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.

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.

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.

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.

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.

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.

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.

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.

Behaviors of providers of traditional korean medicine therapy and complementary and alternative medicine therapy for the treatment of cancer patients.

OBJECTIVES: In Korea, cancer is one of the most important causes of death. Cancer patients have sought alternative methods, like complementary and alternative medicine (CAM) together with Western medicine, to treat cancer. Also, there are many kinds of providers of CAM therapy, including providers of Korean oriental medicine therapy. The purpose of this study is to identify the behaviors of Korean oriental medicine therapy and CAM therapy providers who treat cancer patients and to provide background knowledge for establishing a new policy with the management and quality control of CAM. METHODS: Structured and well organized questionnaires were made, and 350 persons were surveyed concerning the providers of CAM or Korean oriental medicine. The questionnaires were collected and analyzed. RESULTS: The questionnaires (182) were collected. The questionnaires identified a total of 73 known providers, such as medicinal professionals or other providers of CAM suppliers, 35.6% of whom had had experience with treating cancer patients (52.6% vs. 29.6%). The treatment methods were a little different: alternative therapy and nutritional therapy being preferred by medicinal professionals and mind body modulation therapy and alternative therapy being preferred by other CAM providers. Four patients (7.4%) experienced side effects, and 6 patients (12.5%) experienced legal problems. As the method for managing the therapy, CAM providers, medicinal professionals, and other CAM providers had different viewpoints. For example, some CAM providers stated that both legislation and an official education on CAM or a national examination were needed as a first step to establish the provider's qualifications and that as a second step, a license test was needed for quality control. To the contrary, medicinal professionals stated that a license test was needed before legislation. CONCLUSION: Adequate management and quality control of CAM providers is thought to involve both education and legislation.

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.

Intramuscular Single-dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats.

OBJECTIVES: Bufonis venonum (BV) is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP) and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD) rats. METHODS: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly 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 at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. RESULTS: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. CONCLUSION: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal.

Efficacy of pharmacopuncture for treating children with physical disabilities in uzbekistan.

OBJECTIVE: This research was performed to investigate the efficacy of complex rehabilitation combined with pharmacopuncture treatment for the children with neuromotor system diseases. METHODS: Fifty (50) patients aged from 5 to 15 yr old were compared. Twenty (20) patients received conventional treatments and complex rehabilitation as a control group, and fifty (50) patients received complex rehabilitation with pharmacopuncture. At their first visits, the patients had checkups and neurological scales, and after 10 days of pharmacopuncture treatments and 55 days of rehabilitation, they also took neurological scales. We studied the pre and post effects of the treatment group. RESULTS: The number of patients with ankle joint disorder and contracture, knee joint contracture, steppage, horsey hoof, shoulder weakness and contracture, radio-carpal joint disorder and contracture, arm hypotrophia, arm atrophia, leg hypotrophia and total atrophia decreased after treatments. CONCLUSION: This study showed the efficacy of pharmacopuncture combined with complex rehabilitation for the treatment of neuromotor system diseases.