Search

Plant-based anticancer agents have the potential to stimulate the immune system to act against cancer cells. A standardized bioactive subfraction of the Malaysian herb, Strobilanthes crispus (L.) Blume (S. crispus) termed F3, demonstrates strong anticancer effects in both in vitro and in vivo models. The anticancer effects might be attributable to its immunomodulatory properties as S. crispus has been traditionally used to enhance the immune system. The current study examined whether F3 could stimulate anti-tumorigenic immunogenicity against 4T1 cells in vitro and in 4T1 cell-induced mammary carcinoma mouse model. We observed that F3 induced significant increase in MHC class I and class II molecules. CD4+, CD8+ and IL-2+ (p+ macrophages was significantly lower in F3-treated mice. We conclude that the antitumor and antimetastatic effects of S. crispus involve strong infiltration of T cells in breast cancer potentially through increased tumor antigen presentation via MHC proteins, as well as reduction of infiltrating tumor-associated macrophages. more...

Ethnopharmacological relevance Strobilanthes crispus Blume is traditionally consumed among local Malay and indigenous communities for the treatment of cancer and other ailments such as gastrointestinal disorders, inflammatory wounds of snake bite and immune system activation amongst others. We previously demonstrated that a bioactive fraction of S. crispus leaves (F3) was cytotoxic to breast cancer cells in vitro and inhibited tumor growth in N-methyl-N-nitrosourea (NMU)-induced breast cancer rat model. F3 also normalized the white blood cell count in the tumor-bearing animals, indicating its potential immuno-stimulatory effect. Aim of the study To evaluate the immune stimulatory effects of F3 from S. crispus in NMU-induced rat mammary tumor model. Materials and methods Immunohistochemistry analysis of cellular immune parameters (CD4+ or CD8+ T cells, CIITA, MHC-II and CD68) was performed on NMU-induced rat mammary tumor nodules, followed by evaluation of the serum level of 34 cytokines using the cytokine antibody array. Results Significant increase in MHC-II, CD4+ and CD8+ T cell and CIITA expression by tumor cells was observed in F3-treated rats compared to the tumor control group. F3-treated rats also displayed a significant decrease in the serum level of CCL2 and CD68+ infiltrating macrophages. Serum IFN-γ level in this group was increased by 1.7-fold suggesting enhanced infiltration of T cells, and upregulation of CIITA and MHC-II expression in the tumor cells might be triggered by F3-induced production of IFN-γ. Conclusion Our findings demonstrated for the first time that a subfraction from S. crispus, F3, is capable of activating the immune system in rats-bearing NMU-induced mammary tumor, which may contribute to the anticancer effects of F3, and additionally support the traditional use of S. crispus leaves to boost the immune system. more...

The aim of this study was to determine the immunoreactivity of neuronal and inducible nitric oxide synthetase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase in different regions of brain in rats of kainic acid mediated epilepsy. Male Sprague-Dawley rats were used in this study. The acute group animals were sacrificed after 2 hours and the chronic group animals were sacrificed after 5 days of a single subcutaneous injection of kainic acid (15 mg/kg body weight). The cerebral cortex, cerebellum and brain stem slices were fixed and immunohistostained for the above enzymes. Images were captured and analyzed. In acute group, argininosuccinate synthetase and inducible nitric oxide synthetase were increased in cerebral cortex and cerebellum, neuronal nitric oxide synthetase increased in cerebral cortex and brain stem, and there was no change in argininosuccinate lyase immunoreactivity compared to control group. In chronic group, glutamine synthetase was decreased and all other enzymes immunoreactivity was increased in all the brain regions tested. This study demonstrated the up-regulation of citrul-line-nitric oxide cycle enzymes and may contribute to enhancing recycling of citrulline to arginine to support the increased production of nitric oxide in epilepsy. The decreased glutamine synthetase may increase glutamate in chronic epilepsy and may lead to neurodegeneration. more...

The aim of this study was to determine the mRNA expression of nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL) and glutamine synthetase (GS) in different regions of brain in rats subjected to kainic acid (KA) mediated epilepsy. The short term (acute) group animals were sacrificed after 2 h and the long term (chronic) group animals were sacrificed after 5 days of single injection of KA. After decapitation of rats, cerebral cortex (CC), cerebellum (CB) and brain stem (BS) were separated and in their homogenates, the relative amount of nNOS, iNOS, AS, AL and GS mRNA was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Results showed an increased expression of iNOS in all brain regions tested in chronic group as compared to either control or acute group, and it indicate a favorable condition of nitric oxide production. AL expression was significantly increased only in CB in acute group whereas in chronic group it is increased in CC and CB and decreased in BS as compared to control. The aforementioned increased expression of AL may contribute effective recycling of citrulline to arginine. No change in expression of nNOS and AS in both acute and chronic groups of epilepsy. GS expression was significantly decreased only in chronic group of epilepsy in all brain regions tested when compared with control group. The decreased GS may be contributing prolonged availability of glutamate in chronic epilepsy. more...

Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO) in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C), SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME)]. Rats (SHRC) were administered with Clonidine (0.5 mg kg−1 day−1) from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg−1 day−1) from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP) was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS) (P<0.001) and reduced the thibarbituric acid reactive substances (TBARS) (P<0.001) and protein carbonyl content (PCO) (P<0.05). These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME. more...

To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2 h and the long term (chronic) group animals were killed after 5 days of single injection of KA (15 mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy. more...

Background: Increased nitric oxide (NO), neuronal inflammation and apoptosis have been proposed to be involved in excitotoxicity plays a partin many neurodegenerative diseases. To understand the neuro-protective effects of propolis, activities of Nitric oxide synthase (NOS) andcaspase-3 along with NO and tumor necrosis factor-α (TNF-α) levels were studied in cerebral cortex (CC), cerebellum (CB) and brain stem (BS)in rats supplemented with propolis prior to excitotoxic injury with kainic acid (KA).Materials and methods: Male Sprague-Dawley rats were divided into four groups (n=6 rats per group) as Control, KA, Propolis andKA+Propolis. The control group and KA group have received vehicle and saline. Propolis group and propolis + KA group were orallyadministered with propolis (150mg/kg body weight), five times every 12 hours. KA group and propolis +KA group were injected subcutaneouslywith kainic acid (15mg/kg body weight) and were sacrificed after 2 hrs. CC, CB and BS were separated, homogenized and used for estimation ofNOS, caspase-3, NO and TNF-α by commercial kits. Results were analyzed by one way ANOVA, reported as mean + SD (n=6 rats), and p more...

Background : Propolis has been proposed to be protective on neurodegenerative disorders. To understand the neuroprotective effects of honeybee propolis, glutamine synthetase (GS) activity, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAS) were studied in different brain regions- cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats supplemented with propolis and subjected to kainic acid (KA) mediated excitotoxicity. Materials and Methods : Male Sprague-Dawley rats were divided into four groups; Control group and KA group received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150mg/kg body weight), five times every 12 hours. KA group and propolis + KA group were injected subcutaneously with kainic acid (15mg/kg body weight) and were sacrificed after 2 hrs and CC, CB and BS were separated homogenized and used for estimation of GS activity, NO, TBARS, and TAS concentrations by colorimetric methods. Results were analyzed by oneway ANOVA, reported as mean + SD from 6 animals, and p more...