Iranian Journal of Basic Medical Sciences
Volume:26 Issue: 1, Jan 2023

Nowadays, the global interest in the use of herbal medicines and their main components in developing novel effective medications with fewer adverse effects is rising. Precise medicinal plants have potential advantageous applications for several neurodegenerative disorders. Portulaca oleracea L. (purslane) belongs to the Portulacaceae Juss family. In folk medicine, it has been used as a febrifuge, antiseptic, vermifuge, and in treating arthritis, burns, cough, headache, intestine, stomach, liver disorders, as well as shortness of breath. Pharmacological investigations have also disclosed its antioxidant, anti-inflammatory, anti-apoptotic, immunomodulatory, antidepressant, anxiolytic, and neuroprotective properties. The current work prepared an updated and broad literature review on purslane highlighting its therapeutic effects on some nervous system disorders. It has been shown that P. oleracea and its active constituents have considerable neuroregenerative, neuroprotective, and antinociceptive properties. Accordingly, our team classified and discussed the outcomes of some nervous system disorders comprising Alzheimer’s disease, Parkinson’s disease, depression, epilepsy, anxiety, psychosis, drug dependence, hypoxia, and pain; although, additional preclinical and clinical assessments are necessary to reinforce the beneficial effects of purslane on nervous system disorders.

Pulmonary fibrosis (PF) is a global health problem with a high economic burden. Intratracheal administration of bleomycin is the best model that resembles the pathogenesis of PF in humans. Recently, vinpocetine proved to have neuroprotective, cardioprotective, hepatoprotective, anti-aging, and antifibrotic effects through its anti-oxidant, immunomodulating, and anti-inflammatory activities. The present study investigated the antifibrotic potentiality of vinpocetine in a rat model of PF induced by intratracheal bleomycin administration. 

PF induced by a single intratracheal instillation of 5 mg/kg bleomycin in nine-week-old Wister rats. Oral vinpocetine was used at doses of 5, 10, or 20 mg/kg to treat PF for 21 days immediately after the bleomycin instillation. 

Vinpocetine dose-dependently ameliorates PF induced by bleomycin administration since vinpocetine effectively restored the normal body weight gain rates, pulmonary architecture, and collagen fiber distribution and suppressed the elevated BALF cell count, lymphocytes and neutrophils percentage, BALF, IL-6, TNF-α, and TGF-β1 levels and LDH activity, lung tissue MDA level, PDE activity, hydroxyproline content, immunohistochemical expression of α-SMA and CD68 positive macrophage, and fibrosis score. Meanwhile, it efficiently augmented the reduced BALF macrophage percentage, IL-10 level, lung tissue GSH level, CAT, and SOD activities. 

Vinpocetine may propose a new promising agent to manage PF.

Chronic methamphetamine (METH) abuse is recognized as an important risk factor for cognitive impairment. A plant-based isoquinoline alkaloid, Berberine hydrochloride (BER), shows memory and cognition enhancement properties. Due to the aim of the present study which is to investigate the influence of BER administration on METH-induced cognitive deficits, we investigated neurotrophin signaling including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) as a possible mechanism by which BER exerts its cognitive improvement influences. 

In this experimental study, thirty-two male Wistar rats were randomly classified into four groups, including non-treated control, intubated control, METH-inhaled, and METH-inhaled + BER-intubated. Rats in the METH-inhaled group underwent METH inhalation for 14 days, and the BER-inhaled and BER-intubated rats were intubated (100mg/kg) for the following three weeks. A novel object recognition task (NORt) was carried out on days 36 and 37. Rats were sacrificed for histological preparations after the behavioral tests. Neurotrophic factors, including GDNF and BDNF, were evaluated by immunofluorescence staining in the hippocampus. 

This experiment indicated a dramatic improvement in cognitive deficits associated with chronic METH abuse (P<0.001). Furthermore, a significant decrease in the expression of both neurotrophins, GDNF (P<0.001) and BDNF (P<0.001), was observed in the METH-inhaled group compared with the METH-inhaled group treated with BER and non-treated control group. 

