Tuesday, 20 March 2018

Re: A Review of Herbal Treatment Options for the Symptoms of Rheumatoid Arthritis

PDF (Download) Rheumatoid Arthritis Date: 03-15-2018 HC# 091743-588 Yarnell E. Herbs for rheumatoid arthritis. Altern Complement Ther. August 2017;23(4):149-156. Rheumatoid arthritis (RA), a multifactorial progressive autoimmune disease, causes inflammation and hypertrophy in synovial tissue in joints, leading to joint tissue destruction. Treatment of RA includes a multicomponent regimen including herbs. Yarnell organizes herbs for RA by effects as follows: inflammation-modulating, immunomodulating, and "spicy relief." Miscellaneous Asian herbs and formulas and thunder duke vine (Tripterygium wilfordii, Celastraceae) also are covered in this review. Inflammation modulation, distinct from suppression, aims to lower inflammatory "tone," addressing RA causes, pathology, and symptoms. In the inflammation-modulating herbs studied in RA, omega-6 γ-linolenic acid (GLA)-rich seed oils from evening primrose (Oenothera biennis, Onagraceae), black currant (Ribes nigrum, Grossulariaceae), and borage (Borago officinalis, Boraginaceae) show promise. However, benefits of GLA are questionable in diets with high amounts of its precursor, omega-6 linoleic acid (LA). GLA is the precursor for dihomo-gamma-linolenic acid (DGLA), the precursor of anti-inflammatory series 1 prostaglandins, and for arachidonic acid (AA), the precursor of pro-inflammatory series 2 prostaglandins. Positive results in trials and lack of serious adverse effects (AEs) favor GLA-rich herbs in RA management. Adding eicosapentaenoic acid (EPA) from fish oil may prevent GLA to DGLA conversion. In some trials, fish oil alone was just as effective as fish oil with GLA. Black cumin (Nigella sativa, Ranunculaceae) seed oil reduced disease symptoms compared to placebo in two trials, with inflammation-modulating and immunomodulating effects. Devil's claw (Harpagophytum procumbens and H. zeyheri, Pedaliaceae) has been shown to be overall beneficial in clinical investigations. Salicylate glycosides, mainly salicin, from willow (Salix spp., Salicaceae), aspen (Populus tremula, Salicaceae), and cottonwood (Populus spp.) tree barks, have been used historically for RA. One modern trial assessing a salicin-rich extract from European violet willow (Salix daphnoides) found no difference in RA pain scores or AEs compared to placebo. Trials of two European multi-herb products containing salicylate-rich herbs report positive results. One, Phytodolor® (Steigerwald Arzneimittelwerk GmbH; Darmstadt, Germany), has strong evidence for efficacy and "seems appropriate for clinical use." The product, unavailable in North America at time of writing, may be approximated with equal parts aspen, European goldenrod (Solidago virgaurea, Asteraceae), and European ash (Fraxinus excelsior, Oleaceae). Other potentially inflammation-modulating herbs are listed in a table. Immunomodulating herbs are shown to help patients with RA; however, the few published studies are mostly disappointing. Randomized controlled trials (RCTs) of two formulas containing ashwagandha (Withania somnifera, Solanaceae) root, ginger (Zingiber officinale, Zingiberaceae) rhizome, and other herbs, as well as ginger on its own, and of the single Ayurvedic herb bhallataka (marking-nut tree; Semecarpus anacardium, Anacardiaceae), reported that the products had good results and excellent safety. Reishi (Ganoderma lucidum, Ganodermataceae), taken with the Chinese herbal formula Sān Miào Sǎn (Three Wonder Powder), was assessed in two trials with inconclusive results but excellent safety. Andrographis (Andrographis paniculata, Acanthaceae) aerial parts, an important Asian medicine, is an immune stimulant and immunomodulator. An RCT studied the anti-RA effect of an andrographis extract containing 30 mg andrographolide given thrice daily for 14 weeks. Results showed that while the pain scores did not show change or reduction, the severity of swelling and tenderness in joints decreased significantly. "Spicy relief" refers to topical capsaicin from cayenne (Capsicum annuum syn. C. frutescens, Solanaceae). In a double-blind RCT of capsaicin, 31 patients used a capsaicin cream or placebo for pain. The capsaicin group showed significant improvement in pain score. Yarnell includes garlic (Allium sativum, Amaryllidaceae) under this heading, although it is taken orally and may act as an immunomodulator. In one study, Russian patients with RA taking disease-modifying drugs were randomly assigned to receive a garlic extract or no additional therapy for four to six weeks; 87% of the garlic group had at least a partial response but no information was reported for the drug-only group. Among Chinese herbs, white peony (Paeonia lactiflora, Paeoniaceae) may have both inflammation-modulating and immunomodulating effects in RA. It is also a hormone modulator and spasmolytic. Most importantly, white peony is reported to reduce hepatotoxicity of the common RA drugs methotrexate and leflunomide—"For this reason alone, white peony should be considered for use in combination with these drugs … ." RCTs of Chinese and Korean multi-herb formulas (the former including animal products and combined, in one treatment arm, with moxa) report excellent safety and many benefits. Thunder duke vine root and stem without bark is a potent immunosuppressant. The traditional decoction was associated with high rates of serious AEs; in response, two safer extracts were developed. Not easily obtainable in North America, Yarnell states that the extracts should not be recommended without more evidence of efficacy and safety, but a meta-analysis of 10 RCTs found them safer than, and just as effective as, immunosuppressive drugs. Another meta-analysis of six RCTs comparing methotrexate alone to methotrexate with thunder duke vine extracts found the combination more effective and with similar safety compared to methotrexate alone. Chinese licorice (Glycyrrhiza uralensis, Fabaceae), an immunomodulator and inflammation modulator, is a good choice for use with thunder duke vine to reduce toxicity. A topical preparation of thunder duke vine also showed good results in an RCT. —Mariann Garner-Wizard

Re: Combining Curcumin and Boswellic Acid Is More Effective in the Treatment of Osteoarthritis than Curcumin Alone

Date: 03-15-2018 HC# 021831-588 Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. January 9, 2018;18(1):7. doi: 10.1186/s12906-017-2062-z. The symptoms of osteoarthritis (OA), including pain, morning stiffness, joint swelling, limited range of motion, decreased physical function, and restriction of social activities, are treated with analgesic, nonsteroidal anti-inflammatory drugs (NSAIDs), and cortisone. Although those drugs manage the pain and inflammation, they are associated with adverse effects, drug interactions, and contraindications. Curcumin, a component of turmeric (Curcuma longa, Zingiberaceae), has been reported to be a potent anti-inflammatory agent. The boswellic acids found in boswellia (Boswellia serrata, Burseraceae) possess anti-inflammatory and antiarthritic properties. The primary objective of the comparative, randomized, double-blind, placebo-controlled study reported here was to compare the efficacy of curcumin, a combination of boswellic acid and curcumin, and placebo in treating degenerative joint disease by assessing their effects on joint pain, morning stiffness, and limitations of physical function. The secondary objective was to investigate the safety of the treatments. The study, which used Curamin® and CuraMed® (both donated by EuroPharma USA, Inc.; Green Bay, Wisconsin), was conducted between September 2014 and May 2016. The study included 201 males and females aged 40 to 77 years who had been diagnosed with degenerative hypertrophic OA of the knee and were patients at Erebuni Medical Center in Yerevan, Armenia. Each 500-mg capsule of the curcumin supplement CuraMed contained 552-578 mg of BCM-95® (DolCas Biotech, LLC; Landing, New Jersey), a dry turmeric extract with 500 mg curcuminoids and 49-52 mg volatile oil from turmeric rhizome. Inactive excipients (120-149 mg) included phosphatidylcholine, medium-chain triglycerides, glycerol, gelatin, and yellow beeswax. Each 500-mg Curamin capsule contained 350 mg BCM-95 and 150 mg boswellia gum resin extract consisting of 75% boswellic acids and 10% 3-O-acetyl-11-keto-boswellic acid. Each 500-mg placebo capsule (donated by EuroPharma USA, Inc.) contained maltodextrin, calcium phosphate, gelatin, magnesium stearate, silica dioxide, FD&C yellow 5, FD&C yellow 6, and titanium dioxide. The patients were randomly assigned to the Curamin (n = 67), CuraMed (n = 66), or placebo group (n = 68). The patients were instructed to take 1 capsule 3 times daily for 12 weeks. No significant differences in demographic or other measured characteristics were observed among the patients at baseline. The mean age was 56.2 years, the average body mass index was 29 kg/m2, and 93% of the patients were females. In the Curamin group, dropouts during the study included 2 patients who did not respond, 1 who lost interest because of lack of improvement, 1 who was injured, and 1 who reported nausea and vomiting. In the placebo group, 3 patients did not respond, 3 lost interest because of lack of improvement, and 3 reported adverse effects (weight gain, stomach pain, dyspepsia, rash, and itching). In the CuraMed group, dropouts included 3 patients who did not respond, 1 who was unable to attend the study visits, 1 who lost interest because of lack of improvement, and 3 who did not trust the medication. During the study visits at baseline, after 4 weeks, and after 12 weeks, the patients underwent radiography and sonography, completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and physical performance measures (PPM) tests, and provided blood samples. The text stated labs differently than the corresponding