Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.

Effects of Pycnogenol® in people with post-COVID-19 condition (PYCNOVID): study protocol for a single-center, placebo controlled, quadruple-blind, randomized trial.

BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC. METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study. DISCUSSION: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.

Effectiveness and safety of Chaihu-Shugan-San for treating depression based on clinical cases: An updated systematic review and meta-analysis.

BACKGROUND: Chaihu-Shugan-San (CSS), a Traditional Chinese Medicine formula, has been widely used for treating depression since the Ming Dynasty, as recorded in Jingyue Quanshu, but its effectiveness and safety lack comprehensive and objective evaluation. Based on our meta-analysis, we aimed to adequately evaluate the efficacy and risk of CSS by considering the latest clinical literature. METHODS: Multiple databases, including PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang, were used to collect clinical data. The quality of the included clinical studies was assessed using the Cochrane Risk of Bias Tool, and the data were meta-analyzed using Review Manager 5.0 and Stata 17. The data were obtained from a genome-wide association study, and Mendelian randomization (MR) was performed using R Software 4.3.2 with the TwoSampleMR and MR Pleiotropy RESidual Sum and Outlier packages. RESULTS: A total of 15 studies with 1034 patients and 6 antidepressant drugs were included in this work. Meta-analyses revealed that drug combinations of CSS and antidepressants significantly improved depressive symptoms (weighted mean difference = -4.21; 95% confidence interval [CI]: -5.62--2.81), increased the effective rate (odds ratio [OR] = 3.82; 95% CI: 2.44-6.83), and reduced side effects (OR = -3.55; 95% CI: -5.66--1.43) compared with antidepressant monotherapy. Additionally, compared with antidepressant monotherapy, CSS alone exhibited fewer side effects (95% CI:-9.25--6.95). Like antidepressants, CSS also improved depressive symptoms (weighted mean difference = -0.05; 95% CI: -0.63--0.52) and increased the effective rate (OR = 1.07; 95% CI: 0.52-2.20). Additionally, MR was used to evaluate the safety of traditional antidepressants, as there was a causal association between amitriptyline and body mass index. CONCLUSION: This analysis demonstrated that compared with traditional antidepressants, CSS combined with antidepressants was more effective and safer for treating depressed patients. MR showed that a causal relationship may exist between amitriptyline and body mass index. Therefore, clinicians should carefully consider the advantages and potential drawbacks of Traditional Chinese Medicine and classic drugs to serve patients better.

Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial.

BACKGROUND: Acute bronchitis is the most common respiratory disease. Mixture of Ivy Leaf Extract and Coptidis rhizome syrup has shown good treatment efficacy against chronic bronchitis and acute respiratory infections. This study aimed to evaluate the efficacy and safety of Mixture of Ivy Leaf Extract and Coptidis rhizome compared with those of Pelargonium sidoides extract, for the treatment of acute bronchitis. METHODS: We performed a multicenter, randomized, double-blind, active-controlled, parallel phase III study in 220 patients with acute bronchitis. The participants were offered either Mixture of Ivy Leaf Extract and Coptidis rhizome syrup (AGS) and placebo of P. sidoides tablet or placebo syrup and active tablet of P. sidoides (AGU) for 7 days. The primary endpoint was the change in the Bronchitis Severity Score (BSS) from the baseline visit (visit 2) to day 7 (visit 3). RESULTS: For the primary outcome, there was no significant difference in the change of total BSS between visits 2 and 3 (-4.10 ± 1.93 vs. -4.24 ± 1.85, p = 0.5125), and since the upper limit of the confidence interval (1.00) was smaller than the predetermined non-inferiority margin (1.17), it was confirmed that the AGS group was non-inferior to the AGU group. The changes in each symptom in the BSS between visits 2 and 3 also showed no significant differences. The overall improvement rate measured by the investigator (91.7 vs. 89.7%; p = 0.3506) and the satisfaction rate of the participants at visit 3 also showed no significant differences (97.2 vs. 94.4%; p = 0.4388). Regarding safety issues, adverse reactions were noted in both groups similarly, with no serious adverse events (4.55 vs. 3.64%, p > 0.999). CONCLUSION: Mixture of Ivy Leaf Extract and Coptidis rhizome syrup is as effective and safe as P. sidoides in controlling symptoms of acute bronchitis.

