In vitro and in vivo antitumor activity of a methanol extract of Dregea volubilis leaves with its antioxidant effect

Context: In India, Dregea volubilis (L.f.) Benth. ex Hook.f. (Asclepediaceae), a large twining shrub with a woody vine, is used to treat tumors traditionally.

Objective: This study evaluated the in vitro and in vivo antitumor activity of the methanol extract of Dregea volubilis leaves (MEDV) and elucidated its possible mechanism of action.

Materials and methods: In vitro antitumor activity of MEDV was evaluated against Ehrlich ascites carcinoma (EAC) cell-line. In vivo antitumor and antioxidant activity of MEDV at three dose levels (50, 100, and 200?mg/kg) were determined against EAC tumor-bearing mice. After 24?h of EAC inoculation, the extract was administered for 9 consecutive days. After the administration of the last dose on the 9th day followed by 18?h fasting, mice from all groups were sacrificed to determine antitumor activity and hematological profiles along with liver related biochemical parameters like lipid peroxidation, antioxidant enzymatic activity, etc.

Results: For in vitro antitumor activity, IC₅₀ value of MEDV for EAC tumor cells was 85.51?±?4.07 µg/ml. The MEDV showed a decrease in tumor volume, packed cell volume and viable cell count and an increase in the non-viable cell count of the EAC tumor-bearing mice (p?<?0.001). Hematological profile reverted near to normal level in extract treated mice. MEDV decreased the hepatic lipid peroxidation level and enhanced superoxide dismutase and catalase level in tumor-bearing mice (p?<?0.001).

Discussion and conclusion: MEDV exhibited in vitro and in vivo antitumor activity in EAC tumor-bearing mice mediated through augmenting antioxidant defense system.     

Antitumor activity of Sansevieria roxburghiana rhizome against Ehrlich ascites carcinoma in mice

Context: Sansevieria roxburghiana Schult. & Schult. f. (Agavaceae) is a herbaceous perennial plant traditionally used for coughs, rheumatism; as an expectorant, febrifuge, purgative, and tonic.

Objective: To evaluate the hydroalcoholic extract of S. roxburghiana rhizome (HASR) for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.

Methods: Twenty-Four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, HASR was administered at 50 and 100?mg/kg body weight for nine consecutive days. On day 10 half of the mice were sacrificed and rest were kept alive for assessment of increase in life-span. The antitumor effect of HASR was assessed by evaluating tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life-span of EAC bearing hosts. Hematological profiles and serum biochemical parameters were estimated. Further, antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT).

Results and discussion: HASR showed a significant (p < 0.001) decrease in tumor volume, packed cell volume and viable cell count and increased the life span of EAC bearing mice. Hematological and serum biochemical profiles were restored to normal levels in HASR treated mice as compared to EAC control. HASR treatment significantly (p <0.001) decreased lipid peroxidation and recovered GSH, SOD and CAT towards normal as compared to EAC control.

Conclusion: The present study demonstrates that S. roxburghiana rhizome exhibited remarkable antitumor activity in Swiss mice that is plausibly attributable to its augmenting endogenous antioxidant mechanisms.     

Antitumor activity and antioxidant property of Curcuma caesia against Ehrlich’s ascites carcinoma bearing mice

Abstract

Context: Curcuma caesia Roxb. (Zingiberaceae), commonly known as “Kala Haldi” in Bengali, has been traditionally used for the treatment of cancer, bruises, inflammation and as an aphrodisiac.

Objective: To evaluate the antitumor activity and antioxidant status of the methanol extract of Curcuma caesia (MECC) rhizomes on Ehrlich’s ascites carcinoma (EAC)-treated mice.

Materials and methods: In vitro cytotoxicity assay of MECC was evaluated by using Trypan blue method. Determination of in vivo antitumor activity was performed after 24?h of EAC cells (2?×?10⁶?cells/mouse) inoculation; MECC (50 and 100?mg/kg i.p.) was administered daily for nine consecutive days. On day 10, half of the mice were sacrificed and the rest were kept alive for assessment of increase in lifespan. Antitumor effect of MECC was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes.

