A Study of Maternal and Umbilical Cord Blood Lead Levels in Pregnant Women.

Lead is a highly toxic element which can cross the placental barrier and enter the fetus during pregnancy. Parental lead exposure has adverse effect on infant as well as on maternal health. As part of our program to investigate the lead poisoning in human population we investigated the maternal blood lead levels (MBLL) and umbilical cord blood lead (UBLL) levels in 200 pregnant women and collected their socio-demographic details. In the study we found high lead levels in both maternal and umbilical cord blood samples. The results showed 47.5% maternal blood (n = 95) detected with lead while 38.5% umbilical cord blood (n = 77) samples had lead concentration higher than that of reference range of ≤ 5 µg/dL. We also found that the Spearman's correlation coefficient (rs) revealed a strong positive correlation between the MBLL and UBLL (rs = 0.63). The results from socio-demographic questionnaire demonstrated that the recent home painting (p = 0.002) and residing close proximity to traffic congestion (p = 0.05) were significantly associated with MBLL. Education, mother age, fuel and water sources were not significantly associated with MBLL. Iron and calcium deficiency along with tiredness, lethargy, abdominal pain were also reported in women having high lead level > 5 µg/dL. Concludingly, on the basis of results obtained it may be stated that we found elevated BLLs in both pregnant women as well as in umbilical cord blood. The prevalence of elevated lead levels in mothers will expose the fetus to lead through placental barriers mobilization and it can have long term adverse effects on the developing fetus. Therefore, it is recommended that screening of blood lead levels be carried out in high-risk women based on their social, occupational, environmental, and individual factors. In addition, stringent regulations on lead-based products are also required from government agencies/authorities to reduce environmental lead burden and toxicity. Moreover, public awareness programs should be organized on hazardous effect of lead.

Dopamine Gene Polymorphism, Biochemical and Oxidative Stress Parameters in Geriatric Population with and Without Depression: A Pilot Study.

Dopamine transporter takes released dopamine back into presynaptic terminals and has been implicated in several aging disorders including depression. The present study was designed to demonstrate dopamine gene polymorphism, its circulatory levels, biochemical and oxidative stress parameters in geriatric population with and without depression. Thirty geriatric patients with depression and thirty age and sex matched normal controls were genotyped for Dopamine Active Transporter (DAT TaqA1 and DAT VNTR) gene polymorphisms using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. The frequency of genotypes and alleles were compared in study groups. Biochemical markers, oxidative stress parameters, and dopamine levels were also measured using standard protocols and compared between patients and controls. The frequency distribution of DAT TaqA1 and DAT VNTR genotypes and alleles in patients were not statistically significant as compared to controls. At DAT TaqA1 gene polymorphism we found that the levels of dopamine were significantly high in genotypes A1A2 as compared to A2A2 (p ≤ 0.01). The present study demonstrated elevated levels of Catalase, Lipid Peroxide, and Glutathione Reductase, whereas decreased levels of Superoxide Dismutase, Dehydroepiandrosterone, Glutathione Peroxidase and Melatonin, in depressive patients as compared to controls. Our results clearly suggested that elevated mean levels of Catalase, Lipid Peroxides and Glutathione Reductase and decreased levels of Dehydroepiandrosterone, Superoxide Dismutase, Glutathione Peroxidase and Melatonin in depressed individuals may be a consequence of depression. Moreover, DAT TaqA1 allele A1 has a protective effect with high dopamine levels and DAT VNTR genotype 10R/10R has the highest protective effect followed by 9R/10R and 10R/11R.

Blood Lead Levels in Occupationally Exposed Workers Involved in Battery Factories of Delhi-NCR Region: Effect on Vitamin D and Calcium Metabolism.