Efficacy and Safety of Panax ginseng Sprout Extract in Subjective Memory Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Sprout ginseng extract (ThinkGIN™) manufactured through a smart farm system has been shown to improve memory in preclinical studies. This study conducted a 12-week randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of ThinkGIN™ for improving memory in subjective memory impairment (SMI). Subjects aged 55 to 75 years with SMI participated in this study. A total of 80 subjects who met the inclusion/exclusion criteria were assigned to the ThinkGIN™ group (n = 40, 450 mg ThinkGIN™/day) or a placebo group (n = 40). Efficacy and safety evaluations were conducted before intervention and at 12 weeks after intervention. As a result of 12 weeks of ThinkGIN™ intake, significant differences in SVLT, RCFT, MoCA-K, PSQI-K, and AChE were observed between the two groups. Safety evaluation (AEs, laboratory tests, vital signs, and electrocardiogram) revealed that ThinkGIN™ was safe with no clinically significant changes. Therefore, ThinkGIN™ has the potential to be used as a functional food to improve memory.

Efficacy and safety of total glucosides of paeony in treating primary Sjögren's syndrome: a propensity-matched study.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of total glucosides of paeony (TGP) in patients with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: This study included 236 patients with pSS, including 118 TGP users and 118 non-users. Propensity score matching and Binary logistic regression analyses were used to minimize confounding factors and determine the association between TGP treatment and clinical variables. RESULTS: The baseline indexes of TGP users and non-users were basically the same. The median time of follow-up in the two groups was also similar (p < 0.05). Compared with non-users, TGP users showed higher rates of improvement in dry mouth and eyes and musculoskeletal involvement, as well as more significant reductions in serum alanine aminotransferase (ALT) and direct bilirubin (DBIL) levels after treatment. Logistic regression confirmed that the use of TGP was negatively correlated with the increase of ALT and DBIL in pSS patients, and the reduction in these variables was more pronounced after 2 years of treatment. The incidence of adverse reactions in the TGP users was 11.9%, which was compatible with those in non-users. CONCLUSIONS: TGP is often a safe option for treating pSS patients with musculoskeletal features and abnormal ALT levels. Besides, it can help improve dry mouth and dry eyes and decrease DBIL levels.

Boswellia serrata intoxication manifesting with syndrome of inappropriate antidiuretic hormone secretion, hyponatremia, seizure, and rhabdomyolysis.

Boswellia serrata is an herbal extract from the Boswellia serrata tree that has anti-inflammatory and analgesic properties and alleviates pain caused by rheumatoid arthritis, gout, osteoarthritis, and sciatica. Syndrome of inappropriate antidiuretic hormone secretion accompanied by hyponatremia, seizures, and rhabdomyolysis as a manifestation of Boswellia serrata intoxication has not been reported previously. A 38-year-old female suffered clinically isolated syndrome and has since been regularly taking B. serrata capsules (200mg/d) to strengthen her immune system. She experienced hypersensitivity to light, ocular pain, nausea, dizziness, and lower limb weakness four days after receiving her first BNT162b2 vaccine dose, and she increased the dosage of B. serrata to five capsules (1000mg/d) one week after vaccination. After taking B. serrata at a dosage of 1000mg/d for 3 weeks, she was admitted to the intensive care unit because of a first, unprovoked generalized tonic-clonic seizure. The patient's workup revealed syndrome of inappropriate antidiuretic hormone secretion, which resolved completely upon treatment and discontinuation of B. serrata. In summary, B. serrata potentially causes syndrome of inappropriate antidiuretic hormone secretion when it is taken at high doses. Patients should not self-medicate.

