Recent Advances in Inflammation & Allergy Drug Discovery - Volume 19, Issue 1, 2025

Carrageenan, a naturally occurring polysaccharide derived from red seaweed, has been utilized extensively in the food industry as a stabilizer, thickener, and emulsifier due to its unique gel-forming properties. This versatile compound exists in various forms, including kappa, iota, and lambda, each with distinct characteristics suitable for different applications. Its widespread use as a food additive has raised concerns regarding its safety, particularly its potential inflammatory effects on the gastrointestinal tract. While carrageenan has been deemed safe for consumption by regulatory agencies in small amounts, studies have suggested its association with intestinal inflammation and gastrointestinal disturbances, particularly in susceptible individuals. Animal models, including rodents and non-human primates, have been employed to investigate the inflammatory response induced by carrageenan ingestion. These models have provided valuable insights into the molecular mechanisms underlying its pro-inflammatory properties. At the molecular level, carrageenan is believed to trigger inflammation by activating toll-like receptor 4 (TLR4) signaling pathways, leading to the production of pro-inflammatory cytokines and the recruitment of immune cells to the site of exposure. Furthermore, carrageenan-induced inflammation may disrupt the intestinal barrier function, facilitating the translocation of luminal antigens and exacerbating immune responses. This review provides a comprehensive examination of the current understanding of carrageenan's role in inflammation, encompassing its diverse applications in the food industry, safety concerns, experimental findings from animal models, and molecular mechanisms underlying its pro-inflammatory effects.

Background: Acne vulgaris, an alternative term for acne, is a persistent inflammatory skin condition affecting the pilosebaceous unit. Its development involves a combination of factors, including increased sebum production, changes in keratinization leading to comedone formation, colonization of hair follicles by Propionibacterium acnes (P. acnes), and the release of inflammatory mediators in the vicinity of the pilosebaceous unit.

Objective: This review provides a concise overview of acne, covering its pathogenesis, epidemiology, diagnosis, treatment options, and recent advancements involved in acne.

Discussion: Various therapeutic approaches, encompassing topical, systemic, combination, and hormonal treatments, are employed to address acne. Prolonged use of synthetic medications is common in acne therapy, but their potential for severe side effects prompts a preference for herbal-based treatments. Herbal remedies utilizing extracts of natural origin are considered safer due to their lower toxicity and reduced likelihood of adverse drug reactions. Recent advancements, particularly in personalized medicine and microbiome research have enhanced our understanding and opened new avenues for more effective management.

Conclusion: Decoding acne vulgaris has provided insights into its pathogenesis, treatment modalities, diagnostics, and recent advancements. Integrating synthetic and herbal treatments, personalized medicine, microbiome research, and advanced modeling techniques offer promising acne management strategies.

Over the world, millions of individuals suffer from psoriasis, a chronic inflammatory skin disease. It is caused by a multifaceted mixture of environmental, immunological, and genetic factors. This review explores the many aspects of psoriasis, where the introduction gives a context background, emphasizing the prevalence and difficulties that people encounter with this dermatological ailment. Further, the pathogenesis complex systems involving immunological dysregulation, genetic susceptibility, and triggers are clarified, providing insights into the disease's fundamental mechanisms. Examining drugs shows how, over time, therapy modalities have evolved, moving from traditional topical treatments to the introduction of biologics and small molecules. The continuous efforts to control symptoms, reduce inflammation, and improve patient outcomes are highlighted in this section. Furthermore, a thorough review of patents reveals the creative advancements made in the sector, highlighting encouraging advancements in treatment modalities and potential paths forward. This manuscript is a review article and is based on various research and review articles. We have summarized the salient features and findings from different articles and prepared this manuscript.

Background: Andrographolide (AP), a bioactive anti-inflammatory compound of Sambiloto, inhibits NF-κB, TNF-α, and interleukin IL-6. Nowadays, molecular docking simulation between AP and dexamethasone against NF-κB receptor presented the energy AP higher than dexamethasone. This becomes a potential treatment for psoriasis.

Objective: This manuscript reported the effectiveness of AP from Sambiloto in treating psoriasis compared to topical steroids.

Methods: This study conducted TLC analysis of AP content and its metabolite impurities, emulgel formulation, molecular docking, in-silico skin toxicity study, and in-vivo anti-psoriatic activity. This was a combination study of an in-silico study and an in-vivo study. This in-silico study was analyzed through multivariate statistical analysis (PCA) to elucidate the data constellation relationship of andrographolide derivatives with several target proteins. The intervention was performed in seven days. The PASI score, molecular parameters (IL-6, IL-17, VEGF, and TNF-a levels), and histopathological findings were assessed.

Results: Molecular docking results revealed andrographolide to exhibit a relatively high binding affinity towards IL-6, NF-kB, and TNF-α which is comparable to the corticosteroids, andrographolide also shares similar residue interaction profile with each of the respective protein’s native ligand. In the in-vivo study, we found several parameters statistically significantly different regarding the intervention, including final PASI score (p = 0.017), redness (p = 0.017), scale (p = 0.040), thickness (p = 0.023), total histopathology of psoriasis score (p = 0.037), keratin layer score (p = 0.018).

