Synergistic effects of Nepeta menthoides and Melissa officinalis aqueous extracts on reserpine-induced depressive-like behaviors in mice.

Nepeta menthoides Boiss. & Buhse and Melissa officinalis are extensively used in Persian medicine for the treatment of depression. Considering the active ingredients and main phenolic compounds of these plants and possible synergistic effects, this study examined the antidepressant and antioxidant activities of aqueous extract of N. menthoides (NM) and M. officinalis (MO) in reserpinized mice alone and combination. Mice were pretreated orally for 1-week with normal saline (10 ml/kg), fluoxetine (20 mg/kg), imipramine (10 mg/kg), NM (50-100-200-400 mg/kg), MO (150-350-550-750 mg/kg), and combination (NM 50 with MO 150 mg/kg). The behavioral changes were evaluated using forced swim, tail suspension, and open field tests, 24 hr after reserpine injection (4 mg/kg) on eighth day. The amounts of active components in the extracts and catalase (CAT) as a brain oxidative stress were measured with enzyme-linked immunosorbent assay. Data showed that this combination produced a synergistic action on behaviors and a significant increase in CAT activity. High-performance liquid chromatography results showed that rosmarinic acid contents in MO and NM were 6.42 ± 1.1 and 11.03 ± 2.16 mg/g of dried extract, respectively. Total flavonoid and phenolic contents of MO were higher than NM. The findings suggest that the present combination produces an antidepressant-like effect, which is possibly triggered by its antioxidant properties.

Proconvulsant effects of Nepeta menthoides hydro alcoholic extract in different seizure tests: behavioral and biochemical studies.

In Iran, both Nepeta menthoides - the endemic species of Nepeta genus - and Lavandula officinalis are known as Ustukhuddoos and used widely as medicinal herbs. In Iranian traditional medicine, Ustukhuddoos has been recommended for several neuronal diseases including depression and epilepsy. While the antiepileptic effects of Lavandula officinalis have been investigated in a number of studies, no reports are available taking into account the effect of Nepeta menthoides on epilepsy. Since convulsion is an important side effect of some medicinal plants, a thorough study of the effects of Nepeta menthoides on epilepsy seems necessary. This study was designed to investigate the potential anti- or pro-convulsant activity of Nepeta menthoides and its effects on oxidative stress markers. Since an herbal medicine showed opposite effects in two animal models of epilepsy in our laboratory, authers decided to study Nepeta effects through several seizure tests including the intravenous pentylenetetrazol (i.v. PTZ) infusion, the maximal electroshock (MES), acute PTZ and PTZ-kindling tests. These seizure models are generally used for screening pro- or anti-epileptic drugs. Nepeta menthoides (400 mg/kg) significantly reduced the dose of PTZ necessary for clonus seizure induction. Combining either phenytoin (Phen) or Valproate (Val) with Nepeta decreased their antiepileptic effects. Therefore, Nepeta menthoides not only failed to prevent the seizures but also increased sensitivity to them. Nepeta raised brain NO levels in different seizure tests. It seems there is a relation between NO elevation by Nepeta and increased sensitivity to seizures that should be investigated later.

Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats.

CONTEXT: Anxiety and depression are common in Alzheimer's disease (AD). Despite some evidence, it is difficult to confirm Lavandula officinalis Chaix ex Vill (Lamiaceae) as an anxiolytic and antidepressant drug. OBJECTIVE: The effects of L. officinalis extract were studied in scopolamine-induced memory impairment, anxiety and depression-like behaviour. MATERIALS AND METHODS: Male NMRI rats were divided into control, scopolamine alone-treated group received scopolamine (0.1 mg/kg) intraperitoneally (i.p.), daily and 30 min prior to performing behavioural testing on test day, for 12 continuous days and extract pretreated groups received aerial parts hydro alcoholic extract (i.p.) (100, 200 and 400 mg/kg), 30 min before each scopolamine injection. Memory impairment was assessed by Y-maze task, while, elevated plus maze and forced swimming test were used to measure anxiolytic and antidepressive-like activity. RESULTS: Spontaneous alternation percentage in Y maze is reduced by scopolamine (36.42 ± 2.60) (p ≤ 0.001), whereas lavender (200 and 400 mg/kg) enhanced it (83.12 ± 5.20 and 95 ± 11.08, respectively) (p ≤ 0.05). Also, lavender pretreatment in 200 and 400 mg/kg enhanced time spent on the open arms (15.4 ± 3.37 and 32.1 ± 3.46, respectively) (p ≤ 0.001). On the contrary, while immobility time was enhanced by scopolamine (296 ± 4.70), 100, 200 and 400 mg/kg lavender reduced it (193.88 ± 22.42, 73.3 ± 8.25 and 35.2 ± 4.22, respectively) in a dose-dependent manner (p ≤ 0.001). DISCUSSION AND CONCLUSION: Lavender extracts improved scopolamine-induced memory impairment and also reduced anxiety and depression-like behaviour in a dose-dependent manner.

