Physiology and Pharmacology
Volume:25 Issue: 4, Dec 2021

Medicinal plants are used for different purposes in traditional medicine. Boswellia serrata (B. serrata) from Burseracea family has been widely used for human medical purposes. This plant known as frankincense or olibanum has a resin with therapeutic properties. The main constituent of this resin is boswellic acid that plays an important role in various fields. From past to present, many studies had been shown that olibanum and its main constituent, boswellic acid, have antiinflammatory, antioxidant, antitumor, anti-arthritic, antimicrobial and anti-carcinogenic effects. In addition, many findings about effects of B. serrata and its ingredients on central nervous system (CNS) are available. Therefore, the aim of this study is to review in vivo and in vitro evidence attributed to this plant and its constituents on CNS. Databases including Web of Sciences, Scopus, PubMed and Google Scholar were explored for entries from the beginning of January 2000 until the end of November 2020. Findings reveal that B. serrata and its constituents have neuroprtotective effects and ameliorate learning and memory malfunction. These effects mainly are attributed to the antioxidant and anti-inflammatory properties of this plant.

Converging lines of evidence indicate that serotonin transporter has a role in response to selective serotonin reuptake inhibitors pharmacotherapy in a variety of neuropsychiatric disorders. In the present study, the association of four functional loci of the serotonin transporter gene (SLC6A4) with fluvoxamine treatment outcome in Iranian patients with obsessive compulsive disorder (OCD) has been investigated.

A total of 352 Iranian OCD patients were screened for the treatment outcome. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150-300mg). Finally, 132 patients who had completed their treatment were assigned to three groups (responders, non-responders and refractory) and underwent genotyping for SLC6A4 variations (STin2, 5-HTTLPR, rs25531 and rs25532) employing PCR-RFLP.

Results showed no significant differences between different STin2, 5-HTTLPR/rs25531 and rs25532 single locus genotype frequencies. However, significant associations of two SLC6A4 haplotypes with treatment response were detected.

Detected association of two SLC6A4 haplotypes with response to fluvoxamine in OCD patients proposed that the research emphasis of OCD pharmacogenetic studies may be placed on haplotype association analyses in candidate genes. This may represent a significant advance over single-locus investigations as a way to understand the influence of genetic factors on drug response in OCD.

Western diet (WD) activates inflammatory pathways in the myocardium, where jeopardizes contractile function. This study aimed to compare the anti-inflammatory effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) in rats fed a WD.

Wistar rats were assigned to the six groups: normal diet (ND)+HIIT, WD+HIIT, ND+MICT, WD+MICT, sedentary fed a ND or WD (SED+ND and SED+WD, respectively). HIIT and MICT were performed on a motorized treadmill, five consecutive days/week for 12 weeks. In these animals, visceral fat mass and myocardial expression of pro-inflammatory cytokines i.e. tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) were measured. Western blotting was performed to identify cardiac protein expression.

WD+SED significantly increased visceral fat mass compared with ND+SED. WD+SED significantly resulted in TNF-α over-expression compared with ND+SED. There were no significant differences in MPO expression between WD+SED and ND+SED. In trained groups, visceral fat mass and TNF-α expression were lower in WD+HIIT and WD+MICT compared with WD+SED, with similar effects between HIIT and MICT modes. MPO expression was significantly lower in ND+HIIT and ND+MICT compared with ND+SED, with similar effects between HIIT and MICT modes.

WD co-existing with SED paves the way to a pro-inflammatory milieu in the heart. HIIT and MICT exert similar anti-inflammatory effects on the myocardium; therefore, aerobic training, regardless of modality or intensity, can be a practical solution for those who regularly consume WD.

The spinal cord injury is temporary or permanent damage in the spinal cord that disturbs the motor and sensory functions. The neuroprotective effects of steroids has been reported previously. Therefore, we designed a study to investigate the effects of different doses of estradiol (Est) and progesterone (Prog) on unilateral lesion of the spinothalamic tract (STT).

The 77 male adult Wistar rats were under the anesthesia for dorsal laminectomy at the spinal segments T8–T9. A tungsten-electrode was targeted to the right STT and unilateral lesion was made by a brief current pulse (300μA, 90s). Rats were divided into 11 groups and Est or Prog (2, 4, 8 and 16mg/kg) were administered 30min post-injury. Mechanical allodynia and open field as assessed before, 14 and 28 days after the injection then the animals were sacrificed. The western blotting was performed on T8–9 spinal segments to evaluate protein expression of ERK, p-P38, JNK, Iba1 and GFAP at the lesion site.

