Investigation of Drug-Interaction Potential for Arthritis Dietary Supplements: Chondroitin Sulfate, Glucosamine, and Methylsulfonylmethane.

Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions.

Tandem Mass Spectrometry Molecular Networking as a Powerful and Efficient Tool for Drug Metabolism Studies.

Molecular networking (MN) has become a popular data analysis method for untargeted mass spectrometry (MS)/MS-based metabolomics. Recently, MN has been suggested as a powerful tool for drug metabolite identification, but its effectiveness for drug metabolism studies has not yet been benchmarked against existing strategies. In this study, we compared the performance of MN, mass defect filtering, Agilent MassHunter Metabolite ID, and Agilent Mass Profiler Professional workflows to annotate metabolites of sildenafil generated in an in vitro liver microsome-based metabolism study. Totally, 28 previously known metabolites with 15 additional unknown isomers and 25 unknown metabolites were found in this study. The comparison demonstrated that MN exhibited performances comparable or superior to those of the existing tools in terms of the number of detected metabolites (27 known metabolites and 22 unknown metabolites), ratio of false positives, and the amount of time and effort required for human labor-based postprocessing, which provided evidence of the efficiency of MN as a drug metabolite identification tool.

Chemical-based primary human hepatocyte monolayer culture for the study of drug metabolism and hepatotoxicity: Comparison with the spheroid model.

Traditionally cultured monolayers of primary human hepatocytes (PHHs) deteriorate within days and thereby become unsuitable for drug-related studies. PHH spheroids (3D PHHs) maintain liver functions for weeks, but are considerably more demanding. Recently, a chemical-based approach (5C PHHs) succeeded in long-term culture of hepatocyte monolayers, but it remains unclear whether the drug-related functions are preserved. To clarify this, we compared the 5C and 3D PHHs in terms of gene expression analysis, proteomic analysis, functionality (basal and induced activities of representative CYP450 enzymes and urea and albumin secretions), survival in culture, and sensitivity to representative drugs. In all comparisons, which spanned culture durations of up to 4 weeks, the 5C PHHs performed at least as well as the 3D PHHs. Hence, the novel 5C PHH monolayer format combines the convenience of the traditional monolayer format with the functionality and maintainability of the spheroid format. Our results suggest that 5C PHH monolayers can be used more conveniently and efficiently for high-throughput drug screening, preclinical drug safety evaluations, and mechanistic studies.

MS-Based Molecular Networking of Designer Drugs as an Approach for the Detection of Unknown Derivatives for Forensic and Doping Applications: A Case of NBOMe Derivatives.

The NBOMe family is a group of new psychoactive substances (NPSs). In this study, the fragmentation patterns of NBOMe derivatives were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The MS/MS spectral data was used to establish a molecular networking map for NBOMe derivatives. The fragmentation patterns of nine NBOMe derivatives were interpreted on the basis of their product ion spectral data. NBOMe derivatives generally showed similar product ion spectral patterns; among them, the halogen-substituted methoxybenzyl ethanamine type derivatives showed a characteristic product ion of a radical cation. Molecular network analysis of the MS/MS data revealed that all NBOMe derivatives formed one integrated networking cluster that discriminated them from other types of NPSs. NBOMe derivatives were spiked into human urine and identified by connection to the NBOMe database network. Furthermore, the NBOMe compounds that were not registered in the database were also recognized as an NBOMe-related substance by molecular networking. These results demonstrate the potential of using molecular networking-based screening methods for designer drugs, and the proposed method would be useful in forensic or doping analysis.

The role of gut microbiota in the pharmacokinetics of antihypertensive drugs.

The intestine is one of the most important sites for the metabolism of several xenobiotic compounds. In addition to intestinal drug-metabolizing enzymes and drug transporters, gut microbial enzymes modulate the biotransformation of orally administered drugs in the gastrointestinal tract. Antihypertensive drugs such as amlodipine and nifedipine could be metabolized by gut microbial enzymes, which may influence drug absorption, leading to changes in pharmacological potency of the drug and eventual failure of the appropriate blood pressure control or unexpected side effects. This may suggest that there are additional mechanisms that can alter the therapeutic efficacy of antihypertensive drugs, especially in certain pathological conditions of the gastrointestinal tract or with concomitant use of substances such as antibiotics and probiotics that might alter the gut microbial composition. This review describes the metabolism of antihypertensive drugs by hepatic and intestinal microbial enzymes in an attempt to understand the potential effects of gut microbiota on their pharmacokinetics.

