Jundishapur Journal of Natural Pharmaceutical Products
Volume:11 Issue: 3, Jun 2016

Foot and mouth disease (FMD) is an infectious disease of cloven-hoofed animals that has adverse economic impacts. Given the prevalence of this viral infection, the lack of effective treatments, and the presence of resistant strains, the progression of novel antiviral agents is needed.
The purpose of this study was to investigate the anti-FMDV activity of the methanolic extract of Alhagi maurorum Medik (camel thorn), via cell cultures. This study was done to evaluate the biologically active substances in extract of camel thorn and their applications in herbal and traditional medicine.
Extraction of A. maurorum Medik was carried out in an 80% methanol solvent system. The maximum concentration of the extract with non-cytotoxic effects on cells was determined using an MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide)-assay. Then, this concentration was incubated with ten-fold serial dilutions of the virus. The antiviral activity of the tested compounds was evaluated by measuring the reduction in CPEs and calculating and comparing the TCID50, before and after treatment with the extract, via the Reed & Muench method.
The MTT assay revealed that methanolic extract in a concentration of 3 mg/mL or less has no cytotoxic impact, and the 50% cell cytotoxicity (CC50) was about 30 μg/mL. The Reed & Muench method showed that A. maurorum Medik has anti-FMDV activity and it can reduce the titer of the virus by at least 2 × 3.5 log.
The present investigation supports the use of the methanolic extract of A. maurorum as an antiviral drug in folk and modern medicine. This activity may justify its use as a source of natural compounds to control FMDV in infected animals.

Cancer is one of the leading causes of human death. The discovery of new generations of low-cost anticancer drugs with high efficacy and low toxicity is necessary, and is only possible by screening medicinal plants with prior knowledge.
In this study, the bioactivities of three medicinal plants from India, including Alstonia scholaris, Alstonia venenata, and Moringa oleifera, were investigated.
From each plant, hexane, benzene, isopropanol, methanol, and water extracts were prepared. Cytotoxicity assays were determined by Trypan blue exclusion, MTT, and apoptotic methods. Antioxidant activities were assayed by superoxide scavenging, hydroxyl radical scavenging, and lipid peroxidation.
Among the extracts tested for cytotoxicity on DLA cells, the most active extracts from A. scholaris and A. venenata were selected (extracts from M. oleifera did not show 100% cytotoxicity even at a dose of 500 µg/mL, so it was not considered for determining EC50 value), and their EC50 values were determined. Among the extracts of A. scholaris, hexane extract of stem bark showed an EC50 value of 68.75 µg/mL, while n-hexane extract of the leaves showed a higher EC50 value of 118.75 µg/mL. A. venenata showed significant in vitro superoxide scavenging activity, superior to that of quercetin. A. venenata showed less superoxide scavenging activity. The IC50 values of hexane extract (A. scholaris), isopropanol extract (A. venenata), and quercetin were 90.5 ± 6.2, 7.5 ± 1.2, and 31.5 ± 2.5 µg/mL, respectively.
The hexane extract of stem bark from A. scholaris and isopropanol extract of leaves from A. venenata are candidate materials for the discovery of a new generation of anticancer drugs to combat diseases such as lymphoma and leukemia. These can also be used as antioxidants in dietary supplements.

Chromium is a naturally occurring heavy metal found in the environment.
The aim of the present study was to determine the effect of simvastatin (SIMV) on sodium dichromate [Cr(VI)]-induced oxidative stress in the rat lung.
Forty-eight adult male Wistar rats (180 - 220 g weight) were randomly assigned to eight groups (each n = 6). Group one received SIMV 20 mg/kg/day. Group two was given vehicle only. Groups three, five, and seven received intraperitoneal (i.p.) Cr(VI) at doses of 8, 12, and 16 mg/kg body weight, respectively, for eight consecutive days. Groups four, six, and eight were pretreated with 20 mg/kg SIMV 30 minutes prior to administration of Cr(VI) at doses of 8, 12, and 16 mg/kg, respectively, for eight consecutive days. Twenty-four hours after the last administration, the animals were killed with an overdose of sodium pentobarbital. Lung tissues were excised for measurements of malondialdehyde (MDA) and glutathione (GSH), and for histopathological examination.
The level of GSH was significantly decreased in the Cr(VI)-treated rats. In contrast, the lung level of MDA was significantly increased in a dose-dependent manner in the Cr(VI)-treated rats when compared to the control animals. SIMV had no effect on GSH and MDA levels compared to the control rats, but there were significantly increased GSH concentrations and decreased MDA levels in lungs of rats treated with Cr(VI).
The observations suggest that SIMV may have a protective effect against Cr(VI)-induced oxidative stress in the rat lung.