table, so it is unclear at which visits each of these tests were done. After 4 weeks of treatment, significant decreases were seen in total WOMAC scores in all groups (P < 0.05 for all). The scores gradually decreased in the Curamin and CuraMed groups until the end of the study; however, in the placebo group, no significant changes were seen at 12 weeks. At the end of the study, the improvements in the CuraMed group (P < 0.001) were 3.6-fold greater, and in the Curamin group (P < 0.001), 2.7-fold greater, than the improvement seen in the placebo group (P = 0.154). Statistically significant pain relief was observed in all groups, as reported on the WOMAC. In the placebo group, the pain index decreased significantly after 4 weeks of treatment (P < 0.01); however, after 12 weeks, the change was not significant (P > 0.05). Significant decreases in pain were seen in the Curamin and CuraMed groups (P < 0.001 for both) after 12 weeks of treatment. The significant decrease in pain reported in the placebo group after 4 weeks is similar to results from other studies that report placebo effects of OA treatments; meta-analyses have indicated that more than 50% of study patients with OA respond positively to placebo treatment.1,2 Placebo effects can be influenced by the strength of the active treatment, the severity of disease at baseline, the route of medication delivery, and the study's sample size.1 After 12 weeks of treatment, patients in the Curamin and CuraMed groups reported significantly less difficulty in moving their knees and less stiffness compared with baseline (P < 0.05 for both groups). In the placebo group, significant improvement was seen only after 4 weeks (P < 0.05) of treatment. Differences in changes during the study between the Curamin and placebo groups and between the CuraMed and placebo groups were not significant. Among the PPM tests was the chair stand test. The maximum number of chair stand repetitions in 30 seconds increased significantly during the study in the Curamin and CuraMed groups (P < 0.001 for both). Significant differences between the Curamin and placebo groups (P < 0.05) and between the CuraMed and placebo groups (P < 0.01) were observed, with greater improvements in the Curamin and CuraMed groups. A timed walking test (40-m walking speed) revealed significantly increased walking speeds from baseline to week 12 only in the Curamin (P < 0.001) and CuraMed (P < 0.01) groups. Comparing the changes from baseline among the groups revealed significant differences between the CuraMed and placebo groups (P < 0.05) and between the Curamin and placebo groups (P < 0.01), with faster speeds reported in the active treatment groups. Patients were timed as they rose from a chair, walked 3 meters, turned around, walked back to the chair, and sat down. They wore regular footwear and used a walking aid if needed. The time significantly decreased only in the Curamin (P < 0.001) and CuraMed (P < 0.05) groups. Comparing the changes from baseline to the end of the study revealed greater improvement in the Curamin group compared with the placebo group (P < 0.01); improvements in the CuraMed and placebo groups were not significantly different (P > 0.05). The time required to go up and down a flight of stairs significantly decreased by week 12 only in the Curamin (P < 0.001) and CuraMed (P < 0.01) groups. Comparing the changes from baseline to the end of the study revealed greater improvement in the Curamin group compared with the placebo group (P < 0.01); improvements in the CuraMed and placebo groups were not significantly different. Blood levels of inflammation markers significantly increased (P < 0.05) in all groups compared with baseline, with no significant differences seen among the groups. Adverse effects were observed in 13 of the 201 patients as follows: 4 in the placebo group, 2 in the Curamin group, and 7 in the CuraMed group. None of those effects were serious. The types and frequency of adverse effects were similar in all groups and were not related to the treatment. Compared with placebo, Curamin significantly improved the patients' performance on all physical tests and on the factors of the WOMAC. Patients treated with CuraMed saw improvements in 2 physical performance tests and in the WOMAC joint pain index. These results suggest that "these plant extracts are more effective in combination," write the authors, possibly because boswellic acid increases the bioavailability of curcumin. "However, to our knowledge, there is no published study demonstrating the effect of boswellic acid on the bioavailability of curcuminoids." In this study, the 12-week use of a curcumin complex or its combination with boswellic acids reduced pain-related symptoms in patients with OA. The authors conclude that the combination of curcumin and boswellia extract "increases the efficacy of treatment of OA presumably due to synergistic effects of curcumin and boswellic acid." This study was supported in part by EuroPharma USA, Inc. ―Shari Henson References 1Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67(12):1716-1723. 2Zou K, Wong J, Abdullah N, et al. Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2016;75(11):1964-1970.

Student Evaluations Can’t Be Used to Assess Professors Our research shows they’re biased against women. That means using them is illegal.

By KRISTINA MITCHELL MARCH 19, 20189:00 AM TWEET SHARE COMMENT Professor standing in front of a chalkboard marked up with a student evaluation. Photo illustration by Slate. Photos by Thinkstock. Imagine that you’re up for a promotion at your job, but before your superior decides whether you deserve it, you have to submit the comments section of an internet article that was written about you for assessment. Sound a little absurd? That’s in essence what we ask professors in higher education to do when they submit their teaching evaluations in their tenure and promotion portfolios. At the end of each semester, students are asked to fill out an evaluation of their professor. Typically, they are asked both to rate their professors on an ordinal scale (think 1­–5, 5 being highest) and provide written comments about their experience in the course. In many cases, these written evaluations end up sounding more like something out of an internet comments section than a formal assessment of a professor’s teaching. Everything from personal attacks to text-speak (“GR8T CLASS!”) to sexual objectification has been observed by faculty members who dare to read their evaluation comments at the end of the semester. But the fact that the evaluations can be cruel and informal to the point of uselessness isn’t even the problem. The problem is that there’s a significant and observable difference in the way teaching evaluations treat men versus women. A new study I published with my co-author examines gender bias in student evaluations. We looked at the content of the comments in both the formal in-class student evaluations for his courses as compared to mine as well as the informal comments we received on the popular website Rate My Professors. We found that a male professor was more likely to receive comments about his qualification and competence, and that refer to him as “professor.” We also found that a female professor was more likely to receive comments that mention her personality and her appearance, and that refer to her as a “teacher.” The comments weren’t the only part of the evaluation process we examined. We also looked at the ordinal scale ratings of a man and a woman teaching identical online courses. Even though the male professor’s identical online course had a lower average final grade than the woman’s course, the man received higher evaluation scores on almost every question and in almost every category. Think back to that promotion that you only get if you turn in the comments section on that article someone wrote about you. If you’re a woman, your comments are going to talk about whether you’re nice or rude and whether you’re hot or ugly, while for men, the comments will talk about how qualified you are. And on a scale of 1–5, a man is going to receive ratings that are, on average, 0.4 points higher than a woman. This is frustrating, perhaps more so given that we certainly are not the first study to look at the ways that student evaluations are biased against female professors. But we might be among the first to make the case explicitly that the use of student evaluations in hiring, promotion, and tenure decisions represents a discrimination issue. The Equal Employment Opportunity Commission exists to enforce the laws that make it illegal to discriminate against a job applicant or employee based on sex. If the criteria for hiring and promoting faculty members is based on a metric that is inherently biased against women, is it not a form of discrimination? It’s not just women who are suffering, either. My newest work looks at the relationship between race, gender, and evaluation scores (initial findings show that the only predictor of evaluations is whether a faculty member is a minority and/or a woman), and other work has looked at the relationship between those who have accented English and interpersonal evaluation scores. Repeated studies are demonstrating that evaluation scores are biased in favor of white, cisgender, American-born men. This is not to say we should never evaluate teachers. Certainly, we can explore alternate methods of evaluating teaching effectiveness. We could use peer evaluations (though they might be subject to the same bias against women), self-evaluation, portfolios, or even simply weigh the evaluation scores given to women by 0.4 points, if that is found to be the average difference between men and women across disciplines and institutions. But until we’ve found a way to measure teaching effectiveness that isn’t biased against women, we simply cannot use teaching evaluations in any employment decisions in higher education.

