A case of fatal overdose involving both hydromorphone and kratom.

Kratom is a plant originating in Southeast Asia that has been used for its dose-dependent stimulant and opioid effects. The main active compound in kratom is mitragynine, an alkaloid with affinity for the mu-opioid receptor. Toxicity and fatalities related to kratom use have increased substantially in recent years. In this case report, we describe a 44-year-old man who was found deceased in bed. The only significant finding at autopsy was abdominal distension with >4 L of ascites. Toxicology testing was performed on femoral blood which showed 79 ng/mL of hydromorphone, 560 ng/mL of mitragynine, and 240 ng/mL of olanzapine. In addition, creatinine and urea in vitreous humor were significantly elevated, consistent with renal impairment. Death was attributed to hydromorphone toxicity with mitragynine being a contributing factor.

The use of beta-sitosterol for the treatment of prostate cancer and benign prostatic hyperplasia.

Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however, plant sterols make up an abundant ingredient component, with saw palmetto extract or its primary component, beta-sitosterol, often comprising the most abundant sterol. Saw palmetto extract/beta-sitosterol has been shown to promote anti-tumorigenic processes in prostate cancer cells and rodent models of prostate cancer. It has also been shown to inhibit the 5α-reductase enzyme, thereby behaving similarly to finasteride and dutasteride, which are widely used to treat prostatic enlargement, or benign prostatic hyperplasia (BPH). The aim of this study is to critically examine in vitro, in vivo, and human clinical studies to assess the safety and clinical utility of herbal supplements containing saw palmetto extract/beta-sitosterol for prostate health. The results of this study suggest multiple mechanisms through which beta-sitosterol represses prostate cancer in vitro and in vivo, particularly through its pro-apoptotic effect on prostate epithelial cells. Multiple studies also show that beta-sitosterol significantly improves lower urinary tract symptoms (LUTS) associated with BPH, but to an extent that is generally less effective than that achieved by pharmaceutical grade alpha-adrenergic receptor antagonists or 5α-reductase inhibitors. This latter finding suggests that supplements containing beta-sitosterol might be most appropriate for younger men with minimal LUTS who don't wish to embark on a clinical drug regimen for BPH treatment.

Chronic supplementation of a multi-ingredient herbal supplement increases speed of cognitive task performance alongside changes in the urinary metabolism of dopamine and the gut microbiome in cognitively intact older adults experiencing subjective memory decline: a randomized, placebo controlled, parallel groups investigation.

Background: The effects of herbs on brain function are often investigated in isolation, yet herbal preparations are often complex combinations of phytochemicals, designed to target widespread mechanisms. Objective: To assess the effects of chronic, 12 weeks, supplementation of a multi-ingredient herbal supplement (containing Bacopa monnieri, Gotu kola leaf, Turmeric whole powder, Reishi full spectrum, Rosemary, Cardamom, Holy Basil, Turmeric Wholistic™ extract, Green Tea & Seagreens) on cognitive function in older adults with subjective memory decline. Secondly, to investigate whether effects are underpinned by shifts in microbial composition and/or metabolism of the herbs. Methods: Male and female participants (N = 128) aged between 55-75 years completed lab-based cognitive assessments, and provided stool and urine samples, at baseline and then following 90 days of multi-ingredient herb, or placebo, supplementation. Results: Deficits in memory were observed in response to 90 days of multi-ingredient herbal supplement supplementation but the positive effects were all focused on speed of cognitive task performance, with an additional improvement in the false alarm rate on the rapid visual information processing task. These improvements coincided with an increased presence of tyrosine in the urinary metabolome and this may implicate the role of dopamine in these processing and/or motor speed increases. Finally, multi-ingredient herbal supplementation significantly reduced levels of 3 bacterial species in the gut microbiome and one of these, Sutterella, coincides with lower levels of constipation reported in the multi-ingredient herbal supplement condition. Conclusion: A multi-ingredient herbal supplement increases speed of cognitive task performance and increased metabolism of tyrosine suggests that this is modulated by increased dopaminergic activity. Reduced levels of Sutterella in the gut is associated with improved bowel movements of participants. Interpretation of the negative effects on memory are, however, stymied by an unequal randomization of participants into treatment groups pre- and post-COVID 19.Clinical trial registration: identifier NCT05504668.

