Tuina (Chinese massage) for insulin resistance and sensitivity: A protocol for systematic review and meta-analysis of animal and human studies.

INTRODUCTION: Insulin resistance (IR) could be regarded as a therapeutic target for metabolic diseases. Therefore, multiple therapeutic strategies that target IR should be applied to provide a more effective means of treatment. It aims to determine Tuina's efficacy and safety for IR through this systematic review and meta-analysis. METHODS: From the inception to July 31, 2023, we will search four English databases (Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science) and two Chinese databases (China National Knowledge Infrastructure and the Chinese Science and Technology Periodical Database). We will search and include studies of both human and animal models that evaluate Tuina's effects on insulin sensitivity or resistance. Data selection, data extraction, and risk of bias assessment will be made by two independent reviewers. We will evaluate the methodological quality of all included studies and conduct meta-analyses using Review Manager Software 5.4.1. DISCUSSION: In both animal and human studies, the effects and safety of Tuina for IR will be evaluated. The evidence generated bythis study will validate effects and safety of Tuinain treating IR and inform future research and clinical decision-making. TRAIL REGISTRATION: PROSPERO Registration ID: CRD42022360128.

Integrative medicine using East Asian herbal medicine for inflammatory pain in patients with rheumatoid arthritis: A protocol for systematic review and meta-analysis integrated with multiple data mining for core candidate discovery.

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by a wide range of clinical symptoms affecting various bodily functions, including skeletal, vascular, metabolic, and cognitive functions. This review aimed to evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used for the treatment of inflammatory pain in rheumatoid arthritis and to identify key candidate drugs based on the data. METHODS: A comprehensive literature search will be conducted in 4 core databases (PubMed, Excerpta Medica database, Cochrane Library, and Cumulative Index to Nursing & Allied Health Literature) 4 Korean databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Research Information Service System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from December 13, 2022. Statistical analysis will be performed using R version 4.1.2 and R Studio program. The American College of Rheumatology 20/50/70 score and rate of adverse events will be the primary outcomes. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. Sensitivity, meta-regression, and subgroup analyses will be used to identify the sources of any heterogeneity in the study. The revised tool for assessing the risk of bias in randomized trials, version 2.0, will be used to evaluate methodological quality. The overall quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation Pro Framework. ETHICS AND DISSEMINATION: There are no ethical issues, as no primary data will be collected directly from the participants. The results of this review will be reported in a peer-reviewed scientific journal. TRIAL REGISTRATION: PROSPERO registration number: CRD42023412385.

Integrative medicine (East Asian herbal medicine combined with conventional medicine) for psoriasis: A protocol for systematic review and meta-analysis.

BACKGROUND: Psoriasis is a chronic, inflammatory, autoimmune skin disease. The aim of this review is to systematically evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used to treat inflammatory skin lesions of psoriasis. METHODS: A comprehensive literature search will be conducted in 3 English databases (PubMed, Cochrane Library, and Embase), 4 Korean databases (Korean Studies Information Service System, Research Information Service System, Oriental Medicine Advanced Searching Integrated System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from their inception until July 29, 2021. Statistical analysis will be performed using R version 4.1.2 and the R studio program using the default settings of the "meta" and "metafor" packages. The primary outcome will be an improvement in the psoriasis area severity index. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. If heterogeneity is detected in the study, the cause will be identified through sensitivity, meta-regression, and subgroup analyses. Methodological quality will be assessed independently using the revised tool for the risk of bias in randomized trials, version 2.0. The overall quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation pro framework. RESULTS: This study will review all available trials on the same subject and arrive at a more statistically robust conclusion based on a sufficient sample size of participants and additional analysis using data mining techniques will be performed on intervention prescription information in clinical studies collected according to rigorous criteria. CONCLUSION: We believe that this study will provide useful knowledge on managing inflammatory skin lesions of psoriasis vulgaris using integrative medicine using East Asian herbal medicine.