Results: MECC showed direct cytotoxicity (IC₅₀ 90.70?±?8.37?μg/mL) on EAC cell line. MECC exhibited significant (p?<?0.01) decrease in tumor volume, tumor weight, viable cell count and percentage increased the lifespan (57.14 and 88.09%) of EAC-treated mice. Hematological profile, biochemical estimation, tissue antioxidant assay significantly (p?<?0.01) reverted to normal level in MECC-treated mice.

Conclusion: MECC possesses potent antitumor activity that may be due to its direct cytotoxic effect or antioxidant properties. Further research is in progress to find out the active principle(s) of MECC for its antitumor activity.     

Growth inhibition and apoptosis of Ehrlich ascites carcinoma cells by the methanol extract of Eucalyptus camaldulensis

Context: Eucalyptus camaldulensis Dehnh. (Myrtaceae) is a tall evergreen tree found commonly in Bangladesh. Its use in traditional folk medicine for the treatment of various health complications are well known.

Objective: To explore the in vivo antitumor effect of Eucalyptus camaldulensis stem bark methanol extract (ME) against Ehrlich’s ascites carcinoma (EAC) in Swiss albino mice.

Materials and methods: The antitumor activity of ME was studied by determining viable tumor cell count, recording tumor weight and survival time, observing morphological changes and nuclear damage of EAC cells, and estimating hematological as well as biochemical parameters of experimental mice (25, 50 and 100?mg/kg/day for 5?d, i.p.).

Results: ME showed 96% (p?p?p?50 value (1120?mg/kg) of ME indicated its low host toxic effects. ME-treated EAC cells showed membrane blebbing, chromatin condensation, nuclear fragmentation (apoptotic features) in Hoechst 33342 staining under fluorescence microscope. The DNA profile in agarose gel (1.5%) electrophoresis also confirmed that ME caused EAC cell death by apoptosis.

Discussion and conclusion: Results showed that ME exhibits strong anticancer activity through apoptosis and stimulation of host immunity. Thus, E. camaldulensis may be considered as a promising resource in cancer chemotherapy.     

Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma

Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. The present study assessed the influence of treatment of hydroalcoholic extract of Trichosanthes dioica root (TDA) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice with effects on antioxidant systems. Twenty-four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 25 and 50 mg/kg for 8 consecutive days. On the 9(th) day, half of the mice were sacrificed for estimation of tumor proliferation, hematological, and hepatic antioxidative parameters. The rest were kept for assessment of survival parameters. TDA exhibited dose dependent and significant increase in tumor weight, tumor volume, packed cell volume and viable cells and reduced non-viable cells and life span of EAC bearing animals. Hematological parameters were significantly worsened in TDA-treated mice. TDA treatment significantly aggravated the hepatic antioxidative parameters. The present study demonstrated that T. dioica root possessed tumor promoting activity in EAC bearing albino mice, plausibly mediated by attenuation of endogenous antioxidant systems.     

Terpenoids of methanol extract of Clerodendrum infortunatum exhibit anticancer activity against Ehrlich’s ascites carcinoma (EAC) in mice

Context: Clerodendrum infortunatum Linn. is a widely used plant in the Indian indigenous system of medicine for the treatment of tumors.

Objective: The present study evaluated the anticancer activity of methanol extract of C. infortunatum (MECI) against Ehrlich’s ascites carcinoma (EAC) bearing Swiss albino mice and isolation of bioactive terpenoids from it.

Methods: HPLC analysis of the methanol extract showed the presence of three major components. Out of those, two compounds were isolated and characterized as oleanolic acid and clerodinin A. The anticancer activity of MECI was assessed by measuring the tumor growth response, percentage increase of life span, study of hematological parameters, lipid peroxidation, antioxidant enzyme activity like glutathion and CAT. In vitro cytotoxicity assay was also performed using EAC cell lines.