Acute Fulminant Hepatic Failure in 23-Year-Old Female Taking Homeopathic Remedy.

Homeopathic remedies made primarily from eggshells, and therefore calcium, can be marketed for treatment of back pain and vaginal discharge. We present a case of a 23-year-old otherwise healthy woman who presented with acute liver failure (ALF) ultimately requiring liver transplantation as a result of taking increased doses of a homeopathic product with the primary ingredient of eggshells. Although relatively uncommon compared with medications such as acetaminophen, herbal supplements have been reported to cause drug-induced liver injury (DILI), thought to be primarily due to contaminants. This is the first known report of DILI resulting from a homeopathic product with the primary ingredient of eggshells, and it demonstrates the importance of early ALF recognition and treatment, as well as the importance of practicing caution when using homeopathic supplements.

The Role of Rheumatologist in Smoking Cessation of Ankylosing Spondylitis Patients: A Single-Center Cross-Sectional Study.

OBJECTIVES: Smoking has a well-established detrimental effect on the prognosis and treatment success in patients with ankylosing spondylitis. It is important to encourage and convince patients to quit smoking. We aimed to evaluate the contribution of rheumatologists to smoking cessation in patients with ankylosing spondylitis. METHODS: This single-center cross-sectional study was conducted in a tertiary research hospital between March 2022 and June 2022. The data related to demographics, smoking status, duration of smoking, average number of cigarettes smoked per day, reasons for quitting smoking, and methods of quitting smoking were obtained through face-to-face interviews. RESULTS: This study was carried out on 308 patients. A total of 102 ankylosing spondylitis patients quit smoking. Of the patients who quit smoking, 39 (38.3%) patients quit smoking with a recommendation of a rheumatologist and 29 (28.4%) patients quit because of their concerns related to ankylosing spondylitis disease. The most commonly used methods for quitting smoking were herbal supplements in 40 (39.2%) patients and medication for smoking cessation in 40 (39.2%) patients. CONCLUSIONS: It has been shown that about one-fifth of ankylosing spondylitis patients are not questioned by a rheumatologist about smoking. On the other hand, it was seen that the factor with the greatest effect on those who quit smoking was the rheumatologist. Therefore, rheumatologists should question all ankylosing spondylitis patients about smoking and encourage smokers to quit in order to achieve better outcomes in the long term.

A standardized extract of Echinacea purpurea containing higher chicoric acid content enhances immune function in murine macrophages and cyclophosphamide-induced immunosuppression mice.

CONTEXT: Preparations of Echinacea have been used by herbalists to boost the immune system. OBJECTIVE: In this study, Echinacea purpurea (L.) Moench (Asteraceae) extract with enriched chicoric acid content was investigated for immunomodulation. MATERIALS AND METHODS: The standardized hydroalcoholic extract (4% chicoric acid) was prepared from the aerial parts of E. purpurea (SEP). The extract was screened for in vitro antioxidant activities, and immunomodulation in RAW 264.7 cells, at 200 and 400 µg/mL. Further, the male BALB/c mice (20-25 g) were divided into 4 groups (n = 6 per group). All the groups except control, were intraperitoneally injected with 70 mg/kg/day of cyclophosphamide (CTX) for 4 consecutive days. The treatment groups received SEP extract (100 and 200 mg/kg body weight) p.o. from day 5 to 14. RESULTS: The SEP extract inhibited DPPH (IC50 = 106.7 µg/mL), ABTS+ (IC50 = 19.88 µg/mL) and nitric oxide (IC50 = 120.1 µg/mL). The SEP extract's ORAC (oxygen radical absorbance capacity) value was 1931.63 µM TE/g. In RAW 264.7 cells, SEP extract increased the nitric oxide production by 30.76- and 39.07-fold at 200 and 400 µg/mL, respectively, compared to the untreated cells. SEP extract significantly increased phagocytosis and cytokine release (TNF-α, IL-6, and IL-1ß) in the cells. Further, the extract improved immune organ indices, lymphocyte proliferation and serum cytokine levels in CTX-induced mice. The extract at 200 mg/kg significantly increased the natural killer cell activity (24.6%) and phagocytic index (28.03%) of CTX mice. CONCLUSION: Our results strongly support SEP extract with 4% chicoric acid as a functional ingredient for immunomodulation.

