Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise

Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics

Regulation of Apoptotic Effects by Erythrocarpine E, a Cytotoxic Limonoid from Chisocheton erythrocarpus in HSC-4 Human Oral Cancer Cells

The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC50 value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Beliefs in Islamic Tamil Novels

From the Sangam period to the present day, people have been living with some invisible beliefs and many superstitions. They lived by following many beliefs like fortune- telling, omen- seeing in nature and so on. Such beliefs and superstitions can be seen in many novels. Islamic novelists have mentioned beliefs like Sufism, Darha worship, etc. in their novels. At the same time some people create some false superstitious belief in the society. Thus, the article investigates the activities of those who make their living by deceiving and cheating people

Mixed Constraint Fuzzy Transshipment Problem

Abstract In this paper, a Fuzzy Transshipment problem is defined in which the origin and destination consist not only the equality but also of greater than or equal to or less than or equal to type constraints. An algorithm is proposed to change the mixed constraint fuzzy transshipment problem into a standard fuzzy transportation problem. The optimal solution for the fuzzy transportation problem is the optimal solution for the mixed constraint fuzzy transshipment problem

Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells

Menaga Subramaniam,1 Su Ki Liew,1 Lionel LA In,2 Khalijah Awang,3,4 Niyaz Ahmed,5 Noor Hasima Nagoor1,6 1Institute of Biological Science (Genetics & Molecular Biology), Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia; 3Centre for Natural Product Research and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia; 4Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 5Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, India; 6Centre for Research in Biotechnology for Agriculture (CEBAR), University of Malaya, Kuala Lumpur, Malaysia Background: Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects. Materials and methods: In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression Results: All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation. Conclusion: Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities. Keywords: Mycobacterium indicus pranii, 1'S-1'-acetoxychavicol acetate, drug combination, nuclear factor κ

Prevalence of mental illness and their association with sociodemographic factors in the rural geriatric population in Chittoor, Andhra Pradesh, India: A community-based study

BACKGROUND: Mental health problems such as cognitive impairment, depression, anxiety, and sleep disorders arising out of senility, neurosis, and living conditions are common in the geriatric population. OBJECTIVE: The objective of this study was to estimate the prevalence of mental illness and to describe their sociodemographic factors in the rural geriatric population and see their association with other factors. METHODOLOGY: A community-based cross-sectional study was done on individuals aged more than 60 years. The study instruments were predesigned semi-structured questionnaire, Folstein's Mini–Mental Status Examination Scale for assessing dementia in cognitive functioning and Yesavages Geriatric Depression Scale to estimate the prevalence of depression and to assess the activities of the daily living by Barthel index and the anxiety were assessed based on the perception of the participants while conducting the interview. RESULTS: A total of 415 individuals participated, out of them 199 (47.9%) were males and 216 (52.1%) were females. Prevalence of mental illness was 217 (52.2%) with one or the other type of mental illness. The prevalence of cognitive impairment was 47.7% and depression according to Geriatric Depression Scale >5 was 27.7%. The remaining 62 (14.9%) had dementia and 30 (7.2%) had anxiety disorder as the mental illness. The socio-demographic factors such as age more than 70 years, female gender, illiterates, living in joint family, middle and lower socio-economic class, financially totally dependent and had poor and unfair relationship with the family members were strongly associated with the mental illness and it was statistically significant with P < 0.05. CONCLUSION: Measures should be taken to support the elders, establish community elderly societies, advisory offices, and services to help the elderly. The sequence of social interventions required for the management of the elderly psychological problems