Result and conclusion: Treatment with MECI causes significant decrease in the tumor cell volume and increase in the life span. The median survival time (MST) of EAC control group was found as 19.42?±?0.91 d, whereas the MST was increased to 23.44?±?2.69 d and 27.57?±?2.57 d for the groups treated with MECI at 100 and 200?mg/kg, respectively. All the hematological parameters, malonaldehyde content and antioxidant enzymes’ activity were restored towards the normal level. IC₅₀ value of MECI was found as 498.33 µg/mL in cytotoxicity study. The experimental results suggested that MECI has significant anticancer activity, which can be attributed to the presence of oleanolic acid and clerodinin A.     

Antitumor activity and antioxident role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice

AIM: To study the enzyme activity of CYP2C18 variant with exon 5 skipped. METHODS: A full length CYP2C18 cDNA X1 and an exon 5 skipped variant CYP2C18 X2 were separately subcloned into mammalian expression vector pREP9 to transfect HepG2 cells. The expression of CYP2C18 mRNA in transgenic cells and human liver tissues were determined by RT-PCR. The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC. The cytotoxicity of ifosfamide to transgenic cells was evaluated by MTT test. RESULTS: HepG2-CYP2C18 X1 cells showed strong expression of the full length CYP2C18 mRNA. On the other hand, HepG2-CYP2C18 X2 cells had only infinitesimal expression of the exon-skipped CYP2C18 as well as the full length CYP2C18, while non-transfected HepG2 cell only demonstrated an infinitesimal expression of the full length CYP2C18. The expression of CYP2C18 exons 2 to 7 was also analyzed by RT-PCR in 7 extratumoral liver tissues. Among them, 3 samples expressed on     

Effect of curcumin in mice model of vincristine-induced neuropathy

Abstract

Context: Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity.

Objective: The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model.

Materials and methods: Vincristine sulfate (0.1?mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14?d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10?mg/kg, p.o.) and curcumin (15, 30, and 60?mg/kg, p.o.) were administered for 14 consecutive days.

Results: Curcumin at 60?mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p?<?0.001) and allodynia (p?<?0.001); mechanical hyperalgesia (p?<?0.001); functional loss (p?<?0.001); and in the delayed phase of formalin test (p?<?0.001). Curcumin at 30 and 60?mg/kg exhibited significant changes (p?<?0.001) in antioxidant levels and in total calcium levels in vincristine-injected mice.

Conclusion: Curcumin at 30 and 60?mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.     

Antitumor activity and antioxidant role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice [corrected]

AIM: To study the antitumor effect and antioxidant role of Bauhinia racemosa. METHODS: Antitumor activity and antioxidant status of methanol extract (50, 100, and 200 mg/kg) of Bauhinia racemosa stem bark was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice. Acute and short-term toxicity studies were performed initially in order to ascertain the safety of methanol extract of Bauhinia racemosa (MEBR). After 24 h of tumor inoculation, the extract was administered daily for 14 d. After administration of the last dose followed by 18 h fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEBR on the growth of transplantable murine tumor, life span of EAC bearing hosts and simultaneous alterations in the hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. RESULTS: The MEBR showed decrease in tumor volume, packed cell volume and viable cell count, and increased the nonviable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to more or less normal levels in extract treated mice. Treatment with MEBR decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase. CONCLUSION: The methanol extract of Bauhinia racemosa stem bark exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing mice.     

Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model

Objective: In order to increase local drug concentration and reduce systemic side effects of liver cancer chemotherapy, it is desirable to develop novel non-invasive technologies for drug targeting, such as ultrasound-targeted microbubble destruction (UTMD).

Methods: H22 hepatocellular carcinoma (HCC) xenograft transplantation model was generated in UTMD study. BALB/c mice were randomly divided into six groups: doxorubicin HCl liposomal injection (DOX), DOX?+?US, UTMD, DOX?+?UTMD, H22 liver tumor control (CH control) and blank control group. The therapeutic schedule started on day 4 after tumor inoculation.

