Therapeutic potential of bioconstituents in the prevention and treatment of rheumatoid arthritis

Background: Rheumatoid arthritis (RA), a joint disease characterized by inflammation and an autoimmune response, affects approximately 1% of the global population. The disruption of immunological tolerance causes the immune system to attack self-molecules, resulting in autoimmune disease. RA is characterized by synovial swelling, accompanied by morning stiffness and joint soreness. Methodology: Herbal pharmacotherapy is now a meaningful focus in the treatment of rheumatoid arthritis. Medicinal plants contain strong active components like flavonoids, alkaloids, stilbenoids, tannins, and sesquiterpene lactones. Their anti-inflammatory and antioxidant qualities make them a potential treatment option for RA. Results and Discussion: Standard medication aims to prevent further deterioration of the affected joint. This treatment includes several antirheumatic medications, such as methotrexate, biological agents, cytotoxic drugs, immunosuppressants, and NSAIDs. Urinary and respiratory tract infections have been reported in patients treated with certolizumab pegol. Several concerns regarding anti-rheumatoid medication arise during a woman's pregnancy. Therefore, rheumatoid arthritis is now being effectively treated with herbal pharmacotherapy. Conclusion: RA is a chronic autoimmune disorder that primarily affects joints through persistent inflammation. Conventional treatment regimens for RA can lead to the occurrence of adverse effects, such as urinary and respiratory tract infections. Given these challenges, herbal pharmacotherapy is emerging as a safer and more sustainable approach. This review highlights a variety of phytochemicals with anti-inflammatory and antiarthritic properties, including flavonoids, alkaloids, stilbenoids, tannins, and sesquiterpene lactones. It underscores the need for further research to elucidate their mechanisms of action, assess their long-term safety and clinical utility, and compare their efficacy

Chromatographic profiling of leniolisib impurities using HPLC and LC-MS/MS: degradation behaviour, structural characterization, and in-silico toxicity evaluation

Background: This study presents a comprehensive analytical investigation of leniolisib, focusing on impurity profiling, degradation kinetics, structural characterization, and in silico toxicity prediction of degradation products (DPs). Methodology: A systematic approach was employed to optimize the analytical method for leniolisib and its impurities, along with LC–MS/MS-based identification and in-silico toxicity prediction of DPs. Result and Discussion: Method optimized as Waters Symmetry C18 column and an isocratic mobile phase (methanol: sodium acetate buffer, 55:45 v/v) at 0.90 mL/min with UV detection at 229 nm. Leniolisib was most susceptible to acid and oxidative stress, resulting in 31.24% and 39.58% degradation, respectively. Pseudo-first-order kinetics was observed with rate constants of 0.0329 h⁻¹ (acidic) and 0.0414 h⁻¹ (oxidative), with half life of 21.08 h and 16.73 h. LC–MS/MS elucidates the identities of major DPs that enable the proposed degradation pathways. The MS/MS characterization confirms DP 1  with a formula of C13H15N5O with a mass of 257 g/mol, whereas DP 2, 3, and 4 were identified to have formulas of C20H26N6O2, C13H12F3N5O, and C17H19F3N6O with masses of 382, 311, and 380 g/mol, respectively. The In-silico toxicity predictions show DP 1 (LD₅₀ = 500 mg/kg) and DP 2 (729 mg/kg) as moderate toxicity (class 4), DP 4 shows the least toxicity (class 5, LD₅₀ = 1750 mg/kg), whereas DP3 shows the highest toxicity (class 3, LD₅₀ = 250 mg/kg). Conclusion: The developed method and accompanying data provide a critical foundation for routine quality control, stability testing, and regulatory submissions for leniolisib-based formulations

New information on the etiology and biological targets of wounds associated with diabetes