Activation of neurotrophic factors after BER administration resulted in improvement of METH-induced cognitive deficits. Therefore, BER may be considered a promising treatment for METH users who experience cognition deficits.

Epicardial adipose tissue (EpAT) is known for its role in supporting the cardiomyocytes. Lysine-specific demethylase 1 (LSD1), a typical lysine demethylase, is an essential regulator for the maintenance of beige adipocytes. However, the effect of LSD1 in the adipogenic differentiation of beige adipocytes in EpAT, and its function on oxygen and glucose deprivation (OGD)-injured cardiomyocytes remain unclear.

Heart tissues from young mice and elder mice were collected for immunohistochemical staining. LSD1 in 3T3-L1 cells was knocked down by LSD1-shRNA lentivirus infection. The qRT-PCR, western blotting, and Oil Red O staining were employed to detect the adipogenic differentiation of 3T3-L1 cells and formation of beige adipocytes. The cardiomyocytes co-cultured with beige adipocytes were used for OGD treatment. Cell apoptosis was analyzed by flow cytometry. The lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were analyzed using commercially available kits.

The decrease of LSD1 was related to the age-dependent loss of beige adipocytes in mice EpAT. LSD1 knockdown inhibited the adipogenic differentiation of 3T3-L1 cells and formation of beige adipocytes. The down-regulation of LSD1 in 3T3-L1 cells decreased the protective effect of mature adipocytes on OGD-injured cardiomyocytes.

The decreased expression of LSD1 in mice EpAT was associated with age-dependent ablation of beige adipocytes. The protective effect of beige adipocytes on OGD-injured cardiomyocytes is reduced by knockdown of LSD1 in adipocytes. The present study provided exciting insights into establishing novel therapies against age-dependent cardiac diseases.

A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood.

Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted in silico and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the mean-centering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping. 

The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4–50 and 0.5–2.5 µg/ml for MF and CP, respectively. Recovery was 99.61–100.38% for UV and 100.4% for HPLC methods of MF and 100.6–101.4% for UV and 99.5% for HPLC methods of CP.

The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures.

To clarify therapeutic potential of albiflorin and its intrinsic mechanisms against dextran sulfate sodium (DSS)-induced Ulcerative colitis (UC) mice.

Sixty male C57BL/6 mice were randomly divided into five groups: negative control, positive, albiflorin low-dose group, albiflorin high-dose group and treatment control (Salicylazosulfapyridine “SASP”, 100 mg/kg) group. Acute colitis was induced in all groups except NC by administration of 3% DSS for 7 days. Albiflorin and SASP were administered via the intragastric route twice a day for 7 days. The changes of colon tissue were assessed by disease activity index (DAI), HE staining, and ELISA. Adrenodoxin expressions of UC colon tissues were evaluated by immunohistochemistry. Western blotting was performed to investigate related protein of the NF-κB and MAPK signaling pathways. 

It has been found that the albiflorin shares similar influences as the SASP in ameliorating the DSS-induced UC. The reduced DAI and alleviated colon tissue damage were observed in albiflorin intervened groups. Moreover, albiflorin significantly inhibited myeloperoxidase activities and attenuated immuno-inflammatory response and elevated Foxp3 mRNA in colon tissue. Furthermore, investigations revealed that albiflorin could inhibit adrenodoxin isoform and activate activated phosphorylated NF-κB p65 and IκBα, which consequently suppressed phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK).

These findings showed that albiflorin could alleviate DSS-induced murine colitis by activating inhibiting NF-κB and MAPK signaling pathways. It might be a potential therapeutic reagent for UC treatment.

Nanotechnology has helped a lot in diagnosing and treating multiple illnesses, specifically cancer, and increasing the development of targeted drug delivery methods. Nanocomposites are materials with at least one component smaller than 100 nm. Therefore, this study aims to assess the anticancer effects of silver-graphene nanocomposite on MCF-7. 

In this study, the rate of inhibition of cancer cell growth and production of reactive oxygen radicals, malondialdehyde, and glutathione stores in MCF7 cells were investigated. Cancer cells were exposed to nano particles for 48 hr. Silver nanoparticles and graphene both reduced the growth rate of MCF-7. 