Inhibitory Effects of Garcinia cambogia Extract on CYP2B6 Enzyme Activity.

This study assessed the inhibitory effects of Garcinia cambogia extract on the cytochrome P450 enzymes in vitro. G. cambogia extract was incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes and recombinant CYP2B6 isozyme, and the formation of the marker metabolites was measured to investigate the inhibitory potential on cytochrome P450 enzyme activities. The results showed that G. cambogia extract has significant inhibitory effects on CYP2B6 activity in a concentration-dependent manner. Furthermore, the inhibition was potentiated following preincubation with NADPH, indicating that G. cambogia extract is a time-dependent inhibitor of CYP2B6. Meanwhile, hydroxycitric acid, the major bioactive ingredient of G. cambogia extract, did not exhibit significant inhibition effects on cytochrome P450 enzyme activities. G. cambogia extract could modulate the pharmacokinetics of CYP2B6 substrate drugs and lead to interactions with those drugs. Therefore, caution may be required with respect to concomitant intake of dietary supplements containing G. cambogia extract with CYP2B6 substrates.

Suggestion for Objective Evaluation of Comparative Pulse Diagnosis.

Objectives: Pulse is a method of Korean medicine diagnosis and is an important clue to detect the organs, nature, and progress of the disease. Pulse examination is included in the basic examination of Korean medicine doctors, but there is no standardized method for diagnosing pulse although the types and methods of the pulse taking are briefly described in the literature, making it difficult to spread the examination method. In this regard, I would like to propose an objective evaluation method. Methods: Although the importance of pulse examination and the method of pulse examination are known in the literature, it is difficult for undergraduate students or inexperienced Korean medicine doctors to access it, so in this paper a method of marking the size of the pulse power in the blank space for objective evaluation was devised and presented. Results: The size of the pulse power should be indicated using the 1-cell, 3-cell, or 5-cell method according to the left and right wrists and the cun, guan and chi on both sides. Conclusion: The method of pulse diagnosis is an important diagnostic method as a verification process for making a Korean medical diagnosis. The remaining Korean medicine diagnostic methods, including pulse diagnosis, also need to undergo objectification. It is believed that the objectification of these diagnostic methods will lead to an improvement in the treatment rate of Korean medicine.

Evaluating flavonoids as potential aromatase inhibitors for breast cancer treatment: In vitro studies and in silico predictions.

Aromatase inhibitors are commonly employed in the treatment of hormone-dependent breast cancers, and flavonoids have emerged as a promising alternative to existing drug classes with unfavorable side effects. In this study, we conducted in vitro investigations into CYP19A1 (aromatase) inhibitory potential of 14 flavonoids, including pinocembrin, sakuranetin, eriodictyol, liquiritigenin, naringenin, hesperetin, flavanone, baicalein, chrysin, nobiletin, luteolin, sinensetin, tricin, and primuletin. Flavonoids displaying inhibitory activity were further assessed using in silico tools, such as molecular docking to predict binding affinities, as well as SwissADME, admetSAR, and QED (Quantitative Estimate of Drug-likeness) for drug-likeness prediction. Flavonoids with IC50 values less than 10 µM, pinocembrin, eriodictyol, naringenin, liquirtigenin, sakuranetin, and chrysin, exhibited favorable physicochemical properties and ADME profiles, suggesting their potential for development as novel flavonoid-based aromatase inhibitors. This study would provide valuable insights for the development of flavonoid-based aromatase inhibitors for the treatment of breast cancer.

Neural mechanisms of acupuncture for peripheral facial nerve palsy: A protocol for systematic review and meta analysis.

