Channa striatus (CS), or snakehead murrel, is an obligate air-breathing freshwater fish that inhabits all types of water bodies from small ditches to rice fields, rivers, and lakes (Figure 1). It can be found across tropical and subtropical Asian countries from Pakistan and India to Southeast Asia and Southern China (Hossain et al, 2008; Shafri and Abdul Manan, 2012). It belongs to the Channidae family, which has been around since 50 million years ago, with an origin purportedly from the ancient Himalayan Valley (Madeleine, 2004).

Besides its wound healing properties, CS has also been reported to exhibit anti-inflammatory, anti-nociceptive, anti-microbial, and wound healing effects in multiple pre-clinical studies (Jais, 2007; Jais, 2007; Raju et al., 2020; Zakaria, Mat). These pharmacological properties may be contributed by the fact that CS extract contains high levels of major amino acids such as glycine, alanine, lysine, aspartic acid, and proline, as well as fatty acids such as docosahexaenoic acid (DHA), palmitic acid, oleic acid, stearic acid and arachidonic acid (Shafri and Abdul Manan, 2012; Zakaria et al., 2007; Zuraini et al., 2006). Glycine makes up human skin collagen and can also be a polypeptide involved in wound healing together with other amino acids such as alanine, leucine, and phenylalanine, all of which are found in CS extract (Zakaria et al., 2007). Most of these are found in the fillet, but some are found in CS fish roe as well. Roe protein concentrates prepared from CS were also reported to have high antioxidant activity, thus warranting its selection as a functional ingredient in preparing specialty food products (Galla et al, 2012).

Traditionally, CS or more locally known as ‘Haruan' fish, is encouraged to be consumed as part of a post-partum diet, especially for womenwho underwent a cesarean section, because it is believed that CS enhances wound healing as well as improves pain and trauma (Poh et al, 2005; Haniffa et al, 2014). In Malaysia, CS is commonly prepared by frying, roasting, or cooking with curry among the Malay community. Broth or fish tonic made from CS extract are also quite popular as an “energy-restoring” diet (Shafri and Abdul Manan, 2012).

Inflammation is a tissue response to injury caused by hazardous chemicals, physical trauma, or pathological threats (Suhendi et al, 2019). Inflammation is a cascade of events promoted by inflammatory mediators such as histamine, serotonin, kinins, prostaglandins, and interferons (Larsen and Henson, 1983; Weissmann, 2013). Chronic inflammation is universally associated with various diseases such as obesity, cancer, cardiovascular, and neurological disorders (Okin and Medzhitov, 2012). The prevalence of such diseases varies, with symptomatic osteoarthritis occurring in around 10%–13% of Americans older than 60 (Zhang and Jordan, 2010) and allergic rhinitis afflicting an average of 23% of adults in several European countries (Bauchau and Durham, 2004). While there are anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), their long-term use is associated with an increased risk of peptic ulcers, acute renal failure, stroke, and myocardial infarction (Marcum and Hanlon, 2010). Anti-inflammatory drugs also interfere with essential cellular pathways (Ghosh et al., 2016). Combined with the risks associated with their chronic use, they are ineffective for treating chronic inflammatory diseases. Thus, it is essential to look at natural methods such as CS extract. While there is an abundant number of investigative studies on the inflammatory properties of CS, the quality of these studies has not been evaluated effectively. Thus, this review aims to summarise, evaluate, and critically appraise currently available literature regarding the anti-inflammatory properties of CS extract. To our knowledge, this is the first review to evaluate the highly beneficial characteristic of CS extract, therefore establishing this review as a timely topic that may propagate the development of effective future anti-inflammatory interventions for a growing number of debilitating inflammatory diseases, with minimal consequences.

A total of 1,217 articles were identified from the initial database literature search, which was then reduced to 1,100 articles after the removal of duplicates. These 1,100 articles were manually screened according to the aforementioned inclusion and exclusion criteria, and 1,083 articles were excluded as they did not meet the aim of this review or were not full-text original research articles. Thus, based on the PRISMA guidelines, a total of 17 articles were eligible for critical evaluation and appraisal in this study (Figure 2). Among the 16 articles selected, there were seven clinical studies and nine animal studies. These selected articles’ significant findings and characteristics were summarised in Table 1 (animal studies) and Table 2 (clinical studies).

