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Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by Leishmania infantum and L. donovani . Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL's pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans.

The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC 50  = 0.059 ± 0.008  μ g/mL) or carbachol (EC 50  = 0.068 ± 0.007  μ g/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children., Competing Interests: The authors declare that there are no conflicts of interests regarding the publication of this paper., (Copyright © 2023 Railson de Sousa Santos et al.)

Purpose: To investigate the anti-inflammatory and antioxidant activities of N-salicyloyltryptamine (NST) in experimental models of carrageenan (Cg)-induced peritonitis in mice, and evaluation of the effects of NST on Cg-induced joint disability in rats., Methods: Female Swiss mice were submitted to Cg-induced peritonitis in mice or Cg-induced joint disability in rats after intraperitoneal injection of NST (100 or 200 mg/kg). Total leukocyte count, total protein concentration, myeloperoxidase (MPO) and catalase (CAT) activities, and nitrite (NO 2 - ) and thiobarbituric acid reactive species (TBARS) levels were determined., Results: NST significantly decrease the migration of leukocytes to peritoneal exudate. Cg induces inflammatory responses mediated by expression of reactive oxygen species (ROS). The results further showed that NST significantly decreased MPO and CAT activities, as well as reduced NO 2 - and TBARS levels, compared with the vehicle group. Animals treated with NST significantly reduced paw elevation time (PET) on the first hour after induction of joint injury, and this effect was sustained throughout the analysis., Conclusion: NST presented anti-inflammatory and antioxidant effects in experimental models of carrageenan-induced peritonitis and joint disability in mice and rats, respectively, which may be related to the modulation of neutrophils migration as well as the involvement of antioxidant mechanisms., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 B. P. Sousa-Neto et al.)

Ethyl ferulate, a phenylpropanoid derived from rice hulls has aroused interest because of its antioxidant, anti-inflammatory and neuroprotective properties. However, it has low solubility in water which compromises the absorption in the gastrointestinal tract, decreases the bioavailability and compromises the reproducibility of the effects in vivo. To increase the solubility of ethyl ferulate, inclusion complexes were obtained by physical mixing, malaxing, lyophilization and spray drying and characterized using thermal analysis, XRD and FTIR. The complexes obtained were evaluated for ethyl ferulate content, stability, dissolution profile and evaluation of anti-inflammatory activity in vivo through carrageenan-induced paw edema model in rats. The inclusion complexes obtained resulted in increased solubility and stability compared to the isolated ethyl ferulate. In addition, the complexes obtained by malaxage, lyophilization and spray drying showed greater inhibition of the edema formation induced by carrageenan compared to ethyl ferulate 100 mg/kg v.o. The inclusion of ethyl ferulate in B-cyclodextrin resulted in the formation of stable inclusion complexes with potent antidematogenic activity possibly attributed to the increased solubility, dissolution profile of the active., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1β were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1β. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.

Background: Pharmaceutical nanotechnology represents an efficient alternative for the delivery of pharmacologically active plant-derived compounds, considering their protective capacity, oral bioavailability and drug vectorization capacity. In this context, butters obtained from plant seeds have emerged as promising products for the development of pharmacologically active nanostructures. They possess a complex lipid composition, allowing the formation of different emulsion systems with solid cores, since this mixture of different triglycerides is solid at room temperature and body temperature. Therefore, the systematic mapping around the technological development of nanostructures produced from plant-derived butters is potentially valuable for researchers interested in novel alternative formulations for pharmacological therapy, with potential industrial, economic, health and societal impacts., Methods: Systematic review was carried out by the search of scientific papers and patents deposited in official databases concerning the development of nanostructured pharmaceutical products using plantderived butters as starting material. The publications obtained were subjected to sorting and analysis by applying the following inclusion/exclusion criteria., Results: The Solid Lipid Nanoparticle (SLN) was the type of nanostructure produced in all the analyzed scientific papers, due to the physicochemical characteristics of the lipid constituents of plantderived butters. In this sense, 54% of the articles have reported the use of Cocoa Butter for the production of nanostructures; 28% for Shea Butter; 6% for Cupuacu Butter, 6% for Murumuru Butter and 6% for Bacuri Butter., Discussion: In the technological prospection, only two patents exhibited SLN as an invention based on cocoa butter and on shea butter, respectively. The production methods employed have included: phase inversion temperature, microemulsion, hot high pressure homogenization, high shear homogenization and ultrasonication., Conclusion: In light of this prospective review, the encouragement of novel studies in lipids-based nanotechnology is evident, considering the small number of findings so far, in order to stimulate new research involving plant-derived butters from easily cultivated fruits in tropical regions, then stimulating the pharmaceutical development of new therapeutic alternatives using biocompatible and sustainable raw materials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: It is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested., Purpose: The aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters., Study Design: This is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation., Methods: The anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 μl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100  µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 μg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO 2 - ), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20  mg/kg, p.o.)., Results: After treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO 2 - (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions., Conclusion: Taken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions., (Copyright © 2018. Published by Elsevier GmbH.)