BACKGROUND: Peripheral facial nerve palsy (PFNP) is a cranial neuropathy that occurs when the seventh facial nerve is damaged. PFNP seriously affects patients' quality of life, and approximately 30% of patients suffer from sequelae, such as unrecovered palsy, synkinesis, facial muscle contracture, and facial spasm. Many studies have confirmed the effectiveness of acupuncture for the treatment of PFNP. However, the specific mechanism remains unclear and needs to be further explored. Therefore, the purpose of this systematic review is to investigate the neural mechanisms underlying acupuncture treatment for PFNP using neuroimaging methods. METHODS: We will search all published studies from inception to March 2023 using the following databases: MEDLINE, Cochrane Library, EMBASE, CNKI, KMBASE, KISS, ScienceON, and OASIS. All clinical studies evaluating the effectiveness of acupuncture for treating PFNP using functional neuroimaging will be selected without language restrictions. Two reviewers will independently conduct the study selection, data extraction, and risk of bias assessment, according to a predetermined protocol. The outcomes, including the types of functional neuroimaging techniques, brain function alterations, and clinical outcomes, such as the House-Brackmann scale and Sunnybrook Facial Grading System, will also be analyzed. Coordinate-based meta-analysis and subgroup analyses will be performed if possible. RESULTS: This study will analyze the effect of acupuncture on brain activity alterations and clinical improvement in patients with PFNP using functional neuroimaging. CONCLUSION: This study will provide a comprehensive summary and help elucidate the neural mechanisms of acupuncture treatment for PFNP. PROSPERO REGISTRATION NUMBER: CRD42022321827.

Neural mechanisms underlying peripheral facial nerve palsy: A protocol for systematic review and meta-analysis of neuroimaging studies.

BACKGROUND: Peripheral facial nerve palsy is a general term used to describe diseases that cause lower motor neuron lesions in the facial nerve. The most common cause of peripheral facial nerve palsy is idiopathic Bell's palsy (BP), accounting for 60% to 70% of all peripheral facial nerve palsy cases. Idiopathic BP is found in various medical conditions, such as ischemia, viral infection, and neuroinflammation; however, the specific pathophysiology remains unclear. Neuroimaging techniques help understand the neural mechanisms underlying various neurological disorders. In recent years, several studies have applied functional neuroimaging to investigate alterations of brain function in BP patients. However, the results have been inconsistent due to differences in methodology and quality. Moreover, systematic reviews of studies on functional neuroimaging for BP are insufficient. Therefore, the present study aims to verify the neural mechanisms of brain alterations and draw conclusions about the functional reorganization in patients with BP. METHODS: This review includes all suitable studies published on or before October 31, 2022. A thorough search will be conducted using the following databases: MEDLINE, Cochrane Library, Excerpta Medica Database (EMBASE), China Knowledge Resource Integrated Database (CNKI), Korean Medical database (KMBASE), Korean Studies Information Service System (KISS). Clinical studies of BP using functional neuroimaging will be selected. We will apply a coordinate-based meta-analysis because most individual neuroimaging studies provide their results as coordinates in the standard space. The primary outcomes will include the types of functional neuroimaging methods and alterations of brain function in BP patients. The secondary outcomes will include the information about clinical measurement of the disease. Study selection, data extraction, and risk of bias assessment will be conducted. If possible, heterogeneity tests, data synthesis, and subgroup analyses will be conducted. RESULTS: The study will analyze the alterations in brain activity and worsening of clinical symptoms caused by idiopathic BP. CONCLUSION: The aim of this study is to investigate functional reorganization of brain alterations in patients with BP. This review will improve the understanding of the neural mechanisms of BP based on the most recent publications through extensive data retrieval. If sufficient data are collected, a sensitivity analysis is performed to verify the robustness of the conclusions.

Molecular networking-guided strategy for the pharmacokinetic study of herbal medicines: Cudrania tricuspidata leaf extracts.

