Iranian Journal of Basic Medical Sciences
Volume:25 Issue: 12, Dec 2022

Traditional herbal drugs are widely used for the treatment of various diseases. Ellagic acid (EA) as an herbal polyphenol metabolite exists in many medicinal plants. EA has an important role against natural and chemical toxicities due to its antioxidant and anti-inflammatory properties. For this review, several search engines or databases such as PubMed, Scopus, the Web of Science, and Google Scholar were used, and the most relevant published papers till February 2022 were included.The protective effects of EA against natural and chemical compounds are mediated through molecular mechanisms including scavenging of free radicals, modulation of proinflammatory cytokine synthesis, and reduction of lipid peroxidation. These properties make EA a highly fascinating compound that may contribute to different aspects of health; whereas, more studies are needed, especially on the pharmacokinetic profile of EA. In this review, we selected articles that include the protective effect of EA against several synthetic and natural toxins such as aflatoxin, lipopolysaccharide, acrylamide, and rotenone.

The worldwide emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a major therapeutic concern to medical institutions. To date, no study has determined the frequency and risk factors of inpatients with CRE fecal carriage in Southern Iran. We studied the features of carbapenemase-producing Enterobacteriaceae (CPE) collected from the central ICU of a university hospital.

Totally, 173 samples, including 124 stool samples from 46 ICU inpatients on admission and different follow-ups, 9 ICU staff, and 40 environmental samples were included. CRE was identified using microbiological methods. Antimicrobial susceptibility was investigated by using the disk diffusion method and E-test. Carbapenemase producers were detected using the mCIM method. Seven carbapenemase genes were characterized. The genetic relationship among 20 CPE was elucidated by PFGE. 

The overall fecal carriage rate was 28.2%, while CRE acquisition was 6.1%. CRE were classified as Klebsiella pneumoniae (71.4%), Escherichia coli (23.8%), and Enterobacter aerogenes (4.8%). From 21 CRE, 20 (95.2%) produced carbapenemases, of which 10, 15, 10, 25, 5, and 65% were blaKPC, blaSME, blaIMP, blaVIM, blaNDM and blaOXA-48-positive, respectively. Out of 20 CPE, 14 different PFGE patterns were observed, categorized into six clusters, suggestive of non-clonal spread. No difference between the examined risk factors with CRE carriage was shown. 

The data indicate a high CRE fecal carriage rate among inpatients. Our findings implicate the widespread of OXA-48 carbapenemase together with heterogeneity among CRE with great concern for dissemination and therapeutic threat. Early diagnosis and monitoring of CRE among inpatients are urgent.

The study was aimed at synthesis of the new derivatives of the pyrazolone nucleus, and their spectroscopic and pharmacological analysis and evaluation. 

Three series of compounds, with 2-picolinic acid (I a-d), 3-picolinic acid (II a-d), and 4-picolinic acid (III a-d) were synthesized and characterized by FT-IR, 1HNMR, 13C NMR, elemental, and melting points. The new compounds were then evaluated for their anti-oxidant, anti-inflammatory, and anti-epileptic potential. The hind paw edema model was used to screen anti-inflammatory potential, while the anticonvulsant effect was evaluated by employing the acute model of anti-epileptic activity. The in vivo anti-oxidant potential was determined through glutathione (GSH), glutathione-S-transferase (GST), catalase, and lipid peroxidase enzyme (LPO) assays. The expression of key biomarkers involved in inflammation and neuroprotection, including tumor necrotic factors alpha (TNF-α) and phosphorylated nuclear factor kappa B (NF-κB), was detected through enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. 

The tested compounds showed anti-oxidant potential. The selected compounds exhibited good anti-inflammatory potential. The PTZ-induced elevation of these inflammatory mediators and oxidative stress were ameliorated significantly by the selected compound Ic. Results of molecular analysis (ELISA and Western blot analysis) for potent compound Ic showed a prominent inhibitory effect against neuroinflammatory mediators, including TNF-α and NF-κB. 

It is concluded that the derivative Ic ameliorated PTZ-induced seizures, oxidative stress, and inflammatory cascades by regulating the NF-κB/ TNF-α/ROS pathway.