Results: Average survival time of the animal model was approximately 18?d. The UTMD therapy parameters were optimized in the H22 mouse model to be: microbubble (MB) diameter, 2.30?±?0.25?μm; MB density, 4.0?×?10⁹ bubbles/ml; treatment dose, 0.2?ml per 20?g mouse body weight; sonication frequency, 1.3?MHz; and sonication power, 2.06?W/cm². Mice treated with DOX?+?UTMD had the smallest tumor volume and weight (p?<?0.001), and the highest tumor inhibition rate (p?<?0.01), intratumoral DOX concentration (p?<?0.001) and survival rate among all tumor-burden groups (p?<?0.001). Cell viability in different treatment groups was also assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

Conclusion: An improved antitumor effect was observed with the combination therapy of DOX and UTMD, as compared with treatment with DOX, DOX?+?US or UTMD, which implicates a novel approach for HCC treatment.     

Evaluation of in vitro antioxidant,anticancer and in vivo antitumour activity of Termitomyces clypeatus MTCC 5091

Context: Termitomyces clypeatus (Lyophyllaceae) is a filamentous edible mushroom, having ethnomedicinal uses. However, information about the antioxidant, anticancer and antitumour properties of this mushroom remains to be elucidated.

Objective: The study examines the in vitro antioxidant, anticancer and in vivo antitumour activity of T. clypeatus.

Materials and methods: Antioxidant activity was evaluated with seven in vitro assays. Cytotoxicity of T. clypeatus was tested against a panel of cancer cells lines including U373MG, MDA-MB-468, HepG2, HL-60, A549, U937, OAW-42 and Y-79 using MTT assay. The antitumour activity of aqueous extract was evaluated against Ehrlich ascites carcinoma (EAC) tumour model in Swiss albino mice.

Results: HPLC analysis of aqueous extract revealed the presence of sugar entities. Termitomyces clypeatus showed excellent in vitro antioxidant activity. Termitomyces clypeatus was found cytotoxic against all cancer cells, among which it showed higher activity against U937 (IC₅₀ 25?±?1.02?μg/mL). Treatment of EAC-bearing mice with varied doses of aqueous extract significantly (p?<?0.01) reduced tumour volume, viable tumour cell count and improved haemoglobin content, RBC count, mean survival time, tumour inhibition and % increase life span. The enhanced antioxidant status in treated animals was evident from the decline in the levels of lipid peroxidation, increased levels of glutathione, catalase and superoxide dismutase.

Discussion: The analyzed data indicate that the aqueous extract of T. clypeatus exhibits significant antitumour activity, which might be due to the antioxidant effects on EAC bearing hosts.

Conclusion: Termitomyces clypeatus possesses anticancer activity, valuable for application in food and drug products.     

Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis

Abstract

Context: Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties.

Objective: The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9?µmol/mouse/day) against B(a)P (100?mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice.

Materials and methods: Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H₂O₂) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c.

Results: SFN treatment was found to decrease the H₂O₂ production (p?<?0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p?<?0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p?<?0.01) and Bax (p?<?0.001), respectively. Caspase-3 activity was also enhanced (p?<?0.001) which leads to DNA fragmentation in SFN treated groups.

Conclusion: Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.     

Antineoplastic and antioxidant activities of Oxystelma esculentum on Swiss albino mice bearing Ehrlich’s ascites carcinoma

The present study investigated the antitumor effect and antioxidant role of the methanol extract of Oxystelma esculentum R. Br. (Asclepiadaceae) (MEOE) on tumor growth and the host survival time with mice. The antitumor and antioxidant potential of Oxystelma esculentum were studied against Ehrlich’s ascites carcinoma cell line (EAC) treated mice. MEOE was administered at doses of 200 and 400 mg/kg body weight (bw) once a day for 9 days after 24 h of tumor inoculation. Among the treated animals, six animals were sacrificed for biochemical and tumor analysis, and the remaining four groups were kept to study lifespan. On day 10, the parameters of tumor volume, packed cell volume, viable, and non-viable cell count were studied. Hematological and liver biochemical parameters, and antioxidant enzymes such as lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), etc. were estimated. Decreases in tumor volume, packed cell volume, and viable cell count were observed in MEOE-treated mice when compared to EAC-treated mice. Treatment with MEOE at doses of 200 and 400 mg/kg increased the mean survival time to 29.66 ± 0.71 and 34.33 ± 2.34 days, compared with EAC-treated mice at 19.16 ± 1.13 days. The extract also decreased the body weight of the EAC-bearing mice. Hematological profiles indicated a decrease in white blood cells (WBC), an increase in red blood cells (RBC), and, thereby, Hemoglobin (Hb). MEOE restored all the parameters of hematological profiles to approximately normal. Treatment with MEOE decreased the levels of LPO and increased the levels of GSH, SOD, and CAT. These data indicate the methanol extract of Oxystelma esculentum exhibits significant antitumor activity, which might be due to the antioxidant effects on EAC bearing hosts.     