In this study, the pharmacokinetic profiles of the bioactive components in the leaf extract of the medicinal herb, Cudrania tricuspidate, were investigated using an MS/MS-based molecular networking system. To identify the major active components of the C. tricuspidate leaf extract (CLE), HPLC-DAD analysis was conducted with a standard mixture of six flavonoids (rutin, isoquercitrin, nicotiflorin, kaempferol 3-O-glucoside, quercetin, and kaempferol). The unknown peaks were determined via molecular networking analysis using the mass dataset obtained by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). For the subsequent pharmacokinetic study, CLE (1 g/kg) was orally administered to rats, and plasma samples were collected. The product ion mass data of plasma samples using LC-QTOF/MS were obtained and subjected to molecular networking analysis. The resulting molecular networking map indicated that the glucuronide metabolites of quercetin and kaempferol were the major circulating species. Accordingly, quercetin and kaempferol were determined following ß-glucuronidase treatment, and their pharmacokinetic parameters were calculated. These findings indicate that the proposed molecular network-based approaches are potential and efficient methods for the pharmacokinetic study of herbal medicines.

A Severe Cervical Spondylotic Myelopathy Patient Treated with Integrative Korean Medicine Including Acupuncture, Bee Venom Pharmacopuncture and Herbal Medicine: a case report.

Cervical spondylotic myelopathy (CSM) is common in elderly people and severe CSM patients are recommended to receive surgery. However, in some cases, surgery may fail to improve the patients' symptoms. An 80-year-old man diagnosed with CSM complained of right hemiplegia and right arm and leg pain with the presence of a Foley catheter, despite treatment with laminectomy and laminoplasty. Acupuncture, bee venom pharmacopuncture, and herbal medicine were administered for 129 days. As a result, manual muscle testing (MMT) and the Modified Barthel Index (MBI) improved, the pain in his right arm and leg decreased, and he was able to urinate by himself. This case report implies that integrative Korean medicine (IKM) can be an option for patients suffering from muscular weakness resulting from myelopathy.

Ginkgo biloba leaf extract suppresses intestinal human breast cancer resistance protein expression in mice: Correlation with gut microbiota.

In this study, we investigated the effects of treatment with Gingko biloba leaf extract (GLE) on intestinal transporter expression and gut microbiota composition in mice and the correlation between intestinal transporter expression and gut microbiota composition in mice. When GLE was orally administered to mice, intestinal BCRP expression was significantly suppressed. Pharmacokinetic studies showed that the maximum plasma concentration and area under the curve values of sulfasalazine were increased more than twice by treatment with GLE compared with those in the control group. GLE treatment significantly decreased the populations of Proteobacteria and Deferribacteres at the phylum level. Correlation analysis showed that BCRP expression was positively or negatively correlated with the composition of gut bacteria. In Caco-2 cells, GLE treatment did not affect BCRP expression, but treatment with the lysates of GLE-treated mouse feces significantly suppressed BCRP expression. These findings demonstrate that the suppression of intestinal BCRP expression following GLE treatment may occur through modulation of the gut microbiota composition. Thus, the present study suggests that modulation of gut microbiota composition may cause drug transporter-mediated herb-drug interactions.

Efficacy and safety of Onkyeong-tang in treating cold hypersensitivity in the feet of Korean women: protocol for a double-blind, randomized, placebo-controlled, parallel-group, multicenter clinical study.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) commonly affects Asian women, especially Korean women, and it negatively impacts the quality of life of the affected individuals. One commonly used herbal prescription for treating CHHF is Onkyeong-tang (OKT). Although OKT is widely used clinically in treating CHHF, no randomized clinical trial has been performed to evaluate the efficacy and safety of OKT in the treatment of cold hypersensitivity in the feet (CHF). This clinical trial aims to provide objective evidence for the basis of using OKT in the treatment of CHF in Korean women. METHODS: This trial will be a double-blind, randomized, placebo-controlled, parallel-group, multicenter pilot study. A total of 112 participants will be randomly divided into an OKT treatment group or a placebo group with a 1:1 ratio via a web-based randomization system. The OKT and placebo groups will receive prescribed medications orally three times per day (3 g each time) before or between meals for 8 weeks. The primary outcome studied will be the changes in Visual Analog Scale (VAS) scores of CHF from baseline. Secondary outcomes studied will be the VAS score changes of cold hypersensitivity in the hands, changes in the skin temperature of the hands and feet, total scores of the Korean version of the World Health Organization Quality of Life Scale-abbreviated version, and the results of the cold stress test. DISCUSSION: This trial will be the first clinical trial to assess the efficacy and safety of OKT in the treatment of CHF. We anticipate that the findings of the study will provide evidence for the basis of using OKT in treating CHF symptoms and generate basic data for designing a further large-scale randomized clinical trial. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT0003723. Retrospectively registered on 8 April 2019.

