Avicenna Journal of Phytomedicine
Volume:11 Issue: 3, May-Jun 2021

In this study, the impact of arbutin was examined in a gentamicin (GM)-induced nephrotoxicity model.

Forty adult male Wistar rats were randomly assigned to five groups including control group; GM group, and three groups of GM+arbutin (25, 50 and 75 mg/kg). One day after the last injection of GM, creatinine, urea, carbonyl, thiobarbituric acid-reacting substance (TBARs), ferric reducing antioxidant power (FRAP) and 8-hydroxyguanosine levels were assessed in serum samples. Left and right kidneys were used for biochemical assays and histological evaluation, respectively.

Our data showed that the FRAP level (p<0.05), urea (p<0.001), creatinine (p<0.001), and 8-hydroxyguanosine (p<0.001) levels of serum samples, were increased in GM-treated rats compared to the controls. The serum levels of TBARS (p<0.001) and carbonyl increased in serum and renal tissue (p<0.001) of GM-treated animals. Conversely, arbutin attenuated serum creatinine, urea and 8-hydroxyguanosine, and TBARS (p<0.001). Administration of arbutin significantly decreased carbonyl levels in serum and renal tissue samples (p<0.001). Furthermore, the levels of FRAP increased in the serum (p<0.01) and renal tissue samples (p<0.001) of arbutin-treated animals. Histological staining showed that arbutin significantly inhibits kidney damages.

Our data suggest that arbutin attenuates GM-induced nephrotoxicity through its free radicals-scavenging activity.

Royal jelly (RJ) is a honey bee product for which, anti-inflammatory properties were shown in vitro. Nanoparticles, including nano-silver (NS), are plausible inflammation inducers that act by activation of immune cells and consequent production of pro-inflammatory cytokines. This project aimed to explore immunomodulatory effects of royal jelly and nano-silver on the kidney and liver.

In this project, 40 male rats were grouped as follows: 10 rats as controls, 10 rats treated with RJ; 10 rats treated with both NS and RJ and 10 rats treated with NS. Liver and kidney interleukin (IL)-1β, -2, -6, and -33 levels were determined using commercial ELISA kits.

RJ reduced kidney IL-6 levels in comparison to control and NS--RJ groups. RJ and NS reduced kidney and liver IL-1β levels. Kidney IL-33 levels were decreased in the RJ and nano-silver groups in comparison to the NS--RJ group.

Based on this study, it may be concluded that RJ together with NS can play anti-inflammatory roles and may affect the function of immune cells.

Investigation of the antiglycation and antitumoral potential of standardized and saponins-enriched extracts of Tribulus terrestris herbal medicine.
The procedures for the evaluation of the antiglycation activity of the standardized (TtSE) and saponins-enriched (TtEE) extracts of T. terrestris were: determination of relative mobility in electrophoresis (RME), free amino groups using OPA method and advanced glycation end-products (AGEs) fluorescence. Antioxidant activity was determined by DPPH radical scavenging test. In vitro antitumor activity of TtSE and TtEE was evaluated in human tumor cell lines.
The results were obtained by antiglycation tests (RME, OPA method and AGEs fluorescence determination), using BSA as protein and ribose as glycation agent, and antioxidant assay (DPPH test); it was verified that both extracts of T. terrestris have antiglycation and antioxidant activity. In addition, the extracts were able to induce death of more than 50% of human tumor cell lines.
The present study showed that standardized and saponins-enriched extracts of T. terrestris herbal medicine present antiglycation and antioxidant and antiproliferative action in human tumor cells lines. The saponins-enriched extract proved a greater antiglycation and antioxidant activity in comparison to the standardized type.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Several experimental studies have shown neuroprotective and antioxidant effects for Artemisia absinthium. The present study was designed to assess the effect of A. absinthium on 6-hydroxydopamine (6-OHDA)-induced toxicity in SH-SY5Y cells.
SH-SY5Y cells were treated with ethanolic extract of A. absinthium for 24 hr and then, exposed to 6-OHDA (250 μM) for another 24 hr. MTT (3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyl tetrazolium bromide) assay was used for evaluation of cell viability. Moreover, the rate of apoptosis was measured using propidium iodide (PI) staining. The amount of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) was also measured using 2’, 7’–dichlorofluorescin diacetate (DCFDA) fluorometric method. Determination of glutathione (GSH) and superoxide dismutase (SOD) activity was done by colorimetric assay using DTNB [5, 5′-Dithiobis (2-nitrobenzoic acid)] and pyrogallol respectively.
While 6-OHDA significantly increased ROS and apoptosis (p<0.001), the extract of A. absinthium significantly reduced ROS and cell apoptosis at concentrations ranging from 6.25 to 25 μg/mL (p<0.01 and p<0.001 respectively). Also, the extractsignificantly reduced MDA level in comparison with 6-OHDA (p<0.001). The GSH level and SOD activity were increased by the extract.
Findings of the current study showed that A. absinthium exerts it effect throughinhibiting oxidative stress parameters and it can be considered a promising candidate to be used in combination with the conventional medications for the treatment of neurodegenerative disorders, such as Parkinson's disease.

