Understanding the role of zingerone on biochemical and behavioral changes in rat brain inflicted with C6 glioma cells.

Malignant glioma is the deadliest form of brain cancer. Zingerone (ZO), a polyphenolic compound found in ginger, offers pharmacological properties that make it a promising agent for containing the growth of glioma cells. The present study was conducted to understand the efficacy of ZO in containing the growth of C6 glioma cells. The study also assessed the prophylactic role of ZO on rat brain glioma induced by C6 cell lines by addressing its antioxidative action on biochemical, behavioral, and histoarchitectural indices. For dose optimization, the animals were pretreated with different doses of ZO for a period of 2 weeks before the inoculation of glioma cells (1 × 105 /10 µL phosphate-buffered saline) in the caudate region of rat brain and the treatment with ZO continued for 4 more weeks post implantation. In vitro studies were done to assess the radical scavenging activity of ZO and also to determine its effects on viability of C6 glioma cells at different concentrations. Glioma-bearing rats showed significant alterations in memory; exploratory and muscular activities which were appreciably improved upon simultaneous supplementation of ZO administered at a dose of 50 mg/kg body weight and were also visible even at a higher dose. Glioma-bearing rats revealed a significant increase in reactive oxygen species, protein carbonyl contents, and lipid peroxidation, but showed a significant decrease in reduced glutathione and antioxidative enzymes in the brain tissue. Interestingly, all the biochemical indices and altered brain histoarchitecture displaying cellular atypia and hyperplasia showed appreciable improvement when supplemented with ZO at a dose of 50 mg/kg body weight.

4-PBA rescues hyperoxaluria induced nephrolithiasis by modulating urinary glycoproteins: Cross talk between endoplasmic reticulum, calcium homeostasis and mitochondria.

AIM: Urinary glycoproteins such as Tamm Horsfall Protein (THP) and Osteopontin (OPN) are well established key regulators of renal stone formation. Additionally, recent revelations have highlighted the influence of Endoplasmic Reticulum (ER) and mitochondria of crucial importance in nephrolithiasis. However, till date conclusive approach highlighting the influence of ER stress on urinary glycoproteins and chaperone in nephrolithiasis remains elusive. Therefore, the present study was focussed on deciphering the possible effect of 4-PBA mitigating ER stress on urinary glycoproteins and calnexin (chaperone) with emphasis on interlinking calcium homeostasis in hyperoxaluric rats. MATERIAL AND METHODS: Post 9 days of treatment, animals were sacrificed, and renal tissues were investigated for urinary glycoproteins, calnexin, calcium homeostasis, ER environment, redox status, and mitochondrial linkage. KEY FINDINGS: 4-PBA appreciably reversed the altered levels of THP, OPN, and calnexin observed along with curtailing the disrupted calcium homeostasis when assessed for SERCA activity and intra-cellular calcium levels. Additionally, significant improvement in the perturbed ER environment as verified by escalated ER stress markers, disturbed protein folding-aggregation-degradation (congo red assay) pathway, and redox status was found post 4-PBA intervention. Interestingly, linkage of ER stress and mitochondria was established under hyperoxaluric conditions when assessed for protein levels of VDAC1 and GRP75. SIGNIFICANCE: 4-PBA treatment resulted in rectifying the repercussions of ER-mitochondrial caused distress when assessed for protein folding/aggregation/degradation events along with disturbed calcium homeostasis. The present study advocates the necessity to adopt a holistic vision towards hyperoxaluria with emphasis on glycoproteins and ER environment.

Amelioration of cognitive and biochemical impairment in Aß-based rodent model of Alzheimer's disease following fractionated X-irradiation.