Subsequently, by treating the cells with silver-graphene nanocomposite, the rate of inhibition of cell growth at the highest concentration was 84.60%. Nanoparticles also inhibited the growth of cancer cells through the oxidative stress pathway by increasing the amount of intracellular ROS, followed by increasing malondialdehyde and decreasing glutathione stores, so that at the highest combined concentration of nanoparticles, the amounts of LPO and ROS increased  up to 70% and 74 %, and glutathione reserves decreased by 16%. 

Treatment of MCF-7 cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors, such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation. According to the mathematical model, silver graphene nanocomposite> silver nanoparticles> graphene has the best effect in inhibiting the growth of cancer cells, respectively.

We investigated the harmful effects of high fructose corn syrup (HFCS) on learning and memory in the hippocampus and the ameliorative effects of melatonin (Mel). 

Thirty-six adult male Sprague Dawley rats were divided into three groups: Group I, control; Group II, HFCS; and Group III, HFCS+Mel. HFCS form F55 was prepared as a 20% fructose syrup solution. Rats in HFCS and HFCS+Mel groups were given drinking water for 10 weeks. Rats in the HFCS+Mel group have been given 10 mg/kg/day melatonin orally for the 6 weeks, in addition to HFCS 55. The Morris water maze (MWM) test was applied to all animals for 5 days to determine their learning and memory levels. After decapitation, one-half of the hippocampus samples were collected for western blot analysis, and another half of the tissues were collected for histopathological and immunohistochemical analyses. 

In the HFCS group, there was a significant difference between the time to find the platform in the MWM test and time spent in the quadrant between days 1 and 5 (P=0.037 and P=0.001, respectively). In addition, a decreased level of MT1A receptor, TNF-α, iNOS, osteopontin (OPN), and interleukin-6 (IL-6) expressions were significantly increased in the HFCS group. Melatonin treatment reversed MT1A receptor levels and TNF-α, iNOS, OPN, and IL-6 expressions. During the histopathological examination, increased neuronal degenerations were observed in the HFCS group. Melatonin ameliorated these changes.

Consumption of HFCS caused deterioration of learning and memory in adult rats. We suggest that melatonin is effective against learning and memory disorders.

Influenza A virus (IAV) is a contagious illness. Different species of Scutellaria genus are used as a traditional remedy to reduce influenza symptoms. This study aimed to investigate the anti-influenza capacity of several species of Iranian Scutellaria and identify active compounds of the most potent species for the first time.

Some Iranian species of Scutellaria were collected from different regions of Iran, including S. pinnatifida with mucida, viridis, and alpina subspecies; S. tournefortii; S. tomentosa; S. persica. They were fractionated to chloroform and methanol. The total phenols and flavonoids of samples were examined by the folin-ciocalteau and aluminum-flavonoid complex methods, respectively. The 50% cytotoxic concentrations (CC50) on MDCK cells and non-cytotoxic concentrations (NCTC) were determined by MTT assay. The percentage of cell protection against IAV and their effect on virus titer were investigated in pre-, post-, and co-penetration treatment groups. Phytochemicals of the most effective species were isolated by various chromatographic methods and identified by different spectroscopic methods.

Methanol fraction of S. pinnatifida subsp. viridis demonstrated the highest amounts of flavonoid content and best activity against influenza A virus in all combination treatments, which reduced the virus titer by 5 logs with no cytotoxicity. Kaempferol-3-O-glucoside, quercetin-3-O-glucoside, apigenin-4′-methoxy-7-O-glucoside, luteolin, and luteolin-7-O-glucoside were purified and identified from this species.

Scutellaria pinnatifida subsp. viridis can be introduced as a source of flavonoids with acceptable anti-influenza activity. S. tomentosa also showed potent antiviral effects and is a candidate for elucidation in further studies.

