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Biotechnol Rep (Amst). 2020 Dec; 28: e00544.
Serratiopeptidase: Insights into the therapeutic applications
Swati B. Jadhav
aFood Application and Development Laboratory, Advanced Enzymes Technologies Ltd., Louiswadi, Thane, (westward)-400604, Republic of india
Neha Shah
bPulmonary Fibrosis Now! Chino, CA, 91710, United States
Ankit Rathi
aFood Awarding and Development Laboratory, Advanced Enzymes Technologies Ltd., Louiswadi, Thane, (due west)-400604, Bharat
cSpecialty Enzymes and Probiotics, Yorba Ave, Chino, CA, 91710, U.s.a.
Vic Rathi
aFood Application and Development Laboratory, Advanced Enzymes Technologies Ltd., Louiswadi, Thane, (w)-400604, Republic of india
cSpecialty Enzymes and Probiotics, Yorba Ave, Chino, CA, 91710, Usa
Abhijit Rathi
aNutrient Application and Development Laboratory, Advanced Enzymes Technologies Ltd., Louiswadi, Thane, (w)-400604, India
Received 2020 Aug 12; Revised 2020 Sep 29; Accustomed 2020 October 15.
Abstract
Therapeutic applications of enzymes have been widely accepted in clinical practices for decades. Proteolytic enzymes in particular, have been used for the treatment of diseases and disorders. Serratiopeptidase is a proteolytic enzyme having immense applications in therapeutic areas which accept been validated by several in vitro, in vivo, and clinical studies as well equally through anecdotal evidences. These applications are attributable to its versatile backdrop including anti-inflammatory, anti-biofilm, analgesic, anti-edemic, and fibrinolytic effects. The significant bear on of serratiopeptidase reported needs to exist backed by more scientific data. This review encompasses the details of therapeutic applications of serratiopeptidase based on available in vitro, in vivo, and clinical studies. We institute some stiff evidences regarding the efficacy of serratiopeptidase. However information on prophylactic, tolerability, and its mechanism of action need detailing. This review aims to further explore the bachelor literature on serratiopeptidase as well equally provide scientific details for existing applications.
Keywords: Serratiopeptidase, Therapeutic application, Anti-inflammatory, Anti-biofilm, Clinical study
one. Introduction
Enzymes are an essential part of nearly metabolic processes and are directly or indirectly important for the normal performance of the human body. They control many physiological functions such as digestion, metabolism, immune office, reproduction, and respiration. Enzymes are obtained from plant, creature, and microbial sources and currently used in clinical practices for the treatment and management of diverse diseases and disorders. Enzyme-based therapeutics is recently gaining more attention due to its selectivity, efficiency, and safety profile. The therapeutic efficacy of various enzymes including trypsin, chymotrypsin, papain, and bromelain has been proven [one]. Serratiopeptidase (serralysin/ serratia-protease/serrapeptidase) is a widely used proteolytic enzyme in therapeutic applications. Information technology has shown meaning anti-inflammatory, anti-edemic, and analgesic effects in various areas including surgery, orthopaedics, otorhinolaryngology, gynaecology, and dentistry [two]. It is well known amidst researchers for its caseinolytic (proteolytic) and fibrinolytic properties.
Serratiopeptidase is a zinc containing metalloprotease of molecular weight 45–lx kDa. The enzyme has an EC number 3.4.24.40 and belongs to the grouping Serralysin. Information technology is originally obtained from Serratia marcescens isolated from the intestine of the silkworm Bombyx mori L. Extensive review on analytical techniques used in the qualitative and quantitative analysis of serratiopeptidase has been published past [iii], where the authors pointed out a need for selective and specific techniques for the quantification of serratiopeptidase. A detailed review of existing evidences for serratiopeptidase has been reported by [4]. The major role of this enzyme against inflammation is well mapped in the review written by [1]. Other applications of serratiopeptidase in clinical practices majorly include breast affliction, atherosclerosis, Alzheimer's disease, sinusitis, hepatitis, lung disorders, and uterine fibroids [five].
This review is a comprehensive report of the therapeutic potential of serratiopeptidase likewise as its regulatory status. We accept included in vitro, in vivo, and clinical study reports as well as some unconcluded studies from different therapeutic areas to our best capacity. This review helps to elucidate the potential of serratiopeptidase as well as identify lacunas in using information technology to its full extent and hence, place areas of futurity inquiry (Fig. one).
Properties of serratiopeptidase contributing to its wide applications in therapeutics.
2. Role of enzymes in therapeutics
In 1964, de Duve get-go suggested use of enzymes as replacement therapy for genetic disorders [6]. With the emergence of novel diseases and failure of conventional treatments in certain conditions, enzyme-based therapeutics is playing an important role in the current century. Target specificity and multiple quick substrate conversion are ii primary properties which accept made enzymes successful and popular over non-enzymatic drugs in therapeutic areas. Enzymes are widely used to treat cancer, cardiovascular diseases, digestive disorders, wound debridement, lysosomal storage disease, inflammatory reaction, genetic disorders, and bleeding disorders [seven,8]. Several enzymes have been cited in literature for their therapeutic potential including collagenase, proteases, streptokinase, lysostaphin, laccase, glutaminase, and lipase [9]. Specifically, serine proteases have been used to treat blood vascular disorders; l-asparaginase and fifty,fifty-glutaminase have shown efficacy in the treatment of acute lymphoblastic leukemia; and caspases take been used for treating cancer and many classes of viruses [1].
Some obstacles in using enzymes in therapeutic applications include their large size making it difficult for distribution in the body, immunogenicity, short half-life, and impurities. Due to these factors, very few enzymes take been approved by the FDA despite their proven efficacy. Enzymes including altephase, reteplase, tenecteplase, urokinase, streptokinase, and anistreplase are FDA approved for the handling of cardiovascular diseases [8]. Few enzymes with notable divergent properties include serratiopeptidase, superoxide dismutase, adenosine deaminase, phenylalanine ammonia lyase, dornase, and rasburicase [8]. Our review highlights the therapeutic molecule serratiopeptidase and its wide clinical applications.
3. Serratiopeptidase
Conventionally, serratiopeptidase is produced from Serratia marcescens, a Gram negative opportunistic pathogen in nutrient rich growth medium. The details of production process and media optimization were explained in earlier review [5]. It has been shown to accept maximum activity at pH 9.0 and temperature 40 °C and is inactivated at 55 °C in 15 min [2]. It is stable in a wide range of pH (pH 3–10) as revealed in the circular dichroism written report, where it showed stable secondary construction [10]. The gene encoding serratiopeptidase is fabricated upward of 470 amino acids, devoid of sulfur containing amino acids. The enzyme is produced, purified, characterized and modeled using SWISS-MODEL past [11] where authors accept authenticated the structure past assessing the Ramachandran plot using PROCHECK server.
Soon, the demand of serratiopeptidase for the industry and pharmaceuticals is existence satisfied past wild or mutant strains of Serratia marcescens. However, the pathogenic nature of the organism and hazard associated with the bulk biomass released subsequently fermentation necessitates the enquiry on the development of recombinant molecule. Attempts take been carried out to limited serratiopeptidase genes in Escherichia coli using suitable vectors [5]. The failure of many of the attempts attributed to the unregulated intracellular expression of proteases causing prison cell lysis, growth inhibition, instability of the expression plasmids, lack of protein expression, or deposition of the proteins into non-functional misfolded aggregates [12]. Recently, [12] take demonstrated a production of recombinant serratiopeptidase in Escherichia coli successfully. Further, [13] have elucidated the optimized growth media and process atmospheric condition for the large scale production of the recombinant serratiopeptidase.