Alzheimer's disease is characterized by deposition of amyloid-beta plaques in the brain. Available pharmaceuticals provide temporary symptomatic relief without affecting disease progression. Use of radiation was found effective in treating extra-cranial amyloidosis, therefore, the present study was designed to investigate the neuroprotective role of fractionated X-irradiation in Aß1-42-based rodent model of Alzheimer's disease. S.D. female rats were randomly divided into four groups: sham control (Group 1), Aß1-42 injected (Group 2), cranial X-irradiated (Group 3) and Aß1-42 injected followed by cranial X-irradiation (Group 4). A single dose of 5 µL Aß1-42 peptide was administered through intracerebroventricular (icv) injection in Group 2 and 4 animals, while Group 1 animals were administered 5 µL of bi-distilled water (icv). The group 4 animals were further subjected to 10 Gy X-irradiation (fractionated dose, 2 Gy × 5 days) after 4 weeks of Aß1-42 infusion of peptide. The animals in Group 3 were subjected to same dose of cranial fractionated X-irradiation (2 Gy × 5 days) only. Significant decrease in amyloid deposits were observed in the Aß1-42 + radiation-treated animals confirmed by histopathological analysis. These finding were in concordance with neurobehavioral tests that showed a significant improvement in Aß1-42-induced memory impairment in the animals subjected to fractionated cranial X-irradiation. Restoration of alterations in neurochemical and antioxidant defense indices further supported our results. The present study highlights the underexplored role of fractionated X-irradiation in curtailing the Aß1-42-induced neurotoxicity, suggesting a novel treatment option for Alzheimer's disease-associated pathologies.

Hepato-protective role of chemo-preventive probiotics during DMH-induced CRC in rats.

The aim of the study was to assess the hepatotoxicity, and therefore pharmacological safety of probiotics Lactobacillus plantarum (AdF10) and Lactobacillus rhamnosus GG (LGG) for potential use in colorectal cancer (CRC) prevention. Thirty-six female Sprague Dawley (SD) rats were divided into six groups: normal control, AdF10-treated, LGG-treated, 1,2-Dimethyl hydrazine (DMH)-treated, AdF10 + DMH-treated, and LGG + DMH-treated groups. Antioxidant enzyme activity, lipid proxidation, and liver function were assessed. Administration of probiotics in both AdF10 + DMH-treated and LGG + DMH-treated groups downregulated DMH induced a rise in lipid peroxide (LPO), glutathione reductase (GR) activity, and increased the diminished glutathione reduced (GSH) content and catalase (CAT), glutathione-transferase (GST), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. DMH-treated rats receiving the probiotic treatment suffered less liver damage when compared with rats that did not receive probiotics. In conclusion, the study identifies the use of probiotics as an effective and nontoxic chemo-preventive interventional in CRC.

Antimicrobial peptides against colorectal cancer-a focused review.

Despite recent advances in the treatment of colorectal cancer (CRC), low patient survival rate due to emergence of drug resistant cancer cells, metastasis and multiple deleterious side effects of chemotherapy, is a cause of public concern globally. To negate these clinical conundrums, search for effective and harmless novel molecular entities for the treatment of CRC is an urgent necessity. Since antimicrobial peptides (AMPs) are part of innate immunity of living beings, it is quite imperative to look for essential attributes of these peptides which may contribute to their effectiveness against carcinogenesis. Once identified, those characteristics can be suitably modified using several synthetic and computational techniques to further enhance their selectivity and pharmacokinetic profiles. Hence, this review analyses scientific reports describing the antiproliferative action of AMPs derived from several sources, particularly focusing on various colon cancer in vitro/in vivo investigations. On perusal of the literature, it appears that AMPs based therapeutics would definitely find special place in CRC therapy in future either alone or as an adjunct to chemotherapy provided some necessary alterations are made in their natural structures to make them more compatible with modern clinical practice. In this context, further in-depth research is warranted in adequate in vivo models.

Role of Cyclooxygenase-2 in colorectal cancer patients.