In this study, to find scientific evidence for the traditional use of Pergularia tomentosa as an anti-diabetic remedy, the effects of its aqueous extract on streptozotocin-induced diabetes mellitus in rats were evaluated.

Wistar rats were fasted overnight and diabetes mellitus was induced using streptozotocin (50 mg/kg body weight). The rats were randomly and equally divided into four groups (n=5): group I (normoglycaemic control), group II (diabetic rats), group III (diabetic rats treated with 200 mg/kg BW of an aqueous extract of P. tomentosa), group IV (normoglycemic rats treated with 200 mg/kg BW of an aqueous extract of P. tomentosa). Chemical profiling of the aqueous extract was carried out using liquid chromatography coupled with electrospray ionization and multiple-stage linear ion-trap and orbitrap high-resolution mass spectrometry (LC-ESI/LTQOrbitrap/MS/MS). In addition, the quantitative determination of the main cardenolides in the extract was carried out by an analytical approach based on LC coupled to tandem mass spectrometry with ESI source and hybrid triple quadrupole-linear ion trap mass analyzer (LC-ESI/QTrap/MS/MS).

Aqueous extract of P. tomentosa showed a reasonable reduction in blood glucose level. Probably, the P. tomentosa effect on hyperglycemic and hyperlipidemic diabetic animals was associated with antioxidant properties, triglyceride levels, as well as liver enzymes. Meanwhile, LC-ESI/LTQOrbitrap/MS/MS analysis led to identification of double-linked cardenolides along with cardenolides and flavone glycosides as the main bioactive compounds.

The extract decreased the glucose level and induced a beneficial effect on the lipid profile, probably due to the presence of cardenolide glycosides.

This study aims to evaluate the in vivo anticancer activity of arginine-reduced graphene (Gr-Arg) and ginsenoside Rh2-containing arginine-reduced graphene (Gr-Arg-Rh2). 

Thirty-two mice with breast cancer were divided into four groups and treated every three days for 32 days: Group 1, PBS, Group 2, Rh2, Group 3, Gr-Arg, and Group 4, Gr-Arg-Rh2. The tumor size and weight, gene expression (IL10, INF-γ, TGFβ, and FOXP3), and pathological properties of the tumor and normal tissues were assessed. 

Results showed a significant decrease in TGFβ expression for all drug treatment groups compared with the controls (P=0.04). There was no significant difference among the groups regarding IL10 and FOXP3 gene expression profiles (P>0.05). Gr-Arg-Rh2 significantly inhibited tumor growth (size and weight) compared with Rh2 and control groups. The highest survival rate and the highest percentage of tumor necrosis (87.5%) belonged to the Gr-Arg-Rh2 group. Lungs showed metastasis in the control group. No metastasis was observed in the Gr-Arg-Rh2 group. Gr-Arg-Rh2 showed partial degeneration of hepatocytes and acute cell infiltration in the portal spaces and around the central vein. The Gr-Arg group experienced a moderate infiltration of acute cells into the port spaces and around the central vein. The Rh2 group also showed a mild infiltration of acute and chronic cells in portal spaces. 

Based on the results, Gr-Arg-Rh2 can reduce tumor size, weight, and growth, TGF-β gene expression, and increase tumor necrosis and survival time in mice with cancer.

Spiders of the Loxosceles genus, known as violin spiders, produce venom with dermonecrotic and systemic effects, as it is a species widely distributed in the world, its study represents a high medical relevance. Systemic loxoscelism, which occurs in 1 in 5 cases and is the most frequent in children, can be fatal, so the study of effective therapy is of great relevance. In the present study, we compared different therapeutic options to mitigate the systemic effects of Loxosceles boneti venom in a model in which prepubertal rats were used.

A model of systemic intoxication by L. boneti venom was provoked in male Wistar rats. Study groups were formed: healthy control, with venom and untreated control, treatment with N-acetylcysteine, and/or hyperbaric oxygenation therapy. Subsequently, pathological analysis of the kidney and lung was performed. The oxidant-antioxidant response was evaluated, and molecular analysis of the COX-1 and COX-2 enzymes was performed.