East asian herbal medicine for the treatment of children with attention deficit hyperactivity disorder: A Systematic Review and Meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a mental illness that can place a significant burden on individuals, their families, and society. East Asian Herbal Medicine (EAHM) has long been used in East Asian nations to treat mental illness in children. Nevertheless, the evidence for the effectiveness of EAHM for the treatment of ADHD is insufficient. A systematic review was performed to examine the effectiveness and safety. In addition, research on core herbal combinations was also conducted to help clinicians in their prescription selection. MATERIALS AND METHODS: This systematic review and meta-analysis were prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The following databases were searched: 4 English databases (PubMed, Cochrane Library, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE), 4 Korean databases (Korean Studies Information Service System (KISS), Research Information Service System (RISS), Oriental Medicine Advanced Searching Integrated System (OASIS), Korea Citation Index (KCI)), 2 Chinese databases (Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Data), and 1 Japanese database (CiNii) database. The publication bias was evaluated using funnel plots. GRADE pro was used to evaluate the evidence of the study. The core herb combination of EAHM used in this study was revealed using apriori algorithm-based association rule mining. RESULTS: This review assessed 42 studies that evaluated 3484 children and adolescents. In meta-analysis, EAHM monotherapy had a similar clinical efficacy rate to conventional medicine (CM) (n = 2166; random effects RR 1.09, 95% CI 1.05 to 1.13; heterogeneity χ2= 25.08, df = 23, p = 0.35, I2=8%). EAHM-combined therapy showed a better clinical efficacy rate than when conventional therapy was used alone (n = 746; fixed effects RR 1.19, 95% CI 1.12 to 1.26; heterogeneity χ2= 11.80, df = 9, p = 0.22, I2=24%). For adverse events, EAHM had a lower incidence than conventional therapy. In GRADE pro, each outcome varied from moderate to very low quality. The constituents of the herb combinations with consistent association rules were Fossilia Ossis Mastodi, Polygalae Radix, and Acori Graminei Rhizoma. CONCLUSION: EAHM monotherapy has similar effects to CM but with fewer side effects. Hence, it will be helpful for children with ADHD suffering from the side effects of CM. EAHM-combined therapy has a better effect than conventional therapy. Accordingly, it will be useful for children with ADHD who do not respond to treatment with conventional therapy. Nevertheless, more well-designed studies will be needed to confirm this in the future.

Comparative Effectiveness of East Asian Traditional Medicine for Childhood Simple Obesity: A Systematic Review and Network Meta-Analysis.

Childhood obesity leads to various comorbidities and usually persists into adulthood, increasing socioeconomic burden. In the absence of a clearly effective treatment, East Asian traditional medicine (EATM) therapies have been widely used. We aimed to analyze the comparative effectiveness and safety of EATM techniques for children with simple obesity through network meta-analysis (NMA). Twelve databases were searched for randomized controlled trials (RCTs) evaluating the effect of EATMs on childhood simple obesity. Individual EATMs were ranked based on the surface under the cumulative ranking curve. The risk of bias in the individual studies and publication bias in the NMA were evaluated. Thirty-three RCTs were included. Acupuncture, chuna, chuna plus acupressure, cupping plus acupressure, herbal medicine (HM), and HM plus acupuncture significantly reduced BMI compared with lifestyle management. Based on the treatment ranking, cupping plus acupressure was optimal for BMI reduction compared with a non-medical management, followed by chuna and HM. The quality of evidence for individual findings was usually moderate to low, and no serious adverse events of EATM were reported. Cupping plus acupressure might have a large beneficial effect, and chuna or HM probably have a moderate beneficial effect on reducing BMI in children with simple obesity.

Meditation-based intervention for obsessive-compulsive disorder: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to investigate the effects of the meditation-based intervention on obsessive-compulsive disorder (OCD). METHODS: The following databases were searched up to April 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline (via PubMed), PsycARTICLES, 4 Korean databases (Korean Medical Database [KMbase], Koreanstudies Information Service System [KISS], National Digital Science Library [NDSL], and Oriental Medicine Advanced Searching Integrated System [OASIS]), and China National Knowledge Infrastructure (CNKI). The search terms related to meditation-based intervention and OCD were used. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The selected articles were evaluated using the Cochrane risk of bias tool. The Review Manager (RevMan) 5.4 was used to perform the meta-analysis. RESULTS: In all, 16 randomized controlled trials were selected. The meta-analysis showed that the group receiving the treatment combining medication and meditation-based intervention for OCD showed a more significant post-treatment improvement in Yale-Brown obsessive compulsive scale than the group receiving medication only. Compared with other non-medication interventions that are known to be effective in treating OCD, the Yale-Brown obsessive compulsive scale showed a significant improvement immediately after the meditation-based intervention. However, no significant difference was found in the follow-up monitoring data across all examined cases. CONCLUSION: This study was conducted to verify the effects of meditation-based intervention on OCD. The results suggested that combined treatment with medication and meditation-based intervention was more effective in treating OCD than medication alone; the positive effects of meditation-based intervention may be greater than the effects of other non-medication interventions. However, the lack of significant difference in the follow-up indicates that long-term effect of meditation-based interventions is unclear. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021244408.