Many persistent harmful stimuli can result in chronic liver diseases, which lead to about 2 million deaths per year in the whole world. Liver fibrosis was found to exist in all kinds of chronic liver diseases. Many studies suggested that DNA methylation was associated with the pathogenesis of liver fibrosis. This study aimed to quantitatively detect DNA methylation changes in the whole genome in fibrotic liver tissues of mice.

Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) for 4 weeks. A genome-wide methylome analysis was performed using 850K BeadChips assays. The methylation status of 27 CpG dinucleotides located in 3 genes was detected by pyrosequencing to confirm chip data accuracy, and mRNA expressions of these 3 genes were examined by RT-qPCR methods.

A total of 130,068 differentially methylated sites (DMS, 58,474 hypermethylated, and 71,594 hypomethylated) between fibrotic liver tissues and control mice liver tissues were identified by the 850k BeadChips array. Consistency between pyrosequencing data and 850k BeadChips array data was observed (R=0.928; P<0.01). Apoptosis, positive regulation of transcription of Notch receptor target, and negative regulation of p38MAPK signal cascade activities were significantly enriched in the Gene Ontology (GO) analyses. Cholesterol metabolism, bile secretion, and more biosynthesis and metabolism pathways were enriched in KEGG pathway analyses. Ten key genes were identified by the Cytoscape plugin cytoHubba. 

7850 genes were found to have methylation change in fibrotic liver tissues of mice, which facilitates future research for clinical application.

This research was designed to study the prevalence of OqxAB efflux pump genes and also to investigate the relationship between efflux pump and resistance to antibiotics, especially to fluoroquinolones, evaluate the expression levels of OqxAB genes, and molecular typing of Klebsiella pneumoniae isolated from hospitalized patients in Hamadan hospitals, west of Iran.

In a cross-sectional study, 100 clinical strains of K. pneumoniae were isolated from hospitalized patients in three major teaching hospitals from January to June 2021. The antibiotic susceptibility of isolates was evaluated by the disk-diffusion agar method. The frequency of genes encoding oqxA and oqxB of efflux pump genes was investigated by PCR, and the expression of the oqxA efflux pump gene was investigated by the Real-time PCR method. The genetic relationship of K. pneumoniae isolates was analyzed by the Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR technique.

According to our results, the multi-drug resistance phenotype (MDR) in 65% and high prevalence resistance to ciprofloxacin in 89% of K. pneumoniae isolates was detected. The higher prevalence of oqxA (95%) and oqxB (98%) was also detected. There was a significant relationship between ciprofloxacin resistance and the oqxB gene as well as between ceftriaxone and chloramphenicol resistance and the oqxA gene. The expression of the oqxA gene was higher in ciprofloxacin-resistant isolates.

The results of this study suggest a potential reservoir for the spread of OqxAB genes among hospital-acquired bacteria. Infection control strategies should be used prudently to reduce the spread of resistant strains of K. pneumoniae in hospitals.

The current study, the first of its kind in the literature, aimed to observe the toxic effects of Tartrazine, a commonly used dyestuff in industries and foods, on the liver, and investigate whether this toxicity could be eliminated with thymoquinone coadministration. 

32 male Wistar albino rats were procured from İnönü University Experimental Animals Breeding and Research Center. The rats were randomly assigned to 4 equal groups: Control group, Thymoquinone group, Tartrazine group, and Thymoquinone + Tartrazine group. Rat liver tissue and blood samples were obtained and biochemical and histopathological examinations were conducted on the samples.

Tartrazine administration increased the oxidant (malondialdehyde and superoxide dismutase) and oxidative stress index parameters (total oxidant status) in the liver tissue and decreased the antioxidant parameters (glutathione, glutathione peroxidase, catalase, and total antioxidant status) leading to histopathological problems (hematoxylin-eosin staining and Caspase-3 immunoreactivity) and inflammation (tumor necrosis factor-α and interleukin-6) in the serum samples. Thymoquinone, on the other hand, improved antioxidant and anti-inflammatory effects. 

At this time and dose, thymoquinone has a protective effect against tartrazine hepatotoxicity. Thymoquinone can be used as a protective agent against tartrazine toxicity.