Est but not Prog significantly increased the pain threshold and motor activity at the dose of 8mg/kg on post-surgery days 14 and 28. Est but not Prog significantly increased the protein expression of ERK while decreased JNK protein. Both Est and Prog significantly decreased protein expression of p-P38, Iba1 and GFAP.

These results show Est (8mg/kg) is able to decrease mechanical allodynia and improve motor activity 14 and 28 days after spinothalamic tract lesion. It seems ERK, p-P38, JNK, Iba1 and GFAP are involved.

Depression is a common mood disorder in patients with Parkinson’s disease (PD), which negatively influences the quality of life and enhances caregiver burden. MLC901, a traditional medicine, has been demonstrated to be useful in preclinical and clinical studies. The aim was to study the effect of MLC901 on depression behavior in a mouse model of PD, comprising in the unilateral striatal delivery of the neurotoxin 6-hydroxydopamine (6-OHDA).

Female NMRI mice were divided into the following groups: sham/saline group, 6-OHDA/saline group, sham/MLC901 (40μg/kg) group and 6-OHDA/MLC901 group. Intraperitoneal treatments of MLC901 were started one week after the stereotaxic surgery that continued for 4 weeks (5 days/week). Locomotion was monitored using an openfield test and depressive-like responses were measured by forced swim test (FST) and tail suspension test (TST).

We found that MLC901 prevented the increased immobility time in the PD mice in both FST and TST, suggesting an antidepressant efficacy for the MLC901. None of the treatments alter locomotion compared to the sham group.

In conclusion, we propose that MLC901 is a potential candidate to be used in studies for the treatment of depression in PD.

The dorsomedial periaqueductal gray (dmPAG) is located around the cerebral aqueduct with various functions such as cardiovascular regulation and is affected by inflammation. Lipopolysaccharide (LPS) is a complex molecule with an inflammatory effect that is known to affect blood pressure. In the present study, the cardiovascular effect of LPS microinjection into the dmPAG was investigated.

Rats were divided into three groups consisting of 1: control; 2: 50 ng LPS and 3:100 ng LPS. Rats were mounted on a stereotaxic device after anesthesia and a continuous recording of cardiovascular parameters was done by a PowerLab device, connected to a cannulated femoral artery and drugs microinjected into dmPAG. The changes (Δ) in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MA) and heart rate (HR) were calculated at different times and compared to the control group.

Both doses of LPS when microinjected into the dmPAG brought on a significant hypotensive response in the pressure parameters (MAP, SBP, and DBP) when compared to control. A non-significant increase in HR was also documented in both groups.

The results of this experiment indicated that LPS, when microinjected into the dmPAG, induced a hypotensive response in anesthetized rats in both doses in comparison to control.

Mitochondria and peroxisomes are tightly connected organelles that cooperate in lipid oxidation and maintenance of redox homeostasis. However, the peroxisome’s role in the modulation of the mitochondrial regulatory factors has remained unanswered. SIRT1- PGC-1α interaction as a pivotal pathway in energy expenditure leads to mitochondrial biogenesis. Histone deacetylase (HDAC)6 and HDAC10 also regulate mitochondrial dynamics. Mitochondrial dysfunction is a cause and/or consequence of aging and neurodegenerative disorders.

In this study, to disturb importing proteins into the peroxisomes, PEX5 was down-regulated in the dorsal hippocampus by lentivirus-mediated shRNA. The impact of PEX5 reduction on peroxisomes was explored by assessment of catalase activity, a regular peroxisome matrix enzyme, and PMP70 and PEX14 expression. Then, mitochondrial biogenesis factors, PGC-1α, and mitochondrial transcription factor A (TFAM) were measured by quantitative polymerase chain reaction and mitochondrial-related HDACs, SIRT1, SIRT3, HDAC6 and HDAC10, by western blotting. Besides, spatial learning and memory were assessed using the Morris water maze task.

Our results revealed a significant reduction of HDAC6 and SIRT1, alongside with decrease in mitochondrial biogenesis factors PGC-1α and TFAM, and no alteration in HDAC10 and SIRT3. Despite all observed changes, memory performance displayed no detectable alteration in the experimental groups. These data suggest the role of peroxisomes in modulating mitochondrial dynamics via regulation of HDAC6 and SIRT1 expression.

Peroxisome dysfunctions may occur upstream to mitochondrial failure and can be considered as a potential therapeutic target for aging and age-related disorders.