Cyclooxygenase-2 (COX-2) is an inducible enzyme which triggers the biosynthesis of prostaglandins. COX-2 is activated in response to inflammatory stimuli and is one of the major molecules that is involved in the development and progression of colorectal cancer (CRC). Consistent with such a conceptual framework, it has been shown that COX-2 inhibitors prevent the carcinogenesis of CRC and aid in the treatment of sporadic or familial cases of CRC as shown by an overall increase in the survival rate. However, prolonged use of these inhibitors is associated with increase risk of development of cardiovascular complications, implying that further research is required to identify COX-2 inhibitors that are associated with lower risks of such complications.

Efficacy of dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin scintigraphy for the assessment of thyroid nodules.

INTRODUCTION: Radioisotope methods have shown to be useful in the non-invasive diagnosis of thyroid nodules over the past years. The present prospective study aims to evaluate the efficacy of gamma imaging using single and dual tracer using Tc-99m pertechnetate and Tc-99m tetrofosmin for evaluation and management of thyroid nodules. METHODS: Dynamic (perfusion) imaging was performed after injecting 148-185 MBq (4-5 mCi) of Tc-99m pertechnetate followed by static imaging. A second, dynamic (perfusion) imaging study within same week was performed with 296-370MBq (8-10mCi) of Tc-99m tetrofosmin on same group of patients followed by early and delayed images. Results of radionuclide perfusion scan from both studies were compared qualitatively with postsurgical histopathology or fine needle aspiration cytology (FNAC). RESULTS: Total 65 nodules in 50 patients were included in the study. With single tracer, the specificity and accuracy of Tc-99m pertechnetate was 23% and 45% and for Tc-99m tetrofosmin scan was 40% and 49%. When dual tracers were evaluated for the same group of patients, the specificity was 56% and accuracy was 55%. CONCLUSION: Dual Tracer technique with Tc-99m pertechnetate and Tc-99m tetrofosmin could be helpful in selecting nodules need surgical intervention. This technique can be used for convenient and rapid diagnostic evaluation of thyroid nodules non-invasively. We suggest a combination of fine needle aspiration biopsy and dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin as a routine diagnostic approach to thyroid nodules.

Over-Expression of Cyclooxygenase-2 in Colorectal Cancer Patients.

Background: Colorectal carcinoma (CRC) is the most common neoplasm of the gastrointestinal tract. COX-2 plays an important role in CRC development and is a key target for the regression of colorectal tumorigenesis by nonsteroidal anti-inflammatory drugs. The present study was conducted to examine the relationship of the levels of COX-2 in CRC patients with the clinico-pathological parameters and also to assess its usefulness as a potential biomarker for diagnosis of CRC. Methods: Prior to surgery, 30 CRC patients were enrolled and the samples from colon tumors and surrounding tissues were taken after they underwent surgical intervention at PGIMER, Chandigarh. mRNA expression levels of COX-2 were examined in 30 CRC and adjacent normal colonic mucosa by quantitative polymerase chain reaction (qPCR). The expression of COX-2 was assessed by immunohistochemical method using rabbit polyclonal antibodies against human COX-2 protein. Results: The quantitative relative expression of COX-2 mRNA was observed to be significantly higher (p<0.05) in colorectal cancer tissues as compared to adjacent normal colon tissues. Also, female CRC patients showed significantly higher (p<0.009) expression of COX-2 mRNA vis-a-vis male colorectal cancer patients. This is the first study which has reported a direct relationship between COX-2 mRNA expressions in male colorectal cancer patients versus females. Further, immunohistochemistry of COX-2 confirmed the quantitative real time-PCR findings. Conclusion: Our study shows that COX-2 over expression in colorectal carcinoma patients is closely associated with clinico-pathological parameters and is more pronounced in males versus females. Further, COX-2 mRNA expression can serve as a potential biomarker for the diagnosis of CRC.

Increased Nuclear Factor-κB/RelA Expression Levels in Human Colorectal Carcinoma in North Indian Patients.