We aimed to investigate the preventative effect of Qing Fei Hua Xian Decoction (QFHXD) against pulmonary fibrosis (PF) and its potential mechanisms. 

Bleomycin (BLM)-induced rats were respectively treated with 413.3, 826.6, and 1239.9 mg/kg of QFHXD and prednisone for 28 days. The lung tissues of rats were collected on day 28 for histological and western blotting analysis. 

QFHXD significantly reduced alveolus inflammation, collagen accumulation, and fibrosis deposition in BLM-induced PF rats (P<0.05). Collagen I and III, vimentin, and α-smooth muscle actin(α-SMA) expression levels were likewise decreased in PF rats treated with QFHXD (P<0.05). Additionally, QFHXD increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while decreasing NADPH oxidase 4 (NOX4) expression (P<0.05). Furthermore, QFHXD suppressed the PF progression by down-regulating Angiotensin-Converting Enzyme (ACE) -Angiotensin II (AngII) -Angiotensin II Type 1 Receptor (AT1R) axis (P<0.01) and up-regulating Angiotensin-Converting Enzyme 2 (ACE2) -Angiotensin-(1-7) (Ang-(1-7)) -Mas axis (P<0.05). 

QFHXD suppressed inflammatory infiltration and PF brought on by BLM in lung tissues through reducing oxidative stress by maintaining the equilibrium of ACE-AngII-AT1R and ACE2-Ang-(1-7) -Mas axes. This study may provide a novel clinical therapy option for PF.

To investigate the effect of mogroside IIIE (MGIIIE) on isoproterenol (ISO)-induced myocardial fibrosis and explore its possible mechanisms.

Forty C57BL/6 male mice (6-8 weeks) were randomly divided into a control group (n=10), model group (n=10), low MGIIIE dose group (n=10), and high MGIIIE dose group (n=10). Myocardial fibrosis was established by subcutaneous ISO injection. After 2 weeks of continuous gastric administration of MGIIIE, the cardiac structure was evaluated by echocardiography. Myocardial inflammation and fibrosis were evaluated by histology examination. Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-IκBα, p-NF-κB, transforming growth factor β1 (TGF-β1), and α-smooth muscle actin (α-SMA) expression were detected by western blot. Inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the serum were examined by ELISA. In the in vitro study, Ang II (1 μmol/l) was used to stimulate the fibroblasts, then inflammation and fibrosis index were detected.

MGIIIE inhibited inflammation and fibrosis and down-regulated TLR4, MyD88, TGF-β1, and α-SMA expression in the myocardium. In the in vitro study, MGIIIE ameliorates the deposition of Col Ш and Col I and decreases the release of inflammatory cytokines. MGIIIE increased p-IκBα and reduced p-NF-κB expression both in vivo and in vitro.

MGIIIE plays a role in anti-myocardial fibrosis, by inhibiting TLR4/MyD88/NF-κB signaling expression, and decreasing inflammatory cytokine release. MGIIIE may represent a novel therapeutic strategy for treating cardiac fibrosis.

This study was designed to investigate the protective effects of Calocybe indica extract on testosterone-induced benign prostatic hyperplasia in rats. 

In this study, 60 adult Sprague Dawley rats were randomly divided into six equal groups, one group served as the normal control, five of the groups were administered subcutaneous testosterone propionate for 28 days to induce benign prostatic hyperplasia, three of the five groups were simultaneously administered three graded doses of C. indica extract while one group was administered finasteride as the standard drug and the other left as untreated BPH model group given testosterone propionate only. BPH in the prostate gland was detected through gross appearance, prostate weight, and biochemical and histopathological analyses.

Increased prostate weight, serum prostate-specific antigen (PSA), and epithelial thickness were observed in the untreated testosterone-induced BPH model. Administration of finasteride and C. indica extract led to a reduction in prostate weight, prostatic index, serum PSA, serum levels of testosterone, and prostatic epithelial thickness, and increased luminal diameter. 

Administration of C. indica extract suppressed the pathophysiological effects of benign prostatic hyperplasia in rats. Thus, C. indica mushroom is a potential pharmacological candidate for the management of BPH in man or dogs.