Safety Concerns Related to the Simultaneous Use of Prescription or Over-the-Counter Medications and Herbal Medicinal Products: Survey Results among Latvian Citizens.

The use of herbal medicines is increasing worldwide. While the safety profile of many herbal medicines is promising, the data in the literature show important interactions with conventional drugs that can expose individual patients to high risk. The aim of this study was to investigate the experience of the use of herbal medicines and preparations and the risks of interactions between herbal and conventional medicines among Latvian citizens. Data were collected between 2019 and 2021 using a structured questionnaire designed for pharmacy customers in Latvia. Electronic databases such as Drugs.com, Medscape, and European Union herbal monographs were reviewed for the risk of drug interactions and potential side effects when herbal medicines were involved. The survey included 504 respondents. Of all the participants, 77.8% used herbal preparations. Most of the participants interviewed used herbal remedies based on the recommendation of the pharmacist or their own initiative. A total of 38.3% found the use of herbal remedies safe and harmless, while 57.3% of respondents regarded the combination of herbal and regular drugs as unsafe. The identified herbal medicines implicated in the potential risk of serious interactions were grapefruit, St. John's wort, and valerian. As the risks of herb-drug interactions were identified among the respondents, in the future, both pharmacy customers and healthcare specialists should pay more attention to possible herb-drug interactions of over-the-counter and prescription medications.

Patient' and social aspects related to complementary mistletoe therapy in patients with breast cancer: A systematic review commissioned by the German agency for Health Technology Assessment.

PURPOSE: To mitigate side effects of conventional cancer care and improve quality of life, many patients with breast cancer in German-speaking countries opt for mistletoe therapy in addition to standard treatment. To understand the value for users, we evaluated the domain "Patient and Social aspects" in a health technology assessment on complementary mistletoe therapy in patients with breast cancer. METHODS: A systematic review was conducted according to PRISMA guidelines. Fifteen electronic databases and the internet were searched. Qualitative studies were analyzed using qualitative content analysis; quantitative studies were systematically summarized in evidence tables. RESULTS: Seventeen studies out of 1203 screened publications with 4765 patients and 869 healthcare professionals were included in the review. The median proportion of patients using mistletoe therapy was 26.7% (range: 7.3-46.3%). Predictors for use were younger age and higher educational level. Main reasons for patients' use of mistletoe therapy were to leave nothing untried and to be actively involved in the treatment process. Reasons against use were related to a lack of knowledge or uncertainty regarding effectiveness and safety. Physicians mainly aimed to support the patient's physical condition as main reason for use and a lack of resources and knowledge as main reason against use. CONCLUSION: Mistletoe therapy was commonly used in the treatment of breast cancer despite a lack of scientific knowledge among patients and physicians. Transparent communication on motivation for use and its potential effect enables realistic expectations. Relatively small samples of mistletoe therapy users limit the representativeness and validity of our results.

Prostatitis: A Review.

PURPOSE OF REVIEW: Pathologies of the prostate in men are one of the most prevalent clinical conditions today [1]. Specifically, pelvic inflammatory disease such as prostatitis can cause symptoms and syndromes different from urological ones, such as bowel or nervous system manifestations. This has a largely negative impact on the quality of life of patients. Therefore, it is convenient to know and update the information about the therapeutic approach to prostatitis, which is a challenge that involves different medical specialties. The aim of this article is to provide summarized and focused evidence to help in the therapeutic approach of patients with prostatitis. A computer-based search of the PubMed and Cochrane Library databases was used to perform a comprehensive literature review on prostatitis, with special interest in recent findings and latest therapeutic guideline recommendations. RECENT FINDINGS: Recent discoveries about the epidemiology and clinical classifications of prostatitis seem to incur in an increasingly individualized and directed management, with the aim of covering all the confluent factors in prostatic inflammatory pathology. In addition, the role of new drugs and combination with phytotherapy open up a range of new treatment possibilities, although future randomized studies will be necessary to better understand how to use all treatment modalities. Despite all the knowledge acquired about the pathophysiology of prostate diseases, and due to their interrelation with other pelvic systems and organs, there are still gaps that make it difficult for us to provide an optimal and standardized treatment in many of our patients. Being aware of the influence of all the factors potentially involved in prostate symptoms is crucial for a correct diagnosis and establishing an effective treatment plan.

