Plantas medicinais e políticas públicas de saúde: novos olhares sobre antigas práticas / Medicinal plants and public health policies: new perspectives on old practices

Resumo As plantas medicinais são utilizadas nos cuidados a saúde desde a Antiguidade, mas apenas na década de 1970 a OMS se manifestou sobre sua importância para a saúde da população. Este artigo teve por objetivo identificar a sequência temporal e evolução dos marcos legais associados às políticas públicas de plantas medicinais, discutindo as implicações dessa evolução, bem como sua inserção no sistema de saúde, e apresentar essa evolução no Brasil. Foram identificados e analisados os conteúdos de Leis, Decretos, Resoluções, Políticas, Portarias e Instruções Normativas relacionadas ao tema. Apesar do longo histórico de uso da flora nacional, as primeiras legislações sobre seu emprego no campo da saúde são recentes. O Brasil, país com maior biodiversidade do planeta, aprovou, apenas em 2006, a Política Nacional de Práticas Integrativas e Complementares e a Política Nacional de Plantas Medicinais e Fitoterápicos. Necessita-se, entretanto, ampliar o investimento em pesquisas científicas para que haja segurança, qualidade e eficácia no seu uso.

Abstract Medicinal plants have been used in health care since Antiquity, but it was only in the 1970s that the WHO expressed its importance for the health of the population. This article aimed to identify the temporal sequence and evolution of legal frameworks associated with public policies on medicinal plants, discussing the implications of this evolution, as well as its insertion in the health system, and to present this evolution in Brazil. The contents of Laws, Decrees, Resolutions, Policies, Ordinances and Normative Instructions related to the topic were identified and analyzed. Despite the long history of using the national flora, the first legislation on its use in the health field is recent. Only in 2006, Brazil, the country with the greatest biodiversity on the planet, approved the National Policy on Integrative and Complementary Practices and the National Policy on Medicinal Plants and Phytotherapeutics. It is necessary, however, to increase investment in scientific research so that there is safety, quality and effectiveness in its use.

Evaluating traditional and complementary medicines: Where do we go from here?

Traditional and complementary medicines are increasingly considered possible options for prevention and symptomatic treatment of the novel coronavirus, COVID-19. With renewed attention on these therapies from researchers and policy makers alike, the well-documented challenges of evaluating their safety and efficacy are once again of global concern. Between 2005 and 2018, the World Health Organization conducted a series of surveys, in which 88 percent of responding member states confirmed that their biggest challenge in traditional medicine was the need for technical guidance on research and evaluation. As a first step in pursuing this need, our commentary summarizes thirteen international and regional guidance documents by three broad categories on evaluating safety, efficacy, and product quality for market-based approval and distribution of these treatments. We highlight the paucity of updated international recommendations on these subjects and identify gaps that could inform the current evidence base. All available guidance note the need for evidence surrounding the efficacy of these treatments and practices but are also quick to caution against methodological difficulties in the conduct of such evaluations. Evidence suggests that improved evaluation methods on efficacy and effectiveness are crucial toward expanding future research into establishing the cost-effectiveness of these therapies, in the context of shifting acceptance, interest, and integration of traditional medicines into health systems, and as another step toward Universal Health Coverage.

Herbal medicine for cervicogenic dizziness: A protocol for a systematic review and meta-analysis.

BACKGROUND: Herbal medicines are empirically used to treat cervicogenic dizziness. However, till date there have been no systematic review to evaluate the efficacy and safety of these medicines. Therefore, this study protocol describes the methods for evaluating the efficacy and safety of herbal medicine for cervicogenic dizziness. METHODS AND ANALYSIS: The following electronic academic databases will be searched up to December 2019 without language or publication status restrictions: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL), together with Korean, Chinese, and Japanese databases. Any randomized controlled trials related to herbal medicine for cervicogenic dizziness will be included. The functional outcomes and the vertebrobasilar artery hemodynamic states will be evaluated as primary outcomes. The total effective rate, hematological conditions, and adverse events will be assessed as secondary outcomes. Study selection, data extraction, quality assessment of studies, and qualitative evaluation of clinical evidence will be performed by 2 independent reviewers. The methodological quality of the included studies will be evaluated using a revised Cochrane risk-of-bias tool for randomized trials. The strength of evidence from the included data will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data synthesis will be performed as either a fixed-effects or a random-effects model using Review Manager software version 5.3. The results will be reported as a risk ratio for dichotomous outcomes and as a mean difference or standardized mean difference for continuous outcomes. ETHICS AND DISSEMINATION: No ethical approval is required since the individual clinical information of the patient is not used. The findings of this systematic review will be disseminated through the peer-reviewed publications or conference presentations. REVIEW REGISTRY UNIQUE IDENTIFYING NUMBER: reviewregistry1036.

