Association between chemosensory dysfunctions and inflammatory biomarkers in patients with SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: There is evidence that chemosensory dysfunctions, including smell and taste disorders, are common findings in patients with SARS-CoV-2 infection. However, the underlying biological mechanisms and the role of inflammatory markers are still poorly understood. AIM: To investigate the inflammatory biomarkers levels in patients with COVID-19 presenting chemosensory dysfunctions. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic literature search was performed from January 1, 2020, to May 12, 2022. Observational studies that provided data on hematological, biochemical, infection-related indices and cellular immunity, and coagulation function in patients with COVID-19 experiencing smell and/or taste disorders were considered eligible. Effect sizes were reported as standardized mean difference (SMD) with 95% confidence intervals (CI). A negative effect size indicated that the inflammatory biomarker levels were lower among patients with chemosensory dysfunctions. RESULTS: Eleven studies were included. Patients with chemosensory disturbances had lower levels of leukocytes (SMD - 0.18, 95% CI - 0.35 to - 0.01, p = 0.04), lactate dehydrogenase (SMD - 0.45, 95% CI - 0.82 to - 0.09, p = 0.01), IL-6 (SMD - 0.25, 95% CI - 0.44 to - 0.06, p < 0.01), and C-reactive protein (SMD - 0.33, 95% CI - 0.58 to - 0.08, p < 0.01) than patients without chemosensory disturbances. CONCLUSION: Patients with SARS-CoV-2 infection who have olfactory and gustatory disorders have a lower inflammatory response than patients who do not have chemosensory alterations. The presence of these symptoms may indicate a more favorable clinical course for COVID-19.

Antinociceptive effect of Aristolochia trilobata stem essential oil and 6-methyl-5-hepten-2yl acetate, its main compound, in rodents.

Aristolochia trilobata L. is an aromatic plant, popularly known as "mil-homens", and its essential oil (EO) is generally used to treat colic, diarrhea and dysentery disorders. We evaluated the antinociceptive effect of A. trilobata stem EO and of its major compound, the (R)-(-)-6-methyl-5-hepten-2-yl acetate (sulcatyl acetate: SA), using acetic acid (0.85%)-induced writhing response and formalin-induced (20 µL of 1%) nociceptive behavior in mice. We also evaluated the EO and SA effect on motor coordination, using the rota-rod apparatus. EO (25, 50 and 100 mg/kg) or SA (25 and 50 mg/kg) reduced nociceptive behavior in the writhing test (p<0.001). EO (100 mg/kg) and SA (25 and 50 mg/kg) decreased the nociception on the first phase of the formalin test (p<0.05). On the second phase, EO (25: p<0.01; 50: p<0.05 and 100 mg/kg: p<0.001) and SA (25 and 50 mg/kg; p<0.001) reduced the nociceptive response induced by formalin. EO and SA were not able to cause changes in the motor coordination of animals. Together, our results suggest that EO has an analgesic profile and SA seems to be one of the active compounds in this effect.

Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice.

The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions.

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines.

CONTEXT: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment. OBJECTIVE: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

H. pectinata (L.) Poit - Traditional uses, phytochemistry and biological-pharmacological activities in preclinical studies: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: H. pectinata (L.) Poit, popularly known as "sambacaitá" or "canudinho", is a plant endemic to north-eastern Brazil. Its aerial parts, leaves and flowers have traditionally been used to treat gastrointestinal disorders, rhinopharyngitis, nasal congestion, bacterial and fungal infections, fever, colic, inflammation, and pain. AIM OF THE STUDY: The aim of this review was to provide information on the botanical characteristics, ethnomedicinal uses, phytochemistry and biological-pharmacological activities of H. pectinata. MATERIALS AND METHODS: This systematic review followed the Cochrane Handbook Collaboration and the PRISMA guidelines. The review question was what are the biological-pharmacological activities of H. pectinata presented in non-clinical studies. The search for articles was conducted in the Medline (via PubMed), Embase, Web of Science, Scopus, Virtual Health Library, SciELO, Google Scholar and the Brazilian Digital Library of Theses and Dissertations databases. Two reviewers independently selected the studies that met the inclusion criteria, extracted the data, and assessed the risk of bias of the included studies. RESULTS: 39 articles were included in this review, of which 19 reported in vitro experiments, 16 in vivo studies and 4 in vivo and in vitro experiments. H. pectinata is a plant widely used in folk medicine in north-eastern Brazil for the treatment of various ailments, such as respiratory diseases, gastrointestinal disorders, bacterial and fungal infections, and general inflammation. Supporting its popular use, several in vitro and in vivo pharmacological investigations of the essential oil and extract of H. pectinata have demonstrated their anti-inflammatory, antinociceptive, antioxidant, antidepressant, anticancer, hepatoregenerative, healing, and antimicrobial activities. H. pectinata has been reported to contain 75 bioactive constituents, comprising 9 flavonoids, 54 terpenes, and 12 other compounds. CONCLUSION: H. pectinata is a plant commonly used in traditional medicine. Phytochemically, it contains several bioactive constituents, including terpenes and flavonoids, and has been shown to have antinociceptive, anti-inflammatory, antimicrobial and antitumour activity, as well as hepatorregenerative and healing effects, and low toxicity.

Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice.

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P < 0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P < 0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.

Hecogenin and its derivates: A pharmacology review.

Despite the several uses of drugs from natural compounds in the pharmaceutical industry, new molecules have been discovered and associated with pharmacological activities over the years. Hecogenin, a steroidal saponin, has been the subject of several studies due to reports of pharmacological activities. This study combines the articles published to date that show the pharmacological activity and the mechanism of action of hecogenin, its acetate, and its derivates. This compilation shows that the compounds can act in different pathologies that affect many systems of the human body. They showed pharmacological properties in inflammation, mediating cytokines, cells, and environment. Also, it participated in tumoral processes by pathways like PPGARγ, ERK½, and MMP-2 and showed antimicrobial effects against organisms like Candida and Aedes aegypti's larvae. This review indicates that continuing studies with these molecules are essential once they have the potential to be a future drug.

Health functions and related molecular mechanisms of Miconia genus: A systematic review.

The Miconia genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on in vivo and in vitro studies focusing on the therapeutic potentials and related molecular mechanisms of the Miconia genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the Miconia genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords 'Miconia', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus Miconia were examined in 18 in vitro studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight in vivo studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1ß, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus Miconia are safe for consumption. Miconia albicans Sw.Triana and Miconia rubiginosa (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.

Prevalence of SARS-CoV-2 infection among urban cleaning and solid waste management workers during transmission of the Omicron variant in Brazil.

This study estimated the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in urban cleaning and solid waste management workers during the transmission of the Omicron variant in one of the poorest regions of Brazil (the state of Sergipe). Nasopharyngeal swabs were collected from 494 workers, and the presence of SARS-CoV-2 RNA was tested by quantitative reverse-transcriptase polymerase chain reaction. Data on socio-demographic characteristics, comorbidities, vaccination status, mask use, and use of public transport to commute to the workplace were collected. The prevalence with a 95% confidence interval (CI) was calculated from the proportion of SARS-CoV-2 positive cases among the total number of individuals tested. The prevalence ratio (PR) with a 95% CI was the measure of association used to evaluate the relationship between SARS-CoV-2 infection and the exposure variables. The prevalence of SARS-CoV-2 infection was 22.5% (95% CI, 19.0 to 26.4). Individuals under the age of 40 had a higher prevalence of infection (PR, 1.53; 95% CI, 1.03 to 2.30) as well as those who did not believe in the protective effect of vaccines (PR, 1.78; 95% CI, 1.05 to 2.89). Our results indicate the need for better guidance on preventive measures against coronavirus disease 2019 among urban cleaning and solid waste management workers.

Temporomandibular disorders dysfunction in headache patients.

OBJECTIVE: To identify the frequency of signs and symptoms of temporomandibular disorder (TMD) and its severity in individuals with headache. STUDY DESIGN: 60 adults divided into three groups of 20 individuals: chronic daily headache (CDH), episodic headache (EH) and a control group without headache (WH). Headache diagnosis was performed according to the criteria of International Headache Society and the signs and symptoms of TMD were achieved by using a clinical exam and an anamnestic questionnaire. The severity of TMD was defined by the temporomandibular index (TMI). RESULTS: The TMD signs and symptoms were always more frequent in individuals with headache, especially report of pain in TMJ area (CDH, n=16; EH, n=12; WH, n=6), pain to palpation on masseter (CDH, n=19; EH, n=16; WH, n=11) which are significantly more frequent in episodic and chronic daily headache. The mean values of temporomandibular and articular index (CDH patients) and muscular index (CDH and EH patients) were statistically higher than in patients of the control group, notably the articular (CDH=0.38; EH=0.25;WH=0.19) and muscular (CDH=0.46; EH=0.51; WH=0.26) indices. CONCLUSIONS: These findings allow us to speculate that masticatory and TMJ pain are more common in headache subjects. Besides, it seems that the TMD is more severe in headache patients.