Masculinities in Twentieth Century Britain

Ben Mechen's picture Announcement published by Ben Mechen on Thursday, January 11, 2018 Type: Workshop Date: February 4, 2018 Location: United Kingdom Subject Fields: British History / Studies, Cultural History / Studies, Sexuality Studies, Social History / Studies, Women's & Gender History / Studies One-day workshop, Friday 1 June 2018 University of Birmingham This workshop aims to provide a forum for the first systematic reflection on histories of masculinity in modern Britain since the publication, nearly thirty years ago, of Michael Roper and John Tosh’s landmark collection, Manful Assertions (Routledge, 1991). We invite expressions of interest from scholars working on questions of masculinity in any field and any discipline. Our aim is to use this workshop as a starting point for a new collection of essays to be published by Manchester University Press (subject to review). In the period since Manful Assertions was published the history of masculinity has continued to grow as a field. Scholars working in this area have made significant contributions to our appreciation of gender as a necessary and productive category of analysis in the study of the British past. In so doing, they have broken new ground in both isolating the time-and place-specific nature of ideas and experiences of masculinity, and demonstrating how interrogating the dynamics of gender and power can transform our understanding of state and society, politics and culture, economy and environment in modern Britain.* Yet there has been little attempt to take stock and consider the implications of both changing forms of historical knowledge and our present social and political conjuncture for key categories, chronologies, and debates in the history of masculinity. Despite the development of new areas of inquiry and methodologies in the study of the historical formation of masculinities (often associated with histories of the emotions and/or sexualities, and the new cultural history), established frameworks remain intact. These include, most notably, ideas around “domestication” and the private sphere, a focus on the transformative flashpoints of war, and the tired, if culturally pervasive, trope of “masculinity in crisis”. A handful of edited collections have drawn together contributors to reflect on particular themes — notably around masculinity in relation to religion, empire, or war. As yet, however, there has been no explicit consideration of the practice, preoccupations, and politics of histories of masculinity in modern Britain in toto. Three decades on from Manful Assertions, and with the guiding questions, theoretical foundations and archival resources of research in modern British history having undergone significant transformation, this is an important intellectual moment at which to consider the state of the field.** It is also an important political moment at which to think through the practice and politics of writing histories of masculinity. Initial work in this area built on the interventions of women’s history and gender history, as well as the political commitments of feminism and the pro-feminist men’s movement, and responded to the growing cultural purchase in the 1980s of the “new man” and associated models of behaviour and identity. It was an historical project that addressed itself directly to the circumstances, conditions and questions of its own conjuncture. But it was also one that implicitly, perhaps, organised itself around a linear or progressive narrative of change over time: the slow undoing of patriarchy and the fragmentation of a dominant code of masculinity. Our choice of the plural “masculinities” in the workshop’s title, to denote the existence of various codes and expressions of masculinity across time and place, reflects a key outcome of the first phase of research in the field. But the Weinstein scandal and #MeToo campaign, the masculinist rhetoric and posturing of the Alt-Right and pro-Brexit movements, and the endurance of sexism within and beyond the university all indicate that white, hetero-patriarchy has in fact, over the last thirty years, become a more rather than less pervasive and insistent force in public life. This is evident in popular culture and old and new media, but also in patterns of violence in everyday behaviour and language. A history of masculinity written from the vantage point of the present must therefore take patriarchy’s renewal as both a challenge to the politics of its intervention and as the central problematic of its investigation. In doing so, it must also reassert the power of history, and especially women’s, feminist, queer and imperial history, to question and unsettle and denaturalize forms of hegemony and hierarchy in contemporary public life. With these intellectual and political starting points in mind, we seek contributions that address specific problems, processes and episodes in the modern history of masculinity but at the same time think through the analytic categories and concepts around which our work is structured, and that establish conversations between different fields and approaches. In this context, two questions animate this project: how should we write histories of British masculinity, and why write these histories now? Themes for consideration include, but are not limited to: Scales and spaces around which ideas and experiences of masculinity take shape. These include, but are not limited to: local, regional, national, imperial and global; private and public; individuals, families, friendships, partnerships; age, generation, life-cycle; states, institutions, markets, communities, associations. Identity and difference as categories to understand the historical formation of masculinities. Keywords might include intersectionality and relationality as historical problems and ethical imperatives; masculinity and vectors of gender, class, “race” and ethnicity, religion, sexuality, place, “ability”; masculinity and whiteness; histories of queer and/or trans men; masculinity in the age of non-binarism. Frameworks and narratives, old and new, for understanding shifting patterns of masculinity in relation to the wider formation of British modernities and historiographical knowledge. What do we do with analytic categories like patriarchy and power; “the domestication of the male” and “the flight from commitment”; “Oxbridge men” and “temperate heroes”; the “crises” of masculinity, the “New Man”, “fragile” and “toxic” masculinities; long and short twentieth centuries; war, interwar, postwar; masculinities and emergent narratives of decolonization, decline/declinism, neoliberalization, secularization, “revolt on the right”, emotional revolution, Anthropocene? Masculinity in politics and the politics of masculinity: language and rhetoric; political and economic power; masculinity after feminism; radicalisms of left and right; masculinity as crisis. Sources of the self and the ways in which masculinity is lived and felt. Key motifs might include the tension between cultural norms and individual subjectivities, representation and experience; constituting masculinity through or against work, leisure, markets, media, the state, private life, bodies; hegemonic assertions and points of refusal; style and performance; unity and fragmentation; emotional economies; self and other. The history of masculinity as a project that has ethical and political stakes; commitments and energies; unsettling versus reifying; necessity versus distraction; masculinities at work and in the discipline; researching and teaching; public engagement; masculinity and academic capital: experiences of benefit and harm, strategies of resistance and devaluation. Our aim is to use this call for papers as a prompt — a starting point for an edited collection based on real collaboration and discussion that, we believe, can best meet the complexity and urgency of these questions and issues. We would therefore like potential contributors to present their ideas for draft chapters at a one-day workshop at the University of Birmingham on 1st June 2018. If this something you’d like to be involved in, please send a paper proposal (c.300 words) along with a short biography to us on the email addresses below by 4th February 2018. We especially urge contributions from those working on intersections of masculinity and “race” or ethnicity, regional and non-metropolitan masculinities, and transmasculinities. We also warmly encourage submissions from postgraduate and early-career researchers and are seeking funding that will allow us to reimburse PGR/ECR travel to/from the event. *Recent interventions include Roper, Michael, ‘Between Manliness and Masculinity: The “War Generation” and the Psychology of Fear in Britain, 1914–1950’, Journal of British Studies, 44:2, 2005, 343-362; Smith, Helen, Masculinity, Class and Same-Sex Desire in Industrial England, 1895-1957, (London: Palgrave, 2015); Delap, Lucy and Sue Morgan (eds) Men, Masculinities and Religious Change in Twentieth Century Britain, (Palgrave, 2013); Griffin, Ben, The Politics of Gender in Victorian Britain: Masculinity, Political Culture and the Struggle for Women’s Rights, (Cambridge University Press, 2012); Fletcher, Christopher, Sean Brady, Rachel Moss and Lucy Riall (eds), The Palgrave Handbook of Masculinity and Political Culture in Europe, (Palgrave, 2017). **For a recent reflection on the state of the field see Tosh, John, ‘The History of Masculinity: An Outdated Concept?’, in Arnold, John H. and Sean Brady (eds), What is Masculinity? Historical Dynamics from Antiquity to the Contemporary World, (Palgrave, 2011). See also Harvey, Karen and Alex Shephard, ‘What Have Historians Done with Masculinity? Reflections on Five Centuries of British History, circa 1500-1950’, Journal of British Studies, 44:2, 2005, 274-280. Contact Info: Ben Mechen, Teaching Fellow in Modern British and European History, University College London Katie Jones, doctoral researcher, University of Birmingham Matt Houlbrook, Professor of Cultural History, University of Birmingham Contact Email: b.mechen@ucl.ac.uk URL: https://c20masculinities.wordpress.com/

