فهرست مطالب
Physiology and Pharmacology
Volume:26 Issue: 4, Dec 2022
- تاریخ انتشار: 1401/10/12
- تعداد عناوین: 10
-
-
Pages 345-362
Recently, obesity causes vital mortality around the globe. Last decade, obesity-related diseases increased significantly worldwide. Even though, effective drugs are not available to treat metabolic diseases such as cardiovascular diseases, Parkinson’s, obesity, and hypertension. Emergence and identifying new drug moieties to treat such metabolic diseases became imperative. Nature is a vital source of remedies and isolates new effective and nontoxic drug candidates. Ferulic acid is a significant phenolic compound that is abundant in various fruits, rice oil, and vegetables. This study highlighted the beneficial effects of ferulic acid for the treatment of metabolic syndrome or obesity. Similarly, in this study, we have highlighted the therapeutic purpose of ferulic acid in treating metabolic syndrome, its mechanism of action as well as its potential pharmacological effect using animal models. Further investigations are needed to demonstrate the significant mechanism of action in clinical trials using the human species.
Keywords: Obesity, Metabolic diseases, Lipid profiling, Glucose dysregulation, Cardioprotective, Antioxidant, Inflammation, Hepatoprotective -
Pages 363-394
Multiple sclerosis (MS) is a central nervous system (CNS) chronic disease in which axons are demyelinated and signal conduction is slowed or blocked. Unfortunately, current drugs that are used to treat MS have limited efficiency and considerable side effects. The use of bioactive natural products for treating neurodegenerative diseases has become of great interest due to their multimodal mechanism of action and potential safety. However, pharmacokinetic parameters such as bioavailability, absorption, metabolic pathways, and elimination routes are essential for evaluating the efficacy and toxicity of herbal medicines and herbal preparations in the clinic. In this review, we have summarized different pharmacokinetic parameters of neuroprotective natural products with anti-experimental autoimmune encephalomyelitis (EAE) effects and recent developments in strategies to improve their bioavailability and effectiveness.
Keywords: Multiple sclerosis, Demyelination, Natural products, Pharmacokinetics, Experimental autoimmune encephalomyelitis -
Pages 395-411Introduction
Alzheimer’s disease (AD) is marked by the deposition of amyloid-β (Aβ) plaques and tau tangles. Although Erythropoietin (EPO) provides neuroprotective and memory-improving properties, its application has been limited due to the hematopoietic effects. Carbamylated Erythropoietin-Fc (CEPO-Fc) was developed as a non-erythropoietic EPO derivative that possesses neuroprotective potential. However, the molecular mechanisms behind the protective effects of CEPO-Fc’s in AD are still under consideration. Therefore, herein investigated the therapeutic properties of intraperitoneal (i.p.) dose of CEPO-Fc on Aβ-induced neurotoxicity in adult male Wistar rats.
MethodsThe rats received microinjections of Aβ25-35 (5 μg/2.5 μl, per side) in the dorsal hippocampus for four consecutive days. CEPO-Fc was injected intraperitoneally in two doses of 500 and 5000 IU during the next six days. Learning and memory performance were studied (days 10-13) using the Morris Water Maze task. Immunoblotting was also undertaken to assess the molecular levels of leading indicators of apoptosis (Bax, Bcl-2, and caspase-3), necroptosis (Phosphorylated-Receptor-interacting serine/threonine-protein kinase 3 (p-RIP3)), as well as autophagy (phosphorylated-Beclin-1 (p-Beclin-1) and phosphorylated-1A/1B-light chain 3 (p-LC3-II)) in the hippocampus.
ResultsBehavioral analysis indicated that CEPO-Fc 500 and 5000 IU reversed memory impairment. Moreover, the hippocampus’s molecular study showed upregulation of P-LC3-II/LC3-II and suppression of Bax/Bcl-2, Caspase-3, and P-RIP3/RIP3 processes.
ConclusionOur findings imply that the neuroprotective characteristics of CEPO-Fc in the AD rats are mediated through autophagy activation and regulation of apoptosis and necroptosis processes. These results suggest that an i.p. dose of CEPO-Fc could be used to protect against AD-induced neurotoxicity.
Keywords: Apoptosis, Autophagy, Alzheimer’s disease, Necroptosis, Carbamylated Erythropoietin-Fc -
Pages 412-423Introduction
Crocin and stress affect different aspects of brain functions. Chronic isolation stress is prevalent in today’s world. Therefore, this study investigated the impact of crocin and chronic isolation stress on learning, memory, and different brain waves in male rats.
MethodsForty male Wistar rats were allocated to five groups: control, sham, chronic isolation stress (CIS), two stress groups receiving different doses of crocin (CIS-Cr30 and CIS-Cr60). Both chronic isolation stress (6h/day) and crocin administration were induced for 21 days. The passive avoidance test evaluated initial and step-through latencies (IL and STL, respectively), as well as total dark compartment, and stay time. Also, different brain waves were measured by EEG recording.