Prevention of morphine dependence and tolerance by Nepeta menthoides was accompanied by attenuation of Nitric oxide overproduction in male mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Repeated administration of morphine for chronic pain leads to dependence and tolerance that limits clinical usage. Nepeta menthoides is commonly known as Iranian Ustukhuddoos and are administered in traditional medicine for gastrodynia, bone pain, blood depurative and restlessness. AIMS OF STUDY: To investigate the effects of Nepeta menthoides on expression and acquisition of morphine dependence and tolerance in mice with regard to oxidative stress. MATERIALS AND METHODS: Morphine dependence in mice was developed by administration of gradually increasing doses of morphine twice daily for 7 consecutive days. In experimental groups, administration of Nepeta menthoides (200 and 400mg/kg), methadone and their combination were performed 60min prior to each morphine injection (for acquisition) or the last injection of morphine on test day (for expression). Morphine tolerance was measured by the tail-immersion test before and after the administration of a single dose of morphine (100mg/kg; i.p.) on the test day (8th day). Morphine dependence was also evaluated by counting the number of jumps after the injection of naloxone (5mg/kg; i.p.). RESULTS: Nepeta menthoides, similar to methadone, significantly prevented the development (but not the expression) of morphine dependence, tolerance, and potentiated morphine antinociception and also reduced (23.23±1.15) Nitric oxide (NO) overproduction (35.23±3.36) (in compared with naloxone group (6.3±0.52)). However, single and repeated application of the extract could not change high single-dose morphine analgesia. CONCLUSION: It appears that Nepeta menthoides and methadone prevented morphine dependence and tolerance, partly through inhibition of the NO overproduction.

Effect of Withania somnifera (L.) Dunal on Sex Hormone and Gonadotropin Levels in Addicted Male Rats.

BACKGROUND: Opioid consumption has been widely increasing across the globe; how- ever, it can cause adverse effects on the body. Morphine, an opioid, can reduce sex hor- mones and fertility. Withania somnifera (WS) is a traditional herb used to improve sexual activities. This study strives to investigate the effect of WS on sex hormones and gonado- tropins in addicted male rats. MATERIALS AND METHODS: In this experimental study, forty-eight male National Maritime Research Institute (NMRI) rats were randomly divided into four groups: i. Control group, ii. WS-treated control group, iii. Addicted group, and iv. WS-treated addicted group. Wa- ter-soluble morphine was given to rats for 21 days to induce addiction, concurrently the treated groups (2 and 4) also received WS plant-mixed pelleted food (6.25%). At the end of the treatment, the sex hormone and gonadotropin levels of the rats' sera were deter- mined in all the groups. RESULTS: Except for follicle-stimulating hormone (FSH), morphine reduced most of the gonadotropin and sex hormone levels. Whereas WS caused a considerable increase in the hormones in the treated addicted group, there was only a slight increase in the treated control group. CONCLUSION: WS increased sex hormones and gonadotropins-especially testosterone, es- trogen, and luteinizing hormone-in the addicted male rats and even increased the proges- terone level, a stimulant of most sex hormones in addicted male rats.

Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy.