Application to Butterbur Products of a Suggested Daily Intake-Based Safety Evaluation of Individual Herbal Supplements with Cytochrome P450 Expression as a Major Index.

The present paper first proposes a method for ensuring the safety of commercial herbal supplements, termed the suggested daily intake-based safety evaluation (SDI-based safety evaluation). This new method was inspired as a backward analog of the acceptable daily intake (ADI) derivation from the no observed adverse effect level (NOAEL), the basis of food additive risk analysis; namely, rats are dosed with individual herbal supplement products at the SDI for human use multiplied by 100 (the usual uncertainty factor value) per body weight for 8 d. The primary endpoint is the sign of adverse effects on liver, especially gene expression of cytochrome P450 (CYP) isoforms. The proposed method was then applied to three butterbur (Petasites hybridus) products without pyrrolizidine alkaloids but lacking clear safety information. Results showed that two oily products markedly enhanced the mRNA expression of CYP2B (>10-fold) and moderately enhanced that of CYP3A1 (<4-fold) with liver enlargement. These products also caused the renal accumulation of alpha 2-microglobulin. One powdery product showed no significant effect on liver and kidney. The large difference in effects of products was due to the difference in chemical composition revealed by liquid chromatography-mass spectroscopy. The oily and the powdery products required attention in terms of safety and effectiveness, respectively. Finally, the results from the SDI-based safety evaluation of butterbur and other herbal supplement products were grouped into four categories and cautionary notes were discussed. The SDI-based safety evaluation of their products by herbal supplement operators would contribute to safe and secure use by consumers.

New Traditional Chinese Medicine Supplement Reduces Pain Faster than Conventional Pain Pills Alone: A Phase I/II Prospective, Double-Blinded Placebo-Controlled Randomized Trial.

BACKGROUND: The opioid crisis demands novel solutions for postoperative pain control. Traditional Chinese medicine (TCM) has used herbs for the treatment of pain for thousands of years. We studied whether a synergistic multimodal TCM supplement could reduce the need for conventional pain pills for low risk surgical procedures. METHODS: In a Phase I/II, prospective, double-blind, placebo-controlled, randomized clinical trial (PRCT), 93 patients were randomized to either TCM supplement or placebo oral medication for low-risk outpatient surgical procedures. Study medications began 3 days preoperatively and continued for 5 days postoperatively. Conventional pain pill use was not restricted. Patients were monitored postoperatively for all forms of pain pill use (Pain Pill Scoring Sheet) and subjective pain ratings (Brief Pain Inventory Short Form). Primary outcomes included type and number of pain pills used and subjective pain ratings. Secondary outcomes included an assessment of mood, general activity, sleep, and enjoyment of life. RESULTS: TCM use well tolerated. Conventional pain pill use was similar between groups. Linear regression analysis revealed that TCM reduced postoperative pain 3 times faster than placebo (P < .0001) with a 4-fold greater magnitude of relief by postoperative day 5 (P = .008). TCM also significantly improved sleep habits (P = .049) during the postoperative period. TCM effect was independent of type of surgery or amount of preoperative pain. DISCUSSION: This PRCT is the first to show that a multimodal, synergistic TCM supplement is safe and can effectively reduce acute postoperative pain more rapidly, and to a lower level, than conventional pain pills alone.

Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury.

In recent years, cases of liver damage caused by ashwagandha herbal supplements have been reported from different parts of the world (Japan, Iceland, India, and the USA). Here, we describe the clinical phenotype of suspected ashwagandha-induced liver injury and the potential causative mechanism. The patient was admitted to the hospital because of jaundice. In the interview, it was reported that he had been taking ashwagandha for a year. Laboratory results showed an increase in total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), (gamma-glutamyl transpherase (GGT), alkaline phosphatase (ALP), total cholesterol, triglycerides, and ferritin. Based on clinical symptoms and additional tests, the patient was diagnosed with acute hepatitis and referred to a facility with a higher reference rate to exclude drug-induced liver injury. An R-value was assessed, indicative of hepatocellular injury. The result of the 24 h urine collection exceeded the upper limit of normal for copper excretion in urine twice. The clinical condition improved after intensive pharmacological treatment and four plasmapheresis treatments. This case is another showing the hepatotoxic potential of ashwagandha to cause cholestatic liver damage mixed with severe jaundice. In view of several documented cases of liver damage caused by ashwagandha and the unknown metabolic molecular mechanisms of substances contained in it, attention should be paid to patients reporting the use of these products in the past and presenting symptoms of liver damage.

