Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 24, Issue 2, 2025

This study aimed to investigate the effects of genistein, swimming exercise, and their co-treatment on heart oxidative stress, inflammation, and cardiomyopathy in ovariectomized diabetic rats.

It is well-established that diabetes is a major risk factor for cardiovascular disease in both young and postmenopausal women. Genistein is a natural phytoestrogen that has estrogenic effects. Studies have shown that genistein has a positive impact on menopause, cardiovascular disease, and diabetes in women. However, the impact of genistein treatment alone and in combination with exercise training on the management of cardiac disease in diabetic women after ovarian hormone deprivation has not been fully explored.

The objective of this study was to evaluate the effect of genistein alone or in combination with exercise training on the cardiac expression of oxidative/inflammation biomarkers (MDA, OSI, TOS, TNF- α, and NF-κB) and miRNA-133, IGF-1, and Bcl-2 in the diabetic ovariectomized rats.

A group of Wistar rats were randomly divided into seven groups, with eight rats in each group. The groups were named control, sham, ovariectomized group (OVX), OVX +diabetes (OD), OD+ genistein (1 mg/kg, eight weeks; daily SC), OD+exercise (eight weeks), and OD+ genistein+exercise (eight weeks). The rats were given a high-fat diet and low-dose streptozotocin injection to induce diabetes. After eight weeks, the rats were anesthetized, and their hearts were removed. The study assessed the effects of treatment by measuring the expression of miRNA-133 using Real-time Polymerase Chain Reaction (PCR) and the protein levels of Bcl-2, Bax, and IGF-1 using Western blotting. The study also evaluated the levels of inflammation and oxidative stress markers using ELISA. Pathological changes were also assessed using periodic acid Schiff and hematoxylin & eosin.

After ovariectomy, the levels of cardiac miRNA-133, IGF-1, and Bcl-2 expression were down-regulated, and the levels of MDA, OSI, TOS, TNF-α, and NF-κB were increased, with a reduced total antioxidant capacity. Diabetes had an additive effect on these factors. Genistein was found to have a positive impact on oxidative and inflammation levels, and it also increased the expression of miRNA-133, Bcl-2, and IGF-1 in rats with OD. Furthermore, the combination of genistein and exercise had a positive effect on miRNA-133, Bcl-2, and IGF-1 expression in the heart, leading to a decrease in Bax levels. The combined intervention showed a noticeable improvement in oxidative and inflammation conditions. Histological examination revealed some abnormalities in cardiac tissue, which were found to be improved with genistein and/or exercise treatments.

Genistein or/and exercise as a natural replacement therapy could improve diabetic-induced cardiac complications in ovariectomized rats' hearts.

This study assessed the In-vitro Antioxidant and In-vivo Analgesics and Anti-inflammatory Activity of Allamanda blanchetii Leaf Extract in Rats.

Diverse pharmacological applications of plants from the Apocynaceae family are reported in the literature. Allamanda blanchetii; an ornamental species belonging to the Apocynaceae family, is characterized by diverse biological activities, i.e. antioxidant, cytotoxic, thrombolytic, membrane-stabilizing, antimicrobial, and anti-proliferative effects. This species represents a perennial flora that thrives in tropical and subtropical climates.

Ultrasonication-assisted method used for plant extraction. The extracts were subjected to phytochemical screening tests, followed by total phenolic content analysis, using gallic acid as a standard. The antioxidant activity was examined by DPPH scavenging and FRAP assays. The acetic acid-induced writhing test, tail flick, and Hot plate method were used for the determination of analgesic activity. Anti-inflammatory activity by following carrageenan-induced paw edema

ABLE treatments show analgesic effectiveness against the acid-induced pain source, tail flick, and hot plate methods at different doses of ABLE 400,200,100 mg/kg results showed respectively- 55.32, 38.67, and 22.85 (% inhibition), 89.47%, 62.57%, 49.57%, and 100%, 92.40%, 65.33% response after 180 min of drug administration. ABLE 400 and 200 mg/kg exhibit effective results (1.43± 0.005 and 1.50± 0.008) against carrageenan-induced intoxication.

