Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 22, Issue 1, 2023

Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn's Disease (CD), is a continuously increasing healthcare problem mainly characterized by chronic relapsing intestinal inflammation. The common symptoms of UC and CD include inflammation, diarrhea, abdominal pain, bleeding, and weight loss. IBD is generally caused by an interaction between genetic and environmental or microbial factors that influence the body's immune response and is responsible for digestive disorders and inflammation of the intestinal tract. However, a complete understanding of the pathophysiology and work-up of IBD is necessary to ensure appropriate treatment for the management of this complex disease. This review enlightens herbal therapeutics and drug delivery systems for the management of IBD, and thus provides new insights into this field and facilitates access to new treatments.

The significance of Autoimmune Disorders (Ads) is underscored by their chronic nature, high maintenance costs, and complexity affecting numerous organs and tissues. A more comprehensive approach to treating Ads is required across patient populations. A revolutionary area for obtaining an integrated therapeutic option is natural phytoconstituents. Diverse biomolecules with promising properties can be found in abundance in the marine environment. Many substances have been identified from sponges, bacteria, fungi, cyanobacteria, and algae that have been shown to have immunomodulatory activities and may be used as possible treatments for Ads. Marine-derived bioactive substances have been demonstrated to affect immunological responses and to be essential in immunotherapies. The amount of information about the specific effects of substances obtained from marine sources utilized as dietary supplements or for treating immune-related diseases is growing. This paper discusses many sources of potential marine metabolic chemicals, such as maritime flora and fauna. Numerous marine phytoconstituents have recently been isolated, described, and identified, and they are currently undergoing human usage studies. We have attempted to consolidate information concerning phytoconstituents from marine sources with anti-inflammatory and immunomodulatory properties in this review, and we have briefly explored their methods of action. In order to provide a baseline of knowledge for promoting marine flora-based phytoconstituents in the current context of increasing Ads incidence, deprived of the more affordable, safe, and effective medications to combat the terrible human disease, this paper reviews the works thus far conducted on this aspect.

Among inflammatory cytokines, Interleukin-6 (IL-6) is one of the major activators of acute phase response and is also involved in immune response and cancer progression. IL-6 is involved in the up-regulation of enzymes and growth factors acting on the extracellular matrix (ECM) remodelling components in physio-pathological processes. IL-6 enhances the expression of metalloproteases (MMP-)2/9, enzymes that play a key role in ECM degradation and therefore contribute to the process of tumor metastasis. To counteract and/or prevent cancer diseases, many efforts have been devoted to the identification of factors able to inhibit the IL-6-dependent MMP-9/2 expression. Recently, diet polyphenols have been identified as molecules manifesting anti-inflammatory and anti-cancer properties beyond their well-known capacity to promote health on the basis of their antioxidant effects. This review summarizes the recent advances in this field, focusing on the protective effects exerted by diet polyphenols on the proliferation and invasiveness of tumor cells, with specific emphasis on the ability of these molecules to inhibit the IL-6-dependent upregulation of MMP-2/9.

Background: Agave brittoniana subsp. brachypus is an endemic plant of Cuba, which contains different steroidal sapogenins with anti-inflammatory effects. This work aims to develop computational models which allow the identification of new chemical compounds with potential anti-inflammatory activity. Methods: The in vivo anti-inflammatory activity was evaluated in two rat models: carrageenaninduced paw edema and cotton pellet-induced granuloma. In each study, we used 30 Sprague Dawley male rats divided into five groups containing six animals. The products isolated and administrated were fraction rich in yuccagenin and sapogenins crude. Results: The obtained model, based on a classification tree, showed an accuracy value of 86.97% for the training set. Seven compounds (saponins and sapogenins) were identified as potential antiinflammatory agents in the virtual screening. According to in vivo studies, the yuccagenin-rich fraction was the greater inhibitor of the evaluated product from Agave. Conclusion: The evaluated metabolites of the Agave brittoniana subsp. Brachypus showed an interesting anti-inflammatory effect.

Introduction: Atopic dermatitis (AD) is a chronic, inflammatory skin disorder with eczematous and pruritic lesions. Topical moisturisers and either topical corticosteroids or calcineurin inhibitors are usually recommended. Restoring the skin barrier function alleviates AD symptoms. Objective: To evaluate the efficacy of a new moisturiser compared to commercially available products in an AD murine model. Methods: Experimental AD was induced with topical applications of 2,4-DiNitroChloroBenzene (DNCB) on the shaved back skin of BALB/c mice from Day 1 to Day 38. Mice were randomized to either Vehicle/-, DNCB/-, or DNCB/Eczekalm (test product), DNCB/Atopiclair®, or DNCB/Lipikar (reference products) groups. Once daily application of either Eczekalm or Atopiclair® or Lipikar on the AD lesion was performed from Day 32 to Day 38. The AD severity index (ADSI) and animal behaviour were monitored throughout the study. The trans-epidermal water loss (TEWL) was measured on the sacrifice day (Day 39). Results: At Day39, ADSI in the DNCB/Eczekalm, DNCB/Lipikar, and DNCB/Atopiclair® groups were significantly lower by -70%, -68%, and -57%, respectively, as compared to DNCB/- (p < 0.001). No sign of erythema was observed in the DNCB/Eczekalm group. Mean scores of skin oedema, excoriation, and dryness in the DNCB/Eczekalm, DNCB/Lipikar, and DNCB/Atopiclair® groups were significantly lower than in the DNCB/-. No significant difference was observed between DNCB/Eczekalm and DNCB/Lipikar groups. Mean TEWL in DNCB/Eczekalm group was significantly lower than the ones of DNCB/Atopiclair® (-43%, p < 0.001) and DNCB/Lipikar (-15%, p < 0.05). Conclusion: Eczekalm treatment significantly reduced the inflammatory effects due to AD and itching episodes and restored the skin barrier function.

Background & Aim: Spontaneous bacterial peritonitis is considered a precipitating factor for renal impairment in patients with liver cirrhosis. No specific study addressing this problem has been reported. This study aimed to detect the incidence and predictive factors of hepatorenal syndrome in these patients. Materials and Methods: This study enrolled 121 hepatic cirrhotic patients with spontaneous bacterial peritonitis. History taking, clinical examination, and laboratory investigations including ascitic fluid analysis were carried out. Kidney function tests were repeated 3 days after the initiation of treatment. Patients were divided into 2 groups after one week of treatment during the follow-up period: Group I: patients without hepatorenal syndrome, and Group II: patients with hepatorenal syndrome. Multivariate analysis was performed to determine independent predictors of hepatorenal syndrome development. Results: A total of 30 patients (24.8%) developed hepatorenal syndrome. Patients with hepatorenal syndrome had significantly lower sodium and albumin levels as well as higher creatinine, bilirubin, Child-Turcotte-Pugh score, portal vein diameter, Model for End-Stage Liver Disease score. Higher percentage of them had a history of recurrent spontaneous bacterial peritonitis and multiple therapeutic paracentesis of ascites. Multivariate analysis detected that serum bilirubin, Model for End-Stage Liver Disease-Sodium, and portal vein diameter were significant predictors of hepatorenal syndrome. Cutoff values were determined as 3.3 mg/dl for bilirubin, 15.9 mm for portal vein diameter, and 26 for Model for End-Stage Liver Disease-Sodium. Conclusion: Hepatorenal syndrome is a common complication of spontaneous bacterial peritonitis. In our study, high serum bilirubin, Model for End-Stage Liver Disease-Sodium, and portal vein diameter are predictors of the development of hepatorenal syndrome in patients with spontaneous bacterial peritonitis.