Safety assessment of herbal supplement components targeting hepatotoxicity and CYP3A4 induction in cell-based assay using HepG2 cells.

Herbal supplements can cause hepatotoxicity and drug interactions via hepatic cytochrome P-450 (CYP) in some cases. However, there is no simple and stable cell-based assay to conduct a screening for hepatotoxicity and CYP induction. In the present study, we selected 14 components of the herbal supplement based on our previous reports and investigated the safety of the herbal supplement components focusing on toxicity and CYP3A4 induction in a cell-based assay using HepG2. The toxicity of the components was examined by lactate dehydrogenase (LDH) and cell proliferation assays. Then, the CYP3A4 induction of the components were examined by a reporter assay using reporter vectors of CYP3A4. The vector includes the CYP3A4 proximal promoter (CYP3A4PP) and the xenobiotic-responsive enhancer module (XREM) regions. Luteolin (LU) significantly increased LDH activity and decreased cell proliferation activity that suggests LU may cause toxicity in HepG2 cells. Quercetin (QU) increased the transcriptional activity of CYP3A4 (1.5-fold of control) in the reporter assay. However, the induction of QU was slightly in comparison to the validation of the transcriptional activity of CYP3A4 treated with CYP3A4 inducers. The CYP3A4 induction of QU may not involve CYP3A4PP but involves the XREM response. Throughout our results, the method in the present study may be useful for a safety assessment of herbal supplements, primarily focusing on hepatotoxicity and CYP3A4 induction. PRACTICAL APPLICATION: Even though there are problems with herbal supplements, studies related to toxicity are not actively carried out. The present methods may apply to the safety assessment for herbal supplements and be useful for the prevention and verification of health hazards caused by herbal supplements (the summary is shown in Figure S2).

Fifth-Generation Cephalosporins Is Not Spared From Drug-Induced Liver Injury.

Ceftaroline fosamil is a fairly new parenteral cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI). Drug-induced liver injury (DILI) is an important side effect profile to consider with antibiotic use. This case reports DILI in a previously healthy individual associated with a widely used antibiotic, ceftaroline, after only two doses. Discontinuation of the ceftaroline resulted in a resolution of DILI in a three-week period. Ceftaroline-induced liver injury is highlighted in this case report, along with a discussion of how we excluded other potential factors that can cause liver injury with the use of the Roussel Uclaf Causality Assessment Method (RUCAM) score. We also explained why other causes like hemochromatosis, Wilson's disease, celiac disease, and thyroid disease were unlikely.

Drug induced autoimmune hepatitis: An unfortunate case of herbal toxicity from Skullcap supplement: A case report.

BACKGROUND: The surge in traditional herbal dietary supplement (HDS) popularity has led to increased drug-induced liver injuries (DILI). Despite lacking evidence of efficacy and being prohibited from making medical claims, their acceptance has risen over sevenfold in the last two decades, with roughly 25% of United States (US) adults using these supplements monthly. An estimated 23000 emergency room visits annually in the US are linked to HDS side effects. NIH-funded research suggests HDS contribute to 7-20% of DILI cases, with similar trends in Europe-Spain reporting 2% and Iceland up to 16%. Patients with acute liver failure from HDS undergo liver transplantation more frequently than those from prescription medicines. Here we describe a case of drug-induced autoimmune hepatitis due to Skullcap supplements, this association appears to be the first documented instance in literature. CASE SUMMARY: A middle-aged Caucasian woman, previously healthy, presented with sudden jaundice. Four months earlier, her liver enzymes were normal. She mentioned recent use of Skullcap mushroom supplements. Tests for chronic liver disease were negative. The first liver biopsy indicated severe resolving drug-induced liver injury. Despite treatment, she was readmitted due to worsening jaundice. Follow-up tests raised concerns about autoimmune hepatitis. A subsequent biopsy confirmed this diagnosis. The patient responded as expected to stopping the medication with improvement in liver enzymes. CONCLUSION: This scenario highlights an uncommon instance of DILI caused by Skullcap supplements. It's crucial for hepatologists to recognize this connection due to the increasing prevalence of herbal supplements.