Phytotherapy known and applied by head-neck cancer patients and medical students to treat oral discomfort in Germany: an observational study.

BACKGROUND: Plant remedies are often used next to conventional standard of care by cancer patients. However, user rates are often underestimated and physicians usually feel not equipped to counsel patients. Hence, routinely recording the use of phytotherapy and sufficient knowledge on herbal medicine of the medical staff are required to improve the situation. Appraising the current state of knowledge of medical students may offer insight if education on herbals needs improvement. Here, we propose a simple anamnesis tool to assess knowledge and usage pattern of medical plants and demonstrate how to extrapolate symptom cluster participants associated with plants investigated in this study focussing on the common symptom of oral discomfort. METHODS: By screening German literature (popular science, specialist's literature, books for the interested layman) on medical plants used for treating oral discomfort, we were able to deviate a list of plants most often recommended for treating oral discomfort and to develop an anamnesis tool to assess knowledge and usage of 16 different plants. A group of 120 head-neck cancer patients (under surveillance, after receiving treatment) and 168 medical students were questioned at a collaborating out-patient clinic and via an online survey, respectively, in 2020. Students were additionally asked to write down indications of the plants they used in daily life. Knowledge and usage pattern were compared between both groups. Primary component analysis and heat-map analysis were used to visualize common and distinguishing features. Network analysis and VENN diagrams were used to extrapolate data of the medical students' cohort. RESULTS: Head-neck cancer patients and students show similar knowledge. However, students used significantly more plants in daily life than patients (p < 0.001). Overall, the user rate of patients and students were 82.50 and 93.94%, respectively. The top five most commonly known plants were similar in both groups (Marticaria recutita L., Zingiber offinicale ROSCOE, Taraxacum Wigg. Calendula officinalis L.) with the exception of Salvia officinalis L. (patients' cohort) and Carum carvi/Cuminum cyminum L. (students' cohort). Despite this slight difference, usage pattern of the top five most commonly used plants was the same between the groups. Students' indications were compared to indications found in the literature, unmasking several differences between commonly practiced and written knowledge on German phytotherapy. Network analysis revealed, that students associated certain plants with corresponding symptom clusters (e.g., coughing, oral mucositis). CONCLUSION: The majority of surveyed cancer patients as well as medical students use phytotherapy for treating oral discomfort. Both groups know and use similar plants. However, indications of written folk medicine differ from the lived and practiced tradition.

[Phytotherapy in uro-oncology]. / Phytotherapie in der Uroonkologie.

BACKGROUND: Complementary and alternative medicine (CAM) is used by about 40-90% of all patients with cancer. CAM also includes phytotherapy, which is considered to be a biologically based therapy. Depending on the survey, the users of phytotherapy account for up to 80%. The intention of the users is to fight cancer or to alleviate its symptoms. OBJECTIVES: Frequently used phytotherapeutics with their level of evidence and possible pitfalls are presented in a narrative review. Special attention is given to the uro-oncological context. MATERIALS AND METHODS: Popular phytotherapeutics (mistletoe, pomegranate, aloe vera, sage, ginger, ginseng) as well as three uronephrological plants (juniper, horsetail, bearberry) are classified and evaluated according to existing guidelines and by using a selective literature search. RESULTS: A total of nine plants were considered. Currently, there is no sufficient evidence for the use of pomegranate or mistletoe for tumor therapy. Guideline recommendations for or against symptom-oriented use exist for ginger (nausea; may be used), ginseng (fatigue; may be used), aloe vera (radiation dermatitis, should not be recommend), and bearberry (recurrent cystitis, may be used). A small number of studies on other symptoms and medicinal plants could be found (e.g., ginger - xerostomia, aloe vera - constipation, sage - oral mucositis or sweating). CONCLUSIONS: An integration of phytotherapeutic drugs into uro-oncological treatments concept can be considered. The benefits and risks of complementary herbal medicines (e.g., potential interactions with tumor therapy) must always be carefully weighed.

