## 1 Introduction  
The production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is indispensable for aerobic organisms and tightly regulated by a sophisticated system. ROS under normal physiological conditions act as secondary messengers responsible for the regulation of diverse cellular processes including cell proliferation, gene expression, and antimicrobial defenses [1]. However, oxidative and nitrosative stress, caused by an imbalance of redox homeostasis resulting in an excessive and chronic accumulation of ROS/RNS, inhibits the function of various biomolecules and changes the permeability of plasma and subcellular membranes, which in turn triggers cell death [2]. In addition,oxidative stress initiates a vicious cycle of tissue injury by causing the release of diverse damage-associated molecular patterns from injured cells, activating neighboring immune cells, producing proinflammatory cytokines, and accelerating inflammation-mediated tissue injury [3]. Due to the high consumption of oxygen when metabolizing xenobiotic or endogenous substances, the liver is one of the primary organs susceptible to oxidative damage [4]. Hence, oxidative stress remains central to the onset and progression of liver disease regardless of disease etiology, with effects seen in drug- and alcohol-induced liver injury, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, cirrhosis, and cancer [2,4].  
Due to the critical role of oxidative stress in liver disease, herbs possessing antioxidant and anti-inflammatory activities have garnered significant attention due to their potential to manage liver disease with fewer side effects [4]. Lemon balm (_Melisa officinalis_ L.; Lamiaceae family) is an fragrant herb that has been traditionally used for the treatment of anxiety, depression, and heart disease, as well as an enhancer of cognitive function [5,6]. Numerous studies of lemon balm have revealed a wide array of pharmacological activities, including antioxidant, anti-inflammation, anti-nociceptive, neuroprotective, hypoglycemic, and hypolipidemic activities [5]. Furthermore, lemon balm extract has been reported to restore impaired lipids metabolism in the liver [7]. In addition, throughout East Asia, dandelion (_Taraxacum officinal_ [L.] [PERSON] ex [PERSON]; Asteraceae family) is known to reduce inflammation in the liver and lung [8]. Modern scientific studies have sought to validate many of these potential benefits, revealing a range of benefits that include diuretic, antioxidative, anti-inflammatory, and anti-cancer activities [8]. Moreover, dandelion extract was shown to prevent a wide range of liver diseases induced by hepatotoxins (e.g., carbon tetrachloride (CCI\({}_{4}\)), acetaminophen, and alcohol) or diet in experimental animal models [9, 10, 11, 12, 13] and sensitize the tumor necrosis factor (TNF)-related apoptosis-inducing ligand-mediated cell death of hepatocellular carcinoma cells [14]. However, more studies are needed on the hepatoprotective effect of the combination of two herbs.  
As an effort to discover valuable hepatoprotective medicinal herbs, we previously found that leaf extracts from lemon balm and dandelion significantly alleviated CCl\({}_{4}\)-mediated acute liver injury. Of the diverse combination of ratios tested, a 2:1 (\(w/w\)) mixture of lemon balm and dandelion extracts (MLD) exhibited the most potent hepatoprotective effect against CCl\({}_{4}\)[15]. Therefore, the present study investigated the dose-dependent effects of MLD on CCl\({}_{4}\)-induced acute liver injury, in comparison with silymarin, a representative natural product used as protection against diverse stages of liver disease, and each herbal extract alone. Furthermore, the effects of MLD on hepatocyte apoptosis, oxidative stress, and inflammation were assessed to elucidate MLD's response mechanism in CCl\({}_{4}\)-induced acute liver injury.