Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 3, 2024

Helicobacter pylori (H. pylori) is the most thoroughly researched etiological component for stomach inflammation and malignancies. Even though there are conventional recommendations and treatment regimens for eradicating H. pylori, failure rates continue to climb. Antibiotic resistance contributes significantly to misdiagnoses, false positive results, and clinical failures, all of which raise the chance of infection recurrence. This review aims to explore the molecular mechanisms underlying drug resistance in H. pylori and discuss novel approaches for detecting genotypic resistance. Modulation of drug uptake/ efflux, biofilm, and coccoid development. Newer genome sequencing approaches capable of detecting H. pylori genotypic resistance are presented. Prolonged infection in the stomach causes major problems such as gastric cancer. The review discusses how H. pylori causes stomach cancer, recent biomarkers such as miRNAs, molecular pathways in the development of gastric cancer, and diagnostic methods and clinical trials for the disease. Efforts have been made to summarize the recent advancements made toward early diagnosis and novel therapeutic approaches for H. pylori-induced gastric cancer.

Rheumatoid arthritis (RA) is characterized by synovial edema, inflammation, bone and cartilage loss, and joint degradation. Patients experience swelling, stiffness, pain, limited joint movement, and decreased mobility as the condition worsens. RA treatment regimens often come with various side effects, including an increased risk of developing cancer and organ failure, potentially leading to mortality. However, researchers have proposed mechanistic hypotheses to explain the underlying causes of synovitis and joint damage in RA patients. This review article focuses on the role of synoviocytes and synoviocytes resembling fibroblasts in the RA synovium. Additionally, it explores the involvement of epigenetic regulatory systems, such as microRNA pathways, silent information regulator 1 (SIRT1), Peroxisome proliferatoractivated receptor-gamma coactivator (PGC1-α), and protein phosphatase 1A (PPM1A)/high mobility group box 1 (HMGB1) regulators. These mechanisms are believed to modulate the function of receptors, cytokines, and growth factors associated with RA. The review article includes data from preclinical and clinical trials that provide insights into potential treatment options for RA.

The species Mentha Pulegium L. (M. pulegium L.) belongs to the family Lamiaceae, native to Europe, North Africa, and the Middle East, and the genus Mentha. It has been traditionally used in food, cosmetics, and medicines. It is a perennial, fragrant, well-liked, herbaceous plant that can grow up to half a meter tall. It is extensively used as a food flavoring, particularly for Moroccan traditional drinks. Chewing mint and M. pulegium, a relaxing and refreshing plant, can be used to treat hiccups and act as an anticonvulsant and nerve relaxant. Pennyroyal leaves that have been crushed have a pungent, spearmint-like scent. Pennyroyal is used to make herbal teas, which, while not proven to be harmful to healthy adults in small doses, are not recommended due to their liver toxicity. Infants and children can die if they consume it. Pennyroyal leaves, both fresh and dried, are particularly effective at repelling insects. Pennyroyal essential oil should never be taken internally because it is highly toxic, even in small doses, it can be fatal. This plant is used in traditional Moroccan medicine to treat a wide range of conditions, including influenza, rheumatism, migraine, infertility, ulcer, pain, gastrointestinal problems, fever, diabetes, obesity, mental and cardiac disorders, constipation, respiratory ailments, and cough. M. pulegium is a great candidate for contemporary therapeutic usage since it contains a wide variety of biologically active compounds, including terpenoids, flavonoids, alkaloids, tannins, and saponins in all its parts. Among the different parts used are the whole plant, the aerial part, the stem, and the leaves. More interestingly, the entire plant contains a variety of compounds including Pulegone, Isomenthone, Carvone, Menthofuran, Menthol, 1,8-Cineole, Piperitone, Piperitenone, Neomenthol, -humulene, and 3-octanol. Eriocitrin, Hesperidin, Narirutin, Luteolin, Isorhoifolin, Galic acid, and Rosmarinic acid are found in the leaves. p-hydroxybenzoic acid, Ferulic acid, Caffeic acid, Vanillic acid, Syringic acid, Protocatechuic acid, Cinnamic acid, Phloretic acid, o-coumaric acid, p-coumaric acid, Catechin, Epicatechin, Chrysin, Quercetin, Naringenin, Carvacrol are all found in the areal part. Alterporriol G, Atropisomer, Alterporriol H, Altersolanol K, Altersolanol L, Stemphypyrone, 6-O-methylalaternin, Macrosporin, Altersolanol A, Alterporriol E, Alterporriol D, Alterporriol A, Alterporriol B, and Altersolanol J are also found in the stem of fungus. Pulegone, Piperitone, p-Menthane-1,2,3- triol, β-elemenene, guanine (cis-), Carvacrol acetate, and Phenyl ethyl alcohol are all components of this plant's essential oils. Moreover, the study also sought to investigate and document all currently available evidence and information on the nutritional composition and therapeutic uses of this plant ornamental. Its pharmacological applications include antimicrobial, antioxidant, antihypertensive, antidiabetic, anti-inflammatory, antiproliferative, antifungal, anticancer, burn wound healing, antispasmodic, and hepatotoxicity. Finally, toxicological studies have revealed that while low doses of extracts of the plant M. pulegium are not toxic, however, its essential oils of it are extremely toxic. In order to evaluate future research needs and investigate its pharmacological applications through clinical trials, the current assessment focuses on the distribution, chemical composition, biological activities, and primary uses of the plant.