Serum glial fibrillary acidic protein is a body fluid biomarker: A valuable prognostic for neurological disease - A systematic review.

Astrocytes are the most abundant cell type in the human central nervous system, and they play an important role in the regulation of neuronal physiology. In neurological disorders, astrocyte disintegration leads to the release of glial fibrillary acidic protein (GFAP) from tissue into the bloodstream. Elevated serum levels of GFAP can serve as blood biomarkers, and a useful prognostic tool to facilitate the early diagnosis of several neurological diseases ranging from stroke to neurodegenerative disorders. This systematic review synthesizes studies published between January 2012 and September 2021 that used GFAP as a potential blood biomarker to detect neurological disorders. The following electronic databases were accessed: MEDLINE, Scopus, and Web of Science. In all the databases, the following search strategy was used: ¨GFAP¨ OR ¨glial fibrillary acidic protein¨ AND ¨neurological¨ OR ¨neurodegenerative¨ AND ¨plasma¨ OR ¨serum¨. The initial search identified 1152 articles. After the exclusion criteria were applied, 48 publications that reported GFAP levels in neurological disorders were identified. A total of16 different neurological disorders that have plasmatic GFAP levels as a possible biomarker for the disease were described in the articles, being: multiple sclerosis, frontotemporal lobar degeneration, Alzheimer's disease, Parkinson disease, COVID-19, epileptic seizures, Wilson Disease, diabetic ketoacidosis, schizophrenia, autism spectrum disorders, major depressive disorder, glioblastoma, spinal cord injury, asthma, neuromyelitis optica spectrum disorder and Friedreich's ataxia. Our review shows an association between GFAP levels and the disease being studied, suggesting that elevated GFAP levels are a potentially valuable diagnostic biomarker in the evaluation of different neurological diseases.

Anti-inflammatory and modulatory effects of steroidal saponins and sapogenins on cytokines: A review of pre-clinical research.

BACKGROUND: Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models. PURPOSE: The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines. STUDY DESIGN AND METHODS: This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved. RESULTS: Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways. CONCLUSION: Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity.

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.

Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives.

Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects the respiratory tract. Bradykinin (BK) is a hypotensive substance that recently emerged as one of the mechanisms to explain COVID-19-related complications. Concerning this, in this review, we try to address the complex link between BK and pathophysiology of COVID-19, investigating the role of this peptide as a potential target for pharmacological modulation in the management of SARS-CoV-2. The pathology of COVID-19 may be more a result of the BK storm than the cytokine storm, and which BK imbalance is a relevant factor in the respiratory disorders caused by SARS-CoV-2 infection. Regarding this, an interesting point of intervention for this disease is to modulate BK signaling. Some drugs, such as icatibant, ecallantide, and noscapine, and even a human monoclonal antibody, lanadelumab, have been studied for their potential utility in COVID-19 by modulating BK signaling. The interaction of the BK pathway and the involvement of cytokines such as IL-6 and IL1 may be key to the use of blockers, even if only as adjuvants. In fact, reduction of BK, mainly DABK, is considered a relevant strategy to improve clinical conditions of COVID-19 patients. In this context, despite the current unproven clinical efficacy, drugs repurposing that block B1 or B2 receptor activation have gained prominence for the treatment of COVID-19 in the world.

Seroprevalence of SARS-CoV-2 antibodies in radio and television workers.

We investigated the seroprevalence of SARS-CoV-2 antibodies in individuals working in radio and television stations (TV) in Sergipe state, Northeast Brazil. This cross-sectional study was conducted from December 1 to December 20, 2020, a period which was considered as the beginning of the second wave of COVID-19 in the state. One hundred and thirteen professionals from the three largest media companies in the state were included in this study. Venous blood was collected using venipuncture and a fluorescence immunoassay for qualitative detection and differentiation of IgM and IgG antibodies against SARS-CoV-2 was performed. Twenty-eight media workers had detectable levels of SARS-CoV-2 antibodies (11 IgM+, 6 IgM+/ IgG+, and 11 IgG+) and the estimated seroprevalence was 24.8 % (95 % CI 17.7 - 33.5). Our findings showed a high seroprevalence of SARS-CoV-2 antibodies in radio and TV workers during the second wave of COVID-19 in Brazil.