4. Application of serratiopeptidase in therapeutics
Serratiopeptidase has been used past healthcare professionals in Japan and Europe for therapeutic applications for decades. Recently the clinical use of serratiopeptidase solitary or in combination with other drugs is increasing worldwide.
4.i. Serratiopeptidase every bit an anti-inflammatory agent
Inflammation serves as a defense force mechanism confronting injury and infection. The immune system responds rapidly to any foreign substances equally well equally tissue injury by recruiting immune cells and inflammatory mediators to the target site. Hence, inflammation is considered to be the cleaning procedure of the body leading to maintenance of homeostasis [fourteen]. Based on the pathologic conditions of the tissue and intensity of the trigger, inflammation can be acute or chronic. Though acute inflammation is a protective measure out against injury or infection, failure of its resolution leads to chronic inflammation. Inflammatory disorders such as arthritis, sinusitis, bronchitis, fibrocystic breast disease, and carpal tunnel syndrome etc. are common worldwide. Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) alone or in combination with other drugs are prescribed to gainsay acute inflammation, whereas steroidal drugs are combined with NSAIDs to care for chronic inflammation [1]. The enormous limitations of these drugs accept necessitated research on other possible treatments, including natural molecules. Hence, enzyme-based drugs are at present popular in many therapeutic areas including inflammation.
Serine proteases are commonly used in therapeutic areas including inflammation. They were found to have high affinity for cyclooxygenases (COX-I and COX-Ii), central enzymes in the production of dissimilar inflammatory mediators. Serratiopeptidase was kickoff used for its anti-inflammatory effects in Japan in 1957 [1]. Further, many researchers have evaluated the potential of serratiopeptidase against inflammation in unlike therapeutic areas. It has too been used forth with other NSAIDs to achieve a combined effect. Though serratiopeptidase has been proven to be an effective anti-inflammatory molecule in many studies, efforts are needed to optimize its dose based on the application. The concentration of serratiopeptidase in the plasma was establish to vary with body mass. Hence, validated cross over studies and optimization are necessary steps to be taken before recommending and prescribing serratiopeptidase [fifteen].
4.ane.1. Pre-clinical and clinical studies
[16] compared the anti-inflammatory upshot of serratiopeptidase with aspirin and other proteolytic enzymes trypsin and chymotrypsin in albino rats against carrageenan induced paw edema. Serratiopeptidase showed meliorate anti-inflammatory activity alone also every bit showed a synergistic consequence with aspirin in both acute and subacute models of inflammation in rats. Another small pre-clinical report past [17] on 16 Charles Foster albino rats evaluated the anti-inflammatory effect of serratiopeptidase against diclofenac sodium. Serratiopeptidase at (10−20 mg/kg of torso weight) showed comparable results to that of diclofenac sodium (0.5 mg/kg) in inhibiting astute as well as chronic inflammation in mitt edema. The dosage of serratiopeptidase required was higher every bit compared to diclofenac. This may exist due to the low bioavailability of serratiopeptidase, which can be improved using a suitable commitment mode (explained in appropriate section of this review).
Ulcerative colitis is an inflammatory bowel disease caused by overstimulation or inadequate regulation of the mucosal immune arrangement, affecting rectal and colonic mucosa. [xviii] conducted an impactful study to test the potential of serratiopeptidase on acerb acid-induced ulcerative colitis in mice. Several inflammatory markers including C-reactive protein, myeloperoxidase, glutathione, and nitric oxide were examined, along with histopathological examination. Serratiopeptidase reduced the disease activity index and prevented colonic shortening, spleen enlargement, glutathione depletion, lipid peroxidation, and nitric oxide production every bit compared to the control group. Further, there was significant reduction in C-reactive protein level in serratiopeptidase treated mice as compared to command. Moreover, myeloperoxidase, an important enzyme marker of inflammation was reduced by serratiopeptidase treatment. These results confirm the anti-inflammatory potential of serratiopeptidase.
There is much clinical information available on the anti-inflammatory effects of serratiopeptidase on pain, swelling, and trismus, details of which are shown in Table 1.
Tabular array ane
Clinical studies in various therapeutic areas to evaluate efficiency of serratiopeptidase as an anti-inflammatory agent.
| Type of Inflammation | Treatment method (Drug(south) taken forth with oral administration of serratiopeptidase) | Elapsing of handling | Result | Adverse effect reported (Yes/No) | Reference |
|---|---|---|---|---|---|
| Genu osteoarthritis | Metformin | v months | -Reduced hurting score -Low level of Tumor necrosis factor blastoff (TNF-α), interleukin 1 beta (IL-1ß) and interleukin 8 (IL-viii) | No | Ateia et al. [19] |
| Acne vulgaris | Doxycycline with retin A cream application and panoxyl gel | 5 months | Combined therapy showed significantly rapid improvement in acne advent | – | Mikhael and Mohammed [xx] |
| Postoperative pain, swelling and trismus after surgical removal of mandibular third molars | Methylprednisolone | five days | Serratiopeptidase showed moderate analgesic activity just effective control of swelling and trismus compared to methylprednisolone | – | Chappi et al. [21] |
| Postoperative pain, swelling and trismus after surgical extraction of mandibular tertiary molars | – | vii days | Significant reduction in the occurrence of post-surgical swelling and hurting, but no upshot on postoperative trismus | No | Ai-Khateeb and Nusair [15] |
| Acute and chronic inflammation of otorhinolaryngology | – | seven−8 days | Rapid upshot with a significant improvement in symptoms | No | Mazzone et al. [22] |
| Swelling of the talocrural joint produced by supination trauma | – | 5 months | -Swelling decreased past fifty % on the third mail service-operative day, which was faster than the control grouping -Serratiopeptidase treated group was rapidly pain free compared to the command group | – | Esch et al. [23] |
| Postoperative buccal swelling (Caldwell-luc antrotomy) | – | 5 days | Serratiopeptidase treated patients showed bottom caste of swelling than placebo-treated patients at every point of observation | No | Tachibana et al. (1984) |
| Postoperative pain, swelling and trismus later surgical removal of mandibular third molars | – | 3 days | Serratiopeptidase showed proficient upshot on trismus only not on swelling and pain | – | Murugesan et al. [24] |
Nonetheless, some reports on manus showed comparatively lesser result of serratiopeptidase. In a study by [25] the efficacy and rubber of serratiopeptidase and seaprose S in the handling of venous inflammatory disease were compared. Seaprose S had a higher efficacy as compared to serratiopeptidase (85 % vs 65 %) with no adverse effects. Further, in this report, ane out of 20 patients that received serratiopeptidase showed mild gastrointestinal disturbance. [26] found insufficiently lesser analgesic and anti-inflammatory consequence of serratiopeptidase as compared to Betamethasone and Ibuprofen. Further, a combination of trypsin and chymotrypsin had a higher efficacy in wound management as compared to serratiopeptidase in a 75 patient study [27]. Contradictory results were observed in two independent studies done on a rat paw edema model. In a study by [28] comparison serratiopeptidase with diclofenac, serratiopeptidase treatment (5.4 mg/kg of trunk weight) did not result in significant comeback in the inflammation of paw edema. These results are not in agreement with those of [17] where serratiopeptidase (ten mg/kg of body weight) showed promising anti-inflammatory activity. The different dosages used in these ii studies make it difficult to draw conclusion.