The fundamental components of antioxidants that can aid in the reduction of free radicals include phenol, flavonoids, and polyphenols. Applying DPPH and FRAP, ABLE exhibits remarkable antioxidant activity. When it comes to both centrally and peripherally acting analgesics, ABLE exhibits highly effective activity. Methanolic ABLE had a noticeable impact on paw edema caused by carrageenan. Antioxidants, alkaloids, and glycosides were present in methanolic ABLE, which allowed it to efficiently combat inflammatory mediators and the cause of pain.

Ultrasonic assistance is beneficial in isolating active metabolites in plants, with phenolic compounds exhibiting antioxidant activity. ABLE, a plant with 55% squalene, effectively combats inflammatory mediators and pain. Further investigation is needed to identify biomarkers in the plant.

This study aimed at the synthesis of several spiro[benzofuran-3,3'-pyrroles] derivatives by a three-component reaction conducted by mixing DMAD, N-bridgehead heterocycles, and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. Moreover, in vitro evaluation of their cytotoxicity affinities against FMS-like tyrosine kinase 3 was carried out.

The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spiro[benzofuran-3,3'-pyrroles] derivatives.

A novel set of spiro[benzofuran-3,3'-pyrroles] ((11-13)a-e) was synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, N-bridgehead heterocycles and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. The compounds were analyzed using NMR ¹H, ¹³C, 2D-NMR (COSY, HMQC, HMBC), and HRMS. Docking simulations were conducted to elucidate the anticancer activity of synthesized compounds on FLT3 protein, with Gilteritinib as a reference for comparison.

This study demonstrated the successful design, synthesis, and biological evaluation of spiro[benzofuran-3,3'-pyrroles] derivatives as FLT3 inhibitors for AML treatment. The synthesized compounds demonstrated promising binding affinities and significant inhibitory activity against FLT3 kinase. The inhibitors (11a, 11b, 11c, 12d, and 12e) exhibited excellent selectivity profiles against FLT3. Particularly, compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM).

Fifteen new synthetic spiro[benzofuran-3,3'-pyrroles] were prepared, characterized, and evaluated for cytotoxicity affinities against FMS-like tyrosine kinase 3. Compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM), making it a promising candidate for further development as a therapeutic option for AML treatment. These findings lay the groundwork for further optimization and development of spiro[benzofuran-3,3'-pyrroles] derivatives as potential therapeutics for AML treatment. Further studies are needed to explore their efficacy and safety profiles in preclinical and clinical settings.

Indomethacin (IND), classified as class 2 in the Biopharmaceutical Classification System (BCS), has emerged as an anti-inflammatory agent with low solubility and high permeability. Widely used in the treatment of various diseases, such as rheumatoid arthritis and ankylosing spondylitis, this drug is well-known for its adverse effects, particularly in the stomach, and a short biological half-life, which is around 1.5-2 hours.

The aim of this study was to overcome the challenges of low solubility, short half-life, and serious side effects occurring with the use of IND-loaded formulations of Solid Lipid Nanoparticles (SLNs) and Polymeric Nanoparticles (PNPs).

For PNPs, emulsification/solvent evoporation method was employed, and for SLNs, the hot homogenizaton method was applied. Eudragit^® RLPO (RLPO) and Eudragit® RSPO (RSPO) were used as polymers for PNP and Dynasan^®116 (DYN) was used as the solid lipid for SLN. Prepared formulations were characterized for Particle Size (PS), Polydispersity Index (PDI), Zeta Potential (ZP), Encapsulation Efficiency (%EE), and drug-excipient compatibility using DSC, FT-IR, and ¹H NMR; cumulative drug release rates were assessed using HPLC and in vitro cytotoxicities were examined by the MTT assay.

Both PNP and SLN formulations’ zeta potential, particle size, and PDI results indicated the formulations to have good stability. Encapsulation efficiency values were obtained as desired. Drug-excipient compatibility was proved using DSC, FT-IR, and ¹H NMR. In vitro dissolution results have proven both formulations to have longer release than pure indomethacin. In the MTT analysis of indomethacin application for 24 and 48 hours, a linear correlation was observed between drug concentration and cell viability, and it was determined that the PNP formulation exhibited fewer toxic effects among the formulations. This has proven the PNP nanocarrier as safer for normal cells.

IND-loaded PNP and SLN formulations have been successfully prepared in this work and they have achieved drug release in the intestine and prolonged the release duration.