Principales fitoquímicos con potencial terapéutico en el tratamiento de la retinopatía diabética con fitofármacos / Major Phytochemicals with Therapeutic Potential in the Treatment of Diabetic Retinopathy

La diabetes mellitus tipo 2 representa uno de los principales problemas de salud pública a nivel mundial hoy en día. Entre las principales complicaciones generadas por esta enfermedad se encuentra la retinopatía diabética, la cual puede conducir a pérdida de la visión de manera permanente, por lo que investigaciones sobre tratamientos para esta patología van en aumento. Es por esto que tratamientos en base a químicos obtenidos de plantas medicinales están siendo ampliamente investigados debido a que podrían proveer una alternativa más segura, de menor costo y menor toxicidad que la medicina estándar para el tratamiento de esta patología ocular de alta incidencia mundial. El objetivo de este estudio fue identificar los principales fitoquímicos con potencial para ser usados como tratamiento de la retinopatía diabética. Para lograr este cometido se llevó a cabo una revisión de la literatura publicada entre el enero 2017 y de junio 2021 utilizando las bases de datos WOS, PubMed y Scopus en inglés y español, con el fin de recopilar evidencia científica actualizada sobre el uso y efectos de fitoquímicos en la retinopatía diabética. Diversas familias de fitoquímicos útiles fueron identificadas, entre estas las más comunes fueron las de origen fenólico, aunque menos comunes también se encontraron carotenoides, terpenos y preparaciones constituidas por varias especies de plantas y fitoquímicos. Sus mecanismos de acción también fueron identificados, siendo los más comunes la supresión de la neovascularización mediada por VEGF, la protección y restauración de la barrera hematorretinal, la reducción en la actividad de las especies reactivas del oxígeno y el efecto antiinflamatorio. Dada la evidencia respecto a la utilidad de los fitoquímicos para el tratamiento de la retinopatía diabética, mayores investigaciones deben ser realizadas(AU)

Type 2 diabetes mellitus represents one of the main public health problems worldwide today. Among the main complications generated by this disease is diabetic retinopathy, which can lead to permanent vision loss. For this reason, research on treatments for this pathology is increasing. This is why treatments based on chemicals obtained from medicinal plants are widely investigated as they could provide a safer, less costly and less toxic alternative to standard medicine for the treatment of this eye disease of high incidence worldwide. The aim of this study was to identify the main phytochemicals with potential to be used as treatment for diabetic retinopathy. In order to achieve this purpose, a review of the literature published between January 2017 and June 2021 was conducted using the WOS, PUBMED and Scopus databases in English and Spanish, in order to compile updated scientific evidence on the use and impact of phytochemicals in diabetic retinopathy. Several families of useful phytochemicals were identified. Among these, the most common were those of phenolic origin, although less common were also found carotenoids, terpenes and blends consisting of various plant species and phytochemicals. Their mechanisms of action were also identified, the most common being suppression of vascular endothelial growth factor-mediated neovascularization, protection and restoration of the blood-retinal barrier, reduction in reactive oxygen species activity and anti-inflammatory effect. Given the evidence regarding the usefulness of phytochemicals for the treatment of diabetic retinopathy, further research should be conducted(AU)

Use of Herbal Medicine Is Associated With Late-Stage Presentation in Tanzanian Patients With Cancer: A Survey to Assess the Utilization of and Reasons for the Use of Herbal Medicine.

PURPOSE: In Tanzania, patients with cancer present late with advanced stages. Among other reasons, the use of herbal medicine (HM) might contribute to delay in diagnosis and treatment. This study aims to understand the utilization of HM and the reasons for its' use. METHODS: A semistructured 30-item questionnaire with closed- and open-ended questions was applied to a cohort of patients with cancer at Kilimanjaro Christian Medical Centre. Content analysis was performed for answers to open-ended questions. RESULTS: Three hundred two patients were interviewed, 50.9% males and 49.1% females. The mean age was 64 years. 71.6% were in stages III/IV. 70.5% patients used HM and 67.1% started conventional medicine after stopping HM, 7.5% started HM after conventional medicine, and 24.9% combined both. Stage IV patients used HM as first line significantly more often in comparison: stage I 55.6%; II 58.1%; III 57.2%; and IV 70.6%. 77.5% did not tell their doctors about the use of HM. Commonest reasons to use HM were belief in cure, hope of symptom relief, lack of cancer services, and tradition. CONCLUSION: The majority of patients used HM before consulting a doctor, which contributes to stage IV presentation. Use of HM alongside with chemotherapy is mostly not known to the treating physician and may lead to interactions. These findings must alert health care workers and health policymakers to further foster health education about cancer and its treatment. Further research is needed to understand the wide use of HM among Tanzanian patients with cancer and the role that traditional and spiritual healers play in the field of cancer care.