Overall, serratiopeptidase can be seen every bit a promising candidate in modern medicine when used either alone or in combination with other agents, particularly in situations where NSAIDs exercise non testify satisfactory results (Table two, Table 3).
Table 2
In vitro studies of a combination of serratiopeptidase and antibiotics for biofilm treatment.
| Serratiopeptidase combinations with the antibiotics | Biofilms | Results | Reference |
|---|---|---|---|
| Ofloxacin | Staphylococcus epidermidis Pseudomonas aeruginosa | -Serratiopeptidase enhanced the activeness of ofloxacin and inhibited biofilm formation | Selan et al. [29] |
| Azithromycin | Bacterial biofilms growing on vascular graft surface | - Combination of serratiopeptidase and azithromycin was constitute to be very constructive confronting Stayphalococcus strains by showing less minimum inhibitory concentration (MIC) compared to other antibiotic treatments | Thaller et al. [30] |
| Ciprofloxacin | Staphylococcus aureus | - Combination of serratiopeptidase (fifty μg/mL) and ciprofloxacin at sub-MIC concentration cleared biofilm on catheter. | Gupta and Nagarsenke (2015) |
| Vancomycin and rifampicin | Methicillin resistant and methicillin susceptible strains of Southward. aureus | - Effective in dispersing biofilm independent of the strain of organism. | Hogan et al. [31] |
| Levofloxacin | Staphylococcus aureus | - Eradicated >90 % of the preformed biofilm - Combination showed synergistic activeness | Gupta et al. [32] |
Tabular array three
Fashion of delivery of serratiopeptidase for unlike applications.
| Mode of delivery (Entrapement/carrier) | Results | Reference |
|---|---|---|
| Serratiopeptidase loaded albumin nanoparticles | Entrapment efficiency and per centum drug release was constitute to exist 85 % and 79.3 % respectively | Kaur and Singh [33] |
| Encapsulation in liposome | Serratiopeptidase encapsulated in liposome forth with antibiotic levofloxacin helps in biofilm irradiation in S. aureus infected rat | Gupta et al. [32] |
| Clove oil emulsified buccal patch of serratiopeptidase | Significant entrapment efficiency was obtained forth with controlled released for 24h | Shende et al. [34] |
| Poly(D,L-lactic-co-glycolic acid) microspheres of serratiopeptidase and gentamicin entrapped into polyvinyl alcohol-gelatin hydrogel | -The developed commitment system is constructive in promoting natural debridement by hydrating necrotic tissue -It provides straight sustained release of antibiotics and serratiopeptidase for better and faster wound healing | Singh and Singh [35] |
| Serratiopeptidase loaded chitosan nanoparticles | -Sustained release upto 24h -Prolonged anti-inflammatory activity upto 32h | Republic of mali et al. [36] |
| Microsphere of serratiopeptidase in polymer Eudragit RS100 | Prolonged release of serratiopeptidase for sustained therapeutic consequence | Hire et al. [37] |
| Liposomal formulations of serratiopeptidase | -A maximum entrapment efficiency of 86 % was found -Liposomal formulation of serratiopeptidase improved its permeability every bit revealed by an in vitro study using PAMPA and caco-2 model | Sandhya et al. [38] |
| Serratiopeptidase transdermal patch past lipid-based transfersomes | -Entrapment efficiency was 96.76 % -In vitro and in vivo release was controlled and steady | Shende et al. [39] |
| Serratiopeptidase niosomal gel | -Maximum entrapment efficiency was 54.82 % with a consistent release design -Anti-inflammatory activity was comparable to that of diclofenac gel as revealed by in vivo efficacy written report | Shinde and Kanojiya [40] |
| Serratiopeptidase and metronidazole loaded on alginate microspheres past emulsification | -Practiced loading efficiency -Improved wound healing equally observed in in vivo testing in rabbits | Rath et al. [41] |
| Serratiopeptidase immobilized on amino-functionalized magnetic nanoparticles | -Immobilization increased permeation through the membrane as observed in in vitro studies -Immobilization reduced the dose of serratiopeptidase for anti-inflammatory effect as studied in a rat edema model | Kumar et al. [42] |
4.2. Serratiopeptidase as an anti-biofilm agent
Bacterial biofilms are multicellular structures of dense and highly hydrated communities of microorganisms embedded within a matrix of cocky-synthesised polymeric or proteinaceous material [43,44]. They can exist attached to biotic or abiotic surfaces. One of the characteristic properties of biofilms is high resistance to the adaptive and innate allowed systems also as tolerance to high concentrations of antibiotics/antimicrobial agents. This leads to persistent infection, making these entities a medical and economic nuisance [31]. They are associated with a variety of infections including urinary tract infections, chronic lung infections, endocarditis, osteomyelitis, chronic otitis media etc. [44]. Biofilms commonly develop on implants and medical devices like catheters, pacemakers, prosthetic joints, molar surfaces, and various host tissue surfaces leading to chronic infections [44]. They are nearly 100 times more resistant to antimicrobial agents as compared to individual bacterial colonies, thus leading to antibody handling failure.
Various strategies to provide a suitable solution to biofilm associated health issues including inhibition, dispersal, and apply of biofilm eradicating agents (antibiotics) take been attempted. Surface proteins and secreted proteins have establish to play an important office in biofilm germination, stability, and regulation [44]. Hence, proteases were hypothesized to be a potential treatment of biofilms, which was further supported past scientific studies. Proteases purified from unlike organisms have tested successfully confronting biofilm, with metalloproteases in particular, playing an important role [45]. Moreover, commercial proteases take also been successful in the eradication of biofilms [46,47]. Serratiopeptidase, a commercially available bacterial metalloprotease has proven to be effective against a variety of biofilm-associated medical conditions due to the following reasons:
-
1
Information technology can change the virulent phenotype of bacteria in biofilms [48,49]
-
2
Information technology is effective confronting mature biofilms [49]
-
3
It enhances the bactericidal effect of antibiotics against bacterial biofilms [fifty].
4.2.one. In vitro studies
Various in vitro studies evidence a positive bear upon of serratiopeptidase against biofilms. It affects a discrete number of proteins involved in fundamental mechanisms associated with bacterial virulence, such as adhesion, invasion, and biofilm formation [51]. Serratiopeptidase reduces prison cell surface proteins Ami4b, autolysin, internalinB, and ActA and hence reduces the ability of Listeria monocytogenes to grade biofilms and to invade host cells. This leads to the prevention of initial adhesion of Listeria monocytogenes to the human gut [52]. [48] tested the office of iii serine proteases (proteinase 1000, trypsin, and chymotrypsin) and two metalloproteases (serratiopeptidase and carboxypeptidase) against biofilm germination and in man jail cell invasion processes using different strains of Staphylococcus aureus and Staphylococcus epidermidis. Among all the proteases tested, only serratiopeptidase was plant to inhibit the activity of all the tested strains. It slightly affected the adhesion efficiency (20 %) but drastically reduced the invasion efficiency (200-fold) of Staphylococcus aureus. Serratiopeptidase neither afflicted bacterial viability nor showed whatever cytotoxic effects on the eukaryotic cell lines, alluding to its rubber.