This study intended to evaluate if central administration of abscisic acid (ABA) alone or in combination with GW9662, a peroxisome proliferator–activated receptor γ (PPAR-γ) antagonist, could modulate learning and memory as well as hippocampal synaptic plasticity in a rat model of streptozotocin (STZ)–induced diabetes.

Intraperitoneal injection of STZ (65 mg/kg) was used to induce diabetes. Diabetic rats were than treated with intracerebroventricular (i.c.v.) administration of ABA (10, 15 and 20 µg/rat), GW9662 (3 µg/rat) or GW9662 (3 µg/rat) plus ABA (20 µg/rat).Animals’ spatial and passive avoidance learning and memory performances were assessed by Morris water maze (MWM) and shuttle box tasks, respectively. Further, in vivo electrophysiological field recordings were assessed in the CA1 region.

STZ diabetic rats showed diminished learning and memory in both MWM and shuttle box tasks.  The STZ-induced memory deficits were attenuated by central infusion of ABA (10 and 20 µg/rat). Besides, STZ injection impaired long-term potentiation induction in CA1 neurons that was attenuated by ABA at 20 μg/rat. Central administration of GW9662 (3 µg/rat) alone did not modify STZ-induced spatial and passive avoidance learning and memory performances of rats. Further, GW9662 prevented ABA capacity to restore learning and memory in behavioral and electrophysiology trials.

Altogether, ABA ameliorates cognitive deficits in rats via activation of PPAR-γ receptor in diabetic rats.

Chemoprevention of cancer by application of natural phytochemical compounds has been used to prevent, delay or suppress cancer progression. Cuscuta chinensis a traditional Iranian medicinal herb, has biological properties including anticancer, anti-aging, immuno-stimulatory and antioxidant effects. In this study, anti-proliferative effects of hydroalcoholic extract of C. chinensis on prostate (PC3) and breast (MCF7) cancer cell lines were investigated. In the current study, we investigated treatment of PC3 cells with different concentrations of C. chinensis (0, 100, 200, 300, 400, and 500 µg/ml) for 24 and 48 hr; also, MCF7 cells were treated with various concentrations (0-600 µg/ml) of C. chinensis for 48 and 72 hr and cell viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. mRNA expression of BCL2 Associated X (Bax), B-cell lymphoma 2 (Bcl2), Cysteine-aspartic proteases (Caspase3) and Phosphatase and tensin homolog (PTEN) were analyzed by quantitative real-time PCR. Annexin V/PI staining and lactate dehydrogenase (LDH) cytotoxicity assay were used to detect apoptosis. C. chinensis decreased PC3 and MCF7 cells viability in a dose- and time-dependent manner (p BAX/Bcl2 ratio, Caspase3 and PTEN increased in C. chinensis-treated cells compared to the control group. C. chinensis induced apoptosis (p <0.001) and LDH activity (p Our findings suggest that C. chinensis extract is able to inhibit proliferation and induce apoptosis in PC3 and MCF7 cell lines. Therefore, C. chinensis extract exerts antitumor activity against cancer cells.

Hyperglycemia is a severe consequence of diabetes mellitus (DM). Throughinduction of oxidative stress, it plays a major role in the pathogenesis of several complications in DM. Therefore, new strategies and antioxidants should be implemented inthe treatment of DM. Quercetin is a flavonoid with strong antioxidant capacity found dominantly in vegetables, fruits, leaves, and grains. The current study aimed to investigate quercetin protective effects under D-glucose-induced oxidative stress by assessing antioxidant defense enzymes inHepG2 cells as an in vitro model.
HepG2 cells were cultured with different concentrations of D-glucose (5.5, 30 and 50 mM) and/or 25 μM quercetin for 48 and 72 hr, respectively. The effect of treatments on cellular integrity, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) activity, andcellular levels of glutathione (GSH) and malondialdehyde (MDA) wasdetermined.
D-glucose had various effects on intracellular antioxidant defense atdifferent doses and time-points and quercetin could attenuate oxidative stress and modulate antioxidant defenses.
The results of this study indicated that flavonoid quercetin could be proposed as an agent protecting hepatic HepG2 cells against oxidative stress associated with hyperglycemia.