After analyzing the available literature on the use of Channa striatus derived treatments in inflammatory conditions, beneficial effects were found for several conditions. These conditions were gastric ulcers, dermatitis, osteoarthritis, and allergic rhinitis. Beneficial effects of CS were also found in wound healing as well as on inflammation in the presence of tuberculosis. All the studies in this review used some form of CS extract rather than working with isolated extract constituents. Nevertheless, the studies in the review pointed out several constituents which could be responsible for the beneficial effect of CS extract. These include albumin (Suhendi et al., 2019), the fatty acids linoleic acid, stearic acid, oleic acid, and N-arachidonylglycine, (Abedi et al., 2012), omega-6 polyunsaturated fatty acids, vitamins A, B, E, and D, and minerals such as calcium, sodium, magnesium, and zinc (Paliliewu et al., 2013), omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid (Susibalan et al., 2018). Excluding the ubiquitous vitamins and minerals, albumin and fatty acids appear to be leading candidates for the anti-inflammatory action seen in CS extract. The two constituents are related as although albumin has antioxidant properties due to its ability to scavenge free radicals, it is also capable of binding fatty acids (Roche et al, 2008). Thus, not only is albumin anti-inflammatory, but by binding fatty acids and facilitating its transport around the body (van der Vusse, 2009), albumin could be enhancing the anti-inflammatory effects of fatty acids. Omega-3 and 6 polyunsaturated fatty acids (Wall et al, 2010), the omega-9 fatty acid, oleic acid (Santamarina et al., 2021), and stearic acid (Pan et al., 2010) are also are known to be anti-inflammatory. Curiously, CS extract also contains arachidonic acid (Che Ku Daud et al, 2010), a known contributor to inflammation. It is possible that CS extract has a net anti-inflammatory effect overall due to its other constituents, or it could be due to CS extract also containing N-arachidonylglycine (Abdul Kadir et al., 2019), which is derived from arachidonic acid but inhibits inflammation instead (Succar et al, 2007).

Knowing the possible active constituents of CS extract is only half the battle won as the mechanism by which it works is also essential. However, we found that a majority of the studies in the review attributed the positive effects of CS extract on the inflammatory conditions to its anti-inflammatory properties in general without identifying specific mechanisms. One of the rare studies in the review that did postulate a mechanism stated that CS extract has a cytoprotective effect by positively modulating the free radical scavenging action of non-protein sulfhydryl compounds (Azemi et al., 2018). Another study pointed to the inhibition of inflammatory cells due to a downregulation of TNF-α (Isa et al., 2016). Different research hypothesized the mechanism to be a downregulation of not only TNF-α but also IFN-γ and IL-10 (Paliliewu et al., 2013). The final study pointed towards a reduction in IgE levels and the chemokines, IL-5 and IL-8 (Susibalan et al., 2018). While an in-depth discussion regarding the mechanisms of anti-inflammatory action is outside the scope of this review, the previously postulated mechanisms of action point to the involvement of the JAK-STAT signaling pathway due to the participation of IL-10, IFN-γ, and IL -5 (Banerjee et al, 2017). Notably however, IL-10 is an anti-inflammatory cytokine (Iyer & Cheng, 2012), and therefore its apparent downregulation could be due to a lack of need because of the overall anti-inflammatory effect of the CS extract, rather than the extract directly suppressing it.

On the other hand, the involvement of TNF-α and IL-8 suggests an effect on the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinases (JNKs) (Bradley, 2008). In the case of allergic inflammatory responses, the reduction in IgE levels is likely a consequence of a reduction in IL-5 levels, possibly by interfering with its production by T-helper 2 cells. This review also included articles looking into wound healing. While the study on wound healing did not look into the anti-inflammatory effects of CS extract specifically, inflammation is a normal part of wound healing. However, wound healing becomes impaired when the inflammation becomes excessive or persistent (Eming et al, 2007). Thus, the wound healing properties of CS extract could also be related to its ability to dampen the inflammatory response.

From our review, CS has been experimentally shown to positively affect inflammatory conditions such as gastric ulcers, dermatitis, osteoarthritis, and allergic rhinitis. Beneficial effects were also found on inflammation in the presence of tuberculosis and in situations that involve inflammation in some capacity, such as wound healing. While we were able to suggest several anti-inflammatory pathways that CS might act upon, the use of CS extract by all the studies in this review rather than isolated constituents somewhat clouded the exact mechanisms of action. CS extract is anti-inflammatory overall, even though it contains arachidonic acid, which is pro-inflammatory. While CS clearly has potential for treating inflammatory conditions, more work needs to be done on identifying and isolating the active constituents before exact mechanisms of action can be worked out. Proirities should lie in studying the active compounds which contributes to the pharmacological activities of CS extract. Future pre-clinical and clinical studies can be done using these compounds instead of the crude extract. The candidates for active constituents pointed out in this review will hopefully help in the search for future anti-inflammatory medications.