Background: Wound healing is a complex process that advances through inflammation, proliferation, and remodelling phases. Diabetes precipitates numerous ailments that obstruct practically all of these reparative processes. Methodology: We performed a literature search on ScienceDirect and PubMed databases using various keywords, including "Diabetes Wound Healing." The search was refined by applying relevant filters to obtain the most pertinent articles for this review article's objective. Results: Patients with diabetes may incur wounds during or after medical interventions. The wound healing process comprises remodelling, proliferation, and inflammation. Diabetes impedes nearly all of these healing processes through various pathological changes. This study primarily examines the molecular pathways of inflammatory substances, including growth stimulants and other factors that hinder wound healing. It also examines molecular targets and the current advancements in wound care and complete healing. Conclusion: Based on our investigation, we identified several practical approaches for treating wound inflammation and proposed that combining these strategies may yield the most significant results in our research domain

Exploring the structural aspects of alanine racemase enzyme for antitubercular drug discovery – a computational approach

Background: Tuberculosis (TB) is a communicable disease that is a significant cause of ill health and one of the leading causes of death worldwide. The current antibiotics have been pivotal in managing TB to a greater extent. Still, the issue of antitubercular drug resistance is indeed a matter of concern and requires effective drug discovery strategies targeting less explored targets. One of the less explored but promising antitubercular targets, Alanine racemase (AlaR), a prokaryotic enzyme providing the essential peptidoglycan precursor D-alanine (D-Ala) in bacterial cell wall synthesis, is an attractive target for antitubercular drug discovery. Objective: The current study aims to explore the available protein targets of the AlaR enzyme in Mycobacterium tuberculosis and to understand the structural aspects to be followed in designing inhibitors for them. Methodology: As a part of the study, the crystal structure of the alanine racemase enzyme from Mycobacterium tuberculosis was subjected to computational studies using the Schrodinger drug design suite. The significant protocols followed involved protein preparation and fragment-based drug design studies. Results and discussion: The in-silico data suggested that substituted pteridine derivatives, which impart stable interaction at the active site of the alanine racemase enzyme, may be the potential lead moiety for drug design. Conclusion: Although the preliminary screening suggests that the pteridine ring system may be a promising lead, detailed in silico studies must be carried out, such as molecular mechanic generalized born surface area (MM-GBSA), density functional theory (DFT) studies, induced fit docking, molecular dynamics, etc. for further authentication. For effective correlation, detailed in vivo studies on AlaR enzyme inhibition can be carried out from a future perspective

Chitosan-based mucoadhesive patches for buccal delivery of olmesartan in hypertension treatment

Background: Delivering poorly soluble drugs like Olmesartan (OMS) effectively remains a key challenge due to low oral bioavailability and extensive first-pass metabolism. To address this, buccal patches incorporating chitosan were developed as an alternative route to enhance systemic absorption. Methodology: A series of buccal patch formulations (F1–F17) was prepared using combinations of chitosan, polyvinyl alcohol (PVA), HPMC K4M, and Eudragit RL via solvent casting. These patches were evaluated for uniformity in weight, thickness, pH, mechanical strength, folding endurance, and mucoadhesion. Structural and morphological assessments were carried out using X-ray diffraction and SEM. Ex vivo and in vivo studies explored drug release, permeation, pharmacokinetics, and mucosal safety. An HPLC method was employed for accurate quantification, and stability was assessed under both accelerated and ambient conditions. Results and Discussion: The optimised patch (F2) demonstrated consistent physical properties, high flexibility, and strong mucoadhesion. XRD patterns confirmed the amorphous dispersion of OMS in the polymer matrix, aiding solubility. Drug release was sustained over 12 hours, and permeation studies showed controlled transport across the buccal membrane. In vivo results revealed a substantial improvement in drug bioavailability via buccal delivery (83.2%) compared to oral administration (30.2%). Histological analysis indicated no signs of tissue irritation. Patches maintained integrity and potency throughout six months of storage. Conclusion: The findings support the buccal patch as a viable, non-invasive platform for enhancing OMS delivery, offering improved therapeutic efficiency and patient compliance

A comprehensive review of peptic ulcer disease: epidemiology, experimental models, and mechanistic insights