Determination of Urinary Caffeine Metabolites as Biomarkers for Drug Metabolic Enzyme Activities.

Caffeine is commonly taken via the daily dietary consumption of caffeine-containing foods. The absorbed caffeine is metabolized to yield various metabolites by drug-metabolizing enzymes, and measuring the levels of each caffeine metabolite can provide useful information for evaluating the phenotypes of those enzymes. In this study, the urinary concentrations of caffeine and its 13 metabolites were determined, and the phenotypes of drug metabolic enzymes were investigated based on the caffeine metabolite ratios. Human urine samples were pretreated using solid phase extraction, and caffeine and its metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Based on the urinary caffeine metabolite concentrations, the caffeine metabolite ratios were calculated for six human subjects at specified time points after caffeine intake. Variations in urinary metabolite levels among individuals and time points were reported. In addition, the resultant enzyme activities showed different patterns, depending on the metabolite ratio equations applied. However, some data presented a constant metabolite ratio range, irrespective of time points, even at pre-dose. This suggests the possibility of urinary caffeine metabolite analysis for routine clinical examination. These findings show that urinary caffeine and the metabolite analysis would be useful in evaluating metabolic phenotypes for personalized medicine.

A Hydroxypropyl Methylcellulose-Based Solid Dispersion of Curcumin with Enhanced Bioavailability and its Hepatoprotective Activity.

Curcumin is a polyphenol compound derived from the rhizomes of Curcuma longa that exhibits antioxidant, anti-inflammatory, anticancer, and antimicrobial properties. However, its low solubility in aqueous solutions, low absorption following oral administration, and rapid degradation limit its use as a functional food material. In this study, a hydroxypropyl methylcellulose-based solid dispersion of curcumin (DW-CUR 20) was prepared and its bioavailability was evaluated. In addition, its therapeutic efficacy as a hepatoprotective agent was investigated using the model of tert-butyl hydroperoxide (t-BHP)-induced hepatocyte damage. The rat plasma pharmacokinetic study showed that the oral curcumin bioavailability of DW-CUR 20 significantly increased compared to that of non-formulated curcumin. DW-CUR 20 showed a concentration-dependent hepatocyte protective effect on t-BHP-induced HepG2 cells. DW-CUR 20 inhibited the release of lactate dehydrogenase and decreased apoptosis-related proteins such as Poly (ADP-ribose) polymerase, cleaved caspase-7 and cleaved caspase-8 on t-BHP-treated HepG2 cells. These findings suggest that DW-CUR 20 could be a promising formulation for enhancing the therapeutic efficiency of curcumin and for improving the safety.

Herbal Medicines for Cold Hypersensitivity in the Hands and Feet: A Systematic Review and Meta-Analysis.

Objectives: Cold hypersensitivity in the hands and feet (CHHF) and Raynaud's phenomenon (RP) are prevalent among Asian populations, especially among women, who exhibit a higher rate of cold hypersensitivity that may be associated with gynecological problems. In several countries, herbal medicine has effectively treated cold hypersensitivity symptoms. This systematic review and meta-analysis of the literature was undertaken to evaluate the efficacy of herbal medicine for the treatment of CHHF in adults. Design: Through March 31, 2018, comprehensive databases were searched, including MEDLINE, EMBASE, Cochrane Library, Chinese Academic Journal, and Japanese National Institute of Informatics, to identify relevant studies and extract data. Outcome measures: Primary: total effective rate (TER); secondary: skin temperature, peripheral blood flow, adverse events. Results: Fourteen randomized controlled trials (n = 974) were included. Thirteen studies with dichotomous values showed a significant reduction in CHHF and RP (risk ratio 0.31, 0.24-0.40) when comparing herbal medicine with/without Western medicine, and no treatment or Western medicine alone. Reductions in CHHF and RP were also observed between herbal medicine plus Western medicine and Western medicine alone (risk ratio 0.45, 0.24-0.86), as well as between herbal medicine and Western medicine alone (risk ratio 0.30, 0.21-0.41). In the only study using a placebo arm, herbal medicine was found to be superior to placebo in increasing skin temperature and peripheral blood flow. Six participants exhibited minor adverse drug reactions. Herbal medicine showed a superior TER, especially when combined with Western medicine, to Western medicine alone or placebo. However, there was a high risk of bias within all studies. Conclusion: Although herbal medicine shows potential to be a safe and effective treatment for CHHF and RP, the high risk of bias in all studies prevents definitive conclusions; thus, higher quality studies must be performed.