Lemon verbena (Lippia citriodora) has a long history as a folk remedy for the common cold, asthma, colic, fever, diarrhea, indigestion, insomnia, and anxiety. The increasing use of Lippia citriodora and the lack of scientific data on its safety profile make necessary an evaluation of its toxicity.
The present study evaluated the acute, subacute, and cellular toxicity of the aqueous extract of L. citriodora leaves.
The acute and subacute toxicity of the plant was evaluated with a single intraperitoneal (IP) injection of aqueous extract at the dosage range of 0, 1, 2, and 5 g/kg of body weight (acute model) in mice and rats and 21 days’ administration at the dosage range of 0, 50, 100, and 200 mg/kg of body weight. For subacute toxicity, food intake, water intake, body weight, hematological and biochemical parameters, and histopathological changes were evaluated. In our in vitro study, the effect of different concentrations (0, 50, 100, and 200 µg/mL) in HepG2 cells was evaluated using MTT assay.
In the acute toxicity study, the calculated LD50 was 5g/kg of body weight. The subacute toxicity study did not show a significant change in any of the hematological, biochemical, or pathological findings compared to the control group, except for a reduction in triglyceride levels. The cytotoxicity assay also revealed that the viability in all groups was greater than the IC50 value.
Results from the present study elucidated that treatment with the aqueous extract of L. citriodora leaves was well tolerated via daily IP injection at doses up to 200 mg/kg for a period of 21 days and did not produce any toxicity. The safety of L. citriodora aqueous extract was also confirmed by cell viability assay.

Diabetes mellitus is the most common leading cause of cardiovascular-related mortality and morbidity worldwide. Citrullus colocynthis (C. colocynthis) belongs to the Cucurbitaceae family and has been used as an anti-diabetic treatment in traditional medicine.
The aim of this study was to assess the effects of hydro-alcoholic leaf extract of C. colocynthis on the serum biochemical factors and histopathological changes in streptozotocin-induced diabetic rats.
The current experimental study was performed on 24 male rats, which became diabetic with 60 mg/kg body weight intraperitoneal injection of streptozotocin (STZ). The animals were divided into four groups: untreated healthy controls, healthy controls treated with the extract, untreated diabetic and diabetic treated with extract, respectively. The animals were treated with 75 mg/kg body weight orally hydro-alcoholic leaf extract of C. colocynthis for 3 weeks.
The results indicated that fasting blood sugar (FBS), triglycerides (TG), low-density lipoprotein (LDL), total cholesterol, aspartate aminotransferase, alanine aminotransferase, creatinine, urea, and bilirubin (total and conjugated) in diabetic rats treated with the extract significantly decreased compared to the other groups. Conversely, high-density lipoprotein (HDL) and serum albumin were significantly increased in diabetic rats treated with extract. Histopathological findings showed STZ-induced diabetic complications in the pancreas, kidney and liver were improved following treatment with hydro-alcoholic leaf extract of C. colocynthis.
The administration of hydro-alcoholic leaf extract of C. colocynthis had a significant anti-hyperglycemic and anti hyperlipidemic effect and improved diabetic complications. In addition, Citrullus C. leaf extract may have a protective effect on the liver, kidneys, and pancreas.

The antioxidant and anti-inflammatory effects of arbutin protect against a number of diseases.
The present study evaluated the protective effect of arbutin against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats.
Sixty-three Wistar rats were divided into nine groups. Groups I and II were the normal control groups. Group III, the hepatotoxic group, was given CCl4. Groups IV, VI, and VIII received different dosages of arbutin along with CCl4. Groups V, VII, and IX were administered different dosages of arbutin. The albumin content, total protein, and bilirubin were assayed to determine their serum and antioxidant levels; lipid peroxidation was assessed in the serum and liver tissue. Histological studies were carried out to confirm the biochemical results.
Treatment with CCl4 for 28 d decreased the levels of total protein and albumin and increased the level of bilirubin and lipid peroxidation. Arbutin treatment raised the level of albumin and lowered the lipid peroxidation to normal levels. Necrosis and fibrosis were observed in the liver tissue of CCl4-injected rats, and the administration of arbutin had a protective effect on the liver tissue.
The results of this study showed that arbutin may protect the liver against CCl4-induced oxidative damage in rats. This hepatoprotective effect might be correlated with the antioxidant and free radical scavenger effects of arbutin.

The pivotal role of cyclooxygenase-2 (COX-2) inhibitors in inflammatory pain is well documented, but its mechanism is not entirely clear. Nonsteroidal anti-inflammatory drugs (NSAIDs) as inhibitors of COX could inhibit fatty acid amide hydrolase, the enzyme responsible for the metabolism of endocannabinoids. Therefore, it is expected that celecoxib administration (selective COX-2 inhibitor) preserve the increased level of endocannabinoids after noxious stimuli, which leads to more pain suppression.
This study was designed to evaluate the interaction between the intrathecally administered celecoxib in combination with rimonabant, a selective cannabinoid CB1 receptor antagonist/reverse agonist on the pain behavior induced by formalin test in rat.
Male Wistar rats with inserted lumbar intrathecal catheters were randomly grouped and tested in blinded manner by the same experimenter. Antinociceptive effects of different intrathecally doses of celecoxib (0.5, 5 and 10 µg/rat) in absence and with pretreatment of rimonabant at doses of 100 and 200 µg/rat were examined on the formalin test.
Celecoxib reduced the pain behavior in both phases of the formalin test, but this antinociceptive effect was a dose-dependent manner in the late phase. Rimonabant alone induced hyperalgesia as compared with the control group and pretreatment of rats with rimonabant reversed the analgesic activity of celecoxib.
Antinociceptive effect of celecoxib may be mediated partly through the cannabinoid system. These effects are possibly attributed to inhibition of endocannabinoid degradation and consequently enhancement of endocannabinoids concentration at the spinal cord level. However, the hyperalgesic effects of rimonabant are not fully responsible for the reversal of celecoxib analgesia. Accordingly, NSAIDs intensify their effects through maintenance of the endocannabinoid tone. Therefore, combination of NSAIDs and cannabinoid agents could be used for synergistic effects..

Gentamicin is a commonly used antibiotic for the treatment of Gram-negative infections, but nephrotoxicity limits its use. Cyperus scariosus Linn. (CS) has been found to have antioxidant properties in vitro.
The aim of this study was to evaluate the nephroprotective effects of CS in gentamicin-induced acute kidney injury (AKI).
The animals were divided into nine groups. AKI was produced with a 100 mg/kg intraperitoneal (i.p.) injection of gentamicin for 7 days. Next, α-lipoic acid 100 mg/kg i.p. served as the active control, while the test drug (CS) was given in two doses (150 mg/kg and 250 mg/kg orally) for 10 days. Distilled water, 1 ml/day orally for 7 days, served as the vehicle control. The protective and curative effects, respectively, were assessed by the administration of CS before and after the induction of AKI. The effects of CS on AKI were assessed by serological and histopathological parameters.
Serum creatinine was significantly increased (P In our study, hydroalcoholic extract of Cyperus scariosus Linn. offered nephroprotection in the form of AKI prevention and for the treatment of established AKI.