ResultsThe STL declined in the CIS and CIS-Cr30 groups while it significantly increased in only the CIS-Cr60 group. Also, the total dark compartment stay time increased in the CIS group, whereas it decreased by crocin (30 and 60 mg/kg) in the CIS group. The percentages of beta and alpha waves decreased whereas theta waves significantly increased in the CIS group. While the percentage of the beta and alpha waves increased as well as the percentage of the theta and delta waves decreased by crocin at a dose of 60 mg/kg in the CIS group.
ConclusionCronic isolation stress was so destructive and it impaired learning, memory as well as alpha, beta, and theta waves in the brain. Only a dose of 60 mg/Kg of crocin reversed memory deficit and affected all brain waves in subjects under chronic isolation stress. Therefore, the doses of 60 and 30 mg/kg of crocin had different effects on electrophysiological and behavioral brain functions under chronic isolation conditions.
Keywords: Isolation stress, Crocin, Memory, EEG -
Pages 424-432Introduction
Renal Ischemia/Reperfusion (I/R) causes acute kidney injury known by impaired renal function, which has partially been connected to kidney apoptosis as well as the impairment of Cyclooxygenase-2 (COX-2) and Na+/K+-ATPase signaling. Curcuminoids have been proposed to have potential renoprotective effects. Thus, the present research work aimed to assess the effect of Nanomicellar Curcuminoids (NC) in a rat model of renal I/R.
MethodsAdult male Sprague-Dawley rats were allocated to three treatment groups (n=5/ group). NC at the dose of 25 mg/kg/i.p or its vehicle was administered 60 min before renal ischemia induction. Then, the animals were subjected to bilateral renal ischemia for 60 min and reperfusion for 24 h. Subsequently, blood samples were collected to assess Blood Urea Nitrogen (BUN) and Creatinine (Cr) levels. In addition, kidneys were isolated to evaluate renal histopathology, caspase-3 cleavage, and COX-2 and Na+/K+ -ATPase pump levels.
ResultsThe results showed that NC improved kidney function (P<0.0001) and attenuated I/R-induced histopathological injuries (P<0.0001) and caspase-3 cleavage (P<0.01). However, the downregulation of renal COX-2 and Na+/K+ -ATPase expression induced by I/R was not restored by the renoprotective dose of NC.
ConclusionThe findings of the present study indicated that the renoprotective effect of NC in the renal I/R rat model coincided with the inhibition of histopathological injuries and apoptosis, but not with compensation for renal COX-2 and Na+/K+ -ATPase downregulation.
Keywords: Curcuminoids, Nanoparticle, Renal ischemia, reperfusion, Na+, K+ -ATPase, COX-2, Rat -
Pages 433-439Introduction
Zingiber officinale (Ginger) is a commonly used plant for food and herbal treatment of different ailments. There is proof of ginger’s antioxidative and hypoglycemic activity, but the mechanism of action is yet to be understood, especially in a non-disease model. The present study assessed the effects of the methanolic extract of Zingiber officinale (MEZO) on blood glucose, pancreatic antioxidant levels, and histopathological changes.
MethodsFifteen (15) female Wistar rats with an average weight of 147 g were randomly divided into three (3) groups (A-C). Group A was given no treatment and served as the control group. Groups B and C received only oral administration of 400 mg/kg and 800mg/kg of MEZO, respectively. MEZO was administered once a day for 21 days. The animals were euthanized by cervical dislocation for blood collection and retrieval of pancreatic tissue for oxidative stress and histopathological assessment.
ResultsThe serum glucose level was significantly decreased in group C compared to the control (P=0.012). There were no significant changes in the levels of Superoxide dismutase (SOD), Glutathione (GSH), and Catalase (CAT) in all the MEZO groups compared to
the control (P>0.05). Pancreatic histology showed signs of acute pancreatitis, with dense aggregates of polymorphonuclear inflammatory cells infiltrating the surrounding stroma.ConclusionA high-dose ginger extract induces hypoglycemia, but a proinflammatory response is elicited in the pancreas at a lower dose. Thus, ginger extracts should be consumed with caution.
Keywords: Ginger, Pancreas, Hypoglycemia, Antioxidants, Inflammation -
Pages 440-450Introduction
Ascorbic acid is shown to reduce the signs of opioid dependence and addiction. The present experiments investigated the possible influence of ascorbic acid in acquiring and expressing morphine conditioned place preference (CPP) and sensitization in mice.
MethodsMale Swiss-Webster mice (20-25 g) were used. The unbiased method and an open field procedure were conducted for place preference and sensitization studies, respectively. Animals received different doses of morphine (1, 5, 10, and 20 mg/kg), ascorbic acid (1, 10, 100, and 1000 mg/kg), or saline (10 ml/kg) for place preference studies. Ascorbic acid was injected into the animals 20 min before each morphine (5 mg/kg) injection (acquisition) or 20 min before the test of morphine CPP (expression). Mice received morphine (5 mg/ kg) for three consecutive days, followed by five resting days for sensitization. Animals’ hyperactivity after morphine (1 mg/kg) challenge dose confirmed the sensitization. Ascorbic acid was administered 20 min before each morphine (5 mg/kg) injection (acquisition) or 20 min before each morphine challenge dose (1 mg/kg) administration on the test day (expression).