A study of the anti-infective capability of serratiopeptidase against Staphylococcus aureus revealed its effects on a discrete number of surface proteins [49]. 1 such poly peptide is At1 which helps in internalization of staphylococcus in host cells, confirming that serratiopeptidase modulates adhesins and autolysins in Staphylococcus aureus. Further, the action of serratiopeptidase is not simply restricted to initial bacterial attachment on abiotic surface only is too effective on mature biofilms. The writer emphasised that serratiopeptidase hinders the entry of pathogens in human being tissue likewise as impairs adhesion of pathogens to prostheses, catheters, and medical devices.
[53] adult a mutant form of serratiopeptidase with no proteolytic activeness. The adult mutant was found to maintain anti-biofilm belongings, suggesting that this property is independent of the proteolytic activeness of serratiopeptidase. They concluded that serratiopeptidase is a potential antipathogenic amanuensis with or without proteolytic activeness and prevents the formation of biofilms on medical devices [53]. Further, authors suggested the need for enquiry to identify the mechanism of action of serratiopeptidase in biofilm regulation that is unrelated to proteolytic action. Recently, [54] evaluated the anti-biofilm ability of serratiopeptidase against Staphalococcus aureus infection on osteoblastic MG-63 cells. The pro-inflammatory chemokine MCP-one was used as an immunological marker. Serratiopeptidase impaired the invasion adequacy of Staphylococcus aureus in the osteoblastic cells and lowered the secretion of MCP-1. It is worthwhile to note that serratiopeptidase did not impact the viability or proliferation of the osteoblastic cells, indicating its safety in the handling of bone infection.
Further, combined treatment of serratiopeptidase with antibiotics is a novel approach in the treatment against bacterial biofilm infection. The combination has been shown to have synergistic effects. Serratiopeptidase is thought to work like a biological "nanodrill" and disrupt the bacterial biofilm membrane, thus paving the mode for antibiotics to act [32]. Serratiopeptidase was likewise shown to be more than effective as compared to other proteases [29].
4.2.two. Pre-clinical and clinical studies
In an in vivo study on threescore Sprague-Dawley rats, serratiopeptidase eradicated periprosthetic infection acquired by Staphylococcus epidermis [55]. Histological and microbiological testing revealed that 5.half-dozen % of rats showed infection in the serratiopeptidase + antibiotic treated group vs 37.5 % in the antibiotic alone treated group. The authors concluded that the anti-biofilm property of serratiopeptidase enhances the efficacy of antibiotics. The study reported adverse effects on joint cartilage and synovial tissue attributable to serratiopeptidase. However, the authors believe that serratiopeptidase apply is safe every bit shown in previous studies and commented that a lower dose may not show this adverse effect. Hence, enzyme dosage and awarding sites should be advisedly considered earlier using an enzyme-antibiotic combination handling.
Clinical studies of peri-implantitis are important, given the large number of implant surgeries being performed worldwide. Early diagnosis of peri-implantitis is difficult due to initial mild or no symptoms as well as lack of proper diagnostic tests. Antibiotic resistance is another obstacle in its treatment. Colonization of bacteria occurs at the surface of the implant, forming a biofim which causes severe inflammation of the peri-implant tissue and amercement the implant supporting bone. In a controlled study of 64 adults, [50] evaluated the combined effect of serratiopeptidase with antibiotics in peri-implantitis. The combined treatment significantly improved clinical, microbiological, and inflammatory parameters as compared to the control grouping. The authors concluded that serratiopeptidase enhanced the efficacy of antibiotics by increasing tissue concentration of the antibiotics [56,57]. A retrospective study in 544 patients was conducted past [58] on partially edentulous patients treated for peri-implantitis past evaluating clinical charts. The study indicated that serratiopeptidase helps in the repair of bone lesions and speeds up the clinical healing process. The authors strongly believe that the co-administration of serratiopeptidase with antibiotics to be a preferred option in peri-implantitis treatment.
4.iii. Other applications
The analgesic outcome of serratiopeptidase is widely known and has been reported in clinical studies. The ability of serratiopeptidase to hydrolyse bradykinin, histamine, and serotonin contributes to its analgesic action. Serratiopeptidase was found to relieve hurting in patients with root culvert treatment [59] and control toothache when emulsified with clove oil [34]. The analgesic activity of serratiopeptidase has also been proven in cases of surgical extraction of mandibular third molars reported past Al-Khateeb and Nusair, 2008.
A clinical trial by [60] on seventy patients with chest engorgement demonstrated that serratiopeptidase treatment resulted in moderate to marked improvement in breast pain, swelling, and induration with no adverse events reported. A prospective trial to explore the awarding of serratiopeptidase in the handling of carpel tunnel syndrome showed clinical comeback in 65 % of the patients [61]. Serratiopeptidase has been widely used in Japan as an anti-inflammatory and mucolytic agent. Airway mucus is a viscoelastic gel of import for the airway defense system. Notwithstanding, in chronic airway disease, increased secretion of mucus and decreased clearance causes its accumulation. [62] evaluated the effect of serratiopeptidase on viscosity and elasticity of nasal fungus in patients with chronic sinusitis. Serratiopeptidase was plant to reduce viscosity but not elasticity of the mucus. Farther, study done by [63] demonstrated that the Serrapeptidase could enhance fungus clearance in patients with chronic airway disease. This effect was attributed to the power of serratiopeptidase to reduce neutrophil count and alter viscoelasticity of the mucus.
Another innovative and interesting application is in the treatment of Alzheimer's affliction via reduction of amyloidosis. Serratiopeptidase was found to exist every bit effective as nattokinase (an enzyme shown to dethrone amyloid coarse) in relieving Alzheimer'southward affliction pathophysiology in a rat model [64]. Oral administration of an enzyme decreased brain acetylcholinesterase action, equally well as levels of transforming growth factor ß, Fas, and interleukin-half-dozen, all of which were significantly increased in patients with Alzheimer'due south illness. These results were confirmed by histological exam of encephalon tissue. This study demonstrates that serratiopeptidase tin can down-regulate the amyloidogenic pathway due to its proteolytic, anti-oxidant, and anti-amyloidogenic effects. The study was further supported past a recent reports [65,66] showing dissociation of insulin amyloids by serratiopeptidase both in vitro and in vivo. Amyloidosis is a event of misfolding of normal cellular poly peptide to protease resistant β-sheets making insoluble aggregates. These aggregates build up in the body and their clearance is highly difficult. The amyloid dissociation ability of serratiopeptidase was better than that of the standard amyloid dissociating amanuensis, nattokinase. This novel approach paves the style to explore the therapeutic potential of serratiopeptidase in different amyloid related disorders.
A combination therapy consisting of enteric coated Vitamin C, excerpt of Withaferania somnia, and serratiopeptidase has been used to treat thyroid cancer [67]. Consummate remission of thyroid tumor was found after 18 months of combination therapy. Serratiopeptidase plays an of import role in cleaning the expressionless cells from the target site leading to an increased rate of killing of tumor cells. This report further highlights the scope for injecting enzyme directly to the target site of a tumor to raise efficiency.
5. Machinery of activeness
Despite its wide therapeutic applications, the machinery of serratiopeptidase activeness has not been well elucidated.
Wound healing: Serratiopeptidase helps to thin the fluids in inflamed areas, thus facilitating drainage. This results in reduction of swelling, pain, and enhances tissue repair. Serratiopeptidase as well accelerates the healing procedure due to its unique property of dissolving dead tissue surrounding the injured area without harming living tissue. Further, it hydrolyses bradykinin, histamine, and serotonin which helps to decrease hurting and swelling and improve microcirculation, which in turn supports the wound healing procedure [68].