Efficacy and safety of Gyejibokryeong-hwan (GBH) in major depressive disorder: study protocol for multicentre randomised controlled trial.

BACKGROUND: Gyejibokryeong-hwan (GBH) is an herbal medicine composed of five herbs. It has been widely used to treat gynaecological diseases in traditional East Asian medicine. Recent animal studies suggest antidepressant effects of GBH. In this trial, we explore the efficacy and safety of GBH in patients with major depressive disorder and to identify the optimal dose for the next phase III trial. METHODS: This trial will enrol 126 patients diagnosed with major depressive disorder and not treated with antidepressants. Participants will be randomised to receive a high or a low dose of GBH or placebo granules. The study drugs will be administered three times a day, for 8 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) will be used to measure the severity of depressive symptoms at weeks 2, 4, 6, 8, and 12. The primary efficacy endpoint is the change from baseline in HDRS-17 total score post-treatment at week 8. Analysis of covariance will be based on the baseline HDRS-17 total score and site as the covariates. Safety assessment will be based on the frequency of adverse events. The severity and causality of the study drug will be assessed. DISCUSSION: This study is designed to evaluate the efficacy and safety of GBH granules compared with placebo in patients with major depressive disorder. TRIAL REGISTRATION: Clinical Research Information Service KCT0004417 . Registered on November 1, 2019 (prospective registration).

Herbal Formula Shenling Baizhu San for Chronic Diarrhea in Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Shenling Baizhu San (SBS), a well-known Chinese medicine herbal formula, has been widely used for treating chronic diarrhea for thousands of years. However, the efficacy and safety of SBS in treating chronic diarrhea have not been fully assessed. OBJECTIVE: This study evaluates the efficacy and safety of the herbal formula SBS in symptomatic relief of chronic diarrhea. METHODS: English and Chinese language databases (PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, and SinoMed electronic databases) were searched through April 2020 for relevant randomized controlled trials (RCTs). The outcomes in these RCTs included stool frequency, stool consistency, patient-reported satisfaction of chronic diarrhea treatment, quality of life and adverse events. Paired reviewers independently extracted data and conducted qualitative and quantitative analyses. The Cochrane revised risk of bias RoB-2 tool was applied to assess the risk of bias for each trial whereas the RevMan 5.3 software was used for outcomes data synthesis and meta-analysis. Mean difference (MD) and the 95% confidence interval (CI) were used to measure continuous data. The dichotomous data were analyzed via the relative risk (RR) with 95% CIs. RESULTS: Fourteen RCTs including 1158 participants (54% males) with chronic diarrhea were included. Shenling Baizhu San combined with or without conventional medicine (CM) was associated with greater patient-reported satisfaction than CM alone. There was no increased risk of adverse events (AEs) during treatment. CONCLUSION: Treatment with SBS was associated with significant improvement in patient-reported satisfaction, irrespective of conventional medicine use. Rigorous and powered RCTs with objective outcome measures are needed to confirm the effects of SBS in specific gastrointestinal disease populations with chronic diarrhea symptoms. SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO): CRD42020178073.

Mushroom supplements triggering a flare of HMGCR immune mediated necrotising myopathy.

Hydroxyl-methyl-glutaryl-Co-A reductase (HMGCR) immune mediated necrotising myopathy (IMNM) is a rare autoimmune myositis that is thought to be triggered by statins and responds to immunomodulation. We report a case of a woman in her 30s with HMGCR IMNM without a history of statin exposure who had a clear flare of her myositis after beginning mushroom supplements. Mushrooms are natural HMGCR inhibitors, and this is the first case to demonstrate a flare triggered by mushrooms in a patient with known HMGCR IMNM. This case highlights the importance of reviewing diet and supplements in patients with IMNM. It also emphasises the importance of strict statin avoidance for patients with IMNM even when the myositis is under good control.