Futures of Feminist Science Studies, Special Issue

Announcement published by Daniel Rivers on Friday, January 26, 2018 Type: Call for Papers Date: March 20, 2018 Location: United States Subject Fields: American History / Studies, Cultural History / Studies, Ethnic History / Studies, History of Science, Medicine, and Technology, Women's & Gender History / Studies Women's Studies: an interdisciplinary journal invites submissions that work at the intersections of science studies, feminism, and cultural studies. We are especially interested in work that explores the possibilities that emerge from feminist science studies, both as a critique science’s “culture of no culture” and as a pedagogical intervention relevant to the training of Women’s, Gender, and Sexuality Studies students. Submissions for this issue should fall into one of two broad categories: "Gender, Science, and the Practice of Culture" and "Feminist Science Studies in the University Classroom." General topics of interest for the first category include: DIY and citizen science; toxicity and feminized labor; fat studies and the medical gaze; globalization and/or indigenous science; feminism and evolutionary psychology; reproductive justice; queer ecology; ecofeminism and the Anthropocene; WISE; Girls Who Code; and feminism and science writing. Editorial review will prioritize submissions that analyze the production and application of scientific knowledge at the intersections of gender, race, class, ability, and difference. We are also interested in pedagogy and praxis pieces that attend to the goals, opportunities, and challenges of integrating feminist science studies into the gender and sexuality studies classroom—especially as they relate to student engagement with environmental justice, citizen science, and the medicalization of difference. Interested parties should submit a 400-600-word proposal and C.V. To drivers@fullerton.edu by March 20th, 2018. Proposals should outline the article’s projected page length and framework of inquiry, as well as any novel archives, methods or analytical approaches. Notifications will be distributed by April 15 with articles due for review by June 30. Contact Email: drivers@fullerton.edu URL: http://www.tandfonline.com/toc/gwst20/current

Signs Call for Papers: Public Feminisms

Andrew Mazzaschi's picture Announcement published by Andrew Mazzaschi on Friday, March 2, 2018 Type: Call for Papers Date: September 15, 2018 Subject Fields: Women's & Gender History / Studies, Political History / Studies, Political Science, Literature, Sociology Even as antifeminist and right-wing forces have gained footholds worldwide, feminists have forcefully asserted themselves in the public sphere as key voices of resistance. From the Women’s Marches around the world that took place the day after Donald Trump was inaugurated, to the 2012 protests in Delhi, to a new resurgence of writers proudly adopting the moniker, feminists have organized to claim public space and a public voice. It is no overstatement to claim that “the resistance” is being led by women, with intersectional feminism at its core. Meanwhile, a shifting media landscape has enabled contradictory dynamics: feminists—through innovative uses of social media and online media outlets, as well as mainstream media—have found (and created) platforms to amplify their public voices, yet the pool of public intellectuals and the punditry continues to be largely dominated by white men. This special issue seeks to address these dynamics through a multifaceted and interdisciplinary discussion of “Public Feminisms.” Signs has sought—through the creation of the Feminist Public Intellectuals Project—to actively advocate for feminist voices in both the scholarly and the public sphere, building a critical mass of public intellectuals who speak with a feminist voice to audiences outside of academia. These multipronged efforts have engaged feminist theorizing and historicizing with the pressing political and social problems across the globe. This special issue seeks to further extend the discourse of public feminisms. Possible areas of focus might include: How have new forms of media enabled new public forms of feminism (or antifeminism)? How does changing media create new risks for feminist discourse or feminist individuals? How are feminist publics and public feminisms represented in literature, film, television, theater, dance, or other cultural forms today and in prior moments of resistance? How can these forms of expression be put to feminist use? How has feminism either challenged or contributed to the concept of publicness itself? What historical models of publicness has feminism adopted or transformed? How has claiming public space related to claiming discursive space, or vice versa? How have feminisms conjured new publics or counterpublics? How do race, nation, religion, class, sexuality, and caste structure where and which feminisms tend to become public? How have feminists across time challenged these dynamics? How do nonfeminist forces shape what circulates in the name of feminism, and how can feminists combat it? What can comparisons among different historical eras, geographical areas, or political climates tell us about the conditions under which public feminisms can emerge? To what extent are new languages necessary to shifting public discourses about feminism? How are new conceptual languages or vocabularies adopted as part of public discourse? Signs particularly encourages transdisciplinary and transnational essays that address substantive feminist questions, debates, and controversies without employing disciplinary or academic jargon. We welcome essays that make a forceful case for why public feminism demands a specific and thoughtfully formulated interdisciplinary feminist analysis and why it demands our attention now. We seek essays that are passionate, strongly argued, and willing to take risks. The deadline for submissions is September 15, 2018. Please submit full manuscripts electronically through Signs’ Editorial Manager system at http://signs.edmgr.com. Manuscripts must conform to the guidelines for submission available at http://www.journals.uchicago.edu/journals/signs/instruct. Contact Info: Andrew Mazzaschi, PhD Deputy Editor Signs: Journal of Women in Culture and Society Northeastern University 360 Huntington Ave. 261 Holmes Hall Boston, MA 02115 Contact Email: signs@northeastern.edu URL: http://signsjournal.org/for-authors/calls-for-papers/#public

Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of Odisha, India

Parasite. 2018; 25: 10. Published online 2018 Mar 12. doi: 10.1051/parasite/2018008 PMCID: PMC5847338 Language: English | French Sujogya Kumar Panda1,2,* and Walter Luyten2 Author information ► Article notes ► Copyright and License information ► Go to: Abstract The purpose of this review is to survey the antiparasitic plants of the Asteraceae family and their applicability in the treatment of parasites. This review is divided into three major parts: (a) literature on traditional uses of Asteraceae plants for the treatment of parasites; (b) description of the major classes of chemical compounds from Asteraceae and their antiparasitic effects; and (c) antiparasitic activity with special reference to flavonoids and terpenoids. This review provides detailed information on the reported Asteraceae plant extracts found throughout the world and on isolated secondary metabolites that can inhibit protozoan parasites such as Plasmodium, Trypanosoma, Leishmania, and intestinal worms. Additionally, special attention is given to the Asteraceae plants of Odisha, used by the tribes of the area as antiparasitics. These plants are compared to the same plants used traditionally in other regions. Finally, we provide information on which plants identified in Odisha, India and related compounds show promise for the development of new drugs against parasitic diseases. For most of the plants discussed in this review, the active compounds still need to be isolated and tested further. Keywords: Asteraceae, Plasmodium, Trypanosoma, Leishmania, Odisha (India), antiparasitic drugs Go to: Introduction − Antiparasitic research Parasite diseases are a major source of disease in both humans and animals and result in significant economic losses. Protozoan parasites threaten the lives of billions of people worldwide and are associated with significant morbidity and large economic impacts [88]. The lack of proper vaccines and the emergence of drug resistance make the search for new drugs for treatment and prophylaxis more urgent, including from alternative sources like plants. In 2005, Pink et al. published a review emphasizing that new antiparasitic drugs are urgently needed to treat and control diseases such as malaria, leishmaniasis, sleeping sickness and filariasis [124]. The discovery of quinine from Cinchona succirubra (Rubiaceae) and its subsequent development as an antimalarial drug represent a milestone in the history of antiparasitic drugs from nature. The 2015 Nobel Prize in Physiology or Medicine was awarded for the discovery of artemisinin and avermectin, which fundamentally changed the treatment of parasitic diseases around the globe. Both compounds are natural products, once again showing that nature can be a powerful source of medicines. A breakthrough for the development of antimalarial drugs was the identification of the sesquiterpene artemisinin from Artemisia annua (Asteraceae), which can even kill multidrug-resistant strains of Plasmodium falciparum [3,62]. Several semisynthetic derivatives of artemisinin (e.g., the water-soluble artesunate) have been developed and are used in clinical practice today [62]. There are three major protozoan parasitic infections, caused by Plasmodium, Leishmania and Trypanosoma species. Plasmodium is the most significant of the protozoan parasites that infect humans. Found in tropical and sub-tropical regions of the world, malaria parasites threaten the lives of 3.3 billion people and cause 0.6–1.1 million deaths annually [70]. Six species of Plasmodium are responsible for causing malaria in humans [144], with Plasmodium falciparum and Plasmodium vivax being the most common and major causes. Leishmaniasis is caused by Leishmania sp., generating 1–1.5 million new cases annually [104]. The disease is endemic in 98 countries and is one of the neglected tropical diseases where the majority of the affected individuals are rural, underprivileged, and economically disadvantaged. African sleeping sickness (trypanosomiasis), is caused by two parasitic protozoans: Trypanosoma brucei gambiense (West Africa) and Trypanosoma brucei rhodesiense (East Africa) [15]. African trypanosomiasis threatens the lives of approximately 60 million people in sub-Saharan Africa and is fatal if untreated [70]. Another species of Trypanosoma (T. cruzi) is responsible for Chagas disease (American trypanosomiasis), and threatens the lives of millions primarily in Mexico, Latin America and the United States. The World Health Organization estimates that 8–10 million people are infected annually. There is also no vaccine for Chagas disease and no clinical trials of new drugs are under way; current treatment depends on only two chemotherapeutics − benznidazole and nifurtimox. Go to: Medicinal uses of Asteraceae with special reference to the tribes of Odisha (Orissa), India The family Asteraceae (Compositae) is also known as the daisy family, sunflower family or thistle family. Asteraceae is derived from the term “aster” meaning “star” in Latin, and refers to the characteristic inflorescence with flower heads composed of florets (small flowers), and surrounded by bracts [12]. The family Asteraceae is one of the largest families comprising 1600–1700 genera and 24,000–30,000 species [30]. The family has 12 subfamilies and 43 tribes, and is distributed worldwide [16], but is most abundant in the temperate and warm-temperate regions. Most of the species are herbs and shrubs, while trees are fewer in number. Asteraceae have been commonly used in the treatment of various diseases since ancient times, as attested by classical literature. For this review, we collected literature from scientific journals, books, theses and reports via a library and electronic search (using databases viz. PubMed, Google Scholar and Scopus). Several researchers have systematically investigated Asteraceae for their therapeutic utility. More than 7000 compounds have already been isolated, and 5000 have been identified from this family, often associated with some bioactivity [3]. Members of the Asteraceae are claimed to have various properties: antipyretic, anti-inflammatory, detoxifying, antibacterial, wound-healing, antihemorrhagic, antalgic (also for headaches), anti-spasmodic, and anti-tussive, and have been considered beneficial for flatulence, dyspepsia, dysentery, lumbago, leucorrhoea, hemorrhoids, hypotension, and most importantly, some are hepatoprotective, antitumor and antiparasitic [68]. The majority of studies on Asteraceae throughout the world have focused on chemical analysis (nearly 7000 compounds already isolated). There are many papers on in vitro studies, especially on antimicrobial, antioxidant and anticarcinogenic properties, using selected cells and crude extracts or purified compounds. In the few published reviews on pure compounds, the structure-activity relations were studied as well as their mechanism of action. Despite the discovery of a large number of compounds in Asteraceae around the world, and the reported antiparasitic properties of members of the Asteraceae family, not many bioactivity studies on Asteraceae species have yet been carried out. In India, the family is represented by 900 species from 167 genera. Due to their bioactive properties, plants from the Asteraceae family are commonly used in the traditional treatment of various diseases (Table 1). For instance, Ageratum conyzoides has been commonly used in India including in the state of Odisha, where the plant is traditionally used for diarrhoea, dysentery, intestinal colic [118] and malaria. This plant is well-known for the presence of phytochemicals such as alkaloids, coumarins, flavonoids, benzofurans, sterols and terpenoids, with the following identified compounds: friedelin, various sterols (including β-sitosterol and stigmasterol), various flavonoids, caryophyllene, coumarin, quercetin, as well as fumaric and caffeic acid [51]. Bidens pilosa is also found in Odisha, and is moreover widely used as folk medicine by indigenous tribes of the Amazon in the treatment of malaria [13]. About 201 compounds comprising 70 aliphatics, 60 flavonoids, 25 terpenoids, 19 phenylpropanoids, 13 aromatics, 8 porphyrins, and 6 other compounds, have been identified from this plant, as compiled previously [67]. However, the relation between Bidens pilosa phytochemicals and various bioactivities is not yet fully established, and should become a future research focus [7]. Blumea lacera is used for the treatment of all kinds of fever, including malaria, and contains phytocompounds such as fenchone, coniferyl alcohol derivatives, campesterol, flavonoids, lupeol, hentriacontane, hentriacontane, α-amyrin, β-sitosterol and triterpenes [7,80,105]. Calendula officinalis has found many medicinal applications and contains various terpenoids (sitosterols, stigmasterols, erythrodiol, brein, ursadiol and its derivatives; several triterpene glycosides like calendulaglycoside A; glucosides of oleanolic acid, etc.), various flavonoids (quercetin, isoquercetin, isorhamnetin-3-O-β-D-glycoside, narcissin, calendoflaside, calendoflavoside, calendoflavobioside, rutin, quercetin-3-O-glucoside and quercetin-3-O-rutinoside), coumarins, saponins and quinones [87]. Table 1 Table 1 Traditional uses of plants of the Asteraceae family Whole plant extracts of Caesulia axillaris are frequently used by the coastal tribes of Odisha to cure malaria [107,113], but no scientific studies have yet been published on this plant. Centipeda minima is widely distributed in Odisha, and is frequently used by the local tribes for the treatment of parasites [112], but no compounds responsible for its antiparasitic activities have yet been identified. Eclipta prostrata (synonym E. alba) is frequently used by the tribes for the treatment of malaria [113,130]. The plant is well studied for its phytochemistry, with documented presence of compounds such as eclipline, β-amyrin, luteolin-7-O-glucoside, apigenin, cinnaroside, stigmasterol, wedelolactone, columbin, triterpene glycosides and triterpenic acid [47]. Like Eclipta prostrata, Elephantopus scaber is also frequently used by the tribes for the treatment of malaria [118]. This plant is also well studied for its phytochemistry with documented presence of sesquiterpenelactones such as elescaberin, deoxyelephantopin, isodeoxyelephantopin, scabertopin, and isoscabertopin, and lipids like ethyl hexadecanoate, ethyl-9, 12-octadecadienoate, ethyl-(Z)-9-octadecenoate, ethyl octadecanoate, lupeol and stigmasterol [19]. Whole plant paste of Sphaeranthus indicus with a pinch of salt is taken as an anthelmintic by the tribes of Odisha [111]. The phytochemical studies of this plant suggest the presence of eudesmanolides, sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone glycosides, flavonoid C-glycosides, isoflavone glycosides, sterols, sterol glycosides, alkaloids, peptide alkaloids, amino acids and sugars [125]. The essential oil from this plant has been well studied with the documented presence of bioactive compounds like sphaeranthine, sphaeranthol, spharerne, methyl chavicol, ocimene, geraniol, and methoxy frullanolides [71]. Tagetes erecta is an ornamental plant of Odisha and is often used by the tribes for the treatment of various conditions such as anaemia, irregular menstruation, abdominal pain, colic, cough and dysentery. Like Sphaeranthus indicus, this plant is also well known for its phytoconstituents such as β-sitosterol, β-daucosterol, 7-hydroxy