Anti-inflammatory: Serratiopeptidase acts equally an anti-inflammatory agent by regulating inflammatory cytokines and hence the onset of chronic inflammation. It significantly modifies cell adhesion molecules that guide inflammatory cells to the sites of inflammation. It promotes wound healing, repair, and restores the peel temperature at the target inflammation site. It should be noted that serratiopeptidase is more stable and has higher efficacy when used in combination with metallic ions like zinc and manganese [1].
Antibiofilm: The anti-biofilm ability of serratiopeptidase is accredited to its adequacy of modulating the expression of adhesion molecules and reduces cell surface proteins of bacteria [51]. Information technology prevents biofilm formation also as helps to disperse preformed biofilm. Its anti-biofilm ability helps to raise the penetration of antibiotics through the resistant biofilm and hence increases susceptibility of biofilms to antibiotics.
Fibrinolytic: Serratiopeptidase is known to dissolve blood clots and artherosclerotic plaques by breaking down fibrin and other dead or damaged tissue [2]. It can also remove deposits of fatty substances, cholesterol, and cellular waste inside the arteries. The fibrinolytic property of serratiopeptidase may as well assistance with the problems of thick blood, risk of stroke, and thrombophlebitis [1].
6. Assimilation and rubber of serratiopeptidase
Meagre literature is bachelor on the assimilation and condom of serratiopeptidase in the human body. It is known that orally taken serratiopeptidase gets absorbed through the intestine and transported into the claret. The intestinal absorption of serratiopeptidase has been tested in rats by evaluating its concentration in plasma, lymph, and inflammatory tissue extract using the sandwich enzyme immunoassay technique. The study showed that the concentration of serratiopeptidase in plasma and lymph is dose dependent. Meridian plasma concentration was reached at 0.25−0.5 h after intake and the enzyme was measurable upto half-dozen h [69]. Farther, [seventy] demonstrated that the concentration of serratiopeptidase was higher in inflammatory tissue that that of in plasma. The authors proposed that serratiopeptidase is absorbed from the intestine and distributed to inflammatory sites via blood or lymph. Serratiopeptidase forms a circuitous with plasma protease inhibitor alpha-1 macroglobulin in the ratio of 1:i as observed in a rat report [71]. This binding masks its antigenicity with twenty % retention of its original caseinolytic action. This complex helps to transport serratiopeptidase via claret to the target sites. The dosage of serratiopeptidase generally ranges from 10−threescore mg per day (2000/mg Unit of measurement activeness). Information technology is highly recommended to get a prescription for serratiopeptidase from health experts because its dosage requirement varies depending on the application and illness state.
Serratiopeptidase is a natural molecule that is being used for decades, hence unremarkably considered every bit safe. The safety of this enzyme in different areas of therapeutics is supported by several studies [xv,19,22,48,54,72] in which no side effects or adverse events were reported. Yet, some studies take reported adverse effects of this molecule, merely at a rare frequency. The explanation of the same has been provided above in the respective section of this review. Further, Stevens-Johnson syndrome [73] and buccal infinite abscess [74] have likewise been reported every bit side effects of this molecule. These side effects may exist dose dependent or possibly due to a combination effect when used with other drugs. Detailed, scientifically designed controlled clinical studies need to be conducted to further examine the safety profile.
vii. Mode of commitment of serratiopeptidase
Common issues associated with drug delivery are poor solubility, toxicity, instability, incompatibility, and poor penetration [75]. Each drug needs a suitable delivery system depending on its characteristics. Serratiopeptidase suffers high risk of enzymatic degradation in the gastrointestinal tract due to its proteinacious nature. Further, its hydrophilic nature causes low permeability through the intestinal membrane. These factors impose the use of a very high dosage for pregnant furnishings. Controlled and sustained released of serratiopeptidase is vital approach to decrease the frequency of dosing and to improve patient compliance. Hence, dissimilar delivery modes have been studied including magnetic nanoparticles, microspheres, encapsulation in liposomes, and emulsification. In vitro release profiles and in vivo efficacy are important parameters demand to be studied to develop suitable delivery modes.
New modes of commitment accept been evaluated in cases of dentistry and wound healing. Novel effective biocompatible moist system for complete wound management was studied by [35]. Poly(D,Fifty-lactic-co-glycolic acid) microspheres of serratiopeptidase and gentamicin were entrapped into polyvinyl booze-gelatin hydrogel. In vitro and in vivo studies showed the direct sustained release of serratiopeptidase forth with antibiotics at the wound site leading to a better and faster healing process. [76] developed a topical formulation of serratiopeptidase in the form of an ointment and a gel and evaluated its anti-inflammatory effects. The authors highlighted that topical application circumvents the drawbacks of oral commitment including anorexia, nausea, and GI disturbance, if any. An optimized formulation was evaluated for in vitro release contour and in vivo anti-inflammatory action where information technology showed satisfactory inhibition of ear edema in a rat report. The absence of any allergic reaction in rats supports the safety profile of the serratiopeptidase formulation. Enteric dispersion of serratiopeptidase with the polymer Eudragit has shown promising results for controlled release of the drug [37,77].
8. Regulatory aspects
Though serratiopeptidase is widely used in clinical practice around the globe, its regulatory status varies in dissimilar countries. The marketing and use of this molecule in any intended country needs approval past designated regulatory bodies. Background administrative, chemical science, pre-clinical and clinical data are needed for approving where quality, efficacy, and safety are important parameters to exist considered. Serratiopeptidase has been approved in Canada for utilize as an ingredient in dietary supplements to reduce pain and swelling [78]. In India, it is approved equally a pharmaceutical ingredient for the treatment of acute pain in combination with other drugs [80]. Regulatory authorities provide approval status for specific applications. Nevertheless, a few regulatory authorities take published approvals for serratiopeptidase to be used as a dietary supplement or every bit an active pharmaceutical ingredient as listed in Table 4.
Table four
Regulatory condition of serratiopeptidase in major global markets.
| State | Regulatory Agency | Approving status | Details | References |
|---|---|---|---|---|
| USA | U.S. Food & Drug Administration | New Dietary Ingredient Notification (NDIN) | NDIN# vi was filed by Specialty Enzymes & Probiotics | Dietary supplement health and teaching act (DSHEA) [81] |
| Drug Principal file (DMF) | DMF# 23,557 filed by Specialty Enzymes & Probiotics and DMF# 27,172 filed by Newgen Biotech | 21 Code of federal regulations (CFR) function- 314 | ||
| Canada | Health Canada | Natural health production (NHP) | -Enteric coated version is allowed. Can exist used for reduction in pain and swelling and to combat throat infections | NHP Ingredients Database: Serrapeptase [78] |
| Europe | European commission (EC) | Novel Food | Serratiopeptidase is considered as Novel Food. Safety evaluation is needed under 2015/2283 regulation | Regulation (European union) No. 2015/2283 |
| India | Central Drug Standard Control Organisation (CDSO) | Approved as agile pharmaceutical ingredient (API) | Serratiopeptidase is widely available. Information technology is generally sold in combination with other APIs. | The Drug and Cosmetic Act [lxxx] |
Too, in Japan, proprietor, Takeda has voluntarily withdrew serratiopeptidase in 2011 and then later, Singapore government has taken decision to stage out serratiopeptidase containing preparations equally medicinal products due to some controversial results of the trials and lack of noun scientific evidences [79].
