Studies on the antitumor potentials of betulinic acid against murine ascites Dalton’s lymphoma

Background: Betulinic acid, a naturally occurring pentacyclic triterpene, exhibits a variety of biological activities including anticancer properties. Despite the wide importance of ethnobotanical studies on the anticancer therapeutic uses of betulinic acid, its exact role has not been fully elucidated. Therefore, the present studies were undertaken to evaluate the antitumor effect of betulinic acid in a murine malignant tumor model along with various biochemical changes in the tumor cells of the host.Methods: Ascites Dalton’s lymphoma (DL) tumor-transplanted Swiss albino mice were treated with betulinic acid (i.p., 10 mg/kg body weight) and the pattern of host’s survival was analysed. The viability of DL cells was assessed using trypan blue exclusion test. The DL cells were also studied for the determination of apoptosis using fluorescence microscopy. Reduced glutathione and protein estimations were done in DL cells under different treatment conditions.Results: Betulinic acid treatment caused a significant increase in life span (ILS ~150%) of the tumor-bearing hosts, which may indicate tumor regression/antitumor activity. Following betulinic acid treatment, decrease in DL cells viability and damaging changes in the cell membranes and a decrease in reduced glutathione content in DL cells were observed.Conclusions: Present findings reveal the potent antitumor activity of betulinic acid against murine ascites Dalton’s lymphoma. The cytotoxicity of betulinic acid to build up antitumor effects may involve induction of apoptosis as well as a decrease in glutathione level in tumor cells

ETHNOZOOLOGICAL REMEDIAL USES BY THE INDIGENOUS INHABITANTS IN ADJOINING AREAS OF THE POBITORA WILDLIFE SANCTUARY, ASSAM, INDIA

Objective: To comprehend the traditional knowledge on zootherapeutic remedies used by indigenous people inhabiting in adjoining areas of the Pobitora wildlife sanctuary located in the Morigaon district of Assam State, India.Methods: [d1]  The adjoining villages of this wildlife sanctuary are inhabited by different indigenous communities and tribal groups of which Nath community and Karbis constitute the main population. In the present study, field survey was carried out from October 2014 to March 2015 by performing personal interviews through semi-structured questionnaires and in some cases where respondents were uncomfortable with the questionnaires, informal interviews and group discussions were conducted with a total of 50 respondents (33 male and 17 female), who provided the information regarding various uses of animals and their products (local name of animal, mode of preparation, application, etc) in their traditional medicine.Results: A total of 26 ethnomedicinal animals and animal products that are used for the treatment of various ailments including asthma, jaundice, chicken pox, pneumonia, anemia, etc. were recorded. Some protected wild species like the golden jackal (Canis aureus), rhino (Rhinoceros unicornis) and Indian crested porcupine (Hystrix indica) were also mentioned to have important medicinal uses. The highest percentage of animals used for traditional treatment is mammals (~34.62 %) followed by fishes (~30.77 %) and birds (~15.38 %). Most of the information are generally provided by the elderly person in the age group above 50 y.Conclusion: The information on the remedial uses of different animals were collected from Nath community and Karbis who use a variety of zootherapeutic medicines for curing different ailments in their own ways. Such kind of information and documentation should be very helpful in the formulation of strategies on sustainable management and conservation of bio-resources so that the medicinal values of these traditional remedies would go a long way and may lead to novel drug(s) discovery.Keywords: Pobitora wildlife sanctuary, Traditional medicine, Zootherapy [d1]Check fon

Antitumor activity with no toxicity of propolis from Meghalaya, India in ascites Dalton’s lymphoma-bearing mice

Propolis or bee glue is an important natural bee product that has been used by humans to meet the needs of health since ancient times. Despite its many valuable uses, scientific research on propolis is still limited. Despite rich traditional zootherapeutic knowledge of the people and affluent biodiversity of North-east India, almost no research study has been undertaken on the assessment of various biological properties of propolis from this region. Recently, the antibacterial and antitumor activity of the methanolic extract of propolis (MeOH-propolis) from Meghalaya was reported by us only. The present study was undertaken to further examine the antitumor activity and toxicity in ascites Dalton’s Lymphoma bearing mice itself and compare with that of cisplatin, a well established anticancer drug also known to cause different toxicities in the host. MeOH-propolis showed potent anticancer activity against ascites Dalton’s lymphoma. The assessment of various toxicity parameters such as hematotoxicity, nephrotoxicity, hepatotoxicity and sperm abnormality revealed that MeOH-propolis treatment did not develop any toxicity while cisplatin developed these toxicities in the host. It is suggested that the increasing antioxidative defense activity of the MeOH-propolis could be involved in its ability to avoid any toxicity in the host. The findings from the present study showing the combined action of MeOH-propolis as anticancer as well as its ability to stabilize various toxicity parameters in cancer-bearing mice suggest the possibility of using propolis as a natural alternative to chemotherapy to shun the side effects

Antitumor activity with no toxicity of propolis from Meghalaya, India in ascites Dalton’s lymphoma-bearing mice

267-279Propolis or bee glue is an important natural bee product that has been used by humans to meet the needs of health since ancient times. Despite its many valuable uses, scientific research on propolis is still limited. Despite rich traditional zootherapeutic knowledge of the people and affluent biodiversity of North-east India, almost no research study has been undertaken on the assessment of various biological properties of propolis from this region. Recently, the antibacterial and antitumor activity of the methanolic extract of propolis (MeOH-propolis) from Meghalaya was reported by us only. The present study was undertaken to further examine the antitumor activity and toxicity in ascites Dalton’s Lymphoma bearing mice itself and compare with that of cisplatin, a well established anticancer drug also known to cause different toxicities in the host. MeOH-propolis showed potent anticancer activity against ascites Dalton’s lymphoma. The assessment of various toxicity parameters such as hematotoxicity, nephrotoxicity, hepatotoxicity and sperm abnormality revealed that MeOH-propolis treatment did not develop any toxicity while cisplatin developed these toxicities in the host. It is suggested that the increasing antioxidative defense activity of the MeOH-propolis could be involved in its ability to avoid any toxicity in the host. The findings from the present study showing the combined action of MeOH-propolis as anticancer as well as its ability to stabilize various toxicity parameters in cancer-bearing mice suggest the possibility of using propolis as a natural alternative to chemotherapy to shun the side effects

TRADITIONAL HEALING WITH ANIMALS (ZOOTHERAPY) BY THE MAJOR ETHNIC GROUP OF KARBI ANGLONG DISTRICT OF ASSAM, INDIA

Objective: To survey and document the traditional knowledge related to medicinal uses of animals among the ethnic groups in Karbi Anglong district of Assam. Methods: A long term field survey was conducted from July 2008 to October 2009 by performing personal interviews through structured questionnaire with more than 500 respondents, who provided information regarding the use of different animals and their products in their traditional medicine. Most of the information on the use of various animals in traditional medicine by them was provided by elderly people in the age groups of more than 50 years. Results: A total of 48 different animals were recorded to be used for different ethno-medical purposes against various diseases, including tuberculosis, asthma, cancer, paralysis, jaundice, leprosy, toothache, rabies, dysentery, baldness, rheumatism, arthritis, weakness, piles etc. The highest percentage of animals used for traditional treatment is mammals (about 40%) followed by insects (about 21%) and birds (about 19%). Conclusion: The findings reveal a rich traditional knowledge of indigenous people of Karbi Anglong about the use of animals and their product in traditional medicine. It is suggested that this kind of traditional knowledge should be included into the scientific literature for the conservation and management of medicinal faunistic resources

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations. METHODS: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Stanaway JD, Afshin A, Gakidou E, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1923-1994.Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd

Biochemical changes associated with ascorbic acid–cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice

AbstractCisplatin is one of the well-established anticancer drugs being used against a wide spectrum of cancers. However, full therapeutic efficacy of the drug is limited due to development of various toxicities in the host. This study examines the comparative therapeutic effectiveness and toxicities of cisplatin alone and in combination of dietary ascorbic acid (AA) in ascites Dalton's lymphoma-bearing mice. The findings show that the combination treatment of mice with ascorbic acid plus cisplatin has much better therapeutic efficacy against murine ascites Dalton's lymphoma (DL) in comparison to cisplatin alone and this may involve a decrease in reduced glutathione (GSH), catalase activity and increased lipid peroxidation (LPO) in Dalton's lymphoma tumor cells. At the same time, combination treatment indicates a protective role of ascorbic acid against cisplatin-induced tissue toxicities (side effects) in the hosts. Cisplatin-induced histopathological changes in liver, kidney and testes were decreased after combination treatment. The analysis of renal function test (RFT), liver function test (LFT) and sperm abnormalities also suggest an improvement in these parameters after combination treatment. Therefore, it may be concluded that the increased GSH level, catalase activity and decreased LPO in the tissues, i.e., liver, kidney and testes after combination treatment may be involved in its protective ability against cisplatin-induced tissue toxicities in the host