Colorectal cancer is a major cause of cancer-related death in many countries. Inflammatory pathway is considered to play a major role in colorectal carcinogenesis. Nuclear factor kappa B (NF-κB) pathway is a link between inflammation and cancer. NF-κB is a transcription factor which belongs to the Rel family. Activation of NF-κB has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The aim of the present study was to evaluate the expression levels of NF-κB/RelA in colorectal carcinoma using Real-time PCR. For this study, tumor tissue was taken from general surgery OT of PGIMER, Chandigarh from twenty-seven patients of colorectal cancer treated by surgery. Adjacent colonic mucosa specimens were also collected from all patients as normal control tissue. Real-time PCR was performed to determine the nuclear factor-κB/RelA expression levels in twenty-seven pairs of colorectal adenocarcinoma and adjacent normal colonic tissues. Out of 27 CRC patients, 18 were males and 9 females. Mean age of patients was 51.1 ± 14.8 years. Most of the cases were males (67%). Seventy percent of the cases were early (I-II) and 30% were advanced (III-IV) tumor stage. The quantitative relative expression of NF-kB mRNA was found to be significantly higher (p < 0.05) in CRC tissues as compared with that in adjacent normal colon tissues. From this study, we can conclude that RelA/NF-kB pathway is expressed constitutively in colorectal adenoma and adenocarcinomas. Thus, RelA/NF-kB might play an important role in colorectal tumorigenesis.

Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke.

Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

Role of EGCG in Containing the Progression of Lung Tumorigenesis - A Multistage Targeting Approach.

Lung cancer is a prominent form among various types of cancers, irrespective of the sex worldwide. Treatment of lung cancer involves the intensive phase of chemotherapy/radiotherapy which is associated with high rate of adverse events. There is a need of safe and reliable treatment/adjunctive therapy to apprehend the cancer by reducing the undesirable outcome of primary therapy. Epigallocatechin-3-gallate (EGCG), which is a potent antioxidant and anticancer compound extracted from the plant camellia sinensis has proved to be a novel agent to control or reduce lung tumorigenesis by affecting the signaling molecules of cell cycle regulation and apoptotic pathways. In vitro studies have revealed that EGCG can contain carcinogenesis by altering the molecules involved in multiple signal transduction pathways like ERK, VEGF, COX2, NEAT, Ras-GTPase, and kinases. The animal studies have also demonstrated effectiveness of EGCG by inhibiting various molecular pathways which include AKT, NFkB, MAPK, Bcl/Bax, DNMT1, and HIF-1α. Various attempts have been made to see the adjunctive role of EGCG in human lung cancer. Phase I/II clinical studies have recommended that EGCG is quite safe and effective in providing protection against cancer. In this review, we will discuss the role of EGCG and its molecular mechanisms in lung carcinogenesis.

Effect of endoplasmic reticulum stress inhibition on hyperoxaluria-induced oxidative stress: influence on cellular ROS sources.

PURPOSE: Hyperoxaluria-induced calcium oxalate crystallisation is associated with the generation of reactive oxygen species (ROS) via mitochondria and NADPH oxidase. Endoplasmic reticulum (ER) has emerged as an organelle which could influence mitochondrial functioning and ROS generation. Plugging an upstream pathway of mitochondrial and NADPH oxidase-induced ROS generation may have better prophylaxis. Therefore, we propose to investigate the linkage of hyperoxaluria-induced ROS generation with ER stress by inhibiting the later with 4-Phenylbutyric acid (4-PBA). METHODS: Male wistar rats were divided into three groups: a normal control group, an ethylene glycol with ammonium chloride-induced hyperoxaluric group (EA) and a third group which has hyperoxaluric animals given 4-PBA at a dose of 300 mg/kg. After 9 days of treatment, animals were sacrificed and renal tissues were analysed for histopathological examination, ROS, mitochondrial dysfunction, ER stress markers, inflammatory markers and NADPH oxidase subunits expression. RESULTS: Hyperoxaluric rats exhibited a significant increase in the levels of ROS, subsequently up-regulated levels of ER stress markers, inflammatory indicators, NADPH oxidase subunits and compromised mitochondrial functioning. However, ER stress amelioration appreciably curtailed the alterations caused by hyperoxaluric abuse. CONCLUSIONS: Therefore, suggesting the major role of ER in hyperoxaluric manifestations thereby providing an opportunity to target ER stress for future therapeutic interventions.