Phytotherapy for male luts: What happens then? 10-year research.

INTRODUCTION AND OBJECTIVES: Our objective is to assess the long-term results of phytotherapy, focusing on the interval between phytotherapy and pharmacological treatment and the predisposing risk factors to such switch on a 10-year follow-up. MATERIAL AND METHODS: The data of patients taking phytotherapy for mild to moderate male lower urinary tract symptoms (LUTS) from January to December 2010 were retrospectively reviewed from a prospectively maintained database. Patients were followed for 10 years through medical visits and telephone consultations. RESULTS: 102 patients underwent at least one cycle of phytotherapy for LUTS. Twenty (19.6%) patients resolved their symptoms after one phytotherapy cycle and stopped any treatment, 27 (26.4%) continued phytotherapy, and 52 (51%) switched to alpha-blockers and/or 5a-reductase inhibitors after a median interval of 24 months. The reasons for treatment switch were symptoms (n = 45) or clinical progression (increased residual volume n = 15; urinary retention, n = 5). Patients switching to synthetic drugs had median higher age (60 vs 49), prostate volume (40 vs 26 cc), prostate specific antigen (PSA) (1.9 vs 0.9 ng/ml), residual volume (40 vs 0 cc), and a lower maximum flow rate (Qmax) (12 vs 15 ml/s) at presentation. CONCLUSIONS: 46% patients with mild to moderate LUTS undergoing phytotherapy will be either free of treatment or still on phytotherapy at 10 years from disease presentation. Older patients with larger prostates, increased residual volume and PSA, should be informed regarding their higher risk of symptomatic or clinical progression: the risk of a treatment switch to alpha-blockers or 5a-reductase inhibitors becomes an actual fact after an average span of 2 years.

Abdominal pain caused by lead toxicity due to over the counter herbal medicines: A case series.

In the last three decades, the use of herbal medications has been increasing for the treatment of various chronic disorders. Studies in the past have shown that many of these medicines could contain high levels of heavy metals, including lead. Therefore, we planned this study to evaluate the possibility of lead toxicity as the underlying cause in patients consuming these unnamed herbal medicines among patients presenting with significant abdominal pain. (Unexplained abdominal pain means pain in abdomen in which no etiology could be ascertained after all possible routine and specialized investigations including computerized axial tomography [CT] of the abdomen and upper gastrointestinal [UGI] endoscopy/colonoscopy). This is an observational case series of prospectively maintained data of all patients having unexplained abdominal pain and found to have an elevated blood lead level from 2011 to 2019. Lead toxicity was diagnosed when its blood lead level was >25 µg/dL. Total sixty-six patients with unexplained abdominal pain from 2011 to 2019 were recruited. Out of the sixty-six patients, seventeen had elevated blood lead levels. All seventeen patients had a history of ingestion of herbal medicines for more than 6 months. Among the seventeen patients, eight were taking it for infertility and sexual dysfunction, six for diabetes, two for arthritis and one for hypertension. Basophilic stippling was seen in one patient. Fourteen patients had low hemoglobin with a median value of 9.7 g/dL. Mean serum blood lead level was 87.1 µg/dL. None of them required anti-chelating agent. Lead toxicity owing to herbal medicine is not uncommon cause of unexplained abdominal pain. Most of these patients do not require a chelating agent for treatment. There is a need to bring these herbal medicines under strict regulations for displaying its constituents and their concentrations.

A Review of Recent Studies on the Antioxidant and Anti-Infectious Properties of Senna Plants.