The effect of Tribulus terrestris supplementation on inflammation, oxidative stress, and performance of recreational runners: study protocol for a randomized placebo-controlled trial.

BACKGROUND: High intensity and endurance exercises lead to exercise-induced oxidative stress (EIOS), exercise-induced muscle damage (EIMD), and inflammation, which are the influencing factors on muscle soreness, localized swelling, and sports performance decrease. Therefore, the purpose of this study is to determine the effectiveness of Tribulus terrestris (TT) as an herbal supplement with antioxidant and anti-inflammatory properties on the nutritional, oxidative, inflammatory, and anti-inflammatory status, as well as the sports performance of recreational runners. METHODS/DESIGN: This study is a double-blind, randomized, placebo-controlled trial, which will be conducted among recreational runners of Tabriz stadiums, Iran. Thirty-four recreational runners will be selected, and participants will be assigned randomly to two groups: to receive 500 mg TT supplement or placebo capsules twice daily for 2 weeks. Both groups will do high-intensity interval training (HIIT) workouts during the study. Baseline and post-intervention body composition, muscle pain, and aerobic and anaerobic performance will be assessed. In addition, assessment of malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid (UA), 8-iso-prostaglandin F2α (8-iso-PGF2α), protein carbonyl (PC), catalase (CAT), glutathione (GSH), nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), creatine kinase (CK), myoglobin (MYO), lactate dehydrogenase (LDH), insulin-like growth factor-1 (IGF-1) irisin, cortisol, and brain-derived neurotrophic factor (BDNF) will be done during three blood samplings. Changes in oxidative stress, anti/inflammatory biomarkers, and sports performance will be assessed as primary outcomes. DISCUSSION: This study will be the first to assess the potential effects of TT on recreational runners. Our results will contribute to the growing body of knowledge regarding TT supplementation on the nutritional, oxidative, inflammatory, and anti-inflammatory status and sports performance in recreational runners. TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20150205020965N8 ). Registration date: 13 February 2021.

Development and Validation of a Tool to Improve Community Pharmacists' Surveillance Role in the Safe Dispensing of Herbal Supplements.

Background: There has been an appreciable increase in the use of herbal supplements, including immune boosters, during the current COVID-19 pandemic. However, there are concerns with falsified herbal supplements. Objectives: Developed a new questionnaire that can potentially help community pharmacists identify the extent of falsified herbal supplements. Methods: A 9-month cross sectional study was conducted among 500 community pharmacies across United Arab Emirates. A new 5-factor, 24-itmes scale was developed based on current labelling requirements across countries and piloted. This included seven items on identified uses and contraindication, seven items on hazard identification, four items on product identity, three items on packaging and product insert and three items on product handling and storage. The face and content validity of the scale was assessed via the content validity index (CVI). Its construct validity was tested using an exploratory factor analysis (EFA) via principally component analysis (PCA). The model was subsequently confirmed through partial confirmatory factor analysis (PCFA). Its reliability was assessed via test-retest reliability, internal consistency, item internal consistency (IIC), and intraclass correlation coefficients (ICCs). Results: The CVI of the finalized questionnaire was 0.843. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.891, and Bartlett's test of sphericity indicated significance (p-value < 0.001). Confirmation of the subsequent 5-domains was achieved through PCFA using maximum likelihood analysis with oblimin rotation. The PCFA obtained values was 0.962 for NFI, 0.977 for CFI, and 0.987 for the Tucker Lewis Index. All values were greater than 0.95, and the RMSEA value was 0.03 (i.e., less than 0.06). Consequently, the model had a good fit. All domains demonstrated Cronbach's alpha coefficients above 0.70, with 0.940 for the full instrument. Meanwhile, all items met the IIC correlation standard of ≥0.40. The instrument presented good ICC statistics of 0.940 (0.928-0.950) as well as statistical significance (p < 0.001). Community pharmacists with more than 10 experience years were more likely to identify falsified herbal supplements compared to those with 1-10 years experience (p < 0.001). Conclusion: This study developed and validated a new instrument to identify safe herbal supplements, which should enhance the role of the community pharmacists in the safe and effective treatment of suitable patients with herbal supplements.

