The protective effect of methanolic extract of Verbascum cheiranthifolium and Biebersteinia multifida DC on hippocampus damage induced by diazinon in male Wistar rats: An experimental study.

Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement.

Protective effects of hydro-alcoholic extract of Zataria multiflora on lipopolysaccharide-induced inflammation and oxidative stress in rat liver.

Objective: Liver is an important player in regulation of body homeostasis. Study investigated the effects of hydro-alcohol extract of Zataria multiflora (ZM) on oxidative damage, level of IL-6 and enzymes of liver in lipopolysaccharide (LPS)-treated rats. Materials and Methods: The rats were distributed into 5 groups: 1) Control; 2) LPS; and 3-5) ZM-Extract (Ext) 50, ZM-Ext 100, and ZM-Ext 200. ZM-Ext groups received 50, 100 and 200 mg/kg of extract 30 min before LPS. Drugs were injected intraperitoneally. The entire period of this project was 17 days. In first three days, only extract was injected and then, ZM was injected along with LPS. Results: LPS increased the level of ALT (Alanine aminotransferase), AST (Aspartate aminotransferase ), ALK-P (Alkaline Phosphatase), IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) concentration. ZM extract not only reduced ALT, AST, ALK-P, IL-6, MDA, and NO metabolites concentrations but also increased thiol content, and SOD and CAT levels. Conclusion: Extract of ZM prevented LPS-induced hepatotoxicity. This protective effect was associated with reduction in inflammation and oxidative stress.

Zataria multiflora and its constituent, carvacrol, counteract sepsis-induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress.

BACKGROUND: Zataria multiflora and carvacrol showed various pharmacological properties including anti-inflammatory and anti-oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)-induced aortic and cardiac injury. METHODS: Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS) (1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro-ethanolic extract (ZME, 50-200 mg/kg, oral)- and carvacrol (25-100 mg/kg, oral)-treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. RESULTS: Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS-injected rats. CONCLUSIONS: The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

Neuroprotective and memory enhancing effects of Zataria multiflora in lipopolysaccharide-treated rats.

The study was aimed to evaluate the effects of hydro-ethanol extract Zataria multiflora on the brain tissue oxidative damage, and hippocampal interleukin-6 (IL-6) as well as learning and memory capacity in lipopolysaccharide (LPS) - challenged rats. The rats were randomized into five groups as follow: Control group: Rats were treated with saline, LPS group: Rats were treated with LPS 1.00 mg kg-1, ZM50, ZM100 and ZM200 groups in which the rats were treated with Z. multiflora extract (50.00, 100 or 200 mg kg-1 per day, respectively). The treatments including extract or vehicle were administered intraperitoneally and given three days before the behavioral tests and were continued within a6-day behavioral experiment. Injection of LPS was daily done before the behavioral tests. Finally, the brains were collected for biochemical evaluations. Although LPS administration prolonged the latency in Morris water maze and shortened the latency to enter the dark chamber in passive avoidance test, ZM extract restored these changes to approach control group values. Also, LPS increased IL-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites levels and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) levels in the brain, however, Z. multiflora extract reduced IL-6, MDA and NO metabolites concentrations, but increased thiol content, SOD, and CAT levels. The results of this study showed that Z. multiflora ameliorated learning and memory dysfunction in LPS - challenged rats by alleviating of inflammatory responses and brain tissue oxidative damage.

The effects of the combination of Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata on learning and memory deficit and oxidative damage in brain tissue of hypothyroid rats.

In the present study, the impact of a combination of four memory-enhancer herbs on cognitive impairment and brain tissue oxidative damage due to hypothyroidism was evaluated. Propylthiouracil (PTU; 0.05%) was administrated in drinking water. Rats were treated with a combination of four herbal products (Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata) mixed with honey at two doses (640 and 1,280 mg/kg) or donepezil (0.5 mg/kg), for 6 weeks. Memory performance on the Morris water maze (MWM) and avoidance behavior in passive avoidance was impaired by hypothyroidism, and brain tissue oxidative damage occurred. Herbal combination and donepezil significantly improved memory impairment, reduced malondialdehyde concentration, and nitric oxide metabolites while increased the thiol contents and catalase and superoxide dismutase enzymes activity in the brain. Our findings suggest that the mixture of herbal products improves learning and memory deficits caused by hypothyroidism, probably by reducing the brain tissue oxidative damage. PRACTICAL APPLICATIONS: Learning and memory impairment is a common feature of thyroid hormones deficiency. Several studies are showing that hypothyroidism in juvenile and mature rats induces significant cognitive impairment. Likewise, in humans, a close relationship between thyroid hormone deficiency and cognitive impairment has been reported. We used a mixture of herbal products, including Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata, to treat hypothyroidism-induced memory impairment. All these herbs are widely used as a food additive across the world. In Iranian traditional medicine, this herbal combination traditionally used to treat cognitive impairments. Numerous studies have indicated that these herbs show neuroprotective and memory-enhancing properties. Our finding indicated that a traditionally used herbal combination could potentially use as a treatment of cognitive impairment induced by thyroid hormone deficiency.