Efficacy and safety of Ginkgo biloba extract in the treatment of unstable angina pectoris: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba is a traditional Chinese medicine extracted from the Ginkgophyta and is commonly used in the treatment of cardiovascular diseases in China. Clinical trials have demonstrated the clinical benefits of Ginkgo biloba extract (GBE) preparations for patients with unstable angina pectoris (UAP). AIM OF THE STUDY: The efficacy of different GBE preparations in treating UAP may vary, leading to a lack of guidance for physicians when choosing GBE preparations. How to make choices among different GBE preparations is a topic worthy of investigation. In order to clarify the efficacy differences among different GBE preparations, provide a reference for their optimal use conditions, this study was conducted. MATERIALS AND METHODS: This study included literature from eight databases from inception to November 2023. It included UAP patients, with the control group receiving conventional treatment and the treatment group receiving different GBE preparations in addition to conventional treatment. Angina efficacy, electrocardiogram (ECG) improvement, and frequency of angina were chosen as outcomes. This study employed a systematic review and Bayesian network meta-analysis, and the surface under the cumulative ranking (SUCRA) curve was used for estimating the efficacy ranking. RESULTS: A total of 98 studies involving 9513 patients and 9 interventions were included. Compared with conventional treatment, GBE preparations combined with conventional treatment had better efficacy in angina symptoms and ECG improvement. According to the SUCRA ranking, Shuxuening injection was most effective in improving angina symptoms and reducing the frequency of angina. Among oral GBE preparations, Ginkgo tablets had the best performance in improving angina symptoms and ECG manifestations, and reducing the frequency of angina. There was no significant difference in the incidence of adverse events between the treatment group and the control group, and all adverse events were mild and self-limiting. Compared with oral preparations, the incidence of adverse events for injections was higher. CONCLUSIONS: GBE preparations may alleviate angina symptoms and myocardial ischemia in the treatment of UAP with favorable safety. Shuxuening injection may be the most effective among all GBE preparations in improving angina symptoms, while Ginkgo tablets may perform best among oral formulations. The optimal use of GBE injection may be for rapidly alleviating angina symptoms and myocardial ischemia in patients with UAP, and oral formulation of GBE may be more suitable for the long-term treatment of patients with milder symptoms. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361487, ID: CRD42022361487.

Effectiveness of Korean Red Ginseng on fatigue in patients with rheumatic diseases: a randomized, double-blind, placebo-controlled study.

BACKGROUND: To evaluate the effectiveness of Korean Red Ginseng (KRG) in managing fatigue in Korean patients with rheumatic diseases. METHODS: Patients were randomly assigned to KRG (2 g/day, n = 60) or placebo (n = 60) groups for 12 weeks of blind phase and then open-label KRG from weeks 12 to 24 (placebo-KRG, continuous-KRG). The primary outcome was the improvement rate in fatigue, defined by an increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at 12 weeks. Secondary outcomes included changes in FACIT-Fatigue and fatigue visual analog scale (VAS) between 0 and 12 weeks and those changes in both indices at 24 weeks. RESULTS: The study enrolled 120 patients (Sjogren syndrome [n = 53], rheumatoid arthritis [n = 43], or both diseases [n = 24]). The mean age was 50.9 ± 11.6 years, with 97.5% being female. Baseline characteristics were similar between the two groups. The improvement rate in FACIT-Fatigue after 12 weeks was higher in the KRG group than in the placebo group, but the difference was statistically insignificant (38.3% vs. 26.7%, p = 0.242). Improvement in fatigue was observed in both groups by increases in FACIT-F (4.6 vs. 4.0) and reductions in fatigue VAS (-16.0 vs. -12.2) scores at 12 weeks. The most frequently reported adverse events during KRG use were pruritus and urticarial, with no significant difference between the two groups. CONCLUSION: Both KRG and placebo groups showed significant reductions in fatigue. KRG treatment for 24 weeks did not reduce fatigue symptoms more than the placebo in patients with rheumatic diseases.