A Critical Review to Identify the Domains Used to Measure the Effect and Outcome of Adaptogenic Herbal Medicines.

Background: Phytoadaptogens are considered to be herbal medicines with a multi-target effect that strengthen organ systems compromised by stress. Although animal and laboratory studies have identified numerous molecular targets associated with adaptogenic activity, the non-specific characteristic of these herbal medicines has meant there is no known methods to accurately determine efficacy of adaptogens in humans. This critical review of the evidence aims to identify domains which have been used to measure the effect of adaptogens in humans, in order to create pathways for translating laboratory, animal, and clinical studies on adaptogens into practical applications in the future. Methods: EMBASE, AMED, PubMed, Cochrane Library, and WHO ICTRP databases were searched for randomized trials which examined known physiological actions of adaptogens. Results: Twenty-four studies were identified and critically appraised using the Jadad scale. The findings identified three broad categories of outcome measures, including cognitive, mood and biological measures. Conclusions: There was a great heterogeneity in data making it difficult to draw conclusions as to the most effective measurement tools to capture the holistic activity in humans. Cognitive measures hold promise as a reliable measurement tool when used in conjunction with other relevant tools. Further investigation is necessary to determine the most appropriate and diverse tools to measure the complex multi-target action of adaptogens.

A Qualitative Study of the Experiences of Complementary and Alternative Medicine Use in Patients With IBS-C.

The aim of this study was to explore the experiences of complementary and alternative medicine (CAM) among patients with constipation irritable bowel syndrome (IBS-C). This qualitative study consisted of a total of 30 patients who were admitted to a university hospital in Turkey. Data were collected using a descriptive questionnaire and a semistructured interview. Data analysis identified 5 main themes: (1) the constipation-associated difficulties experienced because of IBS; (2) the feeling that CAM is natural and useful; (3) the effect of environmental stimuli in preferring the use of CAM; (4) the feeling that CAM is not negative and relieves symptoms; and (5) suggesting the use of CAM. In conclusion, it was determined that all the patients with IBS-C used various CAM methods. It may be recommended that health care professionals should raise awareness among patients about CAM methods that may be useful.

Dalbergia odorifera: A review of its traditional uses, phytochemistry, pharmacology, and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia odorifera, a traditional herbal medicine, has long been used in China for dissipating blood stasis, regulating the flow of qi, and relieving pain. AIM OF THIS REVIEW: This review aims to provide comprehensive and up-to-date information about the traditional uses, phytochemistry, pharmacology, and quality control of D. odorifera. Additionally, perspectives for possible future investigations on D. odorifera are also discussed. MATERIALS AND METHODS: Information on D. odorifera was obtained from a library database and electronic searches (e.g., Elsevier, Springer, ScienceDirect, Wiley, Web of Science, PubMed, Google Scholar, China Knowledge Resource Integrated). RESULTS: According to classical Chinese herbal texts and the Chinese Pharmacopoeia, D. odorifera promotes blood circulation, relieves pain, and eliminates blood stasis, and it can be used to treat cardio-cerebrovascular diseases in traditional Chinese medicine prescriptions. The chemical constituents of D. odorifera have been well studied, with approximately 175 metabolites having been identified, including flavonoids, phenols, arylbenzofurans, and quinones. The species also contains well-studied volatile oil. Its flavonoids and volatile oil are generally considered to be essential for its pharmacological activity. Modern pharmacology research has confirmed that isolated components and crude extracts of D. odorifera possess wide-ranging pharmacological effects, including anti-inflammatory, anti-angina, anti-oxidative, and other activities. Additionally, there are few quality control studies on D. odorifera. CONCLUSIONS: To date, significant progress has been made in D. odorifera phytochemistry and pharmacology. Thus, modern pharmacological research has provided some evidence for local or traditional uses. D. odorifera also showed therapeutic potential in cardiovascular and coronary heart diseases. However, the present findings are insufficient to explain its mechanisms of action. Additionally, the mechanism of heartwood formation, artificial induction technology for heartwood production, and quality control of D. odorifera require further detailed research.

Toxicological screening and DNA sequencing detects contamination and adulteration in regulated herbal medicines and supplements for diet, weight loss and cardiovascular health.