Conclusion: Emulgel AP 0.1% could lower the anti-inflammatory agent, which is vital to psoriasis progression.

Background: Alopecia is defined by a loss of hair density and is often considered a symptom of multiple illnesses, such as infection and inflammation.

Objective: The molecular mechanisms underlying the hair-promoting effects include inhibition of 5α-reductase activity, reducing the binding affinity of Dihydrotestosterone (DHT) to androgen receptors, and decreasing/down-regulating TGF-β2 activity, which have a suggestive role in androgenetic alopecia. Finasteride and minoxidil are the approved non-surgical treatment alternatives for hair loss, but they cause side effects in patients. Therefore, bioactive phytoconstituents with multiple targets can be used to find novel, secure, and efficacious hair-promoting medicinal products.

Methods: This study has carried out the in silico evaluation of berberine using various software. To find possible interactions between the 5α-reductase enzyme and Transforming Growth Factor-beta 2 (TGF-β2), a critical protein involved in the human hair development cycle, computer-aided drug discovery was employed.

Results: According to in silico studies, berberine has been found to bind well to the 4K7a and 6M2N binding sites. The drug has been found to adhere to Lipinski's rule of five, and its pharmacokinetic characteristics were noteworthy. Drug-likeness and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties showed appreciable results. Furthermore, berberine showed docking scores of -8.4 (5α-reductase) and -7.1 (TGF-β2), which were significantly better than minoxidil (-4.8, -3.2). In general, the drug exhibited improved binding interactions, and the possible toxicity investigations provided very little basis for risk prediction.

Conclusion: The current protocol has offered experimental support for berberine's possible therapeutic use in reducing male pattern baldness. Therefore, it can be a possible target for the therapy of androgenetic alopecia through the regulation of TGF-β2 and 5α-reductase activity.

Background: A neglected zoonosis, Cystic Echinococcosis (CE), is most common in developing nations worldwide. Vaccination is, therefore, helpful in preventing this disease.

Objective: Predicting the main biochemical properties of E. granulosus Calreticulin (CRT) and its possible B-cell and T-cell-binding epitopes as a valuable candidate for immunization was the goal of the current study.

Methods: Predictions were made to determine biochemical, antigenic, structural, and subcellular characteristics, along with the immunogenic epitopes, using several online servers.

Results: The extracellular 48.15 KDa protein exhibited no allergenicity, while possessing hydrophilicity (GRAVY: -0.785), stability (instability: 33.88), tolerance to a wide range of temperatures (aliphatic: 62.45), and 59 post-translational modification sites. The secondary structure mostly comprised random coils and extended strands. The 3D model was generated using the Robetta server (confidence: 0.72), and was rehashed and confirmed subsequently. Common B-cell epitopes were discovered by three servers and screened for antigenic, allergenic, and solubility traits. Moreover, MHC-associated epitopes for mice and humans were predicted in E. granulosus CRT with subsequent screening.

Conclusion: This work offers a foundation for further investigation in order to design an effective vaccination against CE. Further empirical research on the examined protein solely or in combination with other antigens is needed.

Background: Coronary Artery Bypass Graft (CABG) surgery is employed to increase the lifespan of patients with Coronary Artery Disease (CAD). The low serum levels of essential elements have a negative effect on patients undergoing CABG.

Objective: This clinical trial aimed to investigate the effect of trace elements supplements on postoperative outcomes after coronary artery bypass graft.

Methods: Two hundred patients underwent on-pump CABG to randomly receive either Addamel^©, which contains essential trace elements, or isotonic saline for 3 days. We measured postoperative plasma Zn, Se, Cu, Mn, Se, and Fe concentrations, and the levels of highly sensitive C-reactive Protein (hs-CRP) on days 0, 1, and 2. Duration of hospital and Intensive Care Unit (ICU) stay, 30-day mortality, and the incidence of Arterial Fibrillation (AF) have been evaluated as secondary outcomes.

Results: In the supplemented group, the plasma levels of Cu and Mn increased by day 3, and plasma hs-CRP increased by day 1 in both groups, but it decreased in patients who received trace elements supplementation on day 2. The Addamel group had a lower mortality rate, though the difference did not reach a significant level. There was a significant negative correlation observed between plasma Zn level and 30-day mortality, along with another significant negative link between plasma CRP level before operation and Sepsis-related Organ Failure Assessment (SOFA) score. Other measured parameters were similar between the intervention and placebo groups.

Conclusion: The patients undergoing CABG appeared to benefit from trace element supplementation. A brief period of Addamel administration following CABG could prevent a decrease in the serum concentration of trace elements and reduce the circulating plasma CRP.

Clinical Trial Registration Number: IRCT2015110924975N1