First-Time Submassive Pulmonary Embolism Likely Caused by Testosterone-Enhancing Supplement.

Pulmonary embolism (PE) is a potentially fatal occurrence with a broad spectrum of risk factors. A 75-year-old male presented to the emergency room with five days of shortness of breath, back pain, and hemoptysis. A CT angiogram demonstrated bilateral pulmonary emboli with a larger thrombus on the right, as well as signs of right heart strain. The patient was started on IV heparin and ultimately underwent a successful embolectomy. Evaluation to determine the underlying etiology of this patient's first-time PE was performed to further stratify his risk of recurrence and the length of anticoagulation required. The provoking factor for his PE was initially unclear as he lacked any risk factors such as recent surgeries, periods of immobility, or previous diagnosis of malignancy. The patient was noted to be on an erectile dysfunction supplement called "Eroxin," and he had been taking it for the past six months. Eroxin contains an ingredient called fenugreek, which is believed to enhance testosterone levels by inhibiting aromatase and 5-alpha-reductase activity. Fenugreek has previously been associated with the formation of PEs, and likely contributed to the PE in this patient. This is likely due to testosterone-induced polycythemia and increased platelet aggregation. This case highlights the concern around supplements as their ingredients are poorly regulated and occasionally found to be tainted with unlisted ingredients. This also highlights the importance of gathering a complete supplement history from patients as their use can lead to serious illness. Lastly, it encourages considering testosterone use as a potential thrombogenic risk factor.

Suspected cholinergic toxicity due to cevimeline hydrochloride and Bacopa monnieri interaction: a case report.

BACKGROUND: Muscarinic agonists are indicated for the treatment of many conditions including ileus, urinary retention, glaucoma, and Sjögren's syndrome. Due to their lack of tissue specificity, these drugs can lead to undesirable side effects at off-target sites and may be potentiated by supplements that impact the half-life of these drugs. CASE PRESENTATION: A 58-year-old Caucasian female with history of Sjögren's syndrome, who was being managed with cevimeline, presented to the primary care office with reported hyperhidrosis, malaise, nausea, and tachycardia. She reported taking an herbal supplement containing B. monnieri and phosphatidylserine the previous night. It has been previously demonstrated that B. monnieri alters cytochrome P450 enzymes. Electrocardiogram showed no acute ST-T changes. Clinical improvement occurred with hydration and discontinuation of the supplement. CONCLUSIONS: To our knowledge, there has only been one other documented cevimeline overdose, and it was not associated with an herbal supplementation interaction. Physicians should actively elicit herbal supplement information from patients to anticipate possible drug-herb interactions. An additional consideration of clinical relevance is the known genetic variability that may affect drug responsiveness due to differences in metabolism and half-life of drugs that arise from common genetic variants of cytochrome P450 genes.

The Efficacy of Herbal Supplement Danggui Buxue Tang for Relieving Menopausal Symptoms.

OBJECTIVES: This study aimed to further explore the efficacy and safety of Danggui Buxue Tang (DBT), a simple herbal formula, for improving the quality of life of women suffering from menopausal symptoms. METHODS: A third clinical trial to determine the clinical efficacy of high-dose DBT for a period of 12 weeks was carried out. The standard Menopause-Specific Quality of Life (MENQOL) assessment chart was used for the evaluation. Safety was defined as an absence of direct estrogenic effects, serum inflammatory cytokines. Notably, interleukin IL-6, IL-8 and tumor necrosis factor TNF-α, known to be directly related to estrogenic reactions in menopause studies, were monitored. RESULTS: The third clinical trial indicated an overall improvement in the four domains of MENQOL, offering further proof of the efficacy of DBT demonstrated in the two previous trials. The serial checks of the three cytokines related to estrogen activities did not show either upward or downward trends. The haphazard behavior reactions of the three cytokines offered indirect indications that DBT improved the MENQOL independently from estrogen activities. CONCLUSIONS: The three clinical trials using DBT to relieve menopausal syndrome have offered solid evidence for its efficacy. The uncertainty regarding whether the "phytoestrogen" contained in DBT had bioactivities similar to estrogen was alleviated through the confirmation that no strict estrogenic bioactivities were observed. The issue of safety was further clarified via laboratory platform studies on DBT, which not only showed the lack of similarity with estrogen actions but also confirmed the value of combining the two herbs in the classic formula.