Evaluation of antihyperlipidemic and antitumor activities of isolated coumarins from Salvadora indica

Context. Salvadora indica Wight (Salvadoraceae) contains a number of medically beneficial properties including abrasives, astringents and antiseptics. Traditionally, it was used by ancient Arabs to whiten and polish teeth.

Objective: This study explores the antihyperlipidemic and antitumor effects of an ethanol extract of S. indica and its isolated phytoconstituents in rodents.

Material and methods: Flash chromatography was used for the isolation of phytoconstituents from the stems of S. indica. An antihyperlipidemic study was carried out in Triton loaded rats. Animal groups were given intraperitoneal (i.p.) injection of Triton WR 1339 at dose of 400?mg/kg body weight (b.w.). Furthermore, antitumor activity was investigated in hybrid mice (of C57BL strain?+?Swiss albino strain). The animals were observed for tumor growth after injection of B16F10 melanoma cells into the dorsal skin of mice.

Results: The stems of S. indica yielded xanthotoxin and umbelliferone through chromatographic separation techniques. The structures of the compounds were elucidated by spectroscopic data interpretation and showed antihyperlipidemic activity. The study showed significant reduction in total cholesterol (TC) (p?p?p?p?p?p?p?Discussion and conclusion: Acute treatment caused a stimulatory effect on high density lipoprotein level and inhibition in TC and TG elevation induced by Triton. Tumor regression studies showed a regression response for tumor growth in vivo of murine mouse melanoma as demonstrated by increasing the VDT and GD.     

A comparison study between different molecular weight polysaccharides derived from Lentinus edodes and their antioxidant activities in vivo

Context: Polysaccharide purified Lentinus edodes (Berk.) Sing (Tricholomataceae) has been reported to attenuate oxidative stress in vitro.

Objective: This study investigated whether polysaccharides from L. edodes with different molecular weight have protective effects against oxidative stress induced by d-galactose (d-gal) in vivo, and determined the specific relationship between molecular weight and antioxidant activity.

Materials and methods: In the present study, we successfully obtained three purified polysaccharides, coded as LT1, LT2, and LT3, and their molecular weights were 25.5, 306.2, and 605.4?kDa, respectively. The d-gal-treated mice received three polysaccharides once daily for 60 days. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of malondialdehyde (MDA), and erythrocyte membrane fluidity were measured to evaluate the changes of the antioxidant ability.

Results: It was demonstrated that the administration of LT1, LT2, and LT3 could improve the antioxidant status to different levels. Furthermore, LT2 exhibited the highest antioxidant ability among these samples in vivo. Indeed, LT2 significantly decreased the content of MDA in liver (15.91?±?0.31 versus 23.79?±?1.18 nmol/mg protein for the model group, p?<?0.05), enhanced the fluidity of erythrocyte membrane (2.458?±?0.023 versus 2.167?±?0.024 for the model group, p?<?0.05), and increased the activities of SOD (147.19?±?4.90 versus 82.26?±?5.55 units/mg protein for the model group, p?<?0.05) and GSH-Px (310.91?±?6.24 versus 243.64?±?6.77 units/mg protein for the model group, p?<?0.05) in liver.

Discussion and conclusion: The LT2 had a potential to be used as a novel natural antioxidant.     

Antitumor and antioxidant status of Terminalia catappa against Ehrlich ascites carcinoma in Swiss albino mice

Objective:

The present study was undertaken to evaluate the antitumor and antioxidant status of ethanol extract of Terminalia catappa leaves against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.

