Korea, Japan, India, and Laos.Perilla seeds (PS) have been traditionally utilized as a local medicine to treat mental stress and related symptoms or illnesses such as anxiety, asthma, vomiting, coughing, allergies, intoxication, abdominal pain, and indigestion, whereas natives of northern Thailand usually consume sticky rice mixed with ground PS, called as “Kao-Nuk-Nga” [1,2]
400 μg/mL) and rosmarinic acid-rich fraction (RA-RF) (40 μg/mL) markedly decreased the tumor necrosis factor-α (TNF-α)-induced Jun N-terminal kinases (JNKs) phosphorylation. These results indicate that Perilla seed oil (PSO) and rosmarinic acid (RA)-RF inhibit JNK phosphorylation, which in turn, leads to a decrease of pro-inflammatory cytokine production
The present study investigated whether PSO and RA-RF have the ability to suppress the increased generation of reactive oxygen species (ROS) in TNF-α-induced A549 cells

Summary

Introduction

Perilla frutescens L., Nga-mon in Thai, is an edible food and medicinal herb grown in parts of certain Asian countries, including Thailand, China, Korea, Japan, India, and Laos.Perilla seeds (PS) have been traditionally utilized as a local medicine to treat mental stress and related symptoms or illnesses such as anxiety, asthma, vomiting, coughing, allergies, intoxication, abdominal pain, and indigestion, whereas natives of northern Thailand usually consume sticky rice mixed with ground PS, called as “Kao-Nuk-Nga” [1,2]. Dietary PS provide valuable nutrients and hydrophilic antioxidants and anti-inflammatory phytochemicals such as phenolic acids and flavonoids, mainly rosmarinic acid (RA), apigenin, luteolin, procyanidins, phytic acid, catechin, caffeic acid, chrysoeriol, ferulic acid, and quercetin as well as essential oils, triterpenes, carotenoids, phytosterols, tocopherols, and policosanols [3,4]. The PSM should be analyzed and reused because it is rich in numerous bioactive components such as phenolic compounds and others [17,18,19,20]. Because their molecular mechanisms remain unknown, it is worth studying these active pharmaceutical ingredients in PSO and PSM

Methods

Results

Conclusion