## 1 Introduction  
Numerous plants and herbs have been found to possess pharmacological properties, and have been used as medicines for thousands of years. Among them are heather (_Calluna vulgaris_ L.) and marigold (_Calendula officinalis_ L.). These two plants contain several phytochemicals with beneficial health properties, such as antioxidant, antidiabetic, antiproliferative, as well as anti-inflammatory properties [1; 2; 3; 4; 5; 6; 7]. Inflammation is a complex biological process in which immune cells and different mediators, such as prostaglandandins, cytokines and leukotrienes, are involved. They are the principal protective responses to eliminate the cell injuries and tissue damage and to initiate the tissue repair. However, the consequences of chronic inflammation are often associated to metabolic chronical diseases, such as obesity, atherosclerosis and diabetes [8]. Different studies have evaluated the potential anti-inflammatory properties of heather and marigold. [PERSON] et al. [9] obtained hexane, chloroform, ethyl acetate, butanol and water fractions from heather ethanolic extracts. The ethyl acetate fraction showed the most active anti-inflammatory activity. Similarly, [PERSON] et al. [10] carried out the fractionation by hexane and dichloromethane from a marigold ethanolic extract. Extracts presented an anti-inflammatory activity that improved the wound healing process. [PERSON], [PERSON] and [PERSON] [11] observed a significant anti-inflammatory activity of ethanol extracts in mice, obtained from marigold by maceration for two weeks. In a similar manner, [PERSON] et al. [2] also obtained marigold anti-inflammatory extracts by maceration over one week, and the extracts were obtained using methanol. To the best of our knowledge, there are no studies reported regarding optimization of the extraction conditions with the aim of obtaining extracts with improved anti-inflammatory activity. Supercritical carbon dioxide (SCCO\({}_{2}\)) is widely used for the extraction of natural compounds since SCCO\({}_{2}\) is a safe and green solvent and it has moderate critical conditions (31 \({}^{\circ}\)C, 7.38 MPa) [12]. Due to its low critical temperature and the absence of oxygen during extraction, the degradation of natural products is minimized or avoided, contributing to the production of high quality plant extracts. The only information available concerning the SCCO\({}_{2}\) of heather (_Calluna vulgaris_ L.) was reported by [PERSON] et al. [13] in which extracts with activity against hepatitis C virus were obtained at different pressures, temperatures and amounts of co-solvent. Moreover, [PERSON] and [PERSON] carried out the extraction of triterpene acids from heather plants with different harvest time in their respective Ph.D. theses [14; 15]. In the case of marigold (_Calendula officinalis_ L.), several studies have been reported. [PERSON] et al. [16] carried out the extraction of lutein fatty acid esters. [PERSON], [PERSON] and [PERSON] [17], [PERSON] et al. [18], [PERSON] et al. [19] and [PERSON] et al. [20] studied the extraction of essential oil and oleoresin. [PERSON] et al. [21] performed the extraction of faradiol esters. [PERSON] et al. [22] carried out the purification of triterpen esters combining SCCO\({}_{2}\) with chromatography. Nevertheless, only [PERSON] et al. [23] carried out the SCCO\({}_{2}\) of marigold and evaluated the anti-inflammatory activity of the extracts obtained. In this case, just one SFE condition (35 MPa and 50 \({}^{\circ}\)C) was studied. In the present work, the SCCO\({}_{2}\) extraction of heather and marigold was studied with varying pressure, temperature, amount of co-solvent and with or without fractionation, with the aim of evaluating the obtained extracts for their in vitro anti-inflammatory activity. In order to determine potential synergisms, the simultaneous extraction of the two plants was also carried out.