Materials and Methods:

The leaves powder was extracted with Soxhlet apparatus and subjected to hot continuous percolation using ethanol (95% v/v). Tumor bearing animals was treated with 50 and 200 mg/kg of ethanol extract. EAC induced in mice by intraperitoneal injection of EAC cells 1 × 10⁶ cells/mice. The study was assed using life span of EAC-bearing hosts, hematological parameters, volume of solid tumor mass and status of antioxidant enzymes such as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities. Total phenolics and flavonoids contents from the leaves extract were also determined.

Results:

Total phenolics and flavonoids contents from the leaves extract were found 354.02 and 51.67 mg/g extract. Oral administration of ethanol extract of T. catappa (50 and 200 mg/kg) increased the life span (27.82% and 60.59%), increased peritoneal cell count (8.85 ± 0.20 and 10.37 ± 0.26) and significantly decreased solid tumor mass (1.16 ± 0.14 cm²) at 200 mg/kg as compared with EAC-tumor bearing mice (P < 0.01). Hematological profile including red blood cell count, white blood cell count, hemoglobin (11.91 ± 0.47 % g) and protein estimation were found to be nearly normal levels in extract-treated mice compared with tumor bearing control mice. Treatment with T. catappa significantly decreased levels of LPO and GSH, and increased levels of SOD and CAT activity (P < 0.01).

Conclusion:

T. catappa exhibited antitumor effect by modulating LPO and augmenting antioxidant defense systems in EAC bearing mice. The phenolic and flavonoid components in this extract may be responsible for antitumor activity.KEY WORDS: Antioxidant, Ehrlich ascites carcinoma, flavonoids, Terminalia catappa, total phenolic     

Cognitive effects of vanillic acid against streptozotocin-induced neurodegeneration in mice

Abstract

Context: Vanillic acid (VA), a flavoring agent used in food and drug products, obtained naturally from the plant Angelica sinensis (Oliv.) Diels (Apiaceae), used in the traditional Chinese medicine. It is reported to possess strong antioxidant, anti-inflammatory, and neuroprotective effects. However, the pharmacological effects on oxidative stress-induced neurodegeneration are not well investigated.

Objective: This study investigates the neuroprotective effect of VA on streptozotocin (STZ)-induced neurodegeneration in mice through behavioral and biochemical parameters.

Materials and methods: The behavioral effects were determined using the Y-maze and open-field habituation memory. In biochemical parameters, acetylcholinesterase (AChE), corticosterone, tumor necrosis factor (TNF)-α, and antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase) were measured. Five groups of animals used were of control, negative control, and three separate groups treated with 25, 50, and 100?mg/kg of VA, respectively, for 28?d. Intracerebroventricular (ICV) injections of STZ were performed for all groups except control on 14th and 16th of 28?d of VA treatment.

Results: VA improved spatial learning and memory retention by preventing oxidative stress compared with control animals. VA at 50 and 100?mg/kg dose significantly (p?<?0.001) improved the habituation memory, decreased the AChE, corticosterone, TNF-α, and increased the antioxidants (p?<?0.001). VA (100?mg/kg) exhibited dose-dependent effect in all parameters with p?<?0.001 except antioxidants in which VA showed the significance of p?<?0.01.

Discussion and conclusion: VA exhibited reduction in AChE, TNF-α, and corticosterone with improved antioxidants to contribute neuroprotection and could be an effective therapeutic agent for treating neurodegenerative disorders.     

Anticancer activity of Cocculus hirsutus against Dalton’s lymphoma ascites (DLA) cells in mice

Context: Cocculus hirsutus (L.) Diels (Menispermaceae) is used in Indian folk system of alternative medicine for rheumatism, eczema, diabetics, inflammation, and neuralgia.

Objective: To evaluate antitumor activities of C. hirsutus in vitro and in vivo.