Veratrum nigrum L.: A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, toxicity, and incompatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Veratrum nigrum L. (V. nigrum) is a well-known herb with a lengthy history of use in Asian and European countries. V. nigrum has been traditionally used to treat epilepsy, hypertension, malignant sores, and stroke, and it possesses emetic and insecticide properties. AIM OF THE REVIEW: This review summarized the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, and toxicity of V. nigrum as well as its incompatibility with other herbs. Current challenges in the use of V. nigrum and possible future research directions were also discussed. MATERIALS AND METHODS: Information on V. nigrum was collected from electronic databases such as PubMed, Google Scholar, Web of Science, CNKI, and WanFang DATA; Masterpieces of Traditional Chinese Medicine; local Chinese Materia Medica Standards; and relevant documents. RESULTS: In ethnomedical practice, V. nigrum has been used as an emetic and insecticide. Approximately 137 compounds have been isolated from V. nigrum, including alkaloids, stilbenes, flavonoids, organic acids, and esters. Its crude extracts and compounds have shown various effects, including anticancer, hypotensive, insecticidal, and antimicrobial activities as well as the ability to improve hemorheological abnormalities. Pharmacokinetic studies have indicated that veratramine (VAM) and jervine have high bioavailability and possibly enterohepatic circulation. In addition, the sex-related pharmacokinetic differences in V. nigrum alkaloids warrant further attention. Toxicological studies have indicated that cevanine-type alkaloids and VAM may be the main toxic components of V. nigrum, and purine metabolism disorders may be related to V. nigrum toxicity. Furthermore, the neurotoxicity and embryotoxicity of V. nigrum have also been observed. The quality control of V. nigrum and the mechanism underlying its incompatibility with other herbs also deserve further research and refinement. CONCLUSION: This review summarized the existing information on V. nigrum, laying the foundation for further studies on this herb and its safe use. Among the various compounds present in V. nigrum, steroid alkaloids are the most numerous and have high content; furthermore, they are closely related to the pharmacological effects of V. nigrum, but their toxicity can not also be ignored. Given that toxicity is a critical issue limiting the clinical application of V. nigrum, more toxicological studies on V. nigrum and its active ingredients, especially steroid alkaloids, should be conducted in the future to further explore its toxicity targets and the underlying mechanisms and to provide more evidence and recommendations to enhance the safety of its clinical application.

A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.

Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.

Chemopreventive and immunomodulatory effects of phenolic-rich extract of Commiphora leptophloeos against inflammatory bowel disease: Preclinical evidence.

ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.

Nephroprotective effect of cranberry (Vaccinium oxycoccos) in streptozocin-induced diabetic nephropathy in mice.

OBJECTIVES: Diabetic nephropathy is a chief reason of mortality particularly in individuals with renal dysfunction. The current research was aimed to assess the nephroprotective portion of Vaccinium oxycoccos toward mice diabetic nephropathy induced by streptozotocin (STZ). V. oxycoccos was purchased and used for hydroalcoholic extraction. METHODS: Sixty male mice were subjected to STZ-intraperitoneal injection (45 mg/kg). After diabetes induction, mice were divided into five groups of diabetic control (received only STZ), non-diabetic control (received only citrate buffer), two V. oxycoccos treatment (received V. oxycoccos extract (200 and 400 mg/kg) oral daily by gavage), and metformin treatment (received metformin (500 mg/kg) oral daily by gavage). Glucose and weight of mice were checked weekly. RESULTS: After 28 days, the effect of V. oxycoccos extract on serum and urine parameters were assessed. STZ caused significant decreased in the mice body weight. Mice treated with the V. oxycoccos (400 mg/kg) harbored the lowest weight loss at day 28 (70.2±1.38 g). STZ caused significant increase in the mice FBS. Mice treated with the V. oxycoccos (400 mg/kg) harbored the lowest FBS at day 28 (189.2±1.20 mg/dL). Treatment of mice with V. oxycoccos (400 mg/kg) caused the lowest increase in the levels of cholesterol, HbA1c and triglycerides compared to the diabetic control mice. Compared to the diabetic control group, mice treated with V. oxycoccos (400 mg/kg) had the highest HDL, insulin, SOD, and GSH (p<0.05). The lowest serum BUN, CR, and UR were found in mice treated with V. oxycoccos (400 mg/kg). Anti-inflammatory effects of V. oxycoccos (400 mg/kg) was shown by the lowest TNF-α, IL-6, and TGF-ß1 concentration in mice treated with V. oxycoccos (400 mg/kg). CONCLUSIONS: The current study disclosed that treatment with V. oxycoccos resulted in substantial development in the serum and urine parameters and also antioxidant and anti-inflammatory response of STZ-induced diabetic mice.