Multiple sclerosis (MS) is an autoimmune disease. The main aims of the present investigation were to evaluate the effect of royal jelly (RJ) on cognitive and non-cognitive behavior, demyelination and the level of blood-brain barrier (BBB) disruption induced by ethidium bromide (EB).

Twenty-five adult male Sprague Dawley in five groups were used. Control (intact rat); Sham (surgery without EB injection); treatment control (EB injection without treatment); treatment1 and treatment2 (orally administered of RJ 100 and 200 mg/kg/day after EB injection). EB (3μl of 0.01%) injection in the dentate gyrus (DG) was used for demyelination. Demyelination induction was proved by histological examination. For the estimation of BBB integrity, Evans blue extravasation was done using an ELISA reader. Cognitive and non-cognitive behavior was evaluated by Morris water maze.

Data showed that RJ corrected the deficit of demyelination. Cognitive and non-cognitive behavior improved in treatment groups relative to treatment control by RJ. The extent of BBB disruption significantly improved in treatment groups compared to the treatment control group, in the whole brain and hippocampus.

Results indicate that RJ after EB injection in DG can improve cognitive and non-cognitive behavior, demyelination and BBB disruption in rat after EB injection. Therefore, it seems that RJ can be a supplementary drug for MS.

Metals such as silver have special merit in medicine. Recently, it has been shown that silver nanoparticles (Ag-NPs) can present some properties that could be valuable for researchers because of their dual neuroprotective and neurotoxic behaviors. The present study was planned to evaluate the effect of silver nanoparticles on OLN-93 oligodendrocytes through chemical hypoxic situation.

AOLN-93 cell line was selected as an oligodendroglial cell model. The stock of the tested solution contained Ag-NPs with an average size of 40nm and concentration of 20.4 ppm. Chemical hypoxic-ischemic condition was induced by sodium azide (NaN3). After a three-hour pretreatment of OLN-93 cells with Ag-NPs (0.001ppm), the cells were incubated in glucose-free medium with sodium azide (100mM and 1M) and Ag-NPs (0.001ppm) for 15min. Then, the reperfusion condition was set by returning the medium to DMEM with 10% FBS along with Ag-NPs (0.001ppm) for 24h. Next, the viability of the cells was assessed by MTT method. Also, Transmission electron microscopy images were used to evaluate the morphology of the cells.

Our results showed that Ag-NPs with a concentration of 0.001 ppm could significantly increase ONL-93 cells survival through the 15min hypoxic-ischemia condition induced by NaN3 (100mM) followed by reperfusion (93.02±2.83). However, Ag-NPs (0.001ppm) could not protect the cells from hypoxic-ischemic injury induced by NaN3 (1M) through the same procedure.

Although the neurotoxic effects of Ag-NPs have been documented in many studies, the Ag-NPs solution, which was used in this study, could show protective effects on oligodendroglial cells in concentration of 0.001 ppm during the planned model of chemical ischemia. Hence, more investigation is suggested to clarify the protective effect of Ag-NPs (average size of 40 nm) on oligodendrocytes.

Marine seaweeds has received increased attention in the protection or treatment of cancer, because of their bioactive compounds. The aim of the present study was to evaluate the anti-cancer capacity of two green seaweeds, Ulva fasciata and Ulva lactuca.

The phenolic and flavonoid content of the hydro-methanolic extracts was measured, respectively by Folin-Ciocateu and aluminum chloride methods. The antioxidant activity of the extracts was evaluated by FRAP and DPPH assay and were compared to ascorbic acid. Cytotoxic effect of the extracts on the MCF-7 (ER+) and MDA-MB-231 (ER-) breast cancer cell lines was also evaluated by MTT assay after 48 and 72 hours of incubation.

The phenolic and flavonoid content of Ulva fasciata was respectively 14.92±1.38 μgGAE/mg and 72.15±15.4 μgQE/mg which was significantly higher than Ulva lactuca. The reducing power and radical scavenging activity of Ulva fasciata was also higher. The cytotoxic effects of Ulva fasciata on the MCF-7 and MDA-MB-231 cell lines was more than Ulva lactuca, in concentration and time dependent manner. The cytotoxic effects of the both seaweeds were more potent on the MDA-MB-231 compared to the MCF-7 cell line and indicated an estrogen and progesterone receptor independent manner of cellular growth inhibition.

It is appeared that the Ulva fasciata extract was a better drug candidate in treatment of triple negative breast cancer due to higher antioxidant activity, phenolic and flavonoid content. Further studies in fractionation and bioactive extraction of Ulva fasciata are recommended.