Introduction: Ethyl ferulate is a phenylpropanoid with anti-inflammatory, antioxidant and neuroprotective activities of natural and synthetic origin with potential uses in the nutraceutical and pharmaceutical industry. Therefore, the aim of this study was to investigate the current scenario regarding patents and scientific articles available involving the substance in question, regarding aspects such as quantity, areas of knowledge and depositor countries., Areas Covered: To do so, we conducted technological and scientific prospecting on the WIPO, EPO, USPTO and INPI and scientific databases in PubMed, Web of Science and Lilacs databases using the keywords 'ferulic acid ethyl ester' and 'ethyl ferulate' in English and Portuguese. A total of 16 articles and 17 patents of which 10 were Chinese and 11 claimed the use of ethyl ferulate or for the synthesis of other substances or synthetic methods of the same. Five of the patents selected claimed therapeutic applications related to the treatment of mycobacterial infections, use as a cosmetic and neuroprotective activity. The systematic review of the literature revealed antioxidant, neuroprotective, anti-inflammatory, antimutagenic, antiapoptotic, antimutagenic and antiproliferative activities., Expert Opinion: The technological and scientific prospection highlighted ethyl ferulate, despite its known pharmacological activities, is little explored by the pharmaceutical and nutraceutical industries.

Ethnopharmacological Relevance: Pilosocereus gounellei Cactaceae), popularly known as "xique xique", is a species native from Caatinga region of Northeast Brazil, which is used by traditional communities in folk medicine for a variety of health problems, especially inflammatory processes and gastritis., Aim of the Study: The present study investigates the possible gastric antiulceractivity of ethanol extracts obtained from the cladodes and roots of Pilosocereus gounellei (EECPG and EERPG, respectively) and mechanisms of action underlying this effect., Materials and Methods: Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EECPG and EERPG was analyzed in the absolute ethanol in mice, ischemia-reperfusion and cold restraint stress in rats. In the investigation of the gastroprotective mechanisms of EECPG and EERPG, the participation of the NO and prostaglandins, the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed., Results: The animals did not present any signs of acute toxicity for the EECPG and EERPG, and it was not possible to calculate the DL50. EECPG and EERPG (200 and 400 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, ischemia-reperfusion-induced and cold restraint stress gastric lesion models. Gastroprotection of EECPG and EERPG (200 mg/kg) was significantly decreased in pre-treated mice with L-NAME. Our studies revealed that EECPG and EERPG (200 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NPSH) and increased the catalase levels in ethanol-treated animals. However, the gastric secretion parameters (volume, [H+], pH) did not show any alteration., Conclusions: Our results indicate that the ethanolic extract from the cladodes and roots of Pilosocereus gounellei exhibits a significant gastroprotection, because it inhibits the formation of gastric lesions using different models. The participation of the nitric oxide, prostaglandins, the non-protein sulfhydril groups (NP-SH), catalase seem to be involved in the gastroprotection activity of the EECPG and EERPG. Nevertheless, this activity does not seem to be related to antisecretory mechanisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Myrtenol is a bicyclic monoterpene with anti-inflammatory properties. However, the mechanisms involved are partially unknown. Here, we investigated the effect of myrtenol during experimental chronic arthritis and the possible modulating activity of oxidative stress and neutrophil migration. Complete Freund's Adjuvant (CFA)-sensitized rats were treated with vehicle (1 mL/kg, po), myrtenol (12.5, 25 or 50 mg/kg, po), indomethacin (10 mg/kg, po) or dexamethasone (0.4 mg/kg) followed by intra-articular injection of CFA (0.5 mg/mL, 50 μL per joint). Then, paw edema and articular incapacitation (paw elevation time) were evaluated for 14 days. On the last day, a blood concentration superoxide dismutase (SOD) and nitrite was determined. In another experimental setting, human neutrophils were incubated with vehicle (sterile saline, 1 mL) or myrtenol (10-100 ng/mL) and the in vitro chemotaxis to N-formylmethionine-leucyl-phenylalanine (fMLP) (10 -7  M/well) was evaluated. In addition, antiinflammatory effect of myrtenol was investigated in carrageenan-induced peritonitis. We found that CFA induced a prominent paw swelling and incapacitation of the joint, which were significantly prevented by myrtenol (P < 0.05). In addition, blood accumulation nitrite was attenuated by myrtenol when compared with vehicle-treated CFA group (P < 0.05). Furthermore, plasma levels of SOD were significantly increased by myrtenol versus vehicle-treated CFA group (P < 0.05). Moreover, fMLP-triggered neutrophil chemotaxis and carrageenan-induced peritonitis were markedly prevented by myrtenol (P < 0.05). Therefore, myrtenol showed anti-inflammatory and antinociceptive effects on experimental chronic arthritis, which seems to be related to the direct modulation of neutrophil migration and antioxidant activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: We aimed to investigate the modulating effect of α-phellandrene on neutrophil migration and mast cell degranulation processes., Main Methods: Male Wistar rats or Swiss mice were treated p.o. with vehicle (3% Tween 80, p.o.), α-phellandrene (50, 100, or 200mg/kg, p.o.), or dexamethasone (0.5mg/kg, p.o.) 1h before carrageenan injection. Then, the neutrophil migration in 6-day-old air pouches or peritoneal cavities. The leukocyte rolling and adhesion were measured in real time and assessed by intravital microscopy. ELISA was used to detect TNF-α and IL-6 in peritoneal lavage. Compound 48/80-induced mast cell degranulation was assessed in mesenteric rat tissues., Key Findings: In all the tested doses, α-phellandrene prevented carrageenan-induced neutrophil accumulation (P<0.05). As detected by intravital microscopy, α-phellandrene also inhibited leukocyte rolling and adhesion, as well as significantly inhibited the production of the pro-inflammatory cytokines TNF-α and IL-6. Moreover, the degranulation of compound 48/80-induced mast cells was also inhibited by α-phellandrene (P<0.001)., Significance: These results suggest that α-phellandrene plays an important role as an anti-inflammatory agent through neutrophil migration modulation and mast cell stabilization., (Copyright © 2016 Elsevier Inc. All rights reserved.)