Implication of hyperoxaluria on osteopontin and ER stress mediated apoptosis in renal tissue of rats.

Hyperoxaluria is a stress that leads to calcium oxalate crystal deposition which further causes inflammation and renal cell necroptosis. Many studies have linked osteopontin expression with apoptosis and inflammation but so far its association with apoptosis with regard to hyperoxaluria is undiscovered. Moreover, a recent report has suggested that osteopontin induces endoplasmic reticulum stress and subsequently apoptosis in myocytes. In this study, the impact of hyperoxaluria on the modulation of osteopontin expression and endoplasmic reticulum (ER) stress mediated apoptosis in rats is explored. Hyperoxaluria was induced in rats by three different doses viz. ethylene glycol alone, ethylene glycol and ammonium chloride together and third group were fed with hydroxyl-l-proline. After hyperoxaluria induction rats were sacrificed and renal tissue was analysed for crystal depositions, osteopontin expression, inflammation, ER stress and subsequent unfolded protein response intermediates (UPR). Altered histoarchitecture of renal tissue and elevated levels of reactive oxygen species (ROS) along with the presence of calcium oxalate crystals were observed in the hyperoxaluric groups. As expected, inflammation and apoptosis was significantly high in all hyperoxaluria groups. Osteopontin expression showed significant up-regulation following hyperoxaluria. Further, a similar trend between expression of osteopontin and elevated ER stress level was observed. Moreover, UPR intermediates expression was also concurrent with osteopontin levels. It is observed that the extent of calcium oxalate crystal deposition is directly associated with the expression of osteopontin, inflammation and ER stress. The results advocate possible association of osteopontin with ER stress, thus suggesting that the ER could be a new target for developing therapeutic regimes for kidney stones.

Genome Insight and Comparative Pathogenomic Analysis of Nesterenkonia jeotgali Strain CD08_7 Isolated from Duodenal Mucosa of Celiac Disease Patient.

Species of the genus Nesterenkonia have been isolated from different ecological niches, especially from saline habitats and reported as weak human pathogens causing asymptomatic bacteraemia. Here, for the first time we are reporting the genome sequence and pathogenomic analysis of a strain designated as CD08_7 isolated from the duodenal mucosa of a celiac disease patient, identified as Nesterenkonia jeotgali. To date, only five strains of the genus Nesterenkonia (N. massiliensis strain NP1T, Nesterenkonia sp. strain JCM 19054, Nesterenkonia sp. strain F and Nesterenkonia sp. strain AN1) have been whole genome sequenced and annotated. In the present study we have mapped and compared the virulence profile of N. jeotgali strain CD08_7 along with other reference genomes which showed some characteristic features that could contribute to pathogenicity. The RAST (Rapid Annotation using Subsystem Technology) based genome mining revealed more genes responsible for pathogenicity in strain CD08_7 when compared with the other four sequenced strains. The studied categories were resistance to antibiotic and toxic compounds, invasion and intracellular resistance, membrane transport, stress response, osmotic stress, oxidative stress, phages and prophages and iron acquisition. A total of 1431 protein-encoding genes were identified in the genome of strain CD08_7 among which 163 were predicted to contribute for pathogenicity. Out of 163 genes only 59 were common to other genome, which shows the higher levels of genetic richness in strain CD08_7 that may contribute to its functional versatility. This study provides a comprehensive analysis on genome of N. jeotgali strain CD08_7 and possibly indicates its importance as a clinical pathogen.

Development of Lu-177-trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients.

HER2/neu is over expressed in 20-25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed. A preliminary pilot study was conducted on breast cancer patients (n = 6 HER2 positive and n = 4 HER2 negative) to evaluate the ability of Lu-177-trastuzumab for HER2 specific tumor targeting. The conjugates were efficiently labeled with Lu-177 with high radiochemical purity (up to 91%) and specific activity (6-13 µCi/µg). Lu-177-trastuzumab was stable up to 12 hr post labeling. The radioimmunoassay demonstrated good antigen binding ability and specificity for HER2 receptor protein. The patient studies showed the localization of Lu-177-trastuzumab at primary as well as metastatic sites (HER2 positive) in the planar and SPECT/CT images. No tracer uptake was observed in HER2 negative patients that indicated the specificity of Lu-177-trastuzumab. The study demonstrated that in-house developed Lu-177-trastuzumab has specific targeting ability for HER2 expressing lesions and may in future become a palliative treatment option in the form of targeted radionuclide therapy for disseminated HER2 positive breast cancer.

Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach.

BACKGROUND: Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. MATERIALS & METHODS: In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. RESULTS: Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. CONCLUSION: These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects.

Propensity of Withania somnifera to Attenuate Behavioural, Biochemical, and Histological Alterations in Experimental Model of Stroke.

The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

Curcumin and quercetin trigger apoptosis during benzo(a)pyrene-induced lung carcinogenesis.

The aim of the present study was to assess the cumulative effects of curcumin and quercetin in inducing apoptosis during benzo(a)pyrene (BP) (100 mg/Kg body weight)-induced lung carcinogenesis in mice. BP treatment resulted in a significant increase in the protein expression of Bcl-2 whereas expression of Bax was significantly decreased. Further, BP treatment brought about a significant decrease in the activities of caspase 3, caspase 9 as well as the number of apoptotic cells. Interestingly, separate as well as combined supplementation of curcumin (60 mg/kg body weight) and quercetin (40 mg/kg body weight) to BP-treated animals resulted in a significant decrease in the protein expression of Bcl-2 but caused a significant increase in the protein expression of Bax along with a noticeable improvement in the number of apoptotic cells. Also, supplementation with curcumin and quercetin separately to BP-treated mice brought a significant improvement in the enzyme activities of caspase 9 as well as caspase 3 but the improvement was more pronounced following combined treatment. Therefore, curcumin and quercetin, if given in combination shall exhibit enhanced chemopreventive potential against development of lung carcinogenesis by stimulating the apoptotic machinery.

Regulation of biokinetics of (65)Zn by curcumin and zinc in experimentally induced colon carcinogenesis in rats.

This study was conducted to investigate the role of curcumin and zinc on the biokinetics and biodistribution of (65)Zn during colon carcinogenesis. Male wistar rats were divided into five groups, namely normal control, 1,2-dimethylhydrazine (DMH) treated, DMH + curcumin treated, DMH + zinc treated, and DMH + curcumin + zinc treated. Weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks initiated colon carcinogenesis. Curcumin (100 mg/kg body weight orally) and ZnSO4 (227 mg/L in drinking water) were supplemented for 16 weeks. This study revealed a significant depression in the fast (Tb1) and slow component (Tb2) of biological half-life of (65)Zn in the whole body of DMH-treated rats, whereas liver showed a significant elevation in these components. Further, DMH treatment showed a significant increase in the uptake values of (65)Zn in colon, small intestine, and kidneys. Subcellular distribution depicted a significant increase in (65)Zn uptake values in mitochondrial, microsomal, and postmicrosomal fractions of colon. However, curcumin and zinc supplementation when given separately or in combination reversed the trends and restored the uptake values close to normal range. Our study concludes that curcumin and zinc supplementation during colon carcinogenesis shall prove to be efficacious in regulating the altered zinc metabolism.