The efficacy and safety of yukmijihwang-hwan (Liuweidihuang-wan) for type 2 diabetes mellitus without complications: A protocol for systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs) will aim to assess the efficacy and safety of Yukmijihwang-hwan for type 2 diabetes without complications. METHODS: To identify eligible studies, we will perform a systematic search of the following electronic databases: MEDLINE (PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by NII, Korean Information Service System, Korean Medical Database, Oriental Medicine Advanced Searching Integrated System, and ScienceON. Search terms will include "Type 2 Diabetes" for participants as well as "Yukmijihwang-tang" or "Liuwei dihuang tang" for interventions. Two independent researchers will perform data extraction and assessment using Cochrane's risk of bias tool, with disagreements being resolved through discussions with a third researcher. RESULTS: This study will evaluate the antidiabetic effects of Yukmijihwang-hwan from 3 perspectives (blood glucose level, insulin resistance, and ß-cell function) as well as its safety by reviewing the reported adverse effects. CONCLUSION: This systematic review will provide evidence regarding the antidiabetic efficacy and safety of Yukmijihwang-tang in type 2 diabetes mellitus.

Anshen-Buxin-Liuwei pill, a Mongolian medicinal formula could alleviate cardiomyocyte hypoxia/reoxygenation injury via mitochondrion pathway.

BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula that is composed of six medicinal materials: the Mongolian medicine Bos taurus domesticus Gmelin, Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt., Eugenia caryophµllata Thunb., Aucklandia lappa Decne., and Liqui dambar formosana Hance. ABLP is considered to have a therapeutic effect on symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and shortness of breath. METHODS: H9c2 cardiomyocytes were used to construct a hypoxia/reoxygenation (HR) injury model. CCK-8 assay and Annexin V-FITC cell apoptosis assays were used for cell viability and cell apoptosis determination. The LDH, SOD, MDA, CAT, CK, GSH-Px, Na+-K+-ATPase, and Ca2+-ATPase activities in cells were determined to assess the protective effects of ABLP. The mRNA levels of Sirtuin3 (Sirt3) and Cytochrome C (Cytc) in H9c2 cells were determined by quantitative real-time PCR. RESULTS: The results indicate that HR-treated cells began to shrink from the spindle in an irregular shape with some floated in the medium. By increasing the therapeutic dose of ABLP (5, 25, and 50 µg/mL), the cells gradually reconverted in a concentration-dependent manner. The release of CK in HR-treated cells was significantly increased, indicating that ABLP exerts a protective effect in H9c2 cells against HR injury and can improve mitochondrial energy metabolism and mitochondrial function integrity. The present study scrutinized the cardioprotective effects of ABLP against HR-induced H9c2 cell injury through antioxidant and mitochondrial pathways. CONCLUSIONS: ABLP could be a promising therapeutic drug for the treatment of myocardial ischemic cardiovascular disease. The results will provide reasonable information for the clinical use of ABLP.

Traditional uses, phytochemistry, pharmacology, toxicity and quality control of medicinal genus Aralia: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia, which belongs to Araliaceae family, is mainly distributed in Asia, such as China, Japan and South Korea. It has a long medicinal history and is widely used in the treatment of various diseases, such as hepatitis, rheumatoid arthritis, bruises, lumps and carbuncles. AIM OF THE STUDY: The purpose of this review is to systematically evaluate the traditional uses, phytochemistry, pharmacology, toxicity and quality control of main medicinal plants of Aralia, discusses the application of ethnic medicine, modern scientific research and the relationship between them, and put forward some suggestions to promote the further development and utilization of Aralia. MATERIALS AND METHODS: The relevant information on Aralia was collected through electronic databases (PubMed, Web of Science, Science Direct, Springer, CNKI and Wanfang), Chinese herbal classics, Ph.D. and M.Sc. dissertations, Chinese Pharmