N-Methylneolitsine as a new and potent acetylcholinesterase inhibitor of Cissampelos pareira Linn. aerial parts: bioassay-guided isolation and quantitative densitometric analysis.

The rising geriatric population is expected to increase the demand for drugs treating neurodegenerative diseases. The present work is aimed to discover acetylcholinesterase (AChE) inhibitors from Cissampelos pareira Linn. aerial parts (Family: Menispermaceae). Bioassay-guided isolation, AChE inhibition study and estimation of the therapeutic marker in different parts of raw herbs were conducted. The structure of the compound (1) was elucidated as N-methylneolitsine by using NMR (1D and 2D) and ESI-MS/MS spectral data, which is a new natural analogue of neolitsine. It showed good AChE inhibition with an IC50 value of 12.32 µg/mL. It was densitometrically estimated to be 0.074 - 0.33% in aerial parts of C. pareira, collected from various locations. The alkaloid reported here could be potentially useful for the treatment of various neurodegenerative diseases and the aerial part of C. pareira could be used as a promising ingredient for various preparations treating neurodegenerative diseases.

Amelioration of oxidative DNA damage in mouse peritoneal macrophages by Hippophae salicifolia due to its proton (H(+)) donation capability: Ex vivo and in vivo studies.

INTRODUCTION: The present study evaluates the antioxidant effect of methanol extract of Hippophae salicifolia (MEHS) bark with special emphasis on its role on oxidative DNA damage in mouse peritoneal macrophages. MATERIAL AND METHODS: In vitro antioxidant activity was estimated by standard antioxidant assays whereas the antioxidant activity concluded the H(+) donating capacity. Mouse erythrocytes' hemolysis and peritoneal macrophages' DNA damage were determined spectrophotometrically. In vivo antioxidant activity of MEHS was determined in carbon tetrachloride-induced mice by studying its effect on superoxide anion production in macrophages cells, superoxide dismutase in the cell lysate, DNA damage, lipid peroxidation, and reduces glutathione. RESULTS: The extract showed good in vitro antioxidant activities whereas the inhibitory concentrations values ranged from 5.80 to 106.5 µg/ml. MEHS significantly (P < 0.05) attenuated the oxidative DNA damage. It also attenuated the oxidative conversion of hemoglobin to methemoglobin and elevation of enzymatic and nonenzymatic antioxidant in cells. CONCLUSION: The result indicates MEHS has good in vitro-in vivo antioxidant property as well as the protective effect on DNA and red blood cell may be due to its H(+) donating property.

Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by Zanthoxylum alatum.

CONTEXT: Many of the major chemotherapeutic agents are secondary metabolites found in nature. Zanthoxylum alatum Roxb. (Rutaceae) is traditionally used in the treatment of various diseases. OBJECTIVE: The present study evaluates the apoptotic activity of methanol extract of Z. alatum (MEZA) on Ehrlich ascites tumor (EAT) in Swiss albino mice. MATERIALS AND METHODS: The presence of flavonoids in MEZA was standardized by HPLC. The in vitro cytotoxicity of MEZA was measured by the MTT assay. The in vivo antitumor activity of MEZA (100 and 200 mg/kg b.w., i.p. for 9 days) was also evaluated. On the 10th day, EAT tumor volume, cell viability, and hematological parameters were assayed. Apoptotic morphology was determined by acredine orange/ethedium bromide using fluorescence microscopy. Apoptosis percentage was measured by flow cytometric analysis using annexine-V-FITC. Also, DNA damage and bcl-2/bax were estimated by UV-method and western blot, respectively. RESULTS AND DISCUSSION: HPLC analysis revealed presence of three flavonoids, rutin, myricetin, and quercetin. MEZA showed satisfactory cytotoxicity in MTT assay (IC50 = 111.50 µg/ml). The extract significantly (p < 0.01) changed the tumor volume, viable, non-viable cell count, and hematological parameters towards the normal. Apoptotic activity of MEZA was confirmed by acridine orange/ethidium bromide staining, annexin-V-FITC staining, DNA fragmentation, and Bcl-2/Bax ratio. CONCLUSION: The study showed that MEZA has antitumor activity which may be due to the presence of flavonoids in the extract.

Antitumor Potential of Thevetia peruviana on Ehrlich's Ascites Carcinoma-Bearing Mice.

Methanol extracts of Thevetia peruviana (METP) (Apocynaceae) fruit showed antitumor activity against Ehrlich's ascites carcinoma (EAC) cell line in Swiss albino mice. The METP-treated group's tumor volume, tumor weight, and viable cell count were decreased compared to the EAC control group. Tumor volumes were 3.62±0.12 ml, 2.88±0.23 ml, and 1.34±0.17 ml for the EAC control group and the METP-treated groups (50 mg/kg and 100 mg/kg body weight), respectively. Nonviable cell counts were 4.44%±0.42%, 18.57%±3.07%, and 68.12%±5.32% in the EAC control group and the METP-treated groups (50 mg/kg and 100 mg/kg body weight), respectively. METP-treated EAC cell-bearing mice had an increased life span (48.69% and 83.78%) compared to the EAC control group. Hematological and serum biochemical profiles were restored to normal levels in METP-treated mice compared to the EAC control group. METP significantly (P<0.001) decreased lipid peroxidation and recovered reduced glutathione, superoxide dismutase, and catalase toward normal levels compared to the EAC control group. In summary, METP exhibited remarkable antitumor activity in Swiss albino mice, which is plausibly attributable to its augmentation of endogenous antioxidant mechanisms.

Naringenin, a citrus flavonoid, ameliorates arsenic-induced toxicity in Swiss albino mice.

In the present study, we evaluated the ameliorative potential of a citrus flavonoid, naringenin (NRG), against experimentally induced arsenic toxicity in Swiss albino mice. NRG (5 and 10 mg kg-l) was administered orally to mice 30 minutes before oral administration of arsenic trioxide (3 mg kg-l) for 14 consecutive days. On day 15, the following parameters were evaluated: body weight; organ weight; hematological profile; serum biochemical profile; hepatic and renal tissue antioxidative parameters including lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase levels; and DNA fragmentation. Co-treatment with NRG markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profiles and significantly modulated all of the hepatic and renal tissue biochemical parameters and DNA fragmentation in arsenic-intoxicated mice. The present findings indicate that naringenin remarkably ameliorated the effects of arsenic-induced toxicity in albino mice due to its strong antioxidant property.

Antitumor activity and antioxidant role of Streblus asper bark against Ehrlich ascites carcinoma in Swiss albino mice.

The present study assessed the methanol extract of Streblus asper stem bark (MESA) for antitumor effect and antioxidant influence against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Twenty four hours after intraperitonial inoculation of tumor (EAC) cells in mice, MESA was administered at 200 and 400 mg/kg body weight daily for 9 consecutive days. On the 10 th day, half of the mice were sacrificed for estimation of tumor parameters, haematological, liver and kidney antioxidant parameters; and the rest were kept alive for assessment of survival. MESA exhibited dose dependent and significant (p < 0.01) decrease in tumor proliferation and extended the life span of EAC bearing mice. Hematological profiles were significantly (p < 0.01) restored near to normal in MESA treated mice as compared to EAC control. MESA treatment significantly (p < 0.01) modulated the hepatic and renal antioxidant parameters as compared to EAC control. The present study demonstrated that S. asper bark possessed promising antitumor efficacy in mice, plausibly mediated by amelioration of oxidative stress by multiple mechanisms.