Background: Peptic ulcer disease (PUD) is one of the most common gastrointestinal disorders, resulting from an imbalance between aggressive and protective factors, leading to mucosal erosion. Various factors influence its pathogenesis, including Helicobacter pylori infection, NSAID use, and oxidative stress. Objective: We review PUD epidemiology, varying experimental models, and mechanistic insights into PUD and promising therapeutics. Methodology: We systematically reviewed previous literature on PUD, including epidemiological trends, commonly used in vivo, and molecular mechanisms. Results and discussion: The global prevalence of peptic ulcer disease (PUD) follows an epidemiological pattern influenced by geography, lifestyle, and genetic factors. Experimental models using ethanol, NSAIDs, or Helicobacter pylori induction provide valuable insights into disease progression and pathophysiology. Emerging trends:  Recent research in peptic ulcer disease focuses on molecular mechanisms, gut microbiome interactions, personalized therapies, and novel pharmacological agents. Molecular studies explore genetic and epigenetic factors influencing ulcer formation, while microbiome research examines the role of gut bacteria beyond H. pylori. Personalized treatment approaches use genetic profiling and biomarkers to enhance efficacy and reduce toxicity. Additionally, emerging pharmacological agents aim to improve acid suppression, promote mucosal healing, and develop more effective H. pylori eradication strategies. Conclusion: A deeper understanding of PUD pathophysiology through epidemiological studies and experimental models can aid in developing novel, targeted therapies. Future research should focus on alternative treatments, including phytochemicals and probiotics, to enhance ulcer prevention and management

Phytochemical analysis, antioxidant potential, and cytotoxic activity of extracts of Quisqualis indica L.

Background: The present study investigates the antioxidant and cytotoxic potential of the 50% hydroalcoholic extract of Quisqualis indica leaves. Methodology: Phytochemical screening was conducted to determine the presence of phenolics and flavonoids. TPC and TFC were analyzed using the Folin–Ciocalteu method and the aluminum chloride colorimetric assay, respectively. The antioxidant activity was evaluated through the DPPH radical scavenging assay at concentrations ranging from 10 to 100 µg/mL. Cytotoxicity was assessed in A549 human lung carcinoma cells using the MTT assay with extract concentrations from 0 to 1000 µg/mL. Results and Discussion: Phytochemical analysis confirmed the presence of phenolics and flavonoids, with total phenolic content measured as 9.25 ± 0.081 mg gallic acid equivalents (GAE)/g 50% hydroalcoholic extract and total flavonoid content as 4.33 ± 0.24 mg quercetin equivalents (QE)/g 50% hydroalcoholic extract. Antioxidant activity was assessed using the DPPH radical scavenging assay across extract concentrations ranging from 10 to 100 μg/mL. The 50% hydroalcoholic extract exhibited a dose-dependent antioxidant effect with an IC50 value of 48.56 μg/mL. Cytotoxicity was evaluated against A549 human lung carcinoma cells using the MTT assay, with treatments administered at concentrations ranging from 0 to 1000 μg/mL. The extract demonstrated significant cytotoxicity with an IC50 value of 4.76 μg/mL. Conclusion: These findings suggest that Q. indica may serve as a potential source of bioactive compounds with antioxidant and anticancer activities, warranting further investigation through in vivo and mechanistic studies

QbD enabled optimization study of the variable concentration of phospholipid and stabilizer in the development of liposomal pastilles of solid dispersion polymeric composite of antihypertensive drug

Background: The study aimed to develop and optimize liposomes of the antihypertensive drug Felodipine (FH) using the Quality by Design (QbD) approach with a 3² Central Composite Design (CCD) in Design Expert software, followed by the development of pastilles. Methodology: Liposomes were prepared using the solvent injection method, with soya lecithin and cholesterol as key excipients, and a solid dispersion of FH. The impact of their concentrations on particle size (PS), drug content (DC), entrapment efficiency (EE), and in vitro and ex vivo drug release was analyzed using response surface methodology. The optimized formulation was validated using four batches (optimized batch, VC1, VC2, and VC3), ensuring a minimal percentage error. The liposomal formulation was incorporated into pastilles to enhance patient compliance, and these were evaluated for drug content, dissolution, bioadhesion, and stability. Results and Discussion: The optimized liposomes exhibited desirable properties, including a positive surface charge (PS, 1.41±0.12), a high DC (94.323±1.03), a high EE (69.61±1.13), in vitro drug release (70.73±1.08), and ex vivo drug release (66.88±0.23). The validation batches showed minimal percentage error, confirming the optimization process. The pastilles demonstrated excellent physical stability and bioadhesion, indicating their potential for improved patient compliance. Conclusion: The study showed the effectiveness of the QbD approach in optimizing a liposomal drug delivery system for FH, thereby minimizing the need for extensive trials. The incorporation of liposomes into pastilles provided a patient-friendly dosage form with enhanced bioadhesion and stability, making it a promising alternative for antihypertensive drug delivery

