Bromelain is the general term used for a complex group of proteolytic enzymes such as proteases, proteinases, and peptidases, present in the tissues of the Bromeliaceae plant family. The most prominent plant belonging to this family is the pineapple (Ananas comosus)(Hikisz & Bernasinska-Slomczewska, 2021; Varilla et al., 2021).
Bromelain is the primary and most abundant protease of Ananas comosus. This protein-digesting enzyme is a crude aqueous extract, found in the stem and fruit of pineapple, called Stem bromelain(SBM) and Fruit bromelain(FBM) respectively. The SBM contains a high percentage of commercially extractable proteolytic enzymes hence SBM is widely used for therapeutic and commercial purposes. The bromelain extract, in addition to various thiol endopeptidases, also contains other components such as phosphatases, glucosidase, cellulases, peroxidases, glycoproteins, carbohydrates, several protease inhibitors, and organically bound Ca2+(Hikisz & Bernasinska-Slomczewska, 2021).
Commercial bromelain is usually extracted from SBM through ultrafiltration, centrifugation, lyophilization, and two-step Fast Protein Liquid Chromatography (FPLC) (Chakraborty et al., 2021). After extraction, the enzyme is purified through membrane filtration, an Aqueous two-phase system (ATPS), different chromatographic processes and reverse micellar systems(Varilla et al., 2021).
Therapeutic Importance of Bromelain
Bromelain, a phytotherapeutic drug, has been proved to have an essential role as an anti edematous, fibrinolytic, anticancer, anti-inflammatory, anticoagulant, and antithrombotic agent. Additionally, it poses beneficial effects owing to its analgesic properties that can help to heal and decrease post-surgical pain and swelling. (Varilla et al., 2021) Evidence also supports the role of bromelain as a primary therapeutic agent for skin ailments, such as burns, infections, and skin debridement, as well as in the formulation of vaccines and antitumor agents. (Varilla et al., 2021) It is also used as adjunctive therapy for chronic inflammatory, malignant, and autoimmune disorders(Varilla et al., 2021). Bromelain tends to improve bioavailability and lowers the adverse effects of different antibiotics (Ahmad et al. 2007, Bhattacharya et al., 2009; Pavan et al., 2012; Arefin et al., 2020).
Bromelain as a Potential Treatment of COVID-19
COVID-19 is a serious viral infection that can lead to multi-organ failure and subsequent death through the devastating effects of oxidative damage, cytokine storm, and coagulopathy caused by the SARS-COV-2 virus.(Serkan et al., 2021) Based on the available scientific data, and the pharmacological properties of Bromelain, this enzyme has been shown to have potential benefits as a supportive and prophylactic treatment of COVD-19 disease.(Chakraborty et al., 2021; Hikisz & Bernasinska-Slomczewska, 2021)
The SARS-CoV-2 attaches to the host receptor ACE2 by the spike protein (S) on its surface. The binding of SARS-CoV-2 to the angiotensin-converting enzyme-2(ACE2) receptor initiates three main mechanisms: (1) the inflammatory response subsequently terminating into Cytokine Storm Syndrome, (2) the coagulation which may cause DIC, and (3) the bradykinin cascade activation. The activation of these pathways leads to a wide range of clinical complications of COVID-19, from asymptomatic to severe acute respiratory distress syndrome, multiple organ failure, and death. (Hikisz & Bernasinska-Slomczewska, 2021)
Akhter et al. established that bromelain used alone (50 and 100 µg/mL) or in combination with acetylcysteine (50 and 100 µg/20 mg/mL) can interrupt the structural conformation of spike and envelope proteins of the SARS-CoV-2 virus thus preventing the virus attachment to ACE2 receptors and inhibiting clinical complications caused by the deadly virus (Hikisz & Bernasinska-Slomczewska, 2021).
Bromelain has the potential to be an effective health supplement(Varilla et al., 2021). Since Bromelain has a great safety profile, it can be used in combination or as an alternative to various artificially manufactured medicines(Chakraborty et al., 2021). After oral administration, bromelain is thoroughly stored in the body and retains a healthy efficacy and safety even after an extended duration of use.
Extra bromelain cannot be obtained by consuming more pineapples as the inedible stem contains the highest content of the overall bromelain(Chakraborty et al., 2021). Hence commercial preparations such as BIOTEX BROMELAIN Vegetable Capsules, 500mg are readily available. The toxicity studies of Bromelain indicate the lethal dose LD50 is greater than 10 g/kg in mice and after daily administration of bromelain up to 750 mg/kg in dogs, no toxicity was reported after six months. Rats showed no carcinogenic or teratogenic effects even at a high dose of 1500 mg/kg per day. No change in food intake, or pathophysiology of heart, kidney, spleen, growth, or hematological parameters were observed due to bromelain administration(Chakraborty et al., 2021). Hence the BIOTEX BROMELAIN commercial preparation is found to be safe in efficacy and safety profile.
Arefin, P., Habib, S., Arefin, A., & Arefin, S. (2020). A review of clinical uses of bromelain and concerned purification methods to obtain its pharmacological effects efficiently. International Journal of Pharmaceutical Research, 12(July), 469–478. https://doi.org/10.31838/ijpr/2020.SP1.066
Chakraborty, A. J., Mitra, S., Tallei, T. E., Tareq, A. M., Nainu, F., Cicia, D., Dhama, K., Emran, T. Bin, Simal-Gandara, J., & Capasso, R. (2021). Bromelain a potential bioactive compound: A comprehensive overview from a pharmacological perspective. Life, 11(4), 1– 26. https://doi.org/10.3390/life11040317
Hikisz, P., & Bernasinska-Slomczewska, J. (2021). Beneficial properties of bromelain. Nutrients, 13(12). https://doi.org/10.3390/nu13124313
Serkan, S., Ayliz, V.-O., & Ahmet Ozer, S. (2021). Bromelain: A potential therapeutic application in SARS-CoV-2 infected patients. Annals of Antivirals and Antiretrovirals, 5, 015–018. https://doi.org/10.17352/aaa.000011
Varilla, C., Marcone, M., Paiva, L., & Baptista, J. (2021). Bromelain, a group of pineapple proteolytic complex enzymes (Ananas comosus) and their possible therapeutic and clinical effects. a summary. Foods, 10(10). https://doi.org/10.3390/foods10102249