Persistent inflammatory responses characterize some chronic inflammatory diseases in humans. These responses are typically induced due to inappropriate and excessive immune reactions. Sometimes, one or more genetic factors may make individuals more susceptible to these diseases (Chiurchiu & Maccarrone, 2011; Libby, 2007). Inflammatory responses are linked to the release of inflammatory markers, such as cytokines with inflammatory properties (Chen et al., 2018). Cytokines are small, soluble proteins generated in the innate and specific immune systems. They participate in the establishment and regulation of immune and inflammatory responses (Holdsworth & Gan, 2015). Cytokines are categorized into inflammatory and anti-inflammatory types with distinct roles in initiating and resolving inflammation (Chen et al., 2018). Additionally, a decrease in the creation of antioxidants in areas of inflammation can heighten oxidative stress and diminish the cells’ ability to respond to damage from oxidation. This could promote the advancement of inflammation-related diseases, influenced adversely by cytokines (Speer et al., 2020). For instance, interleukin 17 (IL-17) is an inflammatory cytokine synthesized predominantly by a subtype of immune cells known as Th-17 cells (Iwakura et al., 2011). Studies have shown that IL-17 is involved in the process of chronic inflammation in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA) (Van Bezooijen et al., 1999), multiple sclerosis (Kurasawa et al., 2000), psoriasis (Teunissen et al., 1998), and induction of tumour growth (Kato et al., 2001). Pharmacological treatment for inflammation primarily employs synthetic drugs that act through hormones, inhibit inflammatory enzymes and proteins, or induce their anti-inflammatory response (Asirvatham et al., 2019; Pope & Deer, 2018). These medications are classified into three groups: steroid anti-inflammatory drugs (NSAIDs), non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressants (Yatoo et al., 2018). SAIDs like corticosteroids work quickly and effectively against inflammation (Rhen & Cidlowski, 2005; Yatoo et al., 2018), but have some potential side effects, including immune suppression, body weight gain, hormone disruption, dependency, and more (Ayroldi et al., 2012; Juthani et al., 2017). NSAIDs, intended to reduce SAID limitations (Asirvatham et al., 2019), work by inhibiting the enzyme cyclooxygenase, which provides pain relief, reduces inflammation, and lowers fever (Celotti & Laufer, 2001; Yatoo et al., 2018). However, they can also result in gastrointestinal (Sparkes et al., 2010), renal (Su & O’Connor, 2013), and central nervous system problems (Yatoo et al., 2018). Immunosuppressive medications used to treat inflammatory diseases include calcineurin inhibitors and anti-proliferative agents (Stucker & Ackermann, 2011). However, these drugs carry the risk of immune suppression, infections, and genetic effects (Arulselvan et al., 2016; Yatoo et al., 2018).
Herbal medicines, including microalgae, provide a safer alternative for treating inflammation due to the potential side effects of other treatments (Hussein et al., 2019; Martinez et al., 2015). Microalgae have recently received much attention, and different photobioreactors and open ponds have been designed to take advantage of these photosynthetic microorganisms in various applications such as functional foods, cosmetics, wastewater treatment, biofuel, dietary supplements, and medicine (Emamshoushtari et al., 2022; Helchi et al., 2022; Keyvan Hosseini et al., 2022). Spirulina platensis, is a blue-green microalgae from the cyanobacteria branch that is extremely rich in a blueish antioxidant pigment known as phycocyanin (Nasser et al., 2023). C-PC is formed by a polypeptide chain and chromophores named phycocyanobilin (Adjali et al., 2022). phycocyanin improves the human immune system and revitalizes animal blood cells (Soni et al., 2015). Notably, phycocyanin has potential anticancer effects on solid malignant tumors, acting as a toxin to cancer cells while being non-toxic to normal cells (Bechelli et al., 2011; Jiang et al., 2017; Ravi et al., 2015). It is widely utilized in molecular biology, immunology, cytology, and molecular diagnostics (Yu et al., 2017).
Phycocyanin can trigger mechanisms that prevent or reduce the expression of experimental autoimmune encephalitis (EAE) while also inducing a regulatory T cell response in peripheral blood mononuclear cells (PBMCs) from MS patients (Pentón-rol et al., 2011). According to Pentón-Rol et al. (2016), phycocyanin effectively improved clinical and redox status and decreased IL-17 expression in mice's chronic model of experimental autoimmune encephalitis (EAE). Jang et al. (2022), studied the anti-inflammatory properties of phycocyanin in mouse models of imiquimod-induced psoriasis and reported phycocyanin regulated the levels of inflammatory cytokines and psoriasis-related cytokines, including IL-17, interferon-gamma, and calcitonin gene-related peptides.
Nevertheless, phycocyanin appears sensitive to environmental stress, especially temperature, pH, and light (Chaiklahan et al., 2012). This sensitivity can cause instability and undesired outcomes, including decreased antioxidant capacity (Colla et al., 2016). Hence, phycocyanin must be encapsulated to prevent degradation and enhance stability and antioxidant activity; in other words, encapsulating phycocyanin safeguards its integrity and ensures its practical effectiveness as an antioxidant (Adjali et al., 2022).
Before conducting any in vivo assessment and clinical trials, in vitro study is necessary to unveil the effect of phycocyanin on cellular defence mechanisms and inflammatory gene expression under inflammatory conditions to pave the way for more research and development of phycocyanin-based therapies. Therefore, the present study investigated the impact of phycocyanin in encapsulated (ENPC) and non-encapsulated (PC) forms on cellular defence mechanisms by examining the antioxidant activity of catalase, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2), as well as IL-17 inflammatory gene expression in PBMCs under phytohemagglutinin (PHA)-induced inflammatory conditions.