CONTEXT: Temporal lobe epilepsy (TLE) is an intractable neurological disorder. Curcumin is the bioactive component of turmeric with anti-epileptic and neuroprotective potential. OBJECTIVE: The beneficial effect of curcumin on the intrahippocampal kainate-induced model of TLE was investigated. MATERIALS AND METHODS: Rats were divided into sham, curcumin-pretreated sham, kainate and curcumin-pretreated kainate groups. The rat model of TLE was induced by unilateral intrahippocampal injection of 4 µg of kainate. Rats received curcumin p.o. at a dose of 100 mg/kg/d starting 1 week before the surgery. Seizure activity (SE) and oxidative stress-related markers were measured. Furthermore, the Timm index for evaluation of mossy fiber sprouting (MFS) and number of Nissl-stained neurons were quantified. RESULTS: All rats in the kainate group had SE, while 28.5% of rats showed seizures in the curcumin-pretreated kainate group. Malondialdehyde and nitrite and nitrate levels significantly increased in the kainate group (p < 0.01 and p < 0.05, respectively), and curcumin significantly lowered these parameters (p < 0.05). Superoxide dismutase activity significantly decreased in the kainate group (p < 0.05) and curcumin did not improve it. Rats in the kainate group showed a significant reduction of neurons in Cornu Ammonis 1 (CA1) (p < 0.05), CA3 (p < 0.005) and hilar (p < 0.01) regions, and curcumin significantly prevented these changes (p < 0.05-0.005). The Timm index significantly increased in the kainate group (p < 0.005), and curcumin significantly lowered this index (p < 0.01). DISCUSSION AND CONCLUSION: Curcumin pretreatment can attenuate seizures, lower some oxidative stress markers, and prevent hippocampal neuronal loss and MFS in the kainate-induced model of TLE.

Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. MATERIALS AND METHODS: Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. RESULTS: Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. CONCLUSION: This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression.

In vitro cytotoxic effect of garlic extract on malignant and nonmalignant cell lines.

Cancer is one of the major causes of death in the world and despite many years of research, the treatment of cancer is still a problem. Epidemiological observations and laboratory studies have indicated anticarcinogenic potential of garlic, which has been traditionally used for various human diseases around the world. In this study the cytotoxicity of garlic extract against three malignant cancer cell lines including gastric (AGS), breast (MCF-7) and colon (HT-29) and a nonmalignant cell line (L929) were evaluated by the MTT assay. The results of this study reveal MCF-7 and AGS cells were sensitive to garlic extract. Despite a many reports on inhibitory effects of garlic on cancer cell line, our data showed these effects are tumor specific and dose dependent. Further studies on animal models and humans are needed to clarify the important molecules and their mechanisms.

Cytotoxic effect of garlic extract and its fractions on Sk-mel3 melanoma cell line.

Cutaneous cancers are among the most common forms of cancer. Melanoma is an aggressive malignancy which is poor in prognosis. Despite of many years of researches, the treatment of melanoma is still a problem. Historically, plants have been main resources in traditional medicine and natural products are considered as important sources of antitumor drugs. Meanwhile, garlic for a long time has been used in man's food as a medicinal plant. In this study, the garlic extract was prepared and fractionated by ultra-filtration method with Amicon system. Garlic extract and its fractions including residue (R) 100, R50, R30, R10, R5, and filtrate (F) 5 were investigated for their cytotoxic activities on Sk-mel3 cell line of melanoma. The results show that garlic extract induced a significant cytotoxic activity on Sk-mel3 cell line. Among fractions R100 and R10 have more potential in cytotoxic activities against Sk-mel3 melanoma cells. In conclusion, garlic appears to be a good candidate as an antitumor agent against melanoma. To clarify the effective molecules and their mechanisms more studies should be applied on animal models and humans.

Macrophages activation and nitric oxide alterations in mice treated with Pleurotus florida.

Macrophages play an essential role against invading pathogen and malignancies. The present study addresses the in vivo effect of P.florida extract on nitric oxide (NO) production and cell viability of macrophages. Forty Balb/c mice were divided to 8 groups and were treated with different doses of P. florida aqueous extract. MTT test has been performed in order to evaluate viability of intraperitoneal macrophages and Griess method to measure NO production of macrophages. The results indicated that cell viability of macrophages significantly increased by oral administration of P. florida with 200, 500 and 1000mg/kg/day. Also, NO production significantly increased by oral administration of doses of 500 and 1000mg/kg/day of P. florida. but i.p. injection of P. florida with 10,20,50,100mg/kg/day significantly decreased NO production by macrophages. This study showed a macrophage activator function for P. florida and also may confirms its anti inflammatory role. Further studies are needed to address effective phytochemicals of this edible mushroom and their mechanisms.