Label/wellness claim guidelines demand to be followed for products containing serratiopeptidase as a dietary ingredient or pharmaceutical ingredient. The big claiming for manufactures and distributors is to understand the array of label claims that are allowed to be used for serratiopeptidase containing products. In the United States, dietary supplements can make structure/function statements [81]. However, regulatory agencies in Europe and Canada have special provisions to allow broader health claims. Those are approved nether regulation (EC) no. 1924/2006 in Europe and Nutrient and Drugs human action (department 30(j)) in Canada. Manufacturers need detailed case by instance evaluation of the canonical claims in each country before marketing serratiopeptidase.
9. Conclusion
The proteolytic enzyme serratiopeptidase is being widely used in the treatment of many diseases and disorders for decades across the world. In vitro studies, controlled, uncontrolled pre-clinical and clinical studies, and some anecdotal reports highlight its potential in the therapeutics. However, negative and controversial results obtained as well as some reports of mild to moderate side effects cannot exist overlooked. Hence, more research is needed to confirm its therapeutic potential, elucidate the mechanism(southward) of action also every bit safe of unlike doses and formulations. Well designed in vitro, in vivo, and clinical studies volition help to constitute the use of serratiopeptidase in diverse therapeutic areas.
Author contribution statement
The conception and design of the study: South. J and Abhijit R; acquisition of data, assay, and estimation of data: S. J, Ankit R, and N. S; Drafting the article: Southward. J, North. Southward, and Ankit R; revising the article critically for important intellectual content: N. S, S. J and V. R; final approval of the version to be submitted: V. R and Abhijit R.
Proclamation of Competing Interest
The authors report no declarations of involvement.
Acknowledgements
Authors are grateful to Advanced Enzymes Technologies Ltd., India for support.
References
ane. Tiwari One thousand. The role of serratiopeptidase in the resolution of inflammation. Asian J. Pharm. Sci. 2017;12:209–215. [PMC gratuitous article] [PubMed] [Google Scholar]
2. Santhosh K. The emerging role of serratiopeptidase in oral surgery: literature update. Asian J. Clin. Pharm. Res. 2018;11(three):xix–23. [Google Scholar]
3. Gupte V., Luthra U. Analytical techniques for serratiopeptidase: a review. J. Pharm. Anal. 2017;7(four):203–207. [PMC gratis article] [PubMed] [Google Scholar]
4. Bhagat Southward., Agarwal M., Roy 5. Serratiopeptidase: a systematic review of the existing prove. Int. J. Sur. 2013;11:209–217. [PubMed] [Google Scholar]
5. Ethiraj Due south., Gopinath Southward. Product, purification, label, immobilization, and application of Serrapeptase: a review. Front. Biol. 2017;12(5):333–348. [Google Scholar]
6. De Duve C. The significance of lysosome in pathology and medicine. Proc. Inst. Med. Chic. 1966;26:73–76. [PubMed] [Google Scholar]
7. Tasaka Chiliad., Meshi T., Akagi Grand., Kakimoto Thou., Saito R., Okada I., Maki M. Anti-inflammatory action of a proteolytic enzyme, Prozime-10. Pharmacology. 1980;21(1):43–52. [PubMed] [Google Scholar]
8. Kumar South.S., Abdulhammed Due south. Therapeutic enzymes. In: Sugathan S., Pradeep Due north.Southward., Adbulhammed S., editors. Bioresources and Bioprocess in Biotechnology. Springer; Singapore: 2017. pp. 45–73. [Google Scholar]
nine. Reshma C.V. Microbial enzymes: therapeutic applications. Microbiol. Res. J. Int. 2019;27(2):one–8. [Google Scholar]
10. Gupte V., Luthra U., Desai N. Circular dichroism as a process belittling tool to monitor the quality of serratiopeptidase. Int. J. Eng. Tech. Sci. Res. 2017;4(11):590–595. [Google Scholar]
eleven. Nageswara South., Guntuku G., Yakkali B. Purification, label, and structural elucidation of serralysin-like element of group i metalloprotease from a novel source. J. Gent. Eng. Biotechnol. 2019;17:1–fifteen. [PMC costless article] [PubMed] [Google Scholar]
12. Srivastava V., Mishra Due south., Chaudhuri T.G. Enhanced production of recombinant serratiopeptidase in Escherichia coli and its label every bit a potential biosimilar to native biotherapeutic counterpart. Microb. Jail cell Fact. 2019;18:215–230. [PMC free commodity] [PubMed] [Google Scholar]
13. Doshi P., Bhargava P., Singh V., Pathak C., Joshi C., Joshi M. Escherichia coli strain engineering for enhanced production of serratiopeptidase for therapeutic applications. Int. J. Biol. Macromol. 2020;160:1050–1060. [PubMed] [Google Scholar]
15. Ai-Khateeb T.H., Nusair Y. Effect of proteolytic enzyme serrapeptase on swelling, pain and trismus afterwards surgical extraction of mandibular third molars. Int. J. Oral Maxillofac. Surg. 2008;37:264–268. [PubMed] [Google Scholar]
16. Viswanatha Swamy A.H.Chiliad., Patil P.A. Effect of some clinically used proteolytic enzymes on inflammation in rats. Indian J. Pharm. Sci. 2008;seventy:114–117. [PMC free article] [PubMed] [Google Scholar]
17. Jadav S.P., Patel N.H., Shah T.G., Gajera Yard.V., Trivedi H.R., Shah B.K. Comparison of anti-inflammatory activity of serratiopeptidase and diclofenac in albino rats. J. Pharmacol. Pharmacother. 2010;1(two):116–117. [PMC free article] [PubMed] [Google Scholar]
eighteen. Rajinikanth B., Venkatachalam V.5., Manavalan R. Investigations on the potential of serratiopeptidase- a proteolytic enzyme, on acetic acrid induced ulcerative colitis in mice. Int. J. Pharm. Pharm. Sci. 2014;6(5):525–531. [Google Scholar]
xix. Ateia Y.A., Al-Edanni M.S.H., Al-Qurtas M.I. Impact of metformin and serratiopeptidase in obese patients with knee osteoarthritis. Int. J. Pharm. Pharm. Sci. 2018;10(2):37–41. [Google Scholar]
xx. Mikhael Due east.Chiliad., Mohammed Thou.Y. Serratiopeptidase a hope in a rapid and better improvement of inflammatory acne vulgaris. Iraqi. J. Pharm. Sci. 2012;21(1):78–81. [Google Scholar]
21. Chappi D.1000., Suresh Grand.5., Patil Chiliad.R., Desai R., Tauro D.P., Shiva Bharani Thousand.N.S., Parkar Grand.I., Babaji H.V. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae later lower third molar surgery. J. Clin. Exp. Dent. 2015;7:217–222. [PMC gratuitous article] [PubMed] [Google Scholar]
22. Mazzone A., Catalani M., Costanzo Thousand., Drusian A., Mandoli A., Russo S., Guarini E., Vesperini M. Evaluation of serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-bullheaded, randomized trial versus placebo. J. Int. Med. Res. 1990;xviii:379–388. [PubMed] [Google Scholar]
