Inflammation is a vascular response that occurs when the immune system responds to a range of stimuli including viruses, allergens, damaged cells, and toxic substances. Inflammation is accompanied by redness, heat, swelling, discomfort, and loss of function. Natural products have been shown to have considerable therapeutic benefits, and they are increasingly being regarded as feasible alternatives for clinical preventative, diagnostic, and treatment techniques. Natural products, in contrast to developed medications, not only contain a wide variety of structures, they also display a wide range of biological activities against a variety of disease states and molecular targets. This makes natural products appealing for development in the field of medicine. In spite of the progress that has been made in the application of natural products for clinical reasons, there are still factors that prevent them from reaching their full potential, including poor solubility and stability, as well limited efficacy and bioavailability. In order to address these problems, transdermal nanovesicular gel systems have emerged as a viable way to overcome the hurdles that are encountered in the therapeutic use of natural products. These systems have a number of significant advantages, including the ability to provide sustained and controlled release, a large specific surface area, improved solubility, stability, increased targeting capabilities and therapeutic effectiveness. Further data confirming the efficacy and safety of nanovesicles–gel systems in delivering natural products in preclinical models has been supplied by extensive investigations conducted both in vitro and in vivo. This study provides a summary of previous research as well as the development of novel nanovesicular gel formulations and their application through the skin with a particular emphasis on natural products used for treatment of inflammation.

Background and Objectives: Parkinson’s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD.

Sulpiride (Sul) is a medication that blocks dopamine D₂ receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim of this study was to generate a glycerosomal in situ gel of sulpiride for intranasal administration, specifically targeting children with schizophrenia who may have difficulty swallowing traditional solid medications, for enhancing its bioavailability. This study aimed to demonstrate the efficacy of intranasal administration of glycerin-encapsulated lipid-nanovesicles (glycerosomes) mixed with in situ gels for prolonged release of anti-psychotic medication. A Box–Behnken design was utilized to create sulpiride-loaded glycerosomes (Sul-GMs), with the lipid amount (A), glycerin concentration (B), and sonication time (C) acting as independent variables. Their impact on the entrapment efficiency, EE% (Y₁), and in vitro drug release (Y₂) were evaluated. The sulpiride EE% showed an increase when the glycerin concentration was raised to 25% v/v. Nevertheless, when the glycerin concentration was raised to 40% v/v, there was a notable decrease in the EE%. The optimized glycerosome was added to pH triggered carbopol 974P in situ gel formulations including HPMC K15M with different concentrations. The in situ gel formulation (G3) comprising 0.6% carbopol 974P and 0.6% hydroxypropyl methyl cellulose-K15M (HPMC K15M) demonstrated suitable pH, viscosity, desired gel strength, spreadability, and mucoadhesive strength. Consequently, it was selected for in vitro study, ex vivo permeation investigation, and in vivo evaluations. The glycerosomal in situ gel exhibited favorable ex vivo permeability of SU when applied to the nasal mucosa. The pharmacokinetic investigation revealed that the optimized Sul-loaded glycerosomal in situ gel exhibited a significant fourfold and twofold enhancement in systemic bioavailability compared to both the control gel and the commercially available formulation. Finally, the intranasal administration of Sul-loaded glycerosomal in situ gel is a promising alternative to oral treatment for pediatric patients with psychosis.

Background/Objectives: Bleomycin is an antineoplastic antibiotic used in the management of various malignancies. Nevertheless, its benefits are constrained by the development of pulmonary fibrosis. Amentoflavone, a biflavonoid, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, antioxidant, and antitumor effects, whereas alogliptin possesses antioxidant and anti-inflammatory properties. This study aimed to assess the potential protective effects of alogliptin and/or amentoflavone in a murine model of bleomycin-induced pulmonary fibrosis and to clarify the underlying mechanisms. Methods: Fifty male C57BL/6 mice were randomly divided into 5 equal groups: control, bleomycin, bleomycin + alogliptin, bleomycin + amentoflavone, and bleomycin + alogliptin + amentoflavone. The assessed endpoints included lung weight/body weight index, lung tissue fibrotic mediators, oxidative stress parameters, proinflammatory cytokines, and pyroptotic and autophagy mediators. Also, the bronchoalveolar lavage fluid (BALF) was evaluated for total and differential leukocytic counts and lactate dehydrogenase (LDH) activity. Moreover, vascular responses to potassium chloride, phenylephrine, and carbachol, together with tracheal responses to carbachol were determined. Lung tissues were further examined histopathologically and immunohistochemically. Results: Treatment with alogliptin and/or amentoflavone significantly decreased the lung weight/body weight index and BALF LDH activity, concomitant with mitigation of lung tissue oxidative stress parameters, fibrotic mediators, apoptosis, and pyroptosis with a significant augmentation of autophagy signals, alongside marked improvement in the lung architecture and vascular and airway reactivity compared with the bleomycin group. These effects were most pronounced with animals treated with the alogliptin/amentoflavone combination. Conclusions: These findings suggest that combined alogliptin and amentoflavone may constitute a promising strategy to prevent bleomycin-induced lung fibrosis.

Phenformin, a representative of the biguanides class was previously used for treatment of type 2 diabetes and discontinued due to a risk of causing lactic acidosis, has shown promising anticancer activity in numerous studies. Since many types of cancer arise and proliferate due to dysregulation in apoptotic or autophagic pathways, this study aimed to assess the underlying anticancer effects of phenformin in terms of these two processes. We initially set out to examine the antiproliferative effects of phenformin on multiple cancer cell lines including breast, pancreatic, cervical cancers, hepatocellular carcinoma and malignant melanoma. Subsequently, the expression of apoptosis and autophagy related proteins was measured in the cervical cancer cell lines found to be the most susceptible to antiproliferative effects of phenformin. Additionally, the ability of phenformin to potentiate the antitumor effect of resveratrol and vistusertib was assessed. Phenformin increased the expression of pro-apoptotic factor, Bax, and lowered the level of anti-apoptotic protein, Bcl-2. Hence, it was proposed that phenformin promotes antiproliferative activity by inducing apoptosis. Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner and may have an ability to increase the autophagic flux in cervical cancer cells. Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner potentially by inducing apoptosis.