Use of herbal medicines and supplements by consumers to prevent or treat disease, particularly chronic conditions continues to grow, leading to increased awareness of the minimal regulation standards in many countries. Fraudulent, adulterated and contaminated herbal and traditional medicines and dietary supplements are a risk to consumer health, with adverse effects and events including overdose, drug-herb interactions and hospitalisation. The scope of the risk has been difficult to determine, prompting calls for new approaches, such as the combination of DNA metabarcoding and mass spectrometry used in this study. Here we show that nearly 50% of products tested had contamination issues, in terms of DNA, chemical composition or both. Two samples were clear cases of pharmaceutical adulteration, including a combination of paracetamol and chlorpheniramine in one product and trace amounts of buclizine, a drug no longer in use in Australia, in another. Other issues include the undeclared presence of stimulants such as caffeine, synephrine or ephedrine. DNA data highlighted potential allergy concerns (nuts, wheat), presence of potential toxins (Neem oil) and animal ingredients (reindeer, frog, shrew), and possible substitution of bird cartilage in place of shark. Only 21% of the tested products were able to have at least one ingredient corroborated by DNA sequencing. This study demonstrates that, despite current monitoring approaches, contaminated and adulterated products are still reaching the consumer. We suggest that a better solution is stronger pre-market evaluation, using techniques such as that outlined in this study.

Antidiabetic Potential of Mangifera indica L. cv. Anwar Ratol Leaves: Medicinal Application of Food Wastes.

Background and objectives: Anwar Ratol is one of the most famous cultivar of mango in South Asia, especially Pakistan. Mango leaves are left as food waste. This study evaluated the potential of mango (Anwar Ratol) leaves for their use against diabetes mellitus. Material and Methods: In this study, hydro-alcoholic extract of the plant leaves was prepared and evaluated by electrospray ionization mass spectroscopy (ESI-MS) and high-performance liquid chromatography (HPLC) for the presence of phytochemicals. The plant extract was administered to Alloxan induced diabetic mice followed by evaluation through oral glucose tolerance test; determination of postprandial glucose, body weight, lipid profile and histopathological evaluation of pancreas. Results: Chemical evaluation revealed the presence of mangiferin, rhamnetin, catechin, epicatechin, iriflophenone 3-C-ß-D-glucoside, gallic acid and other phenolic and flavonoid compounds. The plant extract exhibited a decrease in postprandial blood glucose following seven days therapy in diabetic mice. The extract also prevented the rise in blood glucose level as determined by glucose tolerance test in diabetic mice. Furthermore, therapy of diabetic mice with the extract prevented a decrease in body weight and decline in beta-cell mass associated with alloxan and improved lipid profile. Conclusion: The findings of the study clearly suggested that the leaf extract of the plant might possess anti-diabetic activity possibly due to the presence of mangiferin and other phytochemicals such as phenolic and flavonoid compounds. This study will serve as a basis for the use of mango leaf extract against diabetes. Furthermore, this study will also provide basis for the bioassay-based fractionation and isolation of active principles responsible for the antidiabetic potential of mango leaves.

Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.

"Green Medicine": The Past, Present, and Future of Botanicals.

Botanicals are plant-derived products that have been consumed by humans for centuries. Today, the marketing and use of botanicals for health and wellness benefits continues to thrive worldwide, with consumers projected to spend more than $140 billion globally by 2024 (Global Analysis, Inc). However, research on the quality and safety of these products has lagged behind sales. Because of this divergence, opportunities abound for collaborations amongst scientists from industry, academia, and government to address these unmet public health needs. Clinical pharmacologists and toxicologists from all of these sectors play critical roles in developing harmonized approaches to achieve the common goal of ensuring botanical products with superior quality and safety.

Safety Surveillance of Dietary Supplements: Importance, Challenges, and New Horizons.

Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other possible drug-related problems.1 While current models of pharmacovigilance, with their tools and methodologies, were developed for prescription drugs, safety surveillance is just as important for over-the-counter health products such as dietary supplements. The practice of pharmacovigilance is challenging in itself; however, there are unique challenges associated with dietary supplements.2.

Challenges and Opportunities for Improving the Safety Assessment of Botanical Dietary Supplements: A United States Pharmacopeia Perspective.

The United States Pharmacopeia (USP) is an independent, nonprofit, science-based organization whose mission is to improve global health through public quality standards for dietary supplements, medicines, and food ingredients.1 Before developing standards for dietary supplement ingredients, the USP performs an "Admission Evaluation" (Figure 1), which includes an assessment to ascertain that an ingredient does not present a serious health risk.2 This article discusses the challenges encountered during the evaluation of botanicals and proposes possible solutions.

Industry Actions to Address Quality Issues for Dietary Supplements, Botanicals, and Other Natural Products.

The concept of "dietary supplements" is either a blessing for those focused on healthy lifestyles and personal management thereof or a crisis fraught with snake oil and drug analogs that are insidiously poisoning the gullible. Lost in this chatter is the role the ethical, and customer-focused industry takes to drive self-directing/self-governing initiatives to demonstrate unequivocally their position as responsible corporate citizens, meeting the needs of the ever-growing body of wellness-seekers.

An experimental study in distinguishing an authentic herbal substance from sham herbal substances.