Materials and methods: C. hirsutus was successively extracted using hexane, petroleum ether, chloroform, ethyl acetate, methanol, and water. In vitro cytotoxicity was assessed by the MTT assay. Phytochemical analyses were conducted with methanol extract of C. hirsutus (MECH) and in vivo antitumor activity was carried out with MECH using Dalton’s lymphoma ascites (DLA) mouse model. Antioxidant properties were assessed by estimating superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation.

Results and discussion: Phytochemical studies indicated a high content of total alkaloid (165.6?mg/100?g), total phenolic (43.5 GAE mg/g), and total flavanoid (4.97 RE mg/g) in MECH. Anti-proliferative activity against the breast cancer cell line MCF-7 showed IC₅₀ values of 221.5?±?16.68, 255?±?17.88, 213?±?8.4, 147?±?7.9, and 229?±?8.02?µg/ml with hexane, petroleum ether, chloroform, ethyl acetate, methanol, and aqueous extracts, respectively. A significant (p?p?Conclusion: C. hirsutus exhibited significant in vitro and in vivo antitumor activities that are reasonably attributed to endogenous antioxidant mechanisms.     

Artemisia pallens alleviates acetaminophen induced toxicity via modulation of endogenous biomarkers

Abstract

Context: Acetaminophen (APAP) leads to severe hepatic and renal necrosis and thus causes significant clinical problems. Artemisia pallens Walls ex D.C. (Asteraceae) possesses various pharmacological properties such as antidiabetic, antioxidant, analgesic, and anti-inflammatory activity.

Objective: The objective was to evaluate the protective effects of Artemisia pallens methanol extract (APME) in APAP-induced hepatic and nephro-toxicity.

Materials and methods: The methanolic extract of aerial parts of Artemisia pallens (APME) was prepared. Toxicity was induced in male Wistar rats (180–220?g) by administration of APAP (700?mg/kg, p.o., 14?d). APME (100, 200, and 400?mg/kg, p.o.) was administered to rats 2?h before APAP oral administration. Various biochemical and molecular parameters along with histopathological aberration were studied in the kidney and liver of rats.

Results: Pretreatment with APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) decreased aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, blood urea nitrogen (BUN), and serum creatinine as compared with APAP-treated rat. Decreased level of serum albumin, serum uric acid, and HDL were significantly (p?<?0.01 and p?<?0.001) restored by APME (200 and 400?mg/kg, p.o.) pre-treatment. Administration of APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) reduced the elevated level of cholesterol, LDL, LDH, triglyceride, and VLDL. It also significantly (p?<?0.01 and p?<?0.001) restored the altered level of hepatic and renal antioxidant enzymes (superoxide dismutase (SOD) and glutathione (GSH)). The increased level of malondialdehyde (MDA) and nitric oxide (NO) in hepatic as well as renal tissue was significantly (p?<?0.01 and p?<?0.001) decreased by APME (200 and 400?mg/kg, p.o.) administration. Histological alternation induced by APAP in liver and kidney was also reduced by the APME (200 and 400?mg/kg, p.o.) pre-treatment.

Conclusion: It is concluded that the methanol extract of Artemisia pallens alleviates APAP induced in rats toxicity through its antioxidative and anti-inflammatory actions.     

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet

Abstract

Context: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties.

Objective: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity.

Materials and methods: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3?ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques.

Results: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100?g body weight) of ovary (Gr-I: 54.3?±?4.2 versus Gr-II: 35.8?±?1.6; p?<?0.001) and uterus (Gr-I: 161.7?±?24.6 versus Gr-II: 94.44?±?13.2; p?<?0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ⁵, 3β-hydroxysteroid dehydrogenase (Gr-I: 3.41?±?0.12 versus Gr-II: 2.31?±?0.09; p?<?0.01) and 17β-hydroxysteroid dehydrogenase (Gr-I: 3.82?±?0.57 versus Gr-II: 1.24?±?0.19; p?<?0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5?±?2.06 versus 34.1?±?2.34; p?<?0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10?±?2.45 versus Gr-II: 29.51?±?3.44; p?<?0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18?±?0.19 versus Gr-II: 1.33?±?0.18; p?<?0.05). The Gr-III rats were significantly protected from these ill effects of arsenic.

Discussion and conclusion: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.