Efficacy and Tolerability of a Scutellaria lateriflora L. and Cistus × incanus L.-Based Chewing Gum on the Symptoms of Gingivitis: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Preclinical studies have shown that the combination of Cistus × incanus L. and Scutellaria lateriflora L. extracts exerts beneficial effects on oral health against gingivitis. Thus, this study aimed to assess the tolerability of a chewing gum and its efficacy on gingivitis in a double-blind, placebo-controlled clinical trial. Enrolled subjects (n = 60, 18-70 years) were randomized to receive two chewing gums or a placebo daily for 3 months. At baseline (t0) and monthly (t1, t2, and t3) timepoints, the Quantitative Gingival Bleeding Index (QGBI), the Modified Gingival Index (MGI), and the Oral Health 15 items (OH-15)] were employed to assess potential improvements in gingivitis. Pain was self-quantified via the Visual Analogue Scale (VAS), and the Clinical Global Impression Scale for Severity of illness (CGI-S) helped in evaluating the oral general conditions. This study is listed on the ISRCTN registry. At t3, the QGBI, MGI, OH-15, VAS, and CGI-S values decreased in the treated but not in the placebo group (ß = 0.6 ± 0.1, t176 = 3.680, p < 0.001; ß = 0.87 ± 0.21, t115 = 4.263, p < 0.001; ß = 5.3 ± 2.5, t172 = 2.086, p = 0.038; ß = 3.16 ± 0.51, t88 = 6.253, p < 0.001; and ß = 1.09 ± 0.32, t83 = 3.419, p < 0.001, respectively). A significant improvement in gingival health occurred after a 3-month intervention with the chewing gums containing S. lateriflora and C. incanus extracts.

The anti-urolithiasis activity and safety of strangury-relieving herbs: A comparative study based on fruit fly kidney stone model.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is one of the oldest and most widespread urological diseases suffered globally. In the long history of Traditional Chinese Medicine, there're numerous herbs documented with strangury-relieving properties playing crucial roles in treating various urological disorders, including dysuria, hematuria, and renal colic, etc., which may be caused by urolithiasis. Exploring these herbs may reveal safer, more effective, and cost-efficient drugs and therapies for urolithiasis. AIM OF THE STUDY: This study aims to assess the anti-urolithiasis efficacy and safety of 46 Chinese traditional and folk herbal drugs using the fruit fly (Drosophila melanogaster) kidney stone model, in order to identify the most valuable ethnomedicinal materials. MATERIALS AND METHODS: Water extract and 50% ethanol extract of each herb were prepared respectively. 0.2% (w/w) sodium oxalate was chosen as appropriate lithogenic agent through fruit fly life span study. Male fruit-flies within three days of emergence were aged for an additional three days, then were randomly divided into experimental groups, model group and control groups (n = 20). The flies in blank control group, model group and positive control group were fed with standard food, standard food containing 0.2% sodium oxalate, standard food containing 0.2% sodium oxalate and 3% (w/w) Garcinia cambogia extract, respectively. Meanwhile, flies in the experimental groups were raised on standard food containing 0.2% sodium oxalate and 3% (w/w) herbal extract. The anti-urolithiasis capability of the extracts was evaluated using stone area ratio (the stone area divided by the area of the Malpighian tubule) and stone-clearing rate. Additionally, the 7-day mortality rate was employed as an indicator of safety. RESULTS: Out of the 46 herbs, 24 exhibited significant anti-urolithiasis effects in their water extracts. Among them, Herba Nephrolepidis, Herba Humuli, Herba Desmodii Styracifolii, Cortex Plumeriae Rubrae, and Herba Mimosae Pudicae showed us a low 7-day mortality rate of fruit-flies as well. However, only a limited number of herbal extracts (8 out of 46) showed obvious anti-urolithiasis activity in their 50% ethanol extracts. CONCLUSION: Highly potential anti-urolithiasis candidates were discovered from strangury-relieving herbs recorded in classical Traditional Chinese Medicine works, highlighting the significant value of traditional and folk ethnopharmacological knowledge.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Comparison of patch test positivity after 24 and 48 hours of occlusion time in patients of allergic contact dermatitis: A prospective study.

