Roles of Natural Compounds from Medicinal Plants in Cancer Treatment: Structure and Mode of Action at Molecular Level.

Every year, cancer takes the life of millions of people. Conventional treatments have produced unsatisfactory results for some types of cancer, and the side effects are extensive, leading to a shift in the focus of treatment towards alternative medicines. Indeed, medicinal plants have long been investigated by scientists for their anti-cancer properties. Some phytochemicals that are important active constituents of plants, including catechins, ursolic acid, silymarin, glycyrrhizin, ellagic acid, gallic acid and various types of flavonoids, have shown promise in future cancer management. The current review covers various aspects of cancer treatment based on medicinal plants at molecular level and sheds light on their structures and modes of action.

Application of Proteomic Tools in Modern Nanotechnological Approaches Towards Effective Management of Neurodegenerative Disorders.

Neurodegeneration is the progressive loss of structure or function of neurons leading to neuronal death, usually associated with ageing. Some of the common neurodegenerative disorders include Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and Huntington's disease. Due to recent advancements in highthroughput technologies in various disciplines such as genomics, epigenomics, metabolomics and proteomics, there has been a great demand for detection of specific macromolecules such as hormones, drug residues, miRNA, DNA, antibodies, peptides, proteins, pathogens and xenobiotics at nano-level concentrations for in-depth understanding of disease mechanisms as well as for the development of new therapeutic strategies. The present review focuses on the management of agerelated neurodegenerative disorders using proteomics and nanotechnological approaches. In addition, this review also highlights the metabolism and disposition of nano-drugs and nano-enabled drug delivery in neurodegenerative disorders.

Recent updates in the treatment of neurodegenerative disorders using natural compounds.

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer's disease, Parkinson's disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

Downregulation of dopamine D1 receptors and increased neuronal apoptosis upon ethanol and PTZ exposure in prenatal rat cortical and hippocampal neurons.

The objective of this study was to evaluate the effect of ethanol and pentylenetetrazol (PTZ) on the expression of dopamine receptors (D1R) and to observe the apoptotic neurodegeneration in prenatal rat cortical and hippocampal neurons at gestational days (GD) 17.5. In the present study, ethanol (100 mM) and PTZ (15 mM) were exposed to the prenatal rat cortical and hippocampal neuronal cell cultures for 1 h. For mRNA RT-PCR and for protein Western blot analysis was done to elucidate D1R, Bax, Bak, Bcl-2 and cleaved caspase-3 expression upon ethanol and PTZ exposure in neuronal cell cultures. Furthermore, ethanol and PTZ-induced apoptotic neurodegeneration was also observed using TUNEL staining and propidium iodide (PI) used as counter stain under confocal microscopy. The results of present study showed that ethanol and PTZ exposure significantly decreased D1R expression and induced neuronal death by significantly increasing the expression of pro-apoptotic Bax, Bak and decreasing anti-apoptotic protein Bcl-2 leading to the apoptosis by increasing cleaved caspase-3 expression in cortical and hippocampal primary neuronal cell cultures. Our findings indicated that ethanol and PTZ exposure to the prenatal neurons showed not only downregulation of D1R but also causes neuronal apoptosis in the developing rat brain. Further, this explains the possibility of higher risk of developmental disturbances and malformations during early developmental stage.

New possibilities in hepatocellular carcinoma treatment.

Hepatocellular carcinoma diagnosis and treatment has witnessed many major changes and challenges in the past two decades. Increasing incidence of HCC has introduced new monitoring systems and increased the efficacy of screening tests, as well as prognosis of the disease, including the staging system, serological testing and diagnostic imaging. Moreover, surgical resection, liver transplantation and herbal therapy have improved treatment. The most encouraging specific serological marker for HCC is alpha fetoprotein (AFP), which, along with ultrasonography, has improved earlier detection of HCC. Most recently, circulating tumor cell measurement has emerged as a promising tool for the prognosis of HCC. Herbal drugs and herbal composite formula drugs are promising towards the prevention of invasion and proliferation of tumor cells. Chemotherapeutic agents, such as sorafenib, bevacizumab and erlotinib, which target growth factor receptors in signaling pathways, are also used as HCC treatments. Furthermore, radiotherapy is employed in the treatment of unresectable tumors. The present report provides an analysis of the above parameters in the management of HCC.

Comparative Study of Alterations in Tri-iodothyronine (T3) and Thyroxine (T4) Hormone Levels in Breast and Ovarian Cancer.

Objective : The present study was designed to investigate variations in the levels of thyroid hormones (T3, T4) in breast and ovarian cancers patients. Methods : A total 120 subjects were recruited (without thyroid history) divided into three groups; A, B and C. Group A as control with healthy individuals. While group B and group C were consisting of breast cancer and ovarian cancer patient respectively. Blood samples (5 ml) were taken and analyzed to estimate the levels of serum T3 (tri-iodothyronine) and T4 (thyroxin) hormones. R esults : Statistically significant difference (P=0.000* and P=0.017*) was obtained among all groups. A significant increase in T3 (P=0.000*) and T4 (0.005*) levels was observed among breast cancer patients as compared to healthy controls. While for ovarian cancer patients conflicting results were found for T3 and T4 levels in the serum i.e. insignificant difference was found in T3 (P=0.209) and T4 (P=0.050) as compared to control. Our results showed that in the breast cancer and ovarian cancer patients the thyroid hormone (T3 and T4) level has been altered from the normal ranges as compared to the normal healthy individuals. Conclusion : We conclude that hyperthyroidism has profound effects on breast cancer and ovarian cancer cells proliferation.

Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease.

It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.

Multiple antigen peptide consisting of B- and T-cell epitopes of F1 antigen of Y. pestis showed enhanced humoral and mucosal immune response in different strains of mice.

Yersinia pestis is a causative agent of plague. F1 and V antigen based vaccines have shown remarkable protection in experimental animals. In order to develop epitope based immunogen, three B and one T-cell epitopes of F1 antigen with palmitate residue at amino terminal were assembled on a lysine backbone as multiple antigen peptide (MAP or F1-MAP). MAP was characterized by SDS-PAGE, immunoblot and immunoreactivity with anti F1 sera. MAP was entrapped in PLGA (polylactide-co-glycolide) microparticles and humoral, mucosal immune responses were studied after intranasal immunization with/without CpG ODN 1826 (CpG)/murabutide in different strains of mice. Serum and mucosal washes were measured for MAP specific IgG, IgA, sIgA and IgG subclasses in three strains of mice. F1-MAP showed high serum antibody and mucosal IgG and IgA peak antibody titers. MAP with CpG showed significantly high (p<0.001) peak antibody titer ranging from 102,400 to 204,800 for IgG and 6400 to 12,800 for IgA. High mucosal sIgA and its secretary component detection confirmed generation of mucosal response in intestinal and lung washes. MAP antisera also showed significant immunoreactivity with individual peptides. Moreover, antibody specific activity (IgG, IgA and sIgA) positively correlates with peak antibody titers. Predominantly IgG2a/IgG2b subclass was observed with CpG formulation but in other formulation a mixed IgG1 and IgG2a response was observed. The present study highlights the importance of multiple antigen peptide approach of F1-antigen with CpG as an alternative approach for subunit vaccine.

An overview on potential neuroprotective compounds for management of Alzheimer's disease.

Alzheimer's disease (AD) is one of the major neurodegenerative diseases affecting almost 28 million people around the globe. It consistently remains one of the major health concerns of present world. Due to the clinical limitations like severe side effects of some synthesized drugs, alternative forms of treatments are gaining global acceptance in the treatment of AD. Neuroprotective compounds of natural origin and their synthetic derivatives exhibit promising results with minimal side effects and some of them are in their different phases of clinical trials. Alkaloids and their synthetic derivatives form one of the groups which have been used in treatment of neurodegenerative diseases like AD. We have further grouped these alkaloids into different sub groups like Indoles, piperdine and isoquinolines. Polyphenols form another important class of natural compounds used in AD management.

New anticancer agents: recent developments in tumor therapy.

Increasing recurrence of mammalian tumors and severe side-effects of chemotherapeutic agents reduce the clinical efficacy of a large variety of anticancer agents that are currently being used. Thus, there is always a constant need to develop alternative or synergistic anticancer drugs with minimal side-effects. One important strategy to develop effective anticancer agents is to study into anticancer agents derived from natural sources. Anticancer agents derived from plants and their derivatives have been proven to be effective for cancer prevention and therapeutics. Vinca alkaloid and their derivatives, alone and in combination with therapeutic agents, have been used for a long time for the treatment of various types of cancers. Polyphenols form one of the most important and extensively used classes of plant-derived therapeutics for cancer prevention or chemotherapy. The present review highlights a plethora of studies focused on the antineoplastic properties of plant-derived chemicals, such as Vinca alkaloid, saponins, and flavonoids.

Structural evidence of substrate specificity in mammalian peroxidases: structure of the thiocyanate complex with lactoperoxidase and its interactions at 2.4 A resolution.

The crystal structure of the complex of lactoperoxidase (LPO) with its physiological substrate thiocyanate (SCN(-)) has been determined at 2.4A resolution. It revealed that the SCN(-) ion is bound to LPO in the distal heme cavity. The observed orientation of the SCN(-) ion shows that the sulfur atom is closer to the heme iron than the nitrogen atom. The nitrogen atom of SCN(-) forms a hydrogen bond with a water (Wat) molecule at position 6'. This water molecule is stabilized by two hydrogen bonds with Gln(423) N(epsilon2) and Phe(422) oxygen. In contrast, the placement of the SCN(-) ion in the structure of myeloperoxidase (MPO) occurs with an opposite orientation, in which the nitrogen atom is closer to the heme iron than the sulfur atom. The site corresponding to the positions of Gln(423), Phe(422) oxygen, and Wat(6)' in LPO is occupied primarily by the side chain of Phe(407) in MPO due to an entirely different conformation of the loop corresponding to the segment Arg(418)-Phe(431) of LPO. This arrangement in MPO does not favor a similar orientation of the SCN(-) ion. The orientation of the catalytic product OSCN(-) as reported in the structure of LPO.OSCN(-) is similar to the orientation of SCN(-) in the structure of LPO.SCN(-). Similarly, in the structure of LPO.SCN(-).CN(-), in which CN(-) binds at Wat(1), the position and orientation of the SCN(-) ion are also identical to that observed in the structure of LPO.SCN.