Ferula spp. have many applications in complementary medicine and are recognized as the most important sources of natural products for bone health and regeneration especially in postmenopausal women. Therefore, the aim of this study was to investigate the effects of the extracts from three Ferula species on proliferation and osteogenesis potential of human menstrual blood-derived mesenchymal stem cells (MenSCs).
The possible cytotoxic activity of three members of Ferula spp. (at concentrations of 5 to 100 μg/ml) was determined using MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay. Alkaline phosphatase (ALP) activity assay, Alizarin Red-S staining, and the expression analysis of an osteoblastic gene were performed to evaluate osteogenic differentiation potential.
The extracts of F. flabelliloba and F. szowitsiana decreased the viability and growth of MenSCs while F. foetida increased the proliferation of cells after 72 hr incubation. Treatment of MenSCs with selected plant extracts revealed that F. foetida and F. szowitsiana could enhance the osteogenic potential of MenSCs in terms of ALP activity. The Runx-2 expression in the presence of F. foetida was significantly greater than observed following treatment with 17β-estradiol (as positive control).
The results of this study suggest that F. foetida and F. szowitsiana may have therapeutic values as a nutraceutical with respect to their considerable influence on osteogenic potential of mesenchymal stem cells.

Polycystic ovary syndrome (PCOS) is an endocrine system disruption that affects 6-10% of women. Some studies have reported the effect of Vitex agnus-castus (Vitagnus) on the hypothalamic-pituitary-gonad axis (HPG). This study was conducted to investigate Vitagnus effect on the expression of kisspeptin gene in a rat model of PCOS.
Thirty-two female rats were distributed into: control, Vitagnus-treatment (365 mg/kg for 30 days), PCOS (Letrozole for 28 days) and PCOS animals treated with Vitagnus (30 days of Vitagnus after PCOS induction). At the end of the treatments, serum and ovaries were collected for analysis. Expression level of KISS-1 gene in the hypothalamus was investigated, using Real-Time-PCR.
In the PCOS group compared to control, FSH, progesterone and estradiol levels were decreased, whereas testosterone and LH levels were significantly increased. No significant changes were observed in the Vitagnus-treated animals in compare to control.  However, Vitagnus treatment in the PCOS group, resulted in a raise in progesterone, estrogen and FSH levels and a reduction in the levels of testosterone and LH. Quantitative gene expression analysis showed that PCOS induction resulted in over-expression of KISS-1 gene, however, Vitagnus treatment reduced this up-regulated expression to normal level.
In conclusion, our results indicated that Vitagnus extract inhibited downregulation of KISS-1 gene in the hypothalamus of PCOS rats. Because of the master role of kisspeptin in adjusting the HPG axis, Vitagnus is likely to show beneficial effects in the treatment of PCOS via regulation of kisspeptin expression. This finding indicates a new aspect of Vitagnus effect and may be considered in its clinical applications.

Depression is one of the most common mood disorders. Considering the evidence on the effect of Cinnamomum on mood disorders, this study investigatedthe effect of hydroalcoholic extract of Cinnamomum (HEC) in an animal model of depression.

Thirty-two male rats were selected and divided into four groups (n=8) including: control, depressed, and depressed treated with200 and 400 mg/kg HEC. Depression induction protocol was conducted in all groups except for the control group. Sucrose preference test (SPT) and forced swimming test (FST) were done to analyze the depression score. After four weeks, the animals brain cortex was removed and BDNF protein and tyrosine receptor kinase B (TrkB) gene expression levels were determined by ELISA and Real Time PCR, respectively.

The results of this study showed that 400 mg/kg of HEC increased the tendency to drink the sucrose solution. Furthermore, immobility time significantly increased in the depressed group compared to the control group while it was attenuated by administration of 400 mg/kg extract on the 28th day versus the depressed group. Also the extract at both doses increased swimming time compared to the depressed group. In addition, an increase in the BDNF protein and TrkB gene expression levels was observed in the prefrontal cortex of the treatment groups.

We found that HEC ameliorated depression symptoms in rats and these effects were probably due to an increase in BDNF proteins and its receptor, TrkB, gene expressions in the prefrontal cortex.