23. Esch P.Yard., Gerngross H., Fabian A. Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle articulation in handling with serrapeptase - A prospective report. Fortschr. Med. 1989;10(4):67–72. 107. [PubMed] [Google Scholar]
24. Murugesan M., Sreekumar K., Sabapathy B. Comparing of the roles of Serration peptidase and dexamethasone in the control of inflammation and trismus post-obit impacted third tooth surgery. Indian J. Dent. Res. 2012;23:709–713. [PubMed] [Google Scholar]
25. Bracale K., Selvetella L. Clinical study of the efficacy of and tolerance to seaprose S in inflammatory venous disease. Controlled study versus serratio-peptidase. Minerva. Cardioangiol. 1996;44:515–524. [PubMed] [Google Scholar]
26. Chopra D., Rehan H.S., Mehra P., Kakkar A.K. A randomized, double-blind, placebo- controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction hurting model. Int. J. Oral Maxillofac. Surg. 2009;38:350–355. [PubMed] [Google Scholar]
27. Chandanwale A., Langade D., Sonawane D., Gavai P. A randomized, clinical trial to evaluate efficacy and tolerability of trypsin:chymotrypsin as compared to serratiopeptidase and trypsin:bromelain:rutoside in wound management. Adv. Ther. 2017;34(1):180–198. [PubMed] [Google Scholar]
28. Joshi Yard.Thou., Nerurkar R.P. Anti-inflammatory outcome of the serratiopeptidase- rationale or fashionable: a study in rat paw oedema model induced past the carrageenan. Indian J. Physiol. Pharmacol. 2012;56(4):367–374. [PubMed] [Google Scholar]
29. Selan 50., Berlutti F., Passariello C., Comodi-Ballanti Grand.R., Thaller M.C. Proteolytic enzymes: a new handling strategy for prosthetic infections? Antimicrob. Agents Chemother. 1993;37:2618–2621. [PMC free article] [PubMed] [Google Scholar]
thirty. Thaller G.C., Selan L., Fiorani P., Passariello C., Rizzo L., Speziale F. A comparative in vitro evaluation of unlike therapeutic protocols for vascular graft infections. Eur. J. Vasc. Endovasc. Surg. 1997;fourteen:35–37. [PubMed] [Google Scholar]
31. Hogan S., Zapotoczna M., Stevens N.T., Humphreys H., O'Gara J.P., O'Neill E. Potential apply of targeted enzymatic agents in the handling of Staphylococcus aureus biofilm-related infections. J. Hosp. Infect. 2017;96(ii):177–182. [PubMed] [Google Scholar]
32. Gupta P.V., Nirwane A.Thousand., Bellubi T., Nagarsenker Chiliad.S. Pulmonary commitment of synergistic combination of fluoroquinolone antibiotic complemented with proteolytic enzyme: a novel antimicrobial and antibiofilm strategy. Nanomedicine. 2017;13(seven):2371–2384. [PubMed] [Google Scholar]
33. Kaur H., Singh A. Design, development and characterization of serratiopeptidase loaded albumin nanoparticles. J. App. Pharm. Sci. 2015;v(two):103–109. [Google Scholar]
34. Shende P.K., Gaud R.S., Bakal R., Yeole Y. Clove oil emulsified buccal patch of serratiopeptidase for controlled release in toothache. J. Bioequiv. 2016;8:134–139. [Google Scholar]
35. Singh D., Singh M.R. Development of antibiotic and debriding enzyme-loaded PLGA microspheres entrapped in PVA-gelatin hydrogel for complete wound management. Artif. Cell. Blood Sub. Biotechnol. 2012;forty(5):345–353. [PubMed] [Google Scholar]
36. Mali N., Wavikar P., Vavia P. Serratiopeptidase loaded chitosan nanoparticles by polyelectrolyte complexation: in vitro and in vivo evaluation. AAPS Pharm. Sci. Tech. 2015;xvi(one):59–66. [PMC free commodity] [PubMed] [Google Scholar]
37. Hire Due north.N., Deore A.B., Derle D.Five., Nathe R. Formulation and evaluation of serratiopeptidase microspheres using eudragit rs100 polymer. World J. Pharm. Res. 2014;3(2):3207–3218. [Google Scholar]
38. Sandhya 1000.V., Devi G.S., Mathew S.T. Liposomal formulations of serratiopeptidase: in vitro studies using PAMPA and Caco-two models. Mol. Pharm. 2008;5(1):92–97. [PubMed] [Google Scholar]
39. Shende P.G., Bakal R.50., Gaud R.S., Batheja M.N., Kawadiwale M.S. Modulation of serratiopeptidase transdermal patch past lipid-based transfersomes. J. Adhes. Sci. Technol. 2015;29(23):2622–2633. [Google Scholar]
40. Shinde U.A., Kanojiya S.S. Serratiopeptidase niosomal gel with potential in topical delivery. J. Pharm. 2014:1–10. [PMC gratis article] [PubMed] [Google Scholar]
41. Rath G., Johal Eastward.Southward., Goyal A.Thou. Development of serratiopeptidase and metronidazole based alginate microspheres for wound healing. Artif. Cells Blood Substit. Immobil. Biotechnol. 2011;39(1):44–50. [PubMed] [Google Scholar]
42. Kumar Due south., Jana A.K., Dhamija I., Singla Y., Maiti 1000. Training, characterization and targeted delivery of serratiopeptidase immobilized on amino-functionalized magnetic nanoparticles. Eur. J. Pharm. Biopharm. 2013;85:413–426. [PubMed] [Google Scholar]
43. Gupta P.V., Nagarsenker Chiliad.S. Antimicrobial and antibiofilm action of enzybiotic against Staphylococcus aureus. In: Mendez-Vilas A., editor. The Boxing Against Microbial Pathogens: Bones Scientific discipline, Technological Advances and Educational Programs. Formatex Inquiry Center; 2015. pp. 364–372. [Google Scholar]
44. Mukherji R., Patil A., Prabhune A. Office of extracellular proteases in biofilm disruption of gram positive bacteria with special emphasis on Staphylococcus aureus biofilms. Enz. Eng. 2015;4(1) [Google Scholar]
45. Saggu Due south.G., Jha Thou., Mishra P.C. Enzymatic degradation of biofilm past metalloprotease from Microbacterium sp. SKS10. Front end. Bioeng. Biotech. 2019;seven:192. [PMC gratuitous article] [PubMed] [Google Scholar]
46. Elchinger P.H., Delattre C., Faure S., Roy O., Badel South., Bernardi T., Taillefumier T., Michaud P. Effect of proteases confronting biofilms of Staphylococcus aureus and Staphylococcus epidermidis. Lett. Appl. Microbiol. 2014;59:507–513. [PubMed] [Google Scholar]
47. Molobela I.P., Cloete T.E., Beukes M. Protease and amylase enzymes for biofilm removal and degradation of extracellular polymeric substances (EPS) produced by Pseudomonas fluorescens bacteria. Afr. J. Microbiol. Res. 2010;four(14):1515–1524. [Google Scholar]
48. Artini M., Papa R., Scoarughi Yard.L., Galano E., Barbato One thousand., Pucci P., Selan L. Comparison of the activeness of different proteases on virulence backdrop related to the staphylococcal surface. J. Appl. Microbiol. 2013;114(1):266–277. [PubMed] [Google Scholar]
49. Papa R., Artini M., Cellini A., Tilotta Grand., Galano E., Pucci P., Amoresano A., Selan L. A new anti-infective strategy to reduce the spreading of antibody resistance past the action on adhesion-mediated virulence factors in Staphylococcus aureus. Microb. Pathog. 2013;63:44–53. [PubMed] [Google Scholar]