Regenerative changes were observed at the cellular level in both treatments, being more noticeable in the HBO group. The anti-oxidant response was outstanding in the same group. 

Both treatments offer considerable benefits, however; further studies are needed to provide adequate therapeutics.

Administration of antidepressants and exercise are among the therapeutic approaches to chronic stress. Therefore, this study compared the therapeutic effects of different doses of escitalopram, exercise, and exercise-accompanied escitalopram on synaptic potency and long-term plasticity in the hippocampal CA1 area in rats under chronic restraint stress.

The rats were allocated to different groups. The chronic restraint stress (6 hr/day) continued for 14 days. Injection of escitalopram (10 and 20 mg/kg) and treadmill running (1 hr/day) were performed after the stress induction. The input/output (I/O) functions and LTP induction were evaluated in the hippocampal CA1 area.

The fEPSP slope and amplitude after the LTP induction significantly decreased in the chronically stressed group. However, the serum corticosterone levels had significant enhancement in this group. In addition to serum corticosterone levels, the fEPSP slope and amplitude after the LTP induction were enhanced by exercise, escitalopram 20 mg/kg alone, and exercise-accompanied escitalopram 10 and/or 20 mg/kg in chronically stressed groups.

Overall, chronic stress impaired synaptic potency and long-term plasticity. These impairments were effectively reversed by exercise, escitalopram 20 mg/kg alone, and exercise-accompanied escitalopram 10 and 20 mg/kg. However, escitalopram 10 mg/kg alone could not alleviate the memory deficits in chronically stressed subjects. Therefore, exercise with both doses of escitalopram seems to have had additive effects on chronic stress conditions.

Adaptive immunity is crucial in controlling Giardia lamblia infection in the intestinal mucosa, and some dietary lipids may improve mucosal immune function. The aim of this study was to evaluate conjugated linoleic acid (CLA) on the Th17/Treg response and secretory IgA production in a model of giardiasis infection.

C3H/HeN male mice were infected with 5×106 G. lamblia trophozoites (GS/M-83-H7, ATCC collection). Mice were assigned randomly to experimental and control groups. CLA was administered to the experimental group and phosphate-buffered saline (PBS) was given to the control group. Parasite load kinetics was determined. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate IgA and cytokines. Nuclear transcription factors and cytokines were measured by RT-qPCR, and histology of small bowel cells was evaluated.

CLA administration reduced the parasite load (P<0.05) and increased early Giardia-specific secretory IgA production. CLA also increased the expression of interleukin-10, transforming growth factor (TGF)-β, and inducible nitric oxide synthase (iNOS) (P<0.05), while infection elevated the expression of Foxp3, with a peak at 40 days post-infection (P<0.05). There were no pathological changes in the colonic mucosa due to infection or treatment. Thus, CLA stimulated mucosal immunity and enhanced the humoral response against G. lamblia, not only for early infection control but also to promote regulatory cytokine production at 40 dpi, restoring the intestinal balance after parasite elimination.

Our findings reveal novel anti-parasitic effects through the immune-modulatory activity of CLA against the intestinal parasite G. lamblia.

In this study, Boltorn® H40-PEG-MTX-anti-VEGFR2 nanobody was fabricated in which nanobody was selected for blocking the receptor, H40 as a nanocarrier for delivery of methotrexate (MTX) to the tumor cells, and polyethylene glycol (PEG) moieties for improving the blood circulation time and safety. 

The synthesis process of the nanosystem has been characterized by different analytical methods. 

The prepared nanoplatform exhibited high drug loading capacity, excellent colloidal stability, and an average particle size of around 105 nm. MTX was successfully conjugated through ester bonds and its release profile clearly showed that the ester bond is in favor of releasing the drug in acidic pH (5.5). The cytotoxicity of the developed nanoplatform exhibited great anti-cancer activity against MCF7 and KDR293 (cells with overexpressed anti-VEGFR2 NB receptors) cell lines while no deleterious toxicity was observed for nanocarrier against HEK293 normal cells.  Furthermore, both hemolysis and LD50 assay results confirmed the hemocompatibility and biocompatibility of the developed nanoplatform. 