Biological properties of terpinolene evidenced by in silico, in vitro and in vivo studies: A systematic review.

BACKGROUND: Terpinolene, a monoterpene that is naturally found in a variety of herbs, is widely used as a flavoring agent in the industry. Although it's well established in the literature that terpinolene is an important component of plant extracts, the biological properties and the potential therapeutic use of this compound remain poorly explored. PURPOSE: This work aimed to answer the following guiding question: "What are the biological activities of terpinolene demonstrated through in silico, in vitro, and in vivo assays?". STUDY DESIGN AND METHODOLOGY: A systematic review was carried out in four electronic databases (Embase, Web of Science, Scopus, and PubMed) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using the following search terms: terpinolene "AND" activity "OR" properties "OR" therapeutic "OR" treatment. This search included manuscripts published between 1960 and June 2020. Study selection was conducted by two independent reviewers according to predefined criteria. RESULTS: The initial search found a total of 2449 articles. However, only 57 of them were selected as they met the inclusion criteria and answered the guiding question. The analysis of these studies indicated that terpinolene presents a series of biological effects, from which the antioxidant, larvicide, and insecticide activities stand out. Despite the evidence demonstrating that terpinolene has the potential to be used in a broad pharmacological context, the mechanisms underlying its cellular and molecular effects remain to be better elucidated. In addition, the in vivo efficacy and safety of the administration of this compound have been poorly evaluated through either preclinical and clinical trials. Therefore, this study highlights the importance of characterizing the biological aspects and mechanisms of action of this natural compound. CONCLUSION: The data summarized in the present systematic review demonstrates the pharmacological potential of terpinolene. Nevertheless, most studies included in this review provide a superficial characterization of terpinolene biological effects and therefore, further research elucidating its mechanism of action and potential therapeutic benefits through preclinical and clinical trials are required. Nevertheless, due to its wide range of different biological activities, terpinolene will certainly attract the interest of scientific research, which could significantly contribute to the development of new products with both therapeutic and environmental applications.

Drug repurposing and cytokine management in response to COVID-19: A review.

Coronavirus disease 2019 (COVID-19), the infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an aggressive disease that attacks the respiratory tract and has a higher fatality rate than seasonal influenza. The COVID-19 pandemic is a global health crisis, and no specific therapy or drug has been formally recommended for use against SARS-CoV-2 infection. In this context, it is a rational strategy to investigate the repurposing of existing drugs to use in the treatment of COVID-19 patients. In the meantime, the medical community is trialing several therapies that target various antiviral and immunomodulating mechanisms to use against the infection. There is no doubt that antiviral and supportive treatments are important in the treatment of COVID-19 patients, but anti-inflammatory therapy also plays a pivotal role in the management COVID-19 patients due to its ability to prevent further injury and organ damage or failure. In this review, we identified drugs that could modulate cytokines levels and play a part in the management of COVID-19. Several drugs that possess an anti-inflammatory profile in others illnesses have been studied in respect of their potential utility in the treatment of the hyperinflammation induced by SAR-COV-2 infection. We highlight a number of antivirals, anti-rheumatic, anti-inflammatory, antineoplastic and antiparasitic drugs that have been found to mitigate cytokine production and consequently attenuate the "cytokine storm" induced by SARS-CoV-2. Reduced hyperinflammation can attenuate multiple organ failure, and even reduce the mortality associated with severe COVID-19. In this context, despite their current unproven clinical efficacy in relation to the current pandemic, the repurposing of drugs with anti-inflammatory activity to use in the treatment of COVID-19 has become a topic of great interest.

The use of cyclodextrin inclusion complexes to improve anticancer drug profiles: a systematic review.

INTRODUCTION: Cyclodextrins (CDs) have been used extensively in inclusion complexes to improve the biological efficacy of complexed substances as well as to provide increased solubility and stability. We reviewed in vivo experimental studies of drug molecules complexed in cyclodextrins to evaluate whether these complexes improved bioavailability and enhanced the treatment of cancer, the second leading cause of death globally. AREA COVERED: The search terms cyclodextrins, anti-cancer, and cancer treatment were used to identify peer-reviewed publications limited to the English language in the PubMed, EMBASE, Scopus, and Web of Science electronic databases published from inception until July 2019. A total of 2760 studies were identified, of which 12 met the inclusion criteria. The review showed that cyclodextrin/anticancer drug complexes enhance solubility, reduce toxicity, and improve therapeutic efficacy in in vivo tumor models in the pharmacokinetic studies detailed and described below. EXPERT OPINION: The use of cyclodextrins combined with anticancer agents can provide better encapsulation and effective delivery of drugs to optimize their efficacy. Cyclodextrin inclusion complexes might also be a promising tool to lower the therapeutic dosage levels and thereby increase the safety and curative potential of the chemotherapeutic molecules.