T-2 toxin is a mycotoxin, exposure to which causes dermal and systemic toxicity. Crataegus pontica (a member of the Rosaceous family) is a small tree with caduceus foliage that is widely distributed throughout the western and central areas of Iran.
This study was performed to examine the healing effects of creams prepared using Crataegus pontica leaf extract on dermal toxicity induced by T-2 toxin.
Iranian rabbits were used for this study. The back left flanks of the animals were shaved and to induce toxicity, a solution of 100 µg/12 µl of T-2 toxin in ethanol was applied to the skin for 2 successive days. Creams were prepared using Crataegus pontica leaf extract in a eucerin base at concentrations of 5%, 10%, and 15% (w/w). Beginning on the third day, the creams were applied to the skin lesions twice per day until complete healing occurred. The positive control group received the toxin only without treatment and the negative control group received solvent (ethanol) only. Healing was defined as a decreased wound margin, as well as treatment of the erythema and blisters.
Our findings indicated that wound healing occurred 15, 15, 12, 10, and 10 days after initial wounding in the negative control, eucerin, 5%, 10%, and 15% C. pontica extract groups, respectively. The most effective treatments were obtained with the creams containing 10% and 15% C. pontica extract. Histological findings confirmed wound reduction in the affected areas.
The results obtained in this study indicate that C. pontica extract has a healing effect on dermal toxicity caused by T-2 toxin and is effective for its treatment.

Topical drug delivery is a painless route of drug administration. Skin is one of the most easily accessible parts of human body for topical administration and also is a main route of topical drug delivery system. There are different skin diseases and infections caused by fungus. An antifungal compound is a pharmaceutical fungicide used to treat mycoses such as dermatophytes which have the ability to attack keratinized tissues and used keratin cause dermatophytosis, the most common human contagious fungal disease. Because of drug resistance, side effects and cytotoxicity associated with long-term treatment with antifungal drugs, finding new useful drugs to treat fungal infections is necessary.
The purpose of the present study was to formulate topical gel containing stabilized extract of Lactobacillus as an antidermatophytic preparation and evaluate its physicochemical properties.
Lactobacillus casei was cultured in MRS anaerobically and then its extract was collected by separating the bacterial cells with centrifugation. Firstly, antifungal activity of the extract against four dermatophyte species (Tricophyton rubrum, Tricophyton verocosum, Microsporum canis, and Microsporum gypseum) was done using the well-plate method. The macrodilution method was used to determine the minimum inhibitory concentration (MIC) of the probiotic extract in the range of 0.0625 mg/mL to 1 mg/mL. To select the best gel formulation, one general formula was considered and then corrected by changing the polymer ratio. Gel formulations were characterized for monotonousness, probiotic extract content, pH determination, viscosity measurement, grittiness and antifungal activity in comparison to topical cream of clotrimazole 1%.
The results showed the same effect of the probiotic extract against 4 pathogens; however, the greatest average zone of inhibition was measured 34 mm against T. rubrum. The MIC test showed that stabilized probiotic extract had more antidermatophyte effect compared to supernatant (P The results of this study show that the beneficial effect of Lactobacillus casei is related to its metabolites. A formulated gel shows a significant antidermatophytosis activity compared to clotrimazole.

Mammalian target of rapamycin (mTOR) is a kinase pathway that regulates the cell cycle progression and growth. Rapamycin inhibits this pathway. The useful effects of rapamycin on cell growth have been widely shown in animal studies. However, its beneficial effects are associated with some success in benign and malignant cancers, which have produced its moderate outcomes in the clinic.
The aim of this study was to investigate whether rapamycin can induce oxidative stress in MCF-7 and MDA MB-231 human breast cancer cell lines.
The MCF-7 and MDA MB-231 cell lines were cultivated and treated with rapamycin for 72 hours. The viability of the cells was determined using the colorimetric MTT assay. Lipid peroxidation (TBARS), protein oxidation (carbonyl groups), total antioxidant capacity assay, and glutathione (GSH) levels were measured in the MCF-7 and MDA MB-231 cells both with and without rapamycin treatment.
The IC50 concentration of rapamycin was 100 nM in MCF-7 cells, whereas the MDA-MB-231 cells were highly resistant to rapamycin. Our data indicated an increase in oxidative status by increasing lipid peroxidation and protein oxidation, GSH, and total antioxidant capacity levels in the MCF-7 and MDA-MB-231 cell lines exposed to rapamycin in comparison with control cells.
These outcomes support our theory that rapamycin increases oxidative stress in MCF-7 and MDA MB-231 cells but also shows high levels of antioxidant effects, which probably limit the effects of the rapamycin on the same issue in the clinic.