Ashwagandha as a Unique Cause of Thyrotoxicosis Presenting With Supraventricular Tachycardia.

Ashwagandha root extract (ARE) is a reputed herbal supplement in Ayurvedic medicine for a variety of health conditions. To date, scant attention has been paid to thyrotoxicosis associated with Ashwagandha and it is rarely reported in the literature. We report a 73-year-old female who presented with supraventricular tachycardia, symptoms of hyperthyroidism and significantly low TSH levels, after two years of using ARE as a self-administered treatment for hypothyroidism. Full symptomatic resolution and biochemical improvement ensued upon cessation of the supplement. Though the pathophysiology remains obscure, we hope to promote awareness concerning this rare yet possible side effect of Ashwagandha.

Identification of phosphodiesterase type-5 (PDE-5) inhibitors in herbal supplements using a tiered approach and associated consumer risk.

The use of herbal supplements for improved sexual performance is a common practice amongst the youth and some senior citizens in Ghana. These products are considered 'natural' and greatly preferred over synthetic alternatives due to the assurance of little to no adverse effects by producers. However, the high rate of adulteration often compromises their safety. Forty herbal supplements, of which 25 were previously shown to result in medium to high intake of phosphodiesterase type-5 (PDE-5) inhibitors using a PDE-Glo bioassay, were further investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to examine the reliability of the bioassay and whether the observed higher responses could be ascribed to inherent plant constituents or adulterants. Results showed significant amounts of vardenafil, tadalafil and especially sildenafil, in 2, 1 and 10 samples, respectively, with total concentration levels resulting in estimated daily intakes (EDIs) above 25 mg sildenafil equivalents with six supplements even having EDIs above 100 mg sildenafil equivalents. Only one sample contained a natural ingredient (icariin), but its concentration (0.013 mg g-1) was too low to explain the observed potency in the bioassay. The estimated concentrations of PDE-5 inhibitors in 35 supplements, according to the bioassay, were in line with those of the LC-MS/MS analysis. However, discrepancies were observed for five supplements. Further examination of one of the latter supplements using the PDE-Glo bioassay to select the positive fraction and further examination with LC-MS/MS and 1H-NMR revealed the presence of hydroxythiohomosildenafil, a sildenafil analogue not yet included in the liquid chromatography-mass spectrometry reference library. This study demonstrates the significance of applying a tiered approach, where the use of a bioassay is followed by chemical analysis of bioactive samples in order to identify unknown bioactive compounds.

Anti-malarial activity in a Chinese herbal supplement containing Inonotus obliquus and Panax notoginseng.

Plasmodium falciparum, the most virulent human malaria parasite, causes serious diseases among the infected patients in the world and is particularly important in African regions. Although artemisinin combination therapy is recommended by the WHO for treatment of P. falciparum-malaria, the emergence of artemisinin-resistant parasites has become a serious issue which underscores the importance of sustained efforts to obtain novel chemotherapeutic agents against malaria. As a part of such efforts, thirty-nine herbal extracts from traditional Chinese medicine (TCM) were assayed for their anti-malarial activity using 3D7 strain of P. falciparum. Three herbal supplements appeared to possess higher specific anti-malarial activity than the others. One of them (D3) was separated by two sequential fractionations with reverse-phase (the first step) and normal-phase (the second step) liquid chromatography, in which some fractions resulted in higher specific activities than those of D3 or the previous fractions. Cell toxicity assay was performed with the fractions of the first fractionation and demonstrated no obvious cell toxicity. These results suggest that structure determination of the major compound for the anti-malarial activity in D3 may help the development of more potent chemicals in the future.