The use of phytochemicals is gaining interest for the treatment of metabolic syndromes over the synthetic formulation of drugs. Senna is evolving as one of the important plants which have been vastly studied for its beneficial effects. Various parts of Senna species including the root, stem, leaves, and flower are found rich in numerous phytochemicals. In vitro, in vivo, and clinical experiments established that extracts from Senna plants have diverse beneficial effects by acting as a strong antioxidant and antimicrobial agent. In this review, Senna genus is comprehensively discussed in terms of its botanical characteristics, traditional use, geographic presence, and phytochemical profile. The bioactive compound richness contributes to the biological activity of Senna plant extracts. The review emphasizes on the in vivo and in vitro antioxidant and anti-infectious properties of the Senna plant. Preclinical studies confirmed the beneficial effects of the Senna plant extracts and its bioactive components in regard to the health-promoting activities. The safety, side effects, and therapeutic limitations of the Senna plant are also discussed in this review. Additional research is necessary to utilize the phenolic compounds towards its use as an alternative to pharmacological treatments and even as an ingredient in functional foods.

Geranium wilfordii maxim.: A review of its traditional uses, phytochemistry, pharmacology, quality control and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Geranium wilfordii Maxim. (family Geraniaceae) has been used as a multifunctional ethnomedicine in China for more than 600 years. There have been records about the edible and medicinal use of G.wilfordii since the Ming Dynasty. Nowadays, G.wilfordii is included in Chinese Pharmacopoeia as the Geranii Herba, and has been widely used to treat rheumatism, infectious diseases, dermatosis and tumors. In addition, more than 30 kinds of Chinese patent medicines containing G.wilfordii have been marketed in China for its high medicinal value. AIM OF THE REVIEW: The present review systematically summarized the traditional uses, phytochemistry, pharmacology, quality control and toxicology of G.wilfordii, discussed the development potential of this plant and analyzed the shortcomings of existing research, in order to provide comprehensive scientific basis for the medical application and help interested researchers discover safe and medicinal natural products from G.wilfordii. MATERIALS AND METHODS: We performed a systematic search of G.wilfordii by collecting the publications between 1995 and 2021 via PubMed, Web of Science, SciFinder, Google Scholar, Chinese National Knowledge Infrastructure database, Wanfang database and other databases using the keywords including Geranium wilfordii Maxim., botany, traditional uses, Chinese patent medicines, patents, preparations, phytochemistry, biological activity, quality and toxicity. Besides, part of the information also came from Chinese botanical and medical monographs. RESULTS: So far, more than 90 components have been identified from G.wilfordii, among which tannins as well as flavonoids have attracted widespread concerns. Due to the multi-components nature, a wide range of beneficial biological activities of G.wilfordii have been demonstrated, including anti-inflammatory, antibacterial, antiviral, anti-tumor, antioxidative, hepatoprotective, gastrointestinal protective, immunoregulatory and uric acid-lowering effects. CONCLUSION: A long history of traditional uses and abundant pharmacochemical and pharmacological studies have shown that G.wilfordii is an important natural medicine, which exerts outstanding therapeutic effects especially in anti-inflammation and anti-microorganisms. However, the present researches on the active ingredients and the mechanism of action are not in-depth enough, and more evidence-based scientific studies are needed to lend credence to the traditional uses of G.wilfordii. Additionally, limited toxicology tests cannot objectively evaluate the safety of G.wilfordii, which needs to be further supplemented. Further, more attention needs to be paid to the selection of index components of quality control research.