Study of Intravenous Single-Dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats.

OBJECTIVES: Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single- dose test with sprague-dawley (SD) rats. METHODS: Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/ animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. RESULTS: No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. CONCLUSION: The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal.

A Pilot Study of Psychological Traits in the Sasang Constitution According to the Braverman Nature Assessment.

OBJECTIVES: The purpose of this study was to investigate the psychological characteristics of the Sasang constitutions by using Braverman nature assessment (BNA). METHODS: One hundred seventy-four students participated in this study, and among them, the 142 individuals who had clearly identified Sasang constitutional types were used for the analysis. Sasang constitutions and the Braverman temperaments of the subjects were determined by using a questionnaire for the Sasang constitution classification (QSCC) II and BNA, respectively. Body mass index (BMI) was used to compare the inclinations of the Sasang constitutions and Braverman temperament types. RESULTS: Significant differences in Braverman temperament type existed among the Sasang constitutions (P = 0.042), and the relations between Soyangin and the dopamine type and between Taeeumin and the gamma-aminobutyric acid (GABA) type were meaningful. Significant differences were also shown in the comparison with the Yin and the Yang constitutions (P = 0.017), and the post-hoc analysis showed a strong and significant relation between the Yang constitution and the dopamine type and between the Yin constitution and the GABA type. The one-way analysis of variance (ANOVA) and the independent t-test were conducted to examine the BMI and the degree of obesity among the Sasang constitutions and the Braverman temperament types. Concerning the BMI, Taeeumin showed a bigger BMI than the other constitutions (P < 0.001), but no significant differences in the BMI were observed between the Braverman temperament types. CONCLUSION: Soyangin has a close relationship to the dopamine type and Taeeumin has a close relationship to the GABA type. The correlation between two types were more clear when the Yin and the Yang types were compared to Braverman temperaments. These results may serve as a basis for identifying the psychological traits of Sasang constitutional types, especially in regard to the characteristics related to the four Braverman temperament types.

Intravenous Toxicity Study of Water-soluble Ginseng Pharmacopuncture in SD Rats.

OBJECTIVES: Radix Ginseng has been used for thousands of years to treat a wide variety of diseases. Radix ginseng has also been used as a traditional medicine for boosting Qi energy and tonifying the spleen and lungs. Traditionally, its effect could be obtained orally. Nowadays, a new method, the injection of herbal medicine, is being used. This study was performed to investigate the single-dose intravenous toxicity of water-soluble ginseng pharmacopuncture (WSGP) in Sprague-Dawley (SD) rats. METHODS: All experiments were carried out at Biotoxtech, an institute authorized to perform non-clinical studies under the regulation of Good Laboratory Practice (GLP). At the age of six weeks, 40 SD rats, 20 male rats and 20 female rats, were allocated into one of 4 groups according to the dosages they would receive. The WSGP was prepared in the Korean Pharmacopuncture Institute under the regulation of Korea-Good Manufacturing Practice (K-GMP). Dosages of WSGP were 0.1, 0.5 and 1.0 mL/animal for the experimental groups, and normal saline was administered to the control group. The rat's general conditions and body weights, the results of their hematological and biochemistry tests, and their necropsy and histopathological findings were investigated to identify the toxicological effect of WSGP injected intravenously. The effect was examined for 14 days after the WSGP injection. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech. RESULTS: No deaths were found in this single-dose toxicity test on the intravenous injection of WSGP, and no significant changes in the rat's general conditions and body weights, the results on their hematological and biochemistry test, and their necropsy findings were observed during the test. The local area of the injection site showed minial change. The lethal dose was assumed to be over 1.0 mL/animal in both sexes. CONCLUSION: These results indicate that WSGP is safe at dosages up to 1 mL/animal.