50. Passariello C., Lucchese A., Pera F., Gigola P. Clinical, microbiological and inflammatory bear witness of the efficacy of combination therapy including serratiopeptidase in the treatment of periimplantitis. Eur. J. Inflam. 2012;10(3):463–472. [Google Scholar]
51. Selan 50., Artini M., Papa R. Compounds from natural sources for new diagnostics and drugs against biofilm infections. In: Dhanasekaran D., editor. Microbial Biofilms - Importance and Applications. 2016. pp. 487–509. [Google Scholar]
52. Longhi C., Scoarughi K.L., Poggiali F., Cellini A., Carpentieri A., Seganti L., Pucci P., Amoresano A., Cocconcelli P.S., Artini M., Costerton J.Westward., Selan L. Protease treatment affects both invasion ability and biofilm formation in Listeria monocytogenes. Microb. Pathog. 2008;45(1):45–52. [PubMed] [Google Scholar]
53. Selan Fifty., Papa R., Tilotta M., Vrenna G., Carpentieri A., Amoresano A., Pucci P., Artini One thousand. Serratiopeptidase: a well-known metalloprotease with a new non-proteolytic activity confronting South. aureus biofilm. BMC microbial. 2015;15:207. [PMC gratuitous article] [PubMed] [Google Scholar]
54. Selan L., Papa R., Ermocida A., Cellini A., Ettorre Eastward., Vrenna Chiliad., Campoccia D., Montanaro Fifty., Arciola C.R., Artini M. Serratiopeptidase reduces the invasion of osteoblasts by Staphylococcus aureus. Int. J. Immunopath. Pharm. 2017;30(4):423–428. [PMC free article] [PubMed] [Google Scholar]
55. Mecikoglu M., Saygi B., Yildirim Y., Karadag-Saygi E., Ramadan S.South., Esemenli T. The effect of proteolytic enzyme serratiopeptidase in the handling of experimental implant-related infection. J. Os Joint Surg. Am. 2006;88(6):1208–1214. [PubMed] [Google Scholar]
56. Aratani H., Tateishi H., Negita Due south. Studies on the distribution of antibiotics in the oral tissues: Experimental staphyloccal infection in rats, and effect of serratiopeptidase on the distribution of antibiotics. Jpn. J. Antibiot. 1980;33:623–635. [PubMed] [Google Scholar]
57. Ishihara Y., Kitamura S., Takaku F. Experimental studies on distribution of cefotiam, a new beta-lactam antibiotic, in the lung and trachea of rabbits. II. Combined effects with serratiopeptidase. Jpn. J. Antibiot. 1983;36:2665–2670. [PubMed] [Google Scholar]
58. Sannino G., Gigola P., Puttini Chiliad., Pera F., Passariello C. Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis. Int. J. Immunopathol. Pharmacol. 2013;26(three):825–831. [PubMed] [Google Scholar]
59. Mane P., Atre K., Mayee R. Comparison between the hurting relieving action of serratiopeptidase, NSAIDs and combination of both in the root canal treatment patients. Int. J. Curr. Res. Rev. 2011;three:eleven–17. [Google Scholar]
sixty. Kee W.H., Tan Southward.L., Lee Five., Salmon Y.One thousand. The treatment of breast engorgement with Serrapeptase (Danzen); a randomized double-blind controlled trial. Singapore Med. J. 1989;thirty:48–54. [PubMed] [Google Scholar]
61. Panagariya A., Sharma A.K. A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome. J. Assoc. Physicians India. 1999;47:1170–1172. [PubMed] [Google Scholar]
62. Majima Y., Inagaki M., Hirata Chiliad., Takeuchi K., Morishita A., Sakakura Y. The event of an orally administered proteolytic enzyme on the elasticity and viscosity of nasal mucus. Curvation. Otorhinolaryngol. 1988;244:355–359. [PubMed] [Google Scholar]
63. Nakamura S., Hashimoto Y., Mikami M., Yamanaka E., Soma T., Hino Thousand., Azuma A., Kudoh S. Outcome of the proteolytic enzyme serrapeptase in patients with chronic airway disease. Respirology. 2003;8:316–320. [PubMed] [Google Scholar]
64. Fadl N.Northward., Ahmed H.H., Booles H.F., Sayed A.H. Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model. Hum. Exp. Toxicol. 2013;32(seven):721–735. [PubMed] [Google Scholar]
65. Metkar S.One thousand., Girigoswami A., Murugesan R., Girigoswami Yard. In vitro and in vivo insulin amyloid degradation mediated by Serratiopeptidase. Mater. Sci. Eng. C. 2017;seventy:728–735. [PubMed] [Google Scholar]
66. Metkar S.One thousand., Girigoswami A., Vijayashree R., Girigoswami Chiliad. Attenuation of subcutaneous insulin induced amyloid mass in vivo using lumbrokinase and serratiopeptidase. Int. J. Biol. Macromol. 2020;163:128–134. [PubMed] [Google Scholar]
67. Jentschura U.D. Enzyme-supported immunotherapy: example written report and possible generalizations. J. Cancer Ther. 2018;ix:156–162. [Google Scholar]
68. Desser 50., Rehberger A., Kokron E., Paukovits W. Cytokine synthesis in human peripheral claret mononuclear cells later on oral administration of polyenzyme preparations. Oncology. 1993;50:403–407. [PubMed] [Google Scholar]
69. Moriya N., Nakata Chiliad., Nakamuma M., Takaoka M., Iwasa S., Kato G., Kakinuma A. Intestinal absorption of serrapeptase (TSP) in rats. Biotechnol. Appl. Biochem. 1994;20:101–108. [PubMed] [Google Scholar]
70. Moriya N., Shoichi A., Yoko H., Fumio H., Yoshiaki K. Abdominal absorption of serrapeptase and its distribution to the inflammation sites. Japan Pharmacol. Therap. 2003;31:659–666. [Google Scholar]
71. Kakinuma A., Moriya N., Kawahara M., Sugino H. Repression of fibrinolysis in scalded rats by administration of serratia protease. Biochem. Pharmaco. 1982;31:2861–2866. [PubMed] [Google Scholar]
72. Tachibana M., Mizukoshi O., Harada Y., Kawamoto K., Nakai Y. A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling. Pharmatherapeutica. 1984;iii:526–530. [PubMed] [Google Scholar]
73. Moitra S., Sen S., Banerjee I., Das P., Tripathi S.K. Diclofenac- Serratio peptidase combination induced stevens–Johnson syndrome - A rare case report with review of literature. J. Clin. Diagn. Res. 2014;8:8–11. [PMC costless article] [PubMed] [Google Scholar]
74. Rajaram P., Bhattacharjee A., Ticku Due south. Serratio peptidase - A crusade for spread of infection. J. Clin. Diagn. Res. 2016;ten:31–32. [PMC free article] [PubMed] [Google Scholar]
75. Patel 5.R., Agarwal Y.K. Nanosuspension: an approach to enhance solubility of drug. J. Adv. Pharm. Technol. Res. 2011;2:81–87. [PMC free commodity] [PubMed] [Google Scholar]
76. Nirale Due north.Chiliad., Menon Grand.D. Topical formulations of serratiopeptidase: evolution and pharmacodynamic evaluation. Indian J. Pharm. Sci. 2010;72(1):65–71. [PMC gratis article] [PubMed] [Google Scholar]
77. Rani A.P., Uppala A. Enteric dispersion of serratiopeptidase with eudragit L100 and conception of controlled release tablets of serratiopeptidase. Int. J. Pharm. Tech. Res. 2019;12(ii):139–144. [Google Scholar]
79. HSA, Singapore, https://www.hsa.gov.sg/about-u.s.a..
80. List of approved drug combinations with CDSO, India. https://cdscoonline.gov.in/CDSCO/Drugs.
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