Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 21, Issue 2, 2022

Alzheimer’s disease (AD), the most prevalent form of age-related dementia, is typified by progressive memory loss and spatial awareness with personality changes. The increasing socioeconomic burden associated with AD has made it a focus of extensive research. Ample scientific evidence supports the role of neuroinflammation and oxidative stress in AD pathophysiology, and there is increasing research into the possible role of anti-inflammatory and antioxidative agents as disease modifying therapies. While, the result of numerous preclinical studies has demonstrated the benefits of anti-inflammatory agents, these benefits however have not been replicated in clinical trials, necessitating a further search for more promising anti-inflammatory agents. Current understanding highlights the role of diet in the development of neuroinflammation and oxidative stress, as well as the importance of dietary interventions and lifestyle modifications in mitigating them. The current narrative review examines scientific literature for evidence of the roles (if any) of dietary components, nutraceuticals and functional foods in the prevention or management of AD. It also examines how diet/ dietary components could modulate oxidative stress/inflammatory mediators and pathways that are crucial to the pathogenesis and/or progression of AD.

Allergies have been known to be an abnormally vigorous immune response in which the immune system fights off an allergen or antigen, initiating mast cells to release histamine into the blood. Substances that prevent mast cells from releasing histamine are considered antiallergic agents. The drugs utilized to treat allergy are mast cell stabilizers, steroids, anti-histamine, leukotriene receptor antagonists, and decongestants. Anti-histamine drugs have side effects such as drowsiness, confusion, constipation, difficulty urinating, blurred vision, etc. The use of medicinal plants for the effective and safe management of diseases has recently received much attention. Various herbs are utilized for their antiallergic and anti-histaminic properties. Some of the herbs useful in the management of allergic diseases of the respiratory tract, like Piper longum, Ocimum tenuiflorum, Solanum xanthocarpum have been discussed. Ample scientific evidence is available for the anti-histaminic and antiallergic activity of Azadirachta indica, Aloe vera, Tinospora cordifolia, and many other such herbs are safer to use as antiallergic agents have been reported. The review summarizes a wide variety of herbs and botanical ingredients with their common scientific names and distribution for easy identification and usage as safe antiallergic agents and discusses their molecular mechanisms involved in combating allergic reactions.

Background: Coronavirus disease-2019 (COVID-19) is a global pandemic health problem that causes a wide spectrum of clinical manifestations and considerable mortality rates. Unfortunately, recovered patients who survive COVID-19 may continue to report a wide variety of clinical manifestations of multisystem affection such as pulmonary embolism, deep vein thrombosis, acute myocardial infarction, depression, anxiety, myalgia, dyspnea, and fatigue. Objective: We aimed to summarize the current literature regarding the prevalence of post-COVID- 19 manifestations. Methods: We conducted a systematic review of post-COVID-19 manifestations by searching MEDLINE via PubMed, Scopus, Web of Science (WOS), EBSCO, Wily, and World health organization (WHO) databases. Screening, study selection, data extraction, data synthesis, and quality assessment were made by two independent reviewers. Results: Of 1,371 references, 817 references remained after removing duplicates. Reviews, case reports, commentaries, and any article containing non-original information were excluded. According to the eligibility criteria for this systematic review, 12 studies were included for qualitative synthesis. The overall prevalence of post-COVID-19 manifestations ranged from 35% to 90.5%. Fatigue, dyspnea, neuropsychological disorders, and pain were the most frequent post-COVID-19 symptoms. Conclusion: This systematic review showed that 35% to 90.5% of recovered patients who survive COVID-19 continue to have a wide variety of clinical manifestations, including fatigue, dyspnea, neuropsychological disorders, and pain as the most frequent post-COVID-19 symptoms.

Background: Saccharumoside-B and its analogs were found to have anticancer potential in vitro. The present study reports acute toxicity, molecular docking, ADMET profile analysis, and in vitro and in vivo anti-inflammatory activity of saccharumoside-B for the first time. Methods: The in vitro enzyme inhibitory activity of saccharumoside-B on PLA2, COX-1, COX-2, and 5-LOX enzymes was evaluated by the cell-free method, and its effect on TNF-α, IL1β, and IL- 6 secretion levels in LPS stimulated THP-1 human monocytes was determined by ELISA-based methods. The anti-inflammatory activity was evaluated in vivo by carrageenan-induced rat paw edema model. To test its binding affinity at the active site pockets of PLA2 enzymes and assess drug-like properties, docking experiments and ADMET studies were performed. Results: Saccharumoside-B showed selective inhibition of the sPLA2 enzyme (IC50 = 7.53 ± 0.232 μM), and thioetheramide-PC was used as a positive control. It showed significant inhibition (P ≤ 0.05) of TNF-α, IL-1β, and IL-6 cytokines compared to the positive control dexamethasone. Saccharumoside-B showed a dose-dependent inhibition of carrageenan-induced rat paw edema, with a maximum inhibition (76.09 ± 0.75) observed at 3 hours after the phlogistic agent injection. Saccharumoside-B potentially binds to the active site pocket of sPLA2 crystal protein (binding energy -7.6 Kcal/Mol). It complies with Lipinski’s Rule of Five, showing a promising safety profile. The bioactivity scores suggested it to be a better enzyme inhibitor. Conclusion: Saccharumoside-B showed significant PLA2 inhibition. It can become a potential lead molecule in synthesizing a new class of selective PLA2 inhibitors with a high safety profile in the future.

Background: Chronic lung diseases are characterized by airway inflammation and remodelling of the lung parenchyma that triggers considerable impairment of respiratory function. Objective: In this study, two compounds belonging to the N-acylhydrazone class were evaluated, aiming to identify new therapeutic agents for pulmonary inflammatory diseases. Materials and Methods: The acute toxicity of 2-cyano-N'-(3-ethoxy-4-hydroxybenzylidene)- acetohydrazide (JR-12) and N'-benzylidene-2-cyano-3-phenylacrylohydrazide (JR09-Bz) was evaluated. Afterwards, they were tested in models of ovalbumin (OVA)-induced allergic asthma and pleurisy, bleomycin-induced pulmonary fibrosis, in addition to mucolytic activity. Results and Discussion: The compounds did not show toxicity at the dose of 2,000 mg/kg, and no animal died. On OVA-induced pleurisy, animals treated with JR-12 or JR09-Bz at a dose of 10 mg/kg (orally) showed significant inhibition of the leukocyte infiltrate in the bronchoalveolar lavage by 62.5% and 61.5%, respectively, compared to the control group. The compounds JR-12 and JR09-Bz were also active in blocking the allergic asthmatic response triggered by OVA, reducing the leukocyte infiltrate by 73.1% and 69.8%, respectively. Histopathological changes and mast cell migration in treated animals with JR-12 or JR09-Bz were similar to treatment with the reference drugs dexamethasone and montelukast. JR-12 and JR09-Bz also reversed airway remodeling in animals on the bleomycin-induced fibrosis model compared to the control group. Furthermore, it was observed that N-arylhydrazone derivatives showed expectorant and mucolytic activities, increasing mucus secretion by 45.6% and 63.8% for JR-12 and JR09-Bz, respectively. Conclusion: Together, the results show that JR-12 and JR09-Bz showed promising activity against airway inflammation, as well as low toxicity.