## 1 Introduction  
Excessive oxidative stress and chronic inflammation are closely linked to the development of multiple chronic inflammation diseases such as cancer, rheumatoid arthritis, cardiovascular diseases, type 2 diabetes, and neurological disorders [1, 2]. An important role of macrophages is to initiate inflammatory responses by producing pro-inflammatory cytokines such as interleukin-1\(\beta\) (IL-1\(\beta\)), IL-6, and tumor necrosis factor \(\alpha\) (TNF\(\alpha\)) [3, 4]. Furthermore, excessive reactive oxygen species (ROS) activate the macrophages that stimulate pro-inflammatory transcription factors such as nuclear factor-\(\kappa\)B (NF\(\kappa\)B) and activating protein-1 (AP-1) [5]. Therefore, the reduction of intracellular ROS levels in macrophages leads to the inhibition of pro-inflammatory pathways in macrophages [3, 6].  
Natural seaweed is an emerging material in the field of biomedicine due to its high content of bioactive compounds with potential as anti-inflammatory and antioxidant agents [7, 8]. Phenolic compounds in edible brown seaweeds play a crucial role in protecting algae from toxic ROS with their strong radical scavenging ability [9]. Phlorotannins are unique phenolic compounds with tridimensional polymerization of phloroglucinol, which can be found abundantly in edible brown seaweeds, but not in terrestrial plants [10].  
Individual compounds in phlorotannins, including phlorotototuroeckol A, dieckol, eckol, and 8,8\({}^{\prime}\)-bieckol showed excellent antioxidant properties [11]. These phlorotannins not only showed higher superoxide and 2,2-diphenyl-1-picrylhydrazaryl (DPPH) radical scavenging capacities than ascorbic acid and \(\alpha\)-tocopherol, but also inhibited phospholipid peroxidation in the liposomal system [11]. Furthermore, brown algal phlorotannins, dieckol, 6,6\({}^{\prime}\)-bieckol, phlorofucofuroeckol A (PFF-A), and PFF-B are the main anti-inflammatory components that inhibit inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) gene expression in lipopolysaccharide-induced macrophages [12]. In addition, eckol, 6,6\({}^{\prime}\)-bieckol, 8,8\({}^{\prime}\)-bieckol, dieckol, and PFF-A inhibited inflammation-related enzymes and pro-inflammatory cytokines, which was attributed to the suppression of the activation of NF\(\kappa\)B and mitogen-activated protein kinases (MAPKs) signaling pathways [13].  
_Agarum cribrosum_ (AC) is one of the brown seaweeds rich in phlorotannins. AC has been distributed along the eastern coast in the Republic of Korea, Russia, Japan, British Columbia, northern Washington, and Alaska [14]. Several studies have demonstrated that AC has antioxidant properties and anti-inflammatory effects. The ultrasound extract of Gangneung-grown AC phlorotannin showed the strongest free-radical scavenging activity against 2,2\({}^{\prime}\)-azino-bis (3-ethylbenzothazoline-6-sulfonic acid) (ABTS), DPPH, and hydrogen peroxide [15]. AC fractions from Gangneung, which are rich in phlorotannins such as trifuhalol A, inhibited the mRNA expression of IL-1\(\beta\), IL-6, and TNF\(\alpha\) through the suppression of the NF\(\kappa\)B and MAPKs signaling pathway in LPS-induced macrophages [16]. However, it has not been confirmed whether Busan-grown AC ethanol extract (ACE) and its fractions have inhibitory effects on inflammation and oxidative stress in LPS-stimulated macrophages. In this study, the total antioxidant activity of ACE and its five different organic solvent fractions such as Hex (n-hexane), CHCl\({}_{3}\) (chloroform), EtOAc (ethyl acetate), BuOH (butanol), and H\({}_{2}\)O (water) from ACE was evaluated. Based on the total antioxidant activity of ACE and its five fractions, we selected one of the fractions of ACE with the best total antioxidant activity to determine whether the ACE and fraction of ACE can inhibit inflammation and oxidative stress in LPS-stimulated RAW 264.7 macrophages.