Periostin is a matricellular, nonstructural protein belonging to the fasciclin family and is encoded by the POSTN gene in humans. Periostin plays an important role in maintaining a normal tissue matrix in the lungs. Despite the vital role as a structural mediator in tissue growth and repair, periostin is involved in the pathogenic mechanism during tissue remodeling and fibrosis. Periostin is a chemoattractant mediator, promotes eosinophil recruitment and adhesion on the airways sub-epithelial membrane of asthmatic patients. POSTN gene was identified as one of the highly expressed genes induced by interleukins IL-13, IL-5 and IL-4 - the key cytokines of Th2 immune responses in the bronchial tissues of asthmatic patients. This review highlights the potential role of periostin as a validated biomarker in respiratory disease progression and its candidacy to predict the response to treatments targeting Th-2 cytokines in bronchial asthma. In addition, its potential role in COPD, IPF, lung cancer and lung infection, is also speculated. Keywords Periostin, Asthma, Pneumonia, COPD, Idiopathic pulmonary fibrosis, Biomarker

Nafaa Hasan Ali, Sana Rehman, Maaz Naqvi, Kavita Gulati, Arunabha Ray. J Pharmacopuncture 2023;26:158-66. https://doi.org/10.3831/KPI.2023.26.2.158

Objectives: Stress is an aversive stimulus which disrupts the biological milieu of the organism and a variety of emotional and environmental stressors are known to influence allergic and immunological disorders like bronchial asthma but the pharmacological basis of such interactions is not clearly defined. Withania somnifera (ashwagandha) is a potent anti-stress agent used widely in Indian traditional medicine and the present experimental study evaluated the effects of W. somnifera extract (WSE) on chronic stress-induced neurobehavioral and immunological responses in an experimental model of allergic asthma in rats. Methods: Wistar rats (200–250 g) were immunized and challenged with ovalbumin (OVA) and exposed to restraint stress (RS) and WSE treatments for 15 days. Following this, anxiety behavior was assessed by the elevated plus maze (EPM) test, and blood and BAL fluid samples were collected for measuring of inflammatory/immune markers by ELISA and biochemical assay. The data of the various treatment groups were analyzed by ANOVA and Tukey’s test. Results: Restraint stress (RS) induced anxiogenic behavior in the (EPM) test in OVA immunized rats, and this was attenuated by WSE (200 and 400 mg/kg), in a dose related manner. Examination of blood and BAL fluid in these RS exposed rats also resulted in elevations in IgE, TNF-α and IL-4 levels, which were also attenuated by WSE pretreatments. Further, WSE pretreatment neutralized the such RS induced changes in oxidative stress markers viz. elevated MDA and reduced GSH levels. Conclusions: The data pharmacologically validates role of stress in asthma and suggests that adaptogens like WSE could be a potential complementary agent for reducing anxiety as well as airway inflammation by a multi-targeted and holistic approach. The study also highlights the significance of integration of traditional and modern medical concepts in such chronic disorders.

The issue of drug resistance and tolerance presents a significant challenge as it diminishes the efficacy and potency of medications, posing a formidable obstacle for physicians striving to enhance pharmacological therapy worldwide. These resistance mechanisms can arise from genetic predispositions or as a consequence of medical interventions. Notably, acquired resistance or tolerance may extend to other drugs within the same or different classes, despite differing mechanisms of action. This phenomenon leads to the ineffectiveness of various pharmacological treatments over time, hindering the attainment of complete remission for numerous illnesses spanning metabolic disorders, autoimmune diseases, carcinomas, infectious diseases, cardiovascular diseases, and neurological disorders. Vitamin D, an essential lipid‐soluble nutrient crucial for regulating calcium and phosphorus levels, is emerging as a potential solution to counteract treatment resistance and tolerance in various conditions such as cancer, tuberculosis, and depression. This review scrutinizes existing research and offers insights for future investigations aimed at fully elucidating the therapeutic potential of vitamin D in mitigating the challenges associated with prolonged medication regimens and drug treatment failures.Trial Registration: ClinicalTrials.gov identifier: NCT01169259 and NCT04342598.

Asthma is a complex respiratory disorder characterized by chronic inflammation and hyperresponsiveness of the bronchial airways. Despite the availability of effective treatments and diagnostic methods, some patients remain symptomatic and exhibit a poor response to conventional asthma therapies. Herbal drugs are considered safe and effective alternative approaches that may target multiple pathogenic pathways involved in asthma. Withania somnifera (WS) is a well-known medicinal plant containing several bioactive compounds and has been extensively studied for its anti-inflammatory and immunomodulatory properties. The present study aimed to explore the potential mechanisms of WS bioactive molecules in the treatment of asthma using an in silico screening approach. Six active phytoconstituents (ligands) of WS were docked against two target receptor proteins, namely the glucocorticoid receptor and the β₂-adrenergic receptor, to predict binding energies and binding patterns. The obtained results were compared with those of known ligands of the glucocorticoid and β₂-adrenergic receptors (fluticasone and salbutamol, respectively). Among all docked ligands, withaferin A, withanolide D, and withanolide B exhibited the highest binding affinities (lowest estimated free binding energy of -8.4 kcal/mol) toward the glucocorticoid receptor (GR). In contrast, the WS alkaloids tropine and anaferine showed lower affinities, as evidenced by higher binding energy values. Furthermore, withanolide D and withanolide B demonstrated the highest affinity for the β₂-adrenergic receptor among the screened compounds, whereas salbutamol and the plant alkaloids tropine and anaferine exhibited lower affinity toward the β₂-adrenergic receptor compared with the plant withanolides. WS bioactive compounds, particularly withanolides, are predicted to possess multitarget anti-inflammatory and bronchodilator potential. Further experimental validation is warranted.