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Pain relieving impacts of chrysin via down-regulation of hypothalamic Tac1 and CGRP in a Rat model of formalin-induced pain
Khadijeh Haghighat , Fariba Mahmoudi , Homayoun Khazali,
Volume 12, Issue 3 (12-2024)
Abstract
Background: Chrysin is a natural bioactive compound belonging to the flavonoid group. The pain-relieving effects of chrysin have been reported in several studies; however, the molecular mechanism underlying its analgesic properties remains unknown. In the present study, the analgesic effect of chrysin was investigated on the hypothalamic Calcitonin Gene-Related Peptide (CGRP) and Tachykinin 1 (Tac1) gene expression in a formalin-induced pain model.
Methods: Twenty male rats weighing 200 ± 10 g were divided into four groups. Pain was induced by injecting 50 μl of formalin into the hind paw. The control and formalin groups received saline. In addition, 20 or 40 µg of chrysin was injected into pain-induced rats via the third cerebral ventricle. After 30 minutes, a behavioral test was conducted. Hypothalamus samples were then dissected, and real-time polymerase chain reaction (PCR) was performed to measure gene expression.
Results: The mRNA levels of CGRP and Tac1 significantly increased in the formalin-treated rats compared to the control group. In contrast, the mRNA levels of CGRP and Tac1 were significantly reduced in the chrysin-treated groups compared to the formalin group. Furthermore, the pain score was significantly lower in the chrysin-treated groups compared to the formalin group.
Conclusion: The pain-relieving effects of chrysin were mediated through the downregulation of hypothalamic CGRP and Tac1 in the pain model rats.

Dorema Aucheri and exercise training in enhancing PPARγ/mTOR/PI3K gene expression in muscle tissue of hypothyroid mice: experimental approaches using a hypothyroid mouse model
Malihe Bakhti, Farzaneh Taghian, Khosro Jalali Dehkordi , Rezvan Mirsafaei Rizi,
Volume 12, Issue 3 (12-2024)
Abstract
Background: Hypothyroidism is typically associated with a decreased basal metabolic rate, reduced energy expenditure, and weight gain. Exercise training and Dorema Aucheri (DA) have been identified as beneficial therapeutic strategies within complementary health approaches. Skeletal muscle metabolism and fiber type are regulated by innervation and soluble factors, such as thyroid hormones. However, the mechanisms between muscle function and hypothyroidism remain unclear.
Methods: Thirty mice were divided into five subgroups: the normal group; hypothyroid mice (HYPO, 8 mg/kg of propylthiouracil administered via intraperitoneal injection for 30 days); hypothyroid mice treated with DA (gavaged at 0.4 mg/kg for two months, five days per week); hypothyroid mice treated with exercise (75% VO2 max, 45 minutes per session, for two months, five days per week); and hypothyroid mice treated with both DA and exercise. The mRNA expression levels were detected via real-time qPCR.
Results: The data indicated that PPARγ, mTOR, and PI3K levels are reduced in hypothyroidism. DA and exercise enhanced PPARγ, mTOR, and PI3K levels in muscle tissue. Notably, DA and exercise significantly increased the expression levels of PPARγ, mTOR, and PI3K.
Conclusion: Exercise and DA, as alternative and complementary medicine, modified the PPARγ/mTOR/PI3K signaling pathways affected by hypothyroidism in mice.
 