Vitamin D3 attenuates lipopolysaccharide-induced cognitive impairment in rats by inhibiting inflammation and oxidative stress.

AIMS: Vitamin D is a well-known endocrine regulator of calcium/phosphate homeostasis and has been reported as having a wide range of activities that are potentially beneficial for human health. This study aimed to investigate the effects of pretreatment of vitamin D3 (100, 1000, and 10,000 IU/kg) against lipopolysaccharide (LPS)-induced cognitive impairment in rats. MAIN METHODS: Male Wistar rats were divided into five groups. The passive avoidance test and Morris water maze (MWM) test were conducted to evaluate the learning and memory function. Oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), total thiol content as well as interleukin (IL)-6 were evaluated in the hippocampus tissue. KEY FINDINGS: The intraperitoneal (i.p.) injection of LPS (1 mg/kg) correlates with deficits in passive avoidance and spatial learning in the systemic inflammation model. However, pretreatment with vitamin D3 improved LPS-induced cognitive impairment. In addition, vitamin D3 decreased IL-6 and MDA levels, whereas the activities of CAT, SOD, and total thiol content in the hippocampus tissue were significantly increased. SIGNIFICANCE: In conclusion, our results suggest that vitamin D3 plays a protective role against memory dysfunction caused by LPS-induced inflammation through inhibition of oxidative stress and inflammation in the hippocampus. Vitamin D may be a promising potential therapeutic supplement for the treatment or prevention of learning and memory disorders.

Zataria multiflora extract reverses lipopolysaccharide-induced anxiety and depression behaviors in rats.

OBJECTIVE: Stressors have an important role in sickness behaviors. We checked the effect of Zataria multiflora (ZM) extract against lipopolysaccharide (LPS)-induced anxiety and depression behaviors in rats. MATERIALS AND METHODS: Rats were distributed in the following groups (n=10): Control, LPS (1 mg/kg), LPS-ZM50, LPS-ZM100 and LPS-ZM200. LPS was syringed intraperitoneally (ip) 2 hr before performing behavioral tests. LPS-ZM groups were treated with 50, 100 and 200 mg/kg (ip) of ZM extract 30 min before LPS administration. Open field (OF), elevated plus maze (EPM) and forced swimming (FS) tests were done. White blood cell (WBC) was counted in all groups. RESULTS: In OF, pretreatment with ZM extract augmented the number of lines crossed and traveled distance in central and peripheral areas. The rats treated with ZM extract spent more time in the central zone and less time in the peripheral area compared to the LPS group. In EPM, the number of entries into the open and closed arms and stop time in the open arms in LPS-ZM groups were higher than the LPS group. The stop time in the closed arms of ZM-LPS groups was less than the LPS group. In FS test, swimming and climbing time in groups treated with ZM extract was more than the LPS group while their immobility time was less. WBC count in the LPS-ZM100 and LPS-ZM200 was lower than that of the LPS group. CONCLUSION: Based on the results, pretreatment with ZM extract restituted anxiety and depression caused by LPS in rats. This effect of ZM was associated with amelioration of LPS-promoted inflammation.

Prediction of neonates' macrosomia with maternal lipid profile of healthy mothers.

BACKGROUND: The aim of this study is to identify the association between the lipid profile of healthy nondiabetic, nonobese pregnant women in the first weeks of the third trimester of pregnancy and macrosomia or large-for-gestational-age (LGA) neonates with normal pregnancies. MATERIALS AND METHODS: In this cohort study, 200 pregnant healthy women without gestational diabetes mellitus (GDM), obesity, or hypertension and carrying a single fetus in a prenatal clinic of a referral hospital were included based on a convenience sampling. Then, we took a blood sample to assess fasting blood sugar (FBS), triglyceride (TG), total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). GDM was assessed after administering 50 g of oral glucose. All cases were followed until the end of pregnancy. The main outcome measurement was neonatal birth weight. RESULTS: Only 154 mothers met eligibility criteria. There were eight cases (5.2%) with macrosomia (birth weight ≥ 4000 g) and 35 cases (22.7%) with LGA. Linear regression showed that mothers' TG and neonates' gender were independent predictors of the birth weight of the children (R-square = 0.52, p < 0.001). Logistic regression analysis showed that maternal FBS and TG are the most independent variables which can predict the presence of macrosomia (Nagelkerke R-square = 0.53, p < 0.001) and maternal TG and child gender are the most independent variables that can predict the presence of LGA in neonates of a healthy mother (Nagelkerke R-square = 0.49, p < 0.001). CONCLUSION: Maternal triglyceride levels may be a significant predictor of fetal size in late pregnancy but not in early pregnancy. Our study reinforces that this is true not only in the case of macrosomia (birth weight > 4500 g), but also for LGA.