Development of a fast-acting nanosuspension nasal drop using a novel co-processed polymer for migraine relief

Background: Effective central nervous system (CNS) drug delivery remains challenging due to the blood-brain barrier. Nasal drug delivery offers a non-invasive alternative, ensuring rapid drug absorption and onset of action. Prochlorperazine Maleate, a drug for migraines, suffers from poor solubility, limiting its therapeutic potential. Methodology: A nanosuspension-based nasal drop was developed and optimized using high-pressure homogenization. A novel co-processed polymer enhances solubility and stability. Key formulation parameters, including particle size, zeta potential, and polymer concentration, were optimized using a central composite design. The optimized nanosuspension was characterized for its physicochemical properties, drug release, and stability. Results and Discussion: The optimized formulation (Batch F9) exhibited a particle size of 78.8 nm and a high drug release rate (93.87% in 8 hours). Stability studies confirmed no significant changes in drug content, pH, or osmolality over a three-month period. The nasal drop provided consistent dosing, with each actuation delivering a precise amount of drug content. In vitro drug release studies demonstrated a sustained release pattern, enabling prolonged migraine relief. Conclusion: The developed nanosuspension nasal drop presents a promising solution for CNS drug delivery, ensuring rapid and sustained therapeutic outcomes. This nanosuspension nasal drop achieved a 5.6-fold enhancement in solubility and demonstrated rapid onset within 10 minutes post-administration. Although promising, the study is limited to in vitro characterization; future research should explore in vivo efficacy and long-term safety

Preliminary phytochemical screening, FT-IR, and HPTLC analysis, and antioxidant, antimicrobial activities of methanolic extracts of Dalbergia sisso leaves

Background: Dalbergia sissoo is a well-known plant known as Shisham. It has medicinal importance, including analgesic, antipyretic, and antiemetic properties. Therefore, the primary objective of this research is to investigate the bioactive constituents in the methanolic leaf extract of Dalbergia sisso by characterizing it using FT-IR and HPTLC techniques, and to determine its antioxidant and antimicrobial activities. Methodology: A Soxhlet apparatus was used for the extraction process. 150 g of Dalbergia sisso powdered leaves was extracted using a Soxhlet apparatus for 30 hours, utilizing methanol as a solvent. The solvent was vaporized and concentrated to produce a dry residue once the extraction was finished. The yield percentages for the methanolic extract were 4.8% respectively. Result and Discussion: FT-IR spectroscopy showed different peak values for functional compounds in the methanolic extract. The FTIR spectrum of the methanolic leaf extract shows the interpretation of the chemical bonds in the methanolic leaf extract. HPTLC studies revealed that the active compound lupeol is present in the methanolic extract. Conclusion: It has been concluded that the methanolic extract of Dalbergia sisso leaves contains lupeol and quercetin bioactive compounds. The methanolic extract of Dalbergia sisso leaves was found to have antioxidant and antimicrobial effects. The HPTLC technique found lupeol, which may possess antioxidant and antimicrobial activities. The FT-IR spectrum revealed the presence of hydroxyl, hydrocarbon, aldehyde, allene, and secondary alcohol groups in the methanolic extract, consistent with the presence of quercetin. The methanolic leaf extracts show the presence of saponin, alkaloids, flavonoids, anthraquinone glycosides, and tannins