Biochemical characterization and phytotoxic activity of protein extract from Euphorbia tirucalli L.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia tirucalli L., a tropical and subtropical plant, also known by the popular name avelós, has been used in folk medicine against many diseases as rheumatism, asthma, toothache, and cancer. Studies have shown that natural compounds contained in this plant species may be associated with these functions. However, little is known about its potential toxicity. AIM OF THE STUDY: Several proteins conduct biological functions, in particular, proteinases, play a crucial role in many mechanisms of living beings, including plants, animals and microorganisms. However, when poorly regulated, they can generate consequences, such as the non-production of certain substances, or even the abnormal multiplication of cells, which leads to tumors. On the other hand, by regulating these enzymes, proteinase inhibitors act by reducing the activity of proteinases, thus preventing their malfunction. The objective of this work was to evaluate the toxicity of the protein extract of E. tirucalli and to purify a protease inhibitor that may be associated with the biological medicinal functions of the plant. MATERIALS AND METHODS: The cytotoxic and mutagenic properties of the protein extract produced from the stem of avelós was investigated using the Ames test. The protein extract was also submitted to a protease inhibitor purification process using the gel filtration chromatography technique and the purified protein was biochemically characterized. RESULTS: A protease inhibitor, called tirustatin, was isolated 1.84-fold by Biogel P100. The calculated molecular mass of the isolated protein is 25.97 kDa. The inhibitor was stable at pH 3-10, with pronounced activity at pH 6. Thermostability was observed even at elevated temperature (100 °C) with inhibitory activity increased by 1.14-fold compared to inhibitor activity at room temperature. Incubation at basic pH values for up to 60 min caused little reduction (0.25-fold) in the papain inhibitory activity of tirustatin. The stoichiometry of the papain-tirustatin interaction was 1.5: 1 and 28.8 pM of the inhibitor effected 50% inhibition. With an equilibrium dissociation constant of 8.74 x 10-8M for the papain enzyme, it is possible to evaluate the isolated protein as a non-competitive inhibitor. In addition, the protein extract of E. tirucalli even at the maximum concentration used (20 µg/mL), did not show a cytotoxic and mutagenic profile in a bacterial model. CONCLUSION: The results presented in this work provide data that reinforce the idea of the potential use of proteins produced in E. tirucalli as pharmacological and biotechnological agents that can be exploited for the development of efficient drugs.

Interactions in cancer treatment considering cancer therapy, concomitant medications, food, herbal medicine and other supplements.

PURPOSE: The aim of our study was to analyse the frequency and severity of different types of potential interactions in oncological outpatients' therapy. Therefore, medications, food and substances in terms of complementary and alternative medicine (CAM) like dietary supplements, herbs and other processed ingredients were considered. METHODS: We obtained data from questionnaires and from analysing the patient records of 115 cancer outpatients treated at a German university hospital. Drug-drug interactions were identified using a drug interaction checking software. Potential CAM-drug interactions and food-drug interactions were identified based on literature research. RESULTS: 92.2% of all patients were at risk of one or more interaction of any kind and 61.7% of at least one major drug-drug interaction. On average, physicians prescribed 10.4 drugs to each patient and 6.9 interactions were found, 2.5 of which were classified as major. The most prevalent types of drug-drug interactions were a combination of QT prolonging drugs (32.3%) and drugs with a potential for myelotoxicity (13.4%) or hepatotoxicity (10.1%). In 37.2% of all patients using CAM supplements the likelihood of interactions with medications was rated as likely. Food-drug interactions were likely in 28.7% of all patients. CONCLUSION: The high amount of interactions could not be found in literature so far. We recommend running interaction checks when prescribing any new drug and capturing CAM supplements in medication lists too. If not advised explicitly in another way drugs should be taken separately from meals and by using nonmineralized water to minimize the risk for food-drug interactions.

Weight gain in menopause: systematic review of adverse events in women treated with black cohosh.

Weight gain is a frequent problem in perimenopausal and postmenopausal women. Cimicifuga racemosa (CR) is a popular treatment option for menopausal symptoms. The aim of this review was to investigate whether there is scientific evidence that CR causes weight gain. We searched our database for medically confirmed, spontaneous adverse events regarding weight gain, literature for case reports and randomized controlled trials. Thirty cases in total were spontaneously reported in 15 years. The causality was not considered certain/likely in any of the cases. A nurse (consumer) assessed the causality as possible. Only one case was published in the literature. However, no change in body fat composition was reported, and the causality seems unlikely. Of the 31 identified studies, 17 were double-blind placebo-controlled, five were double-blind reference-controlled and nine were open reference-controlled. In total, 1839 women were treated with CR for up to 12 months. Two studies reported weight gain as an adverse event; however, no significant differences in weight changes were observed between the groups. One case of weight gain (about 2 kg) was reported, but the authors did not specify in which treatment group. In conclusion, this study provides no scientific evidence that the use of Cimicifuga racemosa causes weight gain in menopausal women.

A system for reporting and evaluating adverse drug reactions of herbal medicine in Taiwan from 1998 to 2016.

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan's herbal medicines adverse reaction database and facilitate epidemiological analysis.