Background: Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multiorgan consequences, as evidenced by the association between depression and T2D. Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D.

Cancer-associated fibroblasts (CAFs) as a major component of cancer stroma contribute to diverse procedures of most solid tumors and might be a targeted cancer therapy approach. Their specified features, related signaling pathways, distinct biomarkers, and sub-populations need to be deciphered. There is a need for CAF extraction or induction for in vitro investigations. Some miRNAs could activate CAF-like phenotype and they also interfere in CAF-mediated drug resistance, aggressiveness, and metastatic behaviors of several cancer cell types. Due to the complex relevance of miRNA and CAFs, these non-coding oligonucleotides may serve as attractive scope for anti-cancer targeted therapies, but the lack of an efficient delivery system is still a major hurdle. Here, we have summarized the investigated information on CAF features, isolation, and induction procedures, and highlighted the miRNA-CAF communications, providing special insight into nano-delivery systems.

Background: Cellular senescence is associated with the formation and progression of a range of illnesses, including ageing and metabolic disorders such as diabetes mellitus and pancreatic beta cell dysfunction. Ageing and reduced glucose tolerance are interconnected. Often, Diabetes is becoming more common, which is concerning since it raises the risk of a variety of age-dependent disorders such as cardiovascular disease, cancer, Parkinson's disease, stroke, and Alzheimer's disease. Objectives: The objectives of this study are to find out the most recent research on how ageing affects the functions of pancreatic beta cells, beta cell mass, beta cell senescence, mitochondrial dysfunction, and hormonal imbalance. Methods: Various research and review manuscripts are gathered from various records such as Google Scholar, PubMed, Mendeley, Scopus, Science Open, the Directory of Open Access Journals, and the Education Resources Information Centre, using different terms like "Diabetes, cellular senescence, beta cells, ageing, insulin, glucose". Results: In this review, we research novel targets in order to discover new strategies to treat diabetes. Abnormal glucose homeostasis and type 2 diabetes mellitus in the elderly may aid in the development of novel medicines to delay or prevent diabetes onset, improve quality of life, and, finally, increase life duration. Conclusion: Aging accelerates beta cell senescence by generating premature cell senescence, which is mostly mediated by high glucose levels. Despite higher plasma glucose levels, hepatic gluconeogenesis accelerates and adipose tissue lipolysis rises, resulting in an increase in free fatty acid levels in the blood and worsening insulin resistance throughout the body.

Background: Diabetic nephropathy (DN) is one of the common complications of diabetes. Plantaginis Semen (PS) has a variety of therapeutic effects, however its mechanism on DN is unclear. Objective: This paper aims to find the ingredients, the key targets, and the action pathways of PS on DN from the perspective of network pharmacology. Methods: The databases of network pharmacology, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pharmmapper, OMIM, DrugBank, Gene- Cards, TTD, Disgenet, STRING, and Cytoscape software, were used to find the main ingredients and targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genome and Genomes (KEGG) pathway enrichment analysis were used to reveal the potential pathways of the PS on DN. The GEO database was used to find the targets of DN based on valid experimental research. The molecular docking technology was used to evaluate the combination between ingredients of PS and the targets. Results: A total of 9 active ingredients and 216 potential therapeutic targets were obtained for PS on DN. Hub targets were discovered by the Cytoscape software analysis. CASP3 was screened by Venn diagram by making intersection between GSE30529 and hub genes. Moreover, CASP3 was combined with one of the nine active ingredients, quercetin, by molecular docking analysis. The KEGG pathways were mainly involved in diabetic nephropathy, and were simultaneously associated with CASP3 as followed: AGE-RAGE signaling pathway in diabetic complications, apoptosis, lipid and atherosclerosis, MAPK signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and p53 signaling pathway. Conclusion: PS can have the treatment on DN through CASP3. Quercetin, as one of the nine active ingredients, can be bounded to CASP3 to inhibit apoptosis in DN. PS can also take action on DN probably through many pathways. The role of PS on DN through other pathways still needs to be further elaborated.