ResultsMorphine induced significant place preference dose-dependently. Furthermore, intraperitoneal (i.p.) administration of ascorbic acid failed to induce any aversion or preference effects. Ascorbic acid reduced the expression and acquisition of morphine place conditioning. Intraperitoneal injections of ascorbic acid also reduced the expression and acquisition of morphine sensitization.
ConclusionAscorbic acid could affect the motivational effects of morphine in mice. The exact mechanism by which the vitamin reduces the morphine effect must be evaluated in future studies.
Keywords: Ascorbic Acid, Conditioned place preference, Morphine, Sensitization -
Pages 451-458Introduction
Diabetic neuropathy is a common complication of diabetes mellitus. It is associated with nerve damage due to oxidative stress and high levels of pro-inflammatory mediators. In the present study, we examined the anti-nociceptive effects of Fullerene nanoparticle, as a potent anti-oxidant, during diabetic neuropathy.
MethodsDiabetes mellitus induced through injection of streptozotocin (STZ) (40 mg/kg). Four groups were used in the study as follows: the control, control+fullerene, diabetes, and diabetes +fullerene groups. All four groups received sesame oil. Treatment rats received fullerene C60 (1mg/kg/day) for 9 weeks by intra-gastric gavage. Then, cold allodynia, histology, and tumor necrosis factor-α (TNF- α) protein expression of the hippocampus were measured 9 weeks after injection of STZ.
ResultsOur data revealed that STZ induces cold allodynia in both hind paws and increases the TNF- α protein expression in the hippocampus. Furthermore, STZ induces neural degeneration in the hippocampus. Additionally, fullerene C60 significantly attenuated cold allodynia and TNF- α protein expression. Also, fullerene C60 has neuro-protective effects on hippocampal neurons. However, fullerene C60 did not significantly reduce serum glucose levels in diabetic animals.
ConclusionOur data suggest that fullerene C60 likely suppressed pain, and neural loss by inhibitory effects on TNF- α protein expression in the hippocampus during diabetes.
Keywords: Fullerene C60, Diabetic Neuropathy, TNF-α, Hippocampus -
Pages 459-467Introduction
Combretum dolichopetalum (CD) is commonly found in the Eastern part of Nigeria where it is used to relieve menstrual pain, enhance labour, facilitate the removal of placenta and promote a rich milk supply after delivery. This study investigates the effect of prenatal consumption of Combretum dolichopetalum by pregnant albino rats on haematological, and biochemical parameters as well as pregnancy outcome.
MethodsMature inbred healthy female albino rats of normal estrus cycles that were 2-3 months of age weighting 120-180 g were used for the study. Examination of the estrus cycle, the introduction of male rats at pro-estrus, and confirmation of pregnancy were adopted using standard method. After initiation of pregnancy, fifty (50) rats were placed in five groups comprising ten rats per group. Distilled water was administered to rats in Group 1 which served as control while rats in Groups 2, 3, 4, and 5 received 100, 200, 400 and 800 mg/kg of Combretum dolichopetalum methanol leaf extract (CDLE) from day 15 to 20 of pregnancy using oral gavage, respectively. Maternal weight, haematological parameters (full blood count), biochemical parameters (renal and liver indices), gestational length, and litter size were measured using standard methods.
ResultsThe result showed a decrease in maternal weight, postpartum weight retained and gestational length, an increase in haematological parameters, and no changes in the renal and liver indices.
ConclusionThis study indicates that CDLE during prenatal did not influence the pregnancy outcome but was beneficial in decreasing postpartum weight retained without any visible sign of toxicity.
Keywords: Combretum dolichopetalum, Biochemical, Haematological parameters, Pregnancy outcome -
Pages 468-479Introduction
Wound healing is one of the most critical issues human has been faced since the beginning of creation. Biodegradable polymers are of particular importance. In this study, cell-free supernatant (CFS) of Bifidobacterium bifidum combined with chitosan (CH) film was evaluated as a wound dressing.
MethodsBiodegradable films (CH and CFS/CH), as a novel wound dressing, were prepared. For the evaluation of dressing efficacy, 45 male Wistar rats weighing 200-250 g were randomly divided into 3 groups: negative control (without wound treatment), positive control (wound treatment by CH film), and probiotic (wound treatment by CFS/CH film). One full thickness wound was created on the dorsal area of the animals. The wound in positive control and probiotic groups were immediately covered by CH and CFS/CH dressing, respectively. Wound healing process was evaluated by macroscopic observation and histological analysis. During the treatment the expression of IL-1, TGF-B and IL-6 were assayed by qRT-PCR.
ResultsOur results showed different infiltration patterns of macrophages, fibroblasts, and neutrophils in CFS/CH treated group. Enhanced disposition of collagen and elastin caused improvement of wound healing process by the film. Based on the gene expression results, use of CFS/CH film caused improvement in wound healing kinetic.
ConclusionThe biodegradable film based on chitosan and CFS of B. bifidum improves the wound healing process.
Keywords: Wound healing, Chitosan, Cell free supernatant, Biodegradable-film, Cytokines