Workers involved in battery manufacturing or recycling factories are occupationally exposed to high concentrations of lead. In humans, lead can cause a wide range of biological effects depending upon the level and duration of exposure. The purpose of this study was to find out the blood lead levels (BLL) in occupationally exposed workers involved in battery industry in Delhi NCR region and to study whether lead affected the vitamin D (vit D) and calcium metabolism. For this study 100 occupationally lead-exposed battery workers (LEBW) and 100 non-lead exposed controls (NLEC) were recruited. BLL were measured using inductively coupled plasma optical emission spectrometer (ICP-OES) technique while ELISA was performed to quantify the serum vit D levels in the study subjects. Routine biochemical parameters were measured by chemistry autoanalyzers. Statistical analysis was done using appropriate statistical tools. Results showed that BLL were significantly higher in LEBW as compared to NLEC (p < 0.0001). Serum vitamin D, calcium and phosphorus levels were significantly decreased in battery workers as compared to controls (p < 0.005). Spearman's rank correlation analysis showed significant negative correlation of BLL with serum Vitamin D and calcium levels. Significant positive correlation was observed between BLL and duration of lead exposure. Weak negative correlation was also observed between BLL and vit D even after adjusting for smoking status. In conclusion, this study demonstrated that higher BLL significantly alters the vit D and calcium metabolism.

Comparative evaluation of extract of Bacopa monnieri and Mucuna pruriens as neuroprotectant in MPTP model of Parkinson's disease.

Parkinson's disease (PD) results primarily from the death of dopaminergic neurons in substantia nigra. Treatment of PD has been shifted recently towards herbal medicines.Bacopa monnieri (L.) Wettst. (BM) and Mucuna pruriens (L.) DC (MP) are traditional herbal plants known to have neuroprotective effects due to the presence of bacosides in whole plant extract of Bacopa monnieri (BME) and L-DOPA in MP seed extract (MPE). In this study, the comparative effect of BME and MPE in Parkinsonian mice induced by chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was evaluated. Twenty four Swiss albino mice (35-45 g) were grouped into Control, MPTP, MPTP+BME and MPTP+MPE (6 mice in each). Experimental mice were given 40 mg/kg body wt. BME, 48 mg/kg body wt. MPE treatment was given orally for one month with prior use of 15 mg/kg body wt. of MPTP for 2 wk. After the treatment period, behavioral study was performed and assessment of neuroprotective effect was done via neurochemical analysis, Immunohistochemical parameters studied included functional viability of dopaminergic neurons in substantia nigra by Tyrosine hydroxylase (TH) using monoclonal antibody against TH and apoptotic study through caspase-3 and m-RNA expression of neurogenic gene in substantia nigra region of brain. Treatment with BME or MPE for one month significantly decreased the elevated levels of oxidative stress found in Parkinsonian mice. In behavioral tests, comparative analysis of BME and MPE showed a significant increase in spontaneous locomotor activity and grip strength test. Moreover, it was found that the use of BME considerably improved the tyrosine hydroxylase activity, caspase-3 and expression of neurogenic gene in the substantia nigra region of the brain. The results suggest that BME may provide a better platform for future drug discoveries and novel treatment strategies for PD as compared to MPE.

Anticancer and Antioxidant activity of Zingiber officinale Roscoe rhizome.

Dietary components present in foods, spices and herbs are source of natural compounds viz. phenols, flavonoids, tocopherols, ascorbic acid and carotenoids with potential benefits. Ginger is one such herb commonly used throughout the world as a spice for dietary as well as medicinal purpose since ancient period. Here, we investigated the methanolic extract of Zingiber officinale rhizome (ZOME) for anticancer activity against human cervical cancer HeLa cells and breast cancer MDA-MB-231 cells and antioxidant activity using 1,1-diphenyl-2-picryl hydroxyl (DPPH) scavenging assay, 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS) cation decolorization test. Antiproliferative activity was substantiated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assay for cell viability and cell proliferation, Hoechst staining was performed to examine apoptosis. Our results demonstrated that ZOME inhibited the proliferation and colony formation in HeLa and MDA-MB-231 cells, in a dose- and time-dependent manner and induced typical changes in nuclear morphology, chromatin condensation and fragmentation, membrane shrinkage and blebbing in both cells indicated apoptotic property of Z. officinale. ZOME exhibited potent antiradical activity against DPPH and ABTS. On the basis of the results of the present study, it may be suggested that Z. officinale has promising anticancer and antioxidant properties. Since, Z officinale has been commonly used throughout the world as a spice for dietary as well as for medicinal purposes since prehistoric times. Therefore, enriched use of Z. officinale as dietary material could be recommended in ethno-medicine for the management of cervical and breast cancers. Moreover, further studies are needed to isolate and characterize the potent compounds for further adjuvant therapy against such malignancies.