BACKGROUND: Patch test is the gold standard for diagnosing allergic contact dermatitis. Conventionally, the patches are applied for 48 h, which in tropical weather conditions causes excessive sweating, leading to irritation, and sometimes the patches come off, making the test inconclusive. OBJECTIVE: To compare the patch test positivity after 24 and 48 h of occlusion time in patients of allergic contact dermatitis, using standard allergen concentration. MATERIALS AND METHODS: Clinically suspected patients of allergic contact dermatitis were enrolled and patch tested using the Indian Standard Series, parthenium acetone extracts (1:50, 1:100 and 1:200 dilutions) and patient material. Patches were applied in duplicate on either side of the back, using a random number table. One set of patches was removed after 24-h of occlusion, while the other set after 48-h. Readings were performed at 48- and 96-h by two independent dermatologists, blinded to the duration of occlusion. RESULTS: The study had 97 adult patients (58 males and 39 females; mean age: 48.12 ± 13.07 years). A total of 133 and 142 positive reactions were observed after 48 h occlusion at 48 and 96 h reading, respectively. Of these 117 (87.9%) and 132 (92.9%) patches were positive and concordant and noted at 24 h occlusion time. The Cohen's kappa coefficient were 0.94 for 48 h and 0.97 for 96 h reading, hence showing an almost complete agreement (ⱪ > 0.81) between patches occluded for 24 and 48 h. CONCLUSION: Though there is no significant difference in patch test positivity among ISS allergens after either occlusion time, 48 h occlusion performs significantly better compared with 24 h, when reactions of all allergens (ISS, patient material and parthenium acetone extract) are analysed together.

Electroencephalographic profile of Salvia amarissima Ortega and amarisolide A in the absence and presence of PTZ-induced seizures in mice.

Salvia amarissima Ortega is a plant used in traditional medicine to treat CNS's affections. Despite its depressant properties in anxiety and fibromyalgia, there is no scientific evidence about its capability to control seizure activity. This study aimed to investigate the effects of the S. amarissima aqueous extract (SAAE) and its metabolite amarisolide A (AMA) on the electrocorticographic (ECoG) activity. The ECoG profiles were previously and concurrently analyzed to the pentylenetetrazole (85 mg/kg, i.p.)-induced seizure behavior after thirty min of the administration of several doses of the SAAE (1, 10, 30, and 100 mg/kg, i.p.) and two doses of AMA (0.5 and 1 mg/kg, i.p.). A dosage of AMA (1 mg/kg,i.p.) was selected to explore a possible mechanism of action by using antagonists of inhibitory receptors such as GABAA (picrotoxin, 1 mg/kg, i.p.) or 5-HT1A of serotonin (WAY100635, 1 mg/kg, i.p.). Significant changes in the frequency bands and the spectral power were observed after the treatment alone. Additionally, SAAE and AMA produced significant and dose-dependent anticonvulsant effects by reducing the incidence and severity of seizures and increasing latency or survival. Both antagonists prevented the effects of AMA in the severity score of seizures and survival during the tonic-clonic seizures. In conclusion, our preclinical data support that S. amarissima possesses anticonvulsant properties, in part due to the presence of amarisolide A, mediated by different inhibitory mechanisms of action. Our scientific evidence suggests that this Salvia species and amarisolide A are potential neuroprotective alternatives to control seizures in epilepsy therapy.