Essential oils and its bioactive compounds modulating cytokines: A systematic review on anti-asthmatic and immunomodulatory properties.

BACKGROUND: Asthma, the main inflammatory chronic condition affecting the respiratory system, is characterized by hyperresponsiveness and reversible airway obstruction, recruitment of inflammatory cells and excessive production of mucus. Cytokines as biochemical messengers of immune cells, play an important role in the regulation of allergic inflammatory and infectious airway processes. Essential oils of plant origin are complex mixtures of volatile and semi volatile organic compounds that determine the specific aroma of plants and are categorized by their biological activities. PURPOSE: We reviewed whether essential oils and their bioactive compounds of plant origin could modulate cytokines' immune responses and improve asthma therapy in experimental systems in vitro and in vivo. METHODS: Electronic and manual search of articles in English available from inception up to November 2018 reporting the immunomodulatory activity of essential oils and their bioactive compounds for the management of asthma. We used PubMed, EMBASE, Scopus and Web of Science. Publications reporting preclinical experiments where cytokines were examined to evaluate the consequence of anti-asthmatic therapy were included. RESULTS: 914 publications were identified and 13 were included in the systematic review. Four articles described the role of essential oils and their bioactive compounds on bronchial asthma using cell lines; nine in vivo studies evaluated the anti-inflammatory efficacy and immunomodulating effects of essential oil and their secondary metabolites on cytokines production and inflammatory responses. The most important immunopharmacological mechanisms reported were the regulation of cytokine production, inhibition of reactive oxygen species accumulation, inactivation of eosinophil migration and remodeling of the airways and lung tissue, modulation of FOXP3 gene expression, regulation of inflammatory cells in the airways and decreasing inflammatory mediator expression levels. CONCLUSION: Plant derived essential oils and related active compounds have potential therapeutic activity for the treatment of asthma by modulating the release of pro-inflammatory (TNF-α, IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10), Th1 (IFN-γ, IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines and the suppression of inflammatory cell accumulation.

Modulation of interleukin expression by medicinal plants and their secondary metabolites: A systematic review on anti-asthmatic and immunopharmacological mechanisms.

BACKGROUND: Asthma is one of the most common chronic inflammatory conditions of the lungs in modern society. Asthma is associated with airway hyperresponsiveness and remodeling of the airways, with typical symptoms of cough, wheezing, shortness of breath and chest tightness. Interleukins (IL) play an integral role in its inflammatory pathogenesis. Medicinal herbs and secondary metabolites are gaining considerable attention due to their potential therapeutic role and pharmacological mechanisms as adjunct tools to synthetic bronchodilator drugs. PURPOSE: To systematically review the literature on the use of single or mixed plants extracts therapy in vivo experimental systems for asthma, emphasizing their regulations on IL production to improve lung. METHODS: Literature searches were performed on PubMed, EMBASE, Scopus and Web of Science databases. All articles in English were extracted from 1999 up to September 2019, assessed critically for data extraction. Studies investigating the effectiveness and safety of plant extracts administered; inflammatory cell count, immunoglobulin E (IgE) production and regulation of pro-inflammatory cytokine and T helper (Th) 1 and Th2-driven cytokine expression in bronchoalveolar lavage fluid (BALF) and lung of asthmatic animals were included. RESULTS: Four hundred and eighteen publications were identified and 51 met the inclusion criteria. Twenty-six studies described bioactive compounds from plant extracts. The most frequent immunopharmacological mechanisms described included reduction in IgE and eosinophilic recruitment, decreased mucus hypersecretion and airway hyperreactivity, enhancement of the balance of Th1/Th2 cytokine ratio, suppression of matrix metallopeptidase 9 (MMP-9) and reversal of structural alterations. CONCLUSION: Plant extract therapies have potential control activities on asthma symptoms by modulating the secretion of pro-inflammatory (IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10, IL-23, IL-31, IL-33), Th1 (IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines, reducing the level of biomarkers of airway inflammation.