Terminalia chebula (T.chebula) fruit is referred as “King of Medicines” in Tibet and is listed as a key plant in “Ayurvedic Materia Medica” due to its diverse pharmacological activity. The present study was aimed to investigate the comorbid antidepressant-like and anxiolytic-like effects of ethanol extract from T.chebula fruit using experimental behavioral tests in mice. In addition, the study explored the effects of extract on monoamine oxidase –A (MAO-A) levels in mouse brain. Two doses of the T.chebula extract (100 or 200 mg/kg, p.o.) were treated continuously for fifteen days to mice. Regarding antidepressant-like effects, the treatment of T.chebula extract at both dose (100 or 200 mg/kg, p.o.) levels resulted with significant (p < 0.001) reduction in duration of immobility time and increase in swimming time as compared to control group in forced swimming test. Moreover, both doses declined the duration of immobility time in the tail suspension test and increased the number of crossing in the center area using open-field test. Additionally, the dose 200 mg/kg treatment showed a significant reduction (p < 0.05) in MAO-A activity in mouse brain. For anxiolytic activity, both doses significantly (p < 0.001) improved the time spent in open arm and the number of head dips in elevated plus maze test. The higher duration of time spent in light chamber and higher number of crossing between the light and dark chambers by extract treatment in light-dark box test also supported the anxiolytic behavior. The obtained results supported the antidepressant-like and anxiolytic-like effects of ethanol extract of T.chebula in mice.
Drug uptake and distribution through cell–receptor interactions are of prime interest in reducing the adverse effects and increasing the therapeutic effectiveness of delivered formulations. This study aimed to formulate silver nanoparticles (AgNPs) conjugated to somatostatin analogs for specific delivery through somatostatin receptors (SSTRs) expressed on cells and by nebulizing the prepared AgNPs formulations into lung cells for in vivo application. AgNPs were prepared using the citrate reduction method, yielding AgNPs–CTT, which was further chemically conjugated to octreotide (OCT) to form AgNPs–OCT through an amide linkage. The AgNPs–OCT formulation was coated using alginate to yield a carrier, AgNPs–OCT–Alg, feasible for drug delivery through nebulization. AgNPs were uniform in size with an acceptable range of zeta potential. Furthermore, the concentrations of AgNP formulations were found safe for the model cell lines used, and cell proliferation was significantly reduced in a dose-dependent manner (p < 0.05). In the healthy lung tissues, AgNPs–OCT–Alg accumulated at a concentration of 0.416 ± 5.7 mg/kgtissue, as determined via inductively coupled plasma optical emission spectrometry. This study established the accumulation of AgNPs, specifically the AgNPs–OCT–Alg, in lung tissues, and substantiated the active, specific, and selective targeting of SSTRs at pulmonary sites. The anticancer efficacy of the formulations was in vitro tested and confirmed in the MCF-7 cell lines. Owing to the delivery suitability and cytotoxic effects of the AgNPs–OCT–Alg formulation, it is a potential drug delivery formulation for lung cancer therapy in the future.
Background: Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, is widely used to treat several types of cancer. Its toxic effects are well-established and include hepatotoxicity, nephrotoxicity, and bone marrow suppression. Metformin (MET) is an anti-diabetic medication that is considered a first-line therapy for type 2 diabetes mellitus. In this study, we aimed to investigate the effect of co-administration of MET on CYP-induced toxicity by recording the survival rate in mice. Methods: Fifty mice (body weight 30-35 gm) were divided into four groups as control and treatments and comprised of 12-13 animals of either sex. The animals in the control group received 4 doses of saline by injection. The animals in the CYP group received 4 doses of CYP (100 mg/kg) (intraperitoneal). The animals in the MET group received lower daily dose (30 mg/kg) in drinking water (3 mg/ml), starting 3 days prior to CYP injection and lasting until the final injection of CYP. Alhowail et al.; JPRI, 30(2): 1-6, 2019; Article no.JPRI.51861 2
Original Research ArticleThe animals in the combination group (CYP and MET) received 4 doses of CYP (100 mg/kg) and a daily dose of MET in drinking water (3 mg/ml). The animals were observed daily to record the mortality and their body weights were recorded every alternate day. The data obtained from the study was statistically analyzed by one-way ANOVA, and p<0.05 was considered significant. Results: The data obtained from the study indicated that CYP administration increased the rate of mortality significantly (p < 0.01) when compared to the control animals, while MET reduced the rate. When the combination of CYP and MET was tested, the mortality rate was found to be increased. Both CYP and MET significantly reduced the body weight compared to the control animals. Conclusion: The results indicated that the combination of CYP and MET reduced the survival rate of animals, suggesting that although MET possesses anti-proliferative action, it has the potential to increase the toxic effects of CYP when combined with CYP.
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