OBJECTIVES: An unblinded randomised trial can result in biased treatment effect estimates and lead to erroneous conclusions on the efficacy of the therapeutic intervention. Unlike pharmaceutical substances, Chinese herbal medicines have special characteristics including texture, colour, odour and taste as the origin of these constituents are different. In addition, its distinctive odour makes blinding of Chinese herbal medicine RCTs very difficult, as the placebo substance needs to match the special characteristics of the herbal substance being investigated. For these reasons, two studies were undertaken to evaluate whether a participant could distinguish a herbal intervention capsule (Ganopoly combination) when compared to three types of capsules containing culinary materials following a visual, odour and taste evaluation. DESIGN: Study One, was a pilot involving eleven participants (n = 11) while Study Two, involved eighty one participants (n = 81) and was conducted to make improvements on Study One. For both studies, participants were asked to identify which of four capsules were a herbal substance following a visual, smell and taste evaluation. RESULTS: For study One it was found that for both odour (p = .484) and visual appearance (p = .077) the number of participants selecting the herbal substance was not significantly different from what may have been selected by chance. This was not the case for taste where significantly more participants selected capsule B as the herbal substance (p = .004). For Study Two test it was found that all three evaluations for odour, visual appearance and taste significantly more participants selected the herbal substance (p < .0001 in all cases). This indicates that the participant guesses were not evenly distributed across the four choices and suggests a failure to blind. CONCLUSION: The failure to blind participants highlights the difficulties in preparing sham herbal substances that look, smell and taste like the real herbal substance.

A Tiered Approach for the Evaluation of the Safety of Botanicals Used as Dietary Supplements: An Industry Strategy.

Exposure to botanicals in dietary supplements is increasing across many geographies; with increased expectations from consumers, regulators, and industry stewards centered on quality and safety of these products. We present a tiered approach to assess the safety of botanicals, and an in silico decision tree to address toxicity data gaps. Tier 1 describes a Threshold of Toxicologic Concern (TTC) approach that can be used to assess the safety of conceptual levels of botanicals. Tier 2 is an approach to document a history of safe human use for botanical exposures higher than the TTC. An assessment of botanical-drug interaction (BDI) may also be necessary at this stage. Tier 3 involves botanical chemical constituent identification and safety assessment and the in silico approach as needed. Our novel approaches to identify potential hazards and establish safe human use levels for botanicals is cost and time efficient and minimizes reliance on animal testing.

" Not Intended to Diagnose, Treat, Cure or Prevent Any Disease." 25 Years of Botanical Dietary Supplement Research and the Lessons Learned.

Botanical dietary supplements (BDS) are complex mixtures of phytochemicals exhibiting complex pharmacology and posing complex research challenges. For 25 years, clinical pharmacologists researching BDS have confronted a litany of issues unlike those encountered with conventional medications. Foundational to these concerns is the Dietary Supplement Health and Education Act of 1994, which exempted BDS from premarket safety and efficacy trials. In the ensuing period, safety concerns regarding multi-ingredient products formulated as "proprietary blends" and herb-drug interactions have garnered significant attention. Idiosyncrasies unique to BDS can affect the outcome and interpretation of in vitro and in vivo studies, and although "omics" approaches hold promise in uncovering BDS efficacy mechanisms, purposeful adulteration threatens their safety. Despite a quarter century of public use, healthcare professionals still know little about BDS, thus it falls to industry, government, and academia to join forces in promoting a new paradigm for BDS research and product development.

Cinnamon and Cassia Nomenclature Confusion: A Challenge to the Applicability of Clinical Data.

Several Cinnamomum species' barks are generally labeled as cinnamon, although only Cinnamomum verum carries the common name of true cinnamon. Cassia, a common name for a related species, is rarely used on labels; instead, various cassia types may also be labeled "cinnamon." Confusion of true cinnamon and cassia spices in foods generally does not present a risk to health, except possibly at the highest intake levels. However, clinical studies with Cinnamomum investigational products have been published that inadequately describe or lack botanical identification information. The results of such studies are confounded by an inability to determine which species was responsible for the observed effects. Due to differences in the quality and composition of various Cinnamomum species, safety and efficacy data are not generalizable or transferable. Pharmacopeial monographs for characterizing the identity, composition, purity, quality, and strength of Cinnamomum investigational products should be applied to remove the ambiguity of cinnamon.

Getting to the Root of the Matter: Challenges and Recommendations for Assessing the Safety of Botanical Dietary Supplements.

The National Toxicology Program's (NTP) mission is "to evaluate agents of public health concern, by developing and applying the tools of modern toxicology and molecular biology." Botanical dietary supplements (BDS) represent agents of public health concern due to widespread exposure to high doses, a lack of safety data for most products, variable quality, and reports of adverse events. This commentary will address lessons learned in NTP testing activities with BDS and recommendations for moving forward.