The most striking result to derive from the data is that the designed nanoplatform could potentially inhibit cell migration and invasion and the anti-angiogenesis properties of the developed nanoplatform may serve as a promising nanosystem to suppress the formation of blood vessels around tumor cells and consequently inhibit tumor progression.

The prevalence of chronic kidney disease in diabetics is progressively increasing with an increased risk of fatal complications. 

Sixty male albino rats were used in the study, and type 2 diabetes mellitus were induced. Diabetic rats were divided randomly into 5 groups, the control diabetic group and 4 treated groups were treated with metformin (group3), dulaglutide (group 4), metformin & cilostazol (group 5), and the last group was treated with dulaglutide & cilostazol (group 6).  At the end of the experiment, the weight of rats and systolic blood pressure were estimated. After overnight fasting, the serum levels of blood glucose, lipid profile, and kidney function were measured. After scarification, gene expression of eNOS and NFKB in kidney tissue were estimated and kidney tissues were examined for histopathology. 

Diabetic rats showed a significant increase in body weight, blood pressure, serum blood glucose, lipid profile, and impaired kidney function. Metformin and dulaglutide are associated with a significant decrease in blood pressure, blood glucose level, serum lipid profile, and improved kidney function. These changes are associated with a significant increase in anti-oxidative markers, and decreased inflammatory and fibrotic markers, especially with the addition of cilostazol. 

Metformin and dulaglutide have been shown to ameliorate kidney damage in diabetics by stimulating the anti-oxidant defense system, normalizing kidney functional parameters, and improving histopathological changes. The addition of cilostazol to metformin or dulaglutide increased some of their anti-oxidants and anti-inflammatory properties.

Activated cells which are called star-shaped cells, are some of the key factors in the development of liver fibrosis. Activation of NADPH oxidase (NOX) is associated with increased HSCs activity and progression of hepatic fibrosis. In this study, the effects of human exosomes derived from WJ-MSCs on NOX1, NOX2, and NOX4 gene expression in TGF-β-induced hepatic fibrosis were investigated.

LX2 cell line was treated with 2 ng/ml TGF-β for 24 hr, in order to induce liver fibrosis after starvation. In the next step, the cells were treated with several concentrations of the exosomes derived from WJ-MSCs (10, 20, 30, 40, and 50 μg/ml). Finally, Smad3C phosphorylated protein expression level and NOX1, NOX2, and NOX4 gene expression levels were measured.

The results demonstrated that the level of NOX1, NOX2, and NOX4 mRNA expressions decreased significantly during 24 hrs at concentrations of 40 and 50 μg/ml of WJ-MSCs exosomes in TGF-β-induced-HSCs. The p-Smad3C proteins were significantly decreased (fold change: 1.83, P-value<0.05) after exposure to WJ-MSC-derived exosomes. 

Treatment with exosomes prevents further activation of HSCs by inhibiting the level of Smad3C phosphorylation. The experimental data of our study suggested that in liver fibrosis, the protection of HSCs activation against TGF-β by inhibiting the NOX pathway via human exosomes of WJ-MSCs is extremely important. It needs further research as a treatment method.

Carveol is a naturally occurring terpenoid with antispasmodic, carminative, astringent, indigestion, and dyspepsia properties, as well as anti-diabetic, anti-oxidant, anti-hyperlipidemia, and anti-inflammatory properties in the liver. Research also suggests that it has memory-enhancing and anti-oxidant properties. The purpose of this research was to see whether carveol could protect rats against scopolamine-induced memory loss in a rat model. 

Thirty male Sprague-Dawley rats (200–250 g) were grouped as the saline group receiving saline, disease group receiving scopolamine, and four treatment groups among which three groups received scopalamine+carveol and one group received scopalamine+donepezil for 28 days. Followed by in vitro, behavioral, anti-oxidant, and molecular studies were done. P<0.005 was considered  statistically significant.

The in vitro assay showed that carveol caused diphenyl-1-picrylhydrazyl inhibition. In-vivo findings revealed that carveol (50, 100, and 200 mg/kg) significantly improved dementia by reducing escape latency and spending more time in the targeted quadrant in the Morris water maze test. Increased number of entries and percent spontaneous alterations were observed in rats’ Y-maze test. In animal brain tissues, i.e., cortex and hippocampus, carveol enhanced glutathione, glutathione-s-transferase, catalase, and reduced lipid peroxide levels. Carveol also improved cellular architecture in histopathological examinations and decreased expression of inflammatory markers such as amyloid-beta, nuclear factor kappa light chain activated B cells, tumor necrosis factor-alpha, cyclooxygenase 2, prostaglandin E2, and interleukin-18, as evidenced by immunohistochemistry and enzyme-linked immunosorbent assays, as well as molecular investigations. 

This study suggests that the compound could be potent against amnesia mediated through anti-oxidant, amyloid-beta inhibition, and anti-inflammatory pathways.

Bioglass scaffolds, which contain a significant percentage of porosity for tissue engineering purposes, have low strength. For increasing the strength and efficiency of such structures for use in tissue engineering, fabrication of hierarchical meso/macro-porous bioglass scaffolds, developing their mechanical strength by hydrothermal treatment and adjusting pH method, and achieving the appropriate mesopore size for loading large biomolecules, were considered in this study.

Mesoporous bioglass (MBG) powders were synthesized using cetyltrimethylammonium bromide as a surfactant, with different amounts of calcium sources to obtain the appropriate size of the mesoporous scaffolds. Then MBG scaffolds were fabricated by a polyurethane foam templating method, and for increasing scaffold strength hydrothermal treatment (90 °C, for 5 days) and adjustment pH (pH=9) method was used to obtain hierarchical meso/macro-porous structures. The sample characterization was done by Simultaneous thermal analysis, Fourier transform infrared spectroscopy, Field Emission Scanning electron microscopy, small and wide-angle X-ray powder diffractions, transmission electron microscopy, and analysis of nitrogen adsorption-desorption isotherm. The mechanical strength of scaffolds was also determined.

The MBG scaffolds based on 80.28 (wt.) % SiO2- 17.89 (wt.) % CaO- 1.81 (wt.) % P2O5 presented interconnected large pores and pores in the range of 100-150 μm and 6-18 nm, respectively and 0.4 MPa compressive strength. 

The total pore volume and specific surface area were obtained from the Brunauer-Emmett-Teller theory, 0.709 cm3 g-1 and 213.83 m2 g-1, respectively. These findings could be considered in bone-cartilage tissue engineering.

We aimed to investigate the gastroprotective effect of lactoferrin (LF; 100 & 300 mg/kg) in male Wistar rats versus gastric ulcers induced by 96% ethanol.

Rats were randomly allocated into 4 groups: control, ethanol, ethanol+LF100, and ethanol+LF300. LF100 & 300 were given 15 days before ulcer induction. At the end of the experiment, the gastric mucosa was examined macroscopically and microscopically.

The ethanol group showed damage and degeneration of the stomach mucosa in addition to elevation of oxidative and inflammatory biomarkers. LF showed explicit healing of the gastric mucosal damage. LF reduced gastric malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), and intracellular adhesion molecule-1 (ICAM-1). On the other hand, LF elevated the depleted reduced glutathione (GSH) and Nuclear factor-erythroid factor 2 (Nrf2).

Our current study is the first to study the antiulcer effect of LF via its potential modulatory effects on the ROS/ICAM-1/Nrf2 signaling pathway. Moreover, we concluded that pretreatment with LF100 & 300 mitigated the ethanol-induced gastric ulcer via modulation of both oxidative stress and inflammatory responses.

Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments. With a growing interest in the therapeutic roles of herbs, in toxicity research, it’s worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt-induced neurotoxicity. 

We treated rats with CoCl2 or CoCl2 in combination with aqueous PA seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments, analysis for oxidative stress, inflammation, and histological and immunohistochemical analysis were performed. 

Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y-maze tests, and reduced open arm entry and duration in elevated plus-maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2-induced surge in hydrogen peroxide, malondialdehyde, TNF-α and IL-1β levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced-glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated. 

These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and inflammation.