Molecular docking reveals curcumin and catechin as potent inhibitors of histamine N-Methyltransferase (HNMT) and its T105I and L208P Variants
Mehrsa Amoozadeh , Mehdi Sadeghi ,
Volume 13, Issue 2 (6-2025)
Abstract
Background: Histamine plays a crucial role in regulating diverse physiological and pathophysiological functions, including gastric acid secretion, vasodilation, and bronchoconstriction. As a neurotransmitter, it is also implicated in allergic reactions, contributing to symptoms such as itching, sneezing, and inflammation. Given the potential adverse effects of histamine activity, antihistamines are frequently prescribed to mitigate its effects. However, the associated side effects of these drugs have prompted researchers to investigate natural alternatives, such as curcumin from turmeric and catechins from green tea. This study investigates the potential effect of curcumin and catechin on the histamine N-methyltransferase (HNMT) receptor and its T105I and L208P mutant variants.
Methods: Molecular docking was employed to analyze ligand-receptor interactions. The protein structure was obtained from the Protein Data Bank (PDB), and ligands were retrieved from PubChem. Ligand structures were optimized using Avogadro software, and docking studies were subsequently performed using AutoDock Tools and the Vina algorithm.
Results: Molecular docking studies have demonstrated strong binding affinities of catechin and curcumin to the target protein, with binding energies of -8.5 and -8.4 kcal/mol, respectively, which is more than twice the binding affinity of histamine (-4.0 kcal/mol). Analysis of docking results with variant proteins revealed a slight reduction in ligand binding energies compared to the normal protein. These findings suggest that both catechin and curcumin hold promise as potential therapeutic agents for patients with the studied variants of the target protein. Furthermore, docking analysis revealed key stabilizing interactions, including π–π stacking and hydrogen bonding.
Conclusion: Phe243 is a key binding site residue in HNMT, showing consistent strong interactions with all tested ligands. Its structural flexibility enables effective binding to compounds like catechin and curcumin, making it a prime target for designing new HNMT inhibitors.

Comparative Antibacterial Activity of Nettle (Urtica dioica) and Mallow (Malva spp.) Essential Oils
Mojtaba Raeisi , Paria Tavakkoli , Masood Aman Mohammadi ,
Volume 13, Issue 2 (6-2025)
Abstract
Background: Essential oils derived from medicinal plants have attracted increasing attention as natural alternatives to synthetic antimicrobial agents, especially in food safety and preservation. Urtica dioica (nettle) and Malva spp. (mallow) are traditionally known for their medicinal properties, yet their combined antibacterial effects remain underexplored. This study investigated the in vitro antibacterial activity of nettle and mallow essential oils, both individually and in combination (1:1 ratio), against ten common foodborne pathogens responsible for spoilage and contamination.
Methods: Essential oils were extracted from U. dioica and Malva spp., then tested alone and in a 1:1 (v/v) combination for their antibacterial efficacy using agar disk diffusion and broth microdilution assays. The tested bacterial strains included Pseudomonas aeruginosa, Streptococcus pyogenes, Alcaligenes faecalis, Serratia marcescens, Salmonella enteritidis, Staphylococcus aureus, Shigella dysenteriae, Listeria monocytogenes, Klebsiella pneumoniae, and Escherichia coli. Gentamicin (10 µg/disk) was used as a positive control. Data were analyzed to calculate the inhibition zone diameter (DIZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). All experiments were performed in triplicate (n = 3), and results were expressed as mean ± standard deviation (SD). Statistical analysis was carried out using one-way ANOVA followed by Tukey’s post hoc test to compare differences among treatment groups.
Results: All essential oil formulations showed antibacterial activity, with MIC values for nettle essential oil (NEO) ranging from 1,250 to 5,000 µg/mL and for mallow essential oil (MEO) from 2,500 to 10,000 µg/mL. The 1:1 combination of NEO and MEO retained NEO’s favorable MIC and delivered a lower MBC for K. pneumoniae compared to MEO alone. Across strains, MIC differences were not uniformly significant. For L. monocytogenes, NEO showed equal MIC and MBC (1,250 µg/mL), indicating its bactericidal activity.
Conclusion: Nettle and mallow essential oils possess significant antibacterial activity against key foodborne pathogens. Their simultaneous application yielded additive effects against some pathogens. These findings support the potential of these essential oils as natural antimicrobial agents to be used in food preservation systems, including for antimicrobial packaging and as edible coatings or surface sanitizers.

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