sitosterol, lupeol, erythrodiol, erythrodiol-3-palmitate, quercetagetin, quercetagetin-7-methyl ether, quercetagetin-7-O-glucoside, gallic acid, syringic acid, quercetin, ocimene and tagetone [135]. Tridax procumbens has been extensively used in Ayurvedic medicine and is well-studied for its phytochemistry, with the presence of compounds like 8,3′-dihydroxy-3,7,4′-trimethoxy-6-O-β-D glucopyranoside flavonol, apigenin-7-O-β-D-glucoside, pentadecane, β-sitosterol, stigmasterol, β-daucesosterol and bis-(2-ethylhexyl)-phthalate [131]. Several species of Vernonia have been used in different traditional medicines all over the world. The tribes of Odisha most frequently use different species of Vernonia: V. anthelmintica, V. albicans and V. cinerea. Seeds of Vernonia anthelmintica are used as an anthelmintic, especially in children: 2-5 g with water on an empty stomach twice a day for three days [111,112]. Fruit powder is used in malaria fever, and stomach ache during amoebic dysentery [81]. Powdered Vernonia albicans plant (10-20 g) is advised to be consumed with 125 mL milk (mixed with 5-7 cardamom fruits and 10 g sugar candy) once in the morning, on an empty stomach for about three months for the treatment of filariasis [37]. The aqueous extract of the whole plant is also used in the treatment of malaria [53]. Root paste of Vernonia cinerea mixed with honey is administered orally twice a day for three days for malaria [108]. Reports are also available on the use of this plant for the treatment of elephantiasis [108]. Toyang and Verpoorte [152] published a review article on this genus Vernonia (109 species) concerning its ethnopharmacology and phytochemistry. Xanthium strumarium is a weed, widely distributed in Odisha, and commonly used as a medicinal plant. Most of its pharmacological effects can be explained by constituents like sesquiterpene lactones, glycosides, phenols, as well as polysterols present in all plant parts. The bioactive compounds reported for this plants are xanthinin, xanthumin, xanthatin (deacetylxanthinin), a toxic principle, namely a sulphated glycoside: xanthostrumarin, atractyloside, carboxyatractyloside, phytosterols, xanthanol, isoxanthanol, xanthinosin, 4-oxo-bedfordia acid, hydroquinone, xanthanolides, caffeoylquinic acids, α- and γ-tocopherol, thiazinedione and deacetyl xanthumin, β-sitosterol, γ-sitosterol, β-D-glucoside of β-sitosterol; isohexacosane, chlorobutanol, stearyl alcohol, stromasterol and oleic acid [52]. Go to: Miscellaneous antiparasitic properties of Asteraceae and their phytochemistry Over the past decades, a lot of research on antiparasitic drugs of plant origin has yielded undisputable metabolites of interest. Many plant-derived secondary metabolites of Asteraceae have exhibited target-specific activity against Plasmodium, Leishmania and Trypanosoma parasites (Table 2). Plants from the Asteraceae family are widely used as medicines due to the presence of a broad range of bioactive metabolites such as alkaloids (pyrrolizidine and pyridine), flavonoids, phenolic acids, coumarins, terpenoids (monoterpenes, sesquiterpenes, diterpenes, and triterpenes), quinoline and diterpenoid types, triterpenoid sesquiterpene lactones, pyrethrins, and saponins. Several sesquiterpenes have been reported as antiprotozoal since the discovery of artemisinin. The sesquiterpene lactone parthenin is effective against Plasmodium falciparum in vitro, with an EC50 value of 1.29 µg/mL [123]. Parthenin is capable of blocking parasite-specific targets responsible for glutathinonylspermidine and trypanothione synthesis from cysteine and glutathione precursors in both Leishmania and Trypanosoma [32]. The sesquiterpene lactones brevilin A from Centipeda minima and dehydrozaluzanin C from Munnozia maronii were discovered and reported as antiparasitic. Similarly, sesquiterpene lactones from Neuroleaena lobata are well established for the treatment of Plasmodium infections [28]. In this plant, structure-activity relationship analysis revealed that germanocrenolide sesquiterpenes, like neurolenin A (EC50 = 0.92 µM) and B (EC50 = 0.62 µM), were more potent than furanoheliangolides like lobatin A and B (EC50 = 15.62 µM and 16.51 µM), respectively, against Leishmania promastigotes and Trypanosoma epimastigotes [28]. Based on ethnozoological studies (wild chimpanzees were observed to chew young stems of Vernonia amygdalina), antiplasmodial sesquiterpenes vernodalin and vernolide, hydroxyverniladin have been isolated [60]. Oketch-Rabah et al. [101] observed that macrocyclic germancrane dilactone 16,17-dihydrobrachycalyxolide from Vernonia brachycalyx has both antileishmanial and antiplasmodial activity. Table 2 Table 2 Therapeutic uses of important plants of the Asteraceae family reported as an antiparasitic Phenols are widely distributed in Asteraceae, and some have the ability to inhibit parasites. Gallic acid and its derivatives inhibit the proliferation of Trypanosoma cruzi trypomastigotes in vitro [58]. Higher activities were observed for the gallic acid esters ethyl-gallate and n-propyl-gallate, which had EC50 values of 2.28 and 1.47 µg/mL, respectively, possibly due to increased lipophilicity. Oketch-Rabah et al. [101] reported the antiprotozoal activity from Vernonia brachycalyx (2́ -epicycloisobrachycoumarinone epoxide and its stereoisomer). Both stereoisomers show similar in vitro activities against chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains for Plasmodium falciparum, as well as Leishmania major promastigotes, with EC50 values of 0.11 µg/mL and 0.15 µg/mL for Plasmodium falciparum, and 37.1 µg/mL and 39.2 µg/mL for Leishmania major, respectively. Like phenols, flavonoids are extensively present in Asteraceae plants. Elford et al. [21] demonstrated that methoxylated flavonones artemetin and casticin act synergistically with artemisinin in vitro against Plasmodium falciparum. Later, exiguaflavanone A and B, isolated from Artemisia indica (Asteraceae), were shown to exhibit in vitro activity against Plasmodium falciparum. The flavonoids can be classified into several subtypes: flavone (1), flavonol (2), flavanone (3), dihydroflavonol (4), flavan-3-ol (5), flavan-3,4-diol (6), chalcone (a structure with one opened ring), aurone, and anthocyanidine (with a positive charge on oxygen O-1). Except for these basic structures, flavonoids also exist in biflavonoid and glycosidic form in the Asteraceae family. Perez-Victoria et al. [122] suggested that flavonoids could affect transport mechanisms in Leishmania. The C-terminal nucleotide-binding domain of a P-glycoprotein-like transporter, encoded by the ltrmdr1 gene in Leishmania tropica and involved in parasite multidrug resistance (MDR), was overexpressed in Escherichia coli as a hexahistidine-tagged protein and purified. The Leishmania tropica recombinant domain efficiently bound different classes of flavonoids with the following relative affinity: flavone>flavanone>isoflavone>glucorhamnosyl-flavone. The affinity was dependent on the presence of hydroxyl groups at positions C-5 and C-3, and was further increased by a hydrophobic 1,1-dimethylallyl substituent at position C-8. Brandio et al. [13] first reported the antimalarial activity of crude extracts and their fractions from different species of Bidens, and provided evidence that this is due to the presence of polyacetylene and flavonoids. Later, Kumari et al. [63] and Tobinaga et al. [151] isolated the polyacetylene compound (R)-1,2-dihydroxytrideca-3,5,7,9,11-pentayne from leaf extracts of B. pilosa, which showed promising antimalarial activity against Plasmodium falciparum (Table 3). Moreover, this compound was tested in an in vivo model (mice infected with Plasmodium berghei NK-65 strain), and results showed that the compound can decrease the average parasitaemia in red blood cells, but further studies addressing its mechanism are required. The genus Calendula is very well studied for its phytochemistry, with triterpene alcohols, triterpene saponins, flavonoids, carotenoids and polysaccharides as the major classes of phytoconstituents. Szakie et al. [145] isolated several oleanolic acid glycoside derivatives and tested them against Heligmosomoides polygyrus; the wormicidal activity of the oleanolic acid glycosides was superior to that of the aglycone, and the level of activity was dependent on the nature of the sugar side-chain at the C-3 position. The first sugar molecule of the glucuronides, i.e., the glucuronic acid attached to the aglycone, appeared to be vital for the antiparasitic properties of these compounds [145]. E. prostrata was studied by several scientists for its antiparasitic properties such as antimalarial [6], antileishmanial [56,138], and anthelmintic activities [11,50]. Khanna et al. [56] isolated dasyscyphin C from the leaves and proved its antileishmanial activities against Leishmania major, Leishmania aethiopica andLeishmania tropica (Table 3). A sesquiterpene lactone (deoxyelephantopin) was isolated by Zahari et al. [165] from E. scaber and proved active against Trypanosoma brucei rhodesience. Similarly, T. procumbens showed significant antileishmanial activity against promastigotes of Leishmania mexicana. The active principle was found to be an oxylipin, namely (3S)-16, 17- didehydrofalcarinol [76]. Table 3 Table 3 List of compounds from Asteraceae commonly reported for their antiparasitic properties. Go to: Antiparasitic activity of flavonoids and terpenoids documented in Asteraceae Flavonoids are the class of compound of highest occurrence, wide structural diversity, and chemical stability. They have been isolated on a large scale from Asteraceae species and can be used as taxonomic markers at lower hierarchical levels [75]. Flavones and flavonols are common throughout the Asteraceae, i.e., glycosides of apigenin, luteolin, kaempferol, quercetin, flavanone derivatives, (−)-epicatechin and (−)-epigallocatechin (Figure 1). Although there are fewer reports on antigiardial activity in Asteraceae, these compounds from other families are well-studied against G. lamblia. From the aerial parts of Helianthemum glomeratum (Cistaceae), kaempferol, quercetin, (−)-epicatechin and (−)-epigallocatechin have shown antigiardial activity against G. lamblia (in vitro), with IC50 values of 26.47, 8.73, 1.64 and 8.06 μg/mL, respectively [17]. Structure-activity correlation implies that the 2,3-double bond and 4-keto group of flavones might not be required for antiprotozoal activity since both (−)-epicatechin and (−)-epigallocatechin lack these structural units, yet maintain biological activity (Figure 1). Also, unlike flavones, the benzenediol moiety of (−)-epicatechin and (−) epigallocatechin is not coplanar with the heterocyclic part because C-2 of their flavan-3-ol structure is an sp3 carbon. In addition, there are several reports that glycosylated flavonoids also possess antigiardial activity. Also, a C-3 glycosylated flavone tiliroside [17,79], obtained from H. glomeratum, has been shown to possess antigiardial inhibitory activity with an IC50 value of 17.36 μg/mL. figure parasite-25-10-fig1 Figure 1 Common flavonoids of the Asteraceae family reported as antiparasitic compounds Recently, Klongsiriwet et al. [57] demonstrated that quercetin and luteolin are highly effective at 250 µM to reduce the in vitro exsheathment of Haemonchus contortus L3 larvae. Tasdemir et al. studied the antitrypanosomal and antileishmanial activities of flavonoids and their analogues in vitro and in vivo, as well as their (quantitative) structure-activity relationship [148]. They showed that fisetin, 3-hydroxyflavone, luteolin, and quercetin are the most potent antileishmanial compounds against Leishmania donovani, with IC50 of 0.6, 0.7, 0.8, and 1.0 µg/mL, respectively (Table 4). Moreover, these authors found moderate antitrypanosomal efficacy of these compounds against Trypanosoma brucei rhodesiense and Trypanosoma cruzi. The authors conclude that 7,8-dihydroxyflavone and quercetin appeared to ameliorate parasitic infections in mouse models, and are potent and effective antiprotozoal agents. Mead and McNair [78] also studied the antiparasitic activity of flavonoids and isoflavones against Cryptosporidium parvum and Encephalitozoon intestinalis. These authors also found that quercetin and apigenin had activity against Encephalitozoon intestinalis at EC50 of 15 and 50 mM, respectively, while low activity of luteolin and quercetin was found against Cryptosporidium parvum. No inhibition was observed with either rutin or epigallocatechin gallate against either parasite. Lehane and Saliba [66] investigated the effects of a range of common dietary flavonoids on the growth of two strains of the human malaria parasite Plasmodium falciparum and concluded that luteolin showed IC50 values of 11 ± 1 µM and 12 ± 1 µM for strains 3D7 and 7G8, respectively. Although luteolin was found to prevent the progression of parasite growth beyond the young trophozoite stage, it did not affect parasite susceptibility to the antimalarial drugs chloroquine or artemisinin. Nour et al., [98] found moderate antiparasitic activity of five methoxylated flavonoids viz. 5,6,7,8,5-pentamethoxy-3,4-methylenedioxyflavone (eupalestin), 5,6,7,5-tetramethoxy-3,4-methylenedioxyflavone; 5,6,7,8,3,4,5-heptamethoxy-flavone (5-methoxynobiletine), 5,6,7,3,4,5-hexamethoxy-flavone and 4-hydroxy-5,6,7,3,5-pentamethoxy-flavone (ageconyflavone) against several parasites: Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum (Table 4). Table 4 Table 4 Selected flavonoids and terpenoids (whose presence has been reported in plants of the Asteraceae family) with antiparasitic activity Terpenoids are the largest group of phytochemicals as they comprise more than 20,000 recognised molecules. Depending on the number of carbons, terpenoids are divided into classes, starting with sesquiterpenes and continuing with diterpenes, sterols, triterpenes and finally tetraterpenes. Several sesquiterpenes, sterols and triterpenes have been isolated from members of the Asteraceae family. The sesquiterpenes commonly found in leaf extracts from Asteraceae are divided into mono- and bicyclic. The most abundant sterols from Asteraceae are stigmasterol and sitosterol. Sequiterpenes isolated from Vernonia spp. have antiparasitic activity against Plasmodium falciparum. Four compounds such as vernodalin, vernodalol, vernolide, and hydroxyvernolide (Figure 2), all derived from the leaves of Vernonia amygdalina, have potent activity with IC50 values of 4, 4.2, 8.4 and 11.4 µg/mL, respectively [60]. Another compound: sesquiterpene dilactone (16,17-dihydrobrachycalyxolide), isolated from the leaves of V. brachycalyx, exhibited anti-plasmodial activity against different multidrug-resistant strains of Plasmodium falciparum (K39, 3D7, V1/S and Dd2) with IC50 values of 4.2, 13.7, 3.0, and 16 µg/mL, respectively [101]. Goffin et al. [38] isolated the sesquiterpene lactone: tagitinin C, from the ether extract of Tithonia diversifolia and demonstrated antiplasmodial activity against Plasmodium falciparum (IC50 of 0.75 µg/mL). Becker et al. [8] identified urospermal A-15-O-acetate and dehydrobrachylaenolide as the main active compound responsible for the antiplasmodial activity against Plasmodium falciparum 3D7 and W2 strains. Ganfon et al. [34] investigated the antiparasitic activities of Acanthospermum hispidum by isolating two sesquiterpene lactones (15-acetoxy-8 β-[(2-methylbutyryloxy)]-14-oxo-4,5-cis-acanthospermolide), and 9 α-acetoxy-15-hydroxy-8β-(2-methylbutyry-499 loxy)-14-oxo-4,5-transacanthospermolide), both of which exhibited in vitro antiplasmodial activity against a chloroquine-sensitive strain (3D7) with IC50 values of 2.9 and 2.23 µM, respectively (Table 4). figure parasite-25-10-fig2 Figure 2 Common terpenoids of the Asteraceae family reported as antiparasitic compounds Among the triterpenes, squalene and lupeol derivatives are the more common ones [67]. Oleanolic acid (3 β-hydroxyolean-12-en-28-oic acid) is a pentacyclic triterpenoid with widespread occurrence in Asteraceae and was found to have antimalarial and antileishmanial activity [89,162]. Recently, Yamamoto et al. [162] studied the activity of ursolic acid on Leishmania amazonensis (in vitro and in vivo). They found that ursolic acid eliminated Leishmania amazonensis promastigotes with an EC50 of 6.4 µg/mL, comparable with miltefosine, while oleanolic acid presented only a marginal effect on promastigote forms at 100 µg/mL. The possible mechanism by which promastigotes were eliminated by ursolic acid was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondrial activity. Also, the ursolic acid was not toxic for peritoneal macrophages from BALB/c mice, and it could eliminate intracellular amastigotes, associated with nitric oxide (NO) production. These authors conclude that ursolic acid can be considered an interesting candidate for future testing as a prototype drug for the treatment of cutaneous leishmaniasis. Enwerem et al. [22] examined the anthelmintic activity of betulinic acid on C. elegans and confirmed its strong anthelmintic activity at 100 µg/mL, comparable to piperazine. Bringmann et al. [14] observed that betulinic acid exhibited moderate to good in vitro antimalarial activity against asexual erythrocytic stages of Plasmodium falciparum. Later, Steele et al. [141] concluded that betulinic acid can inhibit Plasmodium falciparum (in vitro), while in vivo experiments failed to reduce parasitaemia (up to 500 mg/mL in a murine malaria model- mice infected with P. berghei) and exhibited some toxicity. However, Ndjakou Lenta et al. [91] isolated betulinic acid, studied its in vitro activity against the Plasmodium falciparum W2 strain, and found it to be very potent with an IC50 of 2.33 µg/mL. Nweze et al. [99] observed that β-sitosterol has modest anti-trypanosomal activity against Trypanosoma brucei S427 (in vitro IC50 12.5 µg/mL). Go to: Discussion In a review on nature-derived drugs, Zhu et al. [166] analysed “the ranking of drug-productive plant families based on the ratio of the approved drugs to reported bioactive natural products (including leads of the approved and clinical trials drugs)” and concluded that there are a few top-ranked plant families that produce high numbers of approved drugs among plant-derived medicines. According to Zhu et al. [166], Asteraceae is the fourth-largest drug-productive family that has yielded many approved drugs, including antiparasitic, anticancer, antiglaucoma, ant-inflammatory, antihepatotoxic, antiviral and choleretic agents. From 7229 Asteraceae species, 25 clinical drugs (17 approved and 8 in clinical trials) were documented among 1016 searchable drugs [91,99]. There are many FDA-approved nature-derived drugs that originate from Asteraceae as antiparasitics: arteether, artemether, artemisinin, artesunate, coarsucam, co-artemether, dihydroartemisinin and santonin (all from Artemisia species). Also, there are a few drugs still in clinical trials as antiparasitics, such as artemisone, arterolane and artelinic acid [92]. Traditional knowledge has proven a useful tool in the search for new plant-based medicines [18]. It has been estimated that the number of traditionally used plant species worldwide is between 10,000 and 53,000 [77]. In India alone, there are about 25,000 plant-based formulations used in folk and traditional medicine [126]. However, only a small proportion have been screened for biological activity [42,140]. Also, there are many specific regions that are less studied than others (only 1% of tropical floras have been investigated) [42]. Odisha’s unique location in Peninsular India has blessed it with an interesting assemblage of floral and faunal diversity (http://odishasbb.nic.in/index.php?lang=en). The state is on the eastern seaboard of India, located between 17° 49’ and 22° 36’ N latitudes and between 81° 36’ and 8°7 18’ E longitudes. It covers an area of 1,55,707 sq km and is broadly divided into four geographical regions, i.e. the Northern Plateau (Chhotanagpur), Central River Basins, Eastern Hills and Coastal Plains. The confluence of two major biogeographic provinces of India: the Eastern Ghats (South-West) and Chhotanagpur Plateau (North), make Odisha a rich biodiversity repository with two internationally well-recognised areas: the Similipal Biosphere Reserve and the Chilika Lagoon. The state has a biodiversity board (it is a statutory body established under the Biological Diversity Act of 2002), with a network of 19 wildlife sanctuaries, one national park, one proposed national park, one biosphere reserve, two tiger reserves and three elephant reserves (http://odishasbb.nic.in/index.php?lang=en). Throughout the state, one finds varied and widespread forests harbouring different types of vegetation such as semi-evergreen forests, tropical moist deciduous forests, tropical dry-deciduous forests and littoral and tidal swamp forests, as well as mangroves with unique, endemic, rare and endangered floral and faunal species. The climate of Odisha is characterised by tropical monsoon weather as its coast borders the Bay of Bengal. The weather is classified as summer, monsoon and winter. Searing hot summers with considerably high monsoon downpours and cool, pleasant winters mark the Odisha climate. The average rainfall varies from 1200 mm to 1700 mm across the state, and is the main source of water. Moreover, the state is vulnerable to multiple disasters such as tropical cyclones, storm surges and tsunamis due to its sub-tropical littoral location (http://nidm.gov.in/default.asp). About 62 ethnic tribal communities have been reported in Odisha, of which 13 are known as "Particularly Vulnerable Tribal Groups" (https://en.wikipedia.org/wiki/List_of_Scheduled_Tribes_in_Odisha). Districts such as Kandhamala, Koraput, Malkanigiri, Mayurbhanj, Nabrangpur, Rayagada and Sundargarh have scheduled tribes (officially designated groups of historically disadvantaged people in India) above 50% of the total population. The social, cultural and religious life of aboriginal people is influenced by nature and natural resources available in and around their habitat, which provides their food, medicine, shelter, and various other materials and cultural needs [109,110]. Sasil-Lagoudakis et al. [133] published a review entitled “phylogenies reveal the predictive power of traditional medicine in bioprospecting”. Their study, which includes the Asteraceae family, provides unique large-scale evidence that plant bioactivity underlies traditional medicine. According to these authors, “related plants are traditionally used as medicines in different regions, and these plant groups coincide with groups that are used to produce pharmaceutical drugs”. The authors conclude that “phylogenetic cross-cultural comparisons can focus screening efforts on a subset of traditionally used plants that are richer in bioactive compounds, and could revitalise the use of traditional knowledge in bioprospecting”. Gertrude et al. [36] studied the anthelmintic activity of Bidens pilosa leaf against Haemonchus contortus eggs and larvae and concluded that ethanolic extracts have the potential to inhibit the growth of Haemonchus contortus. However, further study on the isolation of the active compounds as well as in vivo studies are needed. Similarly, antileishmanial activity of Bidens pilosa leaf was reported by several researchers [31,85], but no compound responsible for this activity has been identified so far. The anthelmintic and wormicidal properties of Blumea lacera leaf were evaluated against Ascaris lumbricoides and Pheretima posthuma [119], but no bioactive compounds have been acknowledged so far. Calendula officinalis has been used traditionally by the tribes of Odisha for worm infections. Nikmehr et al. [95] found that crude methanolic extracts have antileishmanial activity, but no bioactive molecules have been isolated so far. Caesulia axillaris, a wetland plant, is used very frequently for the treatment of malaria by the coastal peoples of Odisha. However, despite its long traditional use, its scientific validation as an antiparasitic agent has not been established so far. Also, the phytochemistry of this plant is not well known, except for a few studies on its essential oils. Similarly, plants such as Centipeda minima, Sphaeranthus indicus and Tagetes erecta are used as anthelmintic plants by the tribes of Odisha for the treatment of worm infections. Yu et al. [164] found antiparasitic activity of crude extracts of Centipeda minima and its fractions against Giardia intestinalis, Entamoeba histolytica and Plasmodium falciparum. Crude extracts of Sphaeranthus indicus also showed antiparasitic effects on Ascaridia galli, Entamoeba histolytica and Setaria digitate [96,134]. Organic and aqueous extracts of Tagetes erecta show antiparasitic [41], and anthelmintic properties [106]. However, notwithstanding phytochemical studies, no anti-parasitic compounds have been identified, nor have any in vivo studies been conducted so far on these plants. The plant Elephantopus scaber showed anthelmintic activity against Pheretima posthuma in crude extract. However, further study is required to find out the active anthelmintic compounds. Both in vitro and in vivo studies were carried out and proved the anthelmintic properties of Vernonia anthelmintica against Haemonchus contortus [103,106,140]. Further study is needed to determine the active anthelmintic compounds. The tribes of Odisha frequently use two other species of Vernonia: V. albicans and V. cinerea. These plants are also interesting for future study to discover active molecules with antiparasitic properties. The antitrypanosomal activity of a crude 50% ethanol extract of Xanthium strumarium leaves was studied in vitro and in vivo. The extract exhibited trypanocidal activity against Trypanosoma evansi-infected mice [147]. The authors hypothesised that the presence of xanthinin may be responsible for its trypanocidal activity, but further study is needed to definitively identify the antitrypanosomal compound or compounds. Go to: Conclusion A search for new antiparasitic drugs has been under way over the past several decades. However, despite the abundant literature, more work is needed to yield potent, commercially available drugs based on natural products. Fortunately, academic drug discovery for neglected diseases has intensified (e.g. the Drugs for Neglected Disease Initiative http://www.dndi.org/), and this includes efforts to use natural products (e.g. Research Network Natural Products against Neglected Diseases https://www.facebook.com/ResNetNPND/app/435433039823956). Although many Asteraceae species were already studied for different antiparasitic activities, some of the species important in traditional medicines have still hardly been studied for their bioactivity. Therefore, the present review aims to encourage further exploration of their potential bioactivity and particularly their antiparasitic properties, guided by the knowledge on the use of Asteraceae plants by the tribes of Odisha and corresponding traditional uses elsewhere in the world. The work reported here highlights the traditional uses of Asteraceae plants of Odisha for the treatment of parasites. Plants such as Bidens pilosa, Blumea lacera, Caesulia axillaris, Centipeda minima and Sphaeranthus indicus deserve to be studied further, especially concerning their most relevant bioactive properties and significant bioactive compounds that could be purified with state-of-the-art methods. Go to: Conflict of interest The authors declare that they have no conflict of interest. Go to: Acknowledgment The authors are thankful to KU Leuven for providing the necessary facilities during preparation of this review article. This project received funding from the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 633589. This publication reflects only the authors’ views and the Commission is not responsible for any use that may be made of the information it contains. Go to: Notes Cite this article as: Panda SK, Luyten W. 2018. Antiparasitic activity in Asteraceae with special attention to ethnobotanical use by the tribes of Odisha, India. 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