Identification of Anticancer and Antioxidant phytoconstituents from chloroform fraction of Solanum nigrum L. berries using GC-MS/MS analysis.

Solanum nigrum is a traditional Indian plant acclaimed for its medicinal properties since antiquity. Among all plant parts fruit berries have shown to be most pharmacologically active part. In the present investigation, we tried to characterize the bioactive principles of chloroform fraction of S. nigrum (CFSn) fruit berries using GC-MS analysis. We could identify 29 compounds belonging to different chemical classes viz. alkaloids, flavonoids, carbohydrates, glycosides, phytosterols, proteins, phenolic compounds, and saponins. More specifically, we found two novel phenolic compounds, benzoiisovanillin and syringic acid (4-hydroxy-3, 5-dimethoxybenzoic acid), which may be responsible for its pharmacological properties. Our phytochemical investigation of CFSn was well supported by its total phenolic content and antioxidant activity which we evaluated subsequently. Further, we investigated the anticancer activity against breast cancer cell lines (MDA-MB-231 and MCF-7) as well. Our in vitro results indicated that CFSn exhibited significant antiproliferative activity against both these cell lines and due induction of cancer cell death through apoptosis. Our study emphasizes the need for isolation and characterization of specific bioactive compounds of CFSn and determination of their mechanism of action responsible for its anticancer activity in breast cancer cells.

Structure based docking and biological evaluation towards exploring potential anti-cancerous and apoptotic activity of 6-Gingerol against human prostate carcinoma cells.

BACKGROUND: 6-Gingerol (6-G) is the primary active phytocomponent of ginger and has been shown to regulate multiple targets against cancer and its treatment. Androgen receptors (ARs) remain critical in the progression of prostate cancer (PCa). This study focuses on investigating 6-G as a promising anti-cancerous agent that inhibits AR activity significantly. METHODS: In this study, molecular docking simulation was done to investigate the binding affinity of 6-G and control drug Bicalutamide (BT) against oncogenic AR and tumor suppressor estrogen receptor ß (ERß). The crystal structure of AR and ERß was retrieved from Protein Data Bank (PDB) and docked with 3D Pubchem structures of 6-G using iGEMDOCK and AutoDock. Further in vitro study was done to evaluate the antioxidant, anti-cancerous, apoptotic, and wound healing potential of 6-G. RESULTS: The result displays that 6-G shows good binding affinity with AR and ERß. Condensation of the nucleus, change in mitochondrial membrane potential (MMP) and the ability to induce reactive oxygen species (ROS) were done in human PCa PC-3 cells. Results from the MTT assay demonstrated that 6-G and control drug BT showed significant (p < 0.01) dose and time dependent inhibition of human PCa PC-3 cells. 6-G increased the ROS generation intracellularly and decreased the MMP, and cell migration in treated PCa PC-3 cells. 6-G treated cells showed fragmented, condensed chromatin and nuclear apoptotic bodies. CONCLUSIONS: Thus, this study validates 6-G as a potential drug candidate against human PCa. However, further study of the anticancer potency of 6-G has to be done before its use for PCa treatment.

Automated lead toxicity prediction using computational modelling framework.

Background: Lead, an environmental toxicant, accounts for 0.6% of the global burden of disease, with the highest burden in developing countries. Lead poisoning is very much preventable with adequate and timely action. Therefore, it is important to identify factors that contribute to maternal BLL and minimise them to reduce the transfer to the foetus. Literacy and awareness related to its impact are low and the clinical establishment for biological monitoring of blood lead level (BLL) is low, costly, and time-consuming. A significant contribution to an infant's BLL load is caused by maternal lead transfer during pregnancy. This acts as the first pathway to the infant's lead exposure. The social and demographic information that includes lifestyle and environmental factors are key to maternal lead exposure. Results: We propose a novel approach to build a computational model framework that can predict lead toxicity levels in maternal blood using a set of sociodemographic features. To illustrate our proposed approach, maternal data comprising socio-demographic features and blood samples from the pregnant woman is collected, analysed, and modelled. The computational model is built that learns from the maternal data and then predicts lead level in a pregnant woman using a set of questionnaires that relate to the maternal's social and demographic information as the first point of testing. The range of features identified in the built models can estimate the underlying function and provide an understanding of the toxicity level. Following feature selection methods, the 12-feature set obtained from the Boruta algorithm gave better prediction results (kNN = 76.84%, DT = 74.70%, and NN = 73.99%). Conclusion: The built prediction model can be beneficial in improving the point of care and hence reducing the cost and the risk involved. It is envisaged that in future, the proposed methodology will become a part of a screening process to assist healthcare experts at the point of evaluating the lead toxicity level in pregnant women. Women screened positive could be given a range of facilities including preliminary counselling to being referred to the health centre for further diagnosis. Steps could be taken to reduce maternal lead exposure; hence, it could also be possible to mitigate the infant's lead exposure by reducing transfer from the pregnant woman.

Chemical Characterization, In-silico Evaluation, and Molecular Docking Analysis of Antiproliferative Compounds Isolated from the Bark of Anthocephalus cadamba Miq.

AIMS: The present study aimed to isolate and characterize chemical compounds from Anthocephalus cadamba Miq. bark and evaluate their anticancer activity by in silico, molecular docking, and in vitro studies. BACKGROUND: Anthocephalus cadamba is a traditionally used Indian medicinal plant. The anticancer and phytochemical properties of this plant remain unexplored except for a few studies. OBJECTIVES: The objective of the study was to evaluate the antiproliferative activity of extract and fractions against breast cancer and prostate cancer cell lines and isolate and characterize active compounds from bio-active guided fractions. Moreover, the anticancer activity of isolated compounds against breast and prostate cancer cell lines was also evaluated, in addition to in silico and molecular docking interactions of isolated compounds with VEGFR2 and PDGFRα target proteins. METHODS: The compounds were isolated and purified with the help of repeated column chromatography, and spectral techniques, such as 1D, 2D NMR, and GC-MS/MS, were used to identify and elucidate the structure of the compounds. Moreover, prediction of activity spectra for substances, physiochemical properties, bioactivity radar prediction, bioactivity score, natural-product likeness, ADME, and toxicity parameters of isolated compounds (AC-1 to AC-4) was performed through various in-silico databases and servers. To evaluate the docking interaction profile and binding energies of compounds, three docking tools were utilized, such as AutoDock, AutoDock Vina, and iGEMDOCK, against two targets VEGFR2 and PDGFRα. MD simulation was performed through ligand and receptor molecular dynamic server (LARMD). RESULTS: It was found that the A. cadamba bark chloroform fraction demonstrated a significant inhibitory effect against MDA-MB-231, MCF-7, and PC-3 cells in a dose-time-dependent manner. The bioassay-guided isolation afforded four molecules AC-1 to AC-4 from chloroform fraction. Moreover, the GC-MS/MS profiling identified fourteen new molecules which were not reported earlier from A. cadamba. The in-silico study showed that the isolated compounds (AC-1 to AC-4) followed Lipinski's rule and had good oral bioavailability. While compound AC-4 had positive bioactivity scores except for kinase inhibitor activity. The ADMET profiling revealed that AC-4 was non-toxic and easily absorbed in the human intestine, and transportable in the blood-brain barrier compared to AC-1, AC-2, AC-3, and standard drug doxorubicin. Molecular docking and MD simulation assessment also signified AC-4 anticancer activity with dual inhibitory action against the target proteins VEGFR2 and PDGFRα amongst the studied compounds. The in vitro cell viability assay of isolated compounds demonstrated that AC-1 showed IC50 (µg/mL) value of 34.96 ±3.91, 47.76±3.80 69.1±4.96, AC-2; 68.26±4.22, 54.03±5.14, >100, AC-3; 35.34±4.14, 51.5±51.5, 70.8±5.25 and AC-4; 44.2±3.57, 24.2±2.67, 51.2±2.54 for MDA-MB-231, MCF-7, and PC-3 cancer cell lines, respectively and compared with standard drug doxorubicin. Moreover, fluorescence microscopy confirmed the apoptogenic property of compounds. We also found that AC-4 exhibited significant intracellular ROS production in breast cancer cells, thereby inducing apoptosis and eventually cell death. CONCLUSION: In conclusion, A. cadamba afforded four pure molecules AC-1 to AC-4 with the identification of fourteen new compounds. The entire in-silico studies concluded that the AC-4 compound had better oral bioavailability, bioactivity score, and ADMET profile among studied molecules. Molecular docking analysis and MD simulation also supported AC-4 dual inhibitory action against both VEGFR2 and PDGFRα receptors. Moreover, the isolated molecules AC-1, AC-2, AC-3, and AC-4 were found to be active against MDA-MB-231, MCF-7, and PC-3 cancer cells. The molecule AC-4 was found to induce ROS-mediated apoptosis in breast cancer cells. It was found that the anticancer inhibitory potentiality of AC-4 is directed to its molecular stereochemistry which specifically binds to the target proteins of breast cancer cells with no toxicological effect. Therefore, AC-4 is suggested to be an effective aspirant for novel drug design and discovery.

Metal-induced oxidative stress level in patients with fibromyalgia syndrome and its contribution to the severity of the disease: A correlational study.

BACKGROUND: Fibromyalgia syndrome (FMS) is an extra-articular rheumatological disease characterised by widespread chronic musculoskeletal pain. Metal-induced oxidative stress contributes to the severity of FMS. AIMS: First, this study evaluated the association between plasma levels of toxic heavy metals and essential metals with oxidative stress (OS) markers. Second, the OS markers and metal contents were correlated with the disease severity by assessing the Fibromyalgia Impact Questioner Revised (FIQR) and tender points (TP). METHOD: A total of 105 FMS patients and 105 healthy controls of similar age and sex were recruited. OS parameter such as lipid peroxidation (LPO), protein carbonyl group (PCG), nitric oxide (NO) and essential metals such as zinc (Zn), magnesium (Mg), manganese (Mn), copper (Cu) and toxic heavy metals such as aluminium (Al), arsenic (As), lead (Pb) were estimated. RESULTS: Levels of LPO, PCG, NO (p< 0.001) and Cu, Mn, and Al (p< 0.001), were significantly higher, and Mg (p< 0.001) and Zn (p< 0.001) were significantly lower in patients compared to controls. A positive association was observed between OS parameters, FIQR and TP with Cu, Al and Mn. A significant negative association was observed between Zn and Mg with FIQR, TP and OS parameters. CONCLUSION: Heavy metals such as Al induce OS parameters and decrease the levels of essential trace elements such as Mg and Zn, which may be responsible for the severity of FMS.

Blood Lead Levels in Children Living Near an Informal Lead Battery Recycling Workshop in Patna, Bihar.

BACKGROUND: Lead can cause significant biological and neurologic damage, even at small concentrations, and young children are at higher risk. Informal recycling of lead batteries and lead-based workshops/industries have increased the burden of lead toxicity in developing countries, including India. Many informal recycling lead battery workshops have been established by the local people of Patna, Bihar as self-employment opportunities. However, most of the residents are not aware of the risk factors associated with lead poisoning. OBJECTIVES: The present pilot study aimed to assess blood lead levels (BLLs) and hemoglobin levels among children aged between 3 to 12 years in the settlement of Karmalichak near Patna, India. MATERIALS AND METHODS: Children residing near the informal lead battery manufacturing unit were selected for BLL assessment. A total of 41 children were enrolled in the questionnairebased survey. RESULTS: All the children in the present study had detectable lead concentrations in their blood. Only 9% of the studied children had a BLL ≤5 µg/dl, while 91% children had a BLL above >5 µg/dl. CONCLUSIONS: The present study carried out in children of Karmalichak region of Patna, India was an attempt to better understand the problem of lead toxicity, describe the epidemiology of its adverse effects, identify sources and routes of exposure, illustrate the clinical effects and develop strategies of prevention so that remedial measures may be taken by government agencies and regulatory bodies. In view of the high lead levels in children in the study area, attempts are being made to develop strategies for future prevention by relocating the informal battery recycling workshops from the area. Moreover, parents have been advised to increase nutritional supplementation of children by providing calcium-, iron- and zinc-rich foods, including milk and vegetables. PARTICIPANT CONSENT: Obtained. ETHICAL APPROVAL: The study was approved by the ethical committee of Era's Lucknow Medical College & Hospital, Era University, Lucknow (India). COMPETING INTERESTS: The authors declare no competing financial interests.

Case of Lead Poisoning Associated with Herbal Health Supplements.

BACKGROUND: Lead poisoning is a chronic health condition arising from prolonged ingestion and exposure to lead above permissible limits. Although reported globally, developing countries like India and neighboring countries are amongst the most affected by lead. OBJECTIVES: The aim of the present study was to evaluate lead poisoning associated with herbal health supplements in a suspected case. MATERIALS AND METHODS: A 31-year-old male reported consuming sixteen different herbal health supplements. The case and supplements were assessed for lead levels. The patient came from one of the metro cities of Uttar Pradesh state, India. RESULTS: The blood lead level of the case was found to be 78.40 µg/dL, which was much higher than the permissible limit of ≤5 µg/dL. Moreover, one of the supplements was found to have a very high lead content. CONCLUSIONS: The present study demonstrated a case of lead poisoning which was very likely due to high lead content present in one of the supplements. The case had typical neurological signs of lead toxicity such as irritability, frequent headache, mental dullness, generalized pain, muscle weakness, numbness and tingling, and twitching and shaking of the legs while sleeping. PATIENT CONSENT: Obtained. COMPETING INTERESTS: The authors declare no competing financial interests.

ROS mediated pro-apoptotic effects of Tinospora cordifolia on breast cancer cells.

The inevitable development of chemoresistance and unmanageable side effects are the major therapeutic challenges in management of breast cancer imposing an urgent need for identification of novel therapeutic agents. In the present investigation, we report anti-proliferative activity of chloroform fraction of Tinospora cordifolia (TcCF), an Ayurvedic medicinal plant, on breast cancer cells. We found that TcCF inhibited growth of breast cancer cells, MDA-MB-231 and MCF-7. More interestingly, we observed TcCF treatment increased intra-cellular ROS levels, altered expression of pro and anti-apoptotic genes, decreased colony formation ability and induced apoptosis in breast cancer cells. We also found that inhibition of ROS abrogated TcCF induced apoptosis in breast cancer cells, emphasizing the role ROS in TcCF induced breast cancer cell death. Furthermore, we identified the presence of pharmacologically active compounds like rutin and quercetin which account for the anti-cancer property of TcCF against breast cancer cells. These data show TcCF is a promising anti-cancer agent against breast cancer cells.

Anticancer, antioxidant potential and profiling of polyphenolic compounds of Wrightia tinctoria Roxb. (R.Br.) bark.

Wrightia tinctoria Roxb. (R.Br.) is an Ayurvedic remedy, ethnomedically used in the treatment of various ailments. The present work was carried out to evaluate the anticancer and antioxidant activity as well as total phenolic and phytochemical contents of W. tinctoria bark methanolic extract (WTBM) by high-performance liquid chromatography (HPLC)-diode array detector. Antiproliferative activity of WTBM was evaluated against MDA-MB-231 and MCF-7 cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation, and Hoechst staining. In addition, the antioxidant potential was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and 2,2- azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation decolorization assay. Total phenolic content was assessed by Folin-Ciocalteu method. The results demonstrated that WTBM exhibited significant antiproliferative effect against MDA-MB-231 (IC50 = 88.9 ± 1.27 µg/ml) and MCF-7 (IC50 = 45.71 ± 7.74 µg/ml) cancer cells in time- and dose-dependent manner. WTBM significantly suppresses colony formation and induces apoptosis in both MDA-MB-231 and MCF-7 cells as evident by morphological assessment, clonogenic assay, and Hoechst staining. The total phenolic content of WTBM was found to be 30.3 gallic acid equivalent mg/g dry weight of bark extract while IC50 value for DPPH and ABTS radical scavenging activity was 72.2 ± 2.8 µg/ml and 45.16 ± 1.95 µg/ml, respectively. HPLC analysis showed the presence of gallic acid, rutin, and quercetin in WTBM. These findings demonstrated that WTBM significantly inhibited proliferation of breast cancer cells and induced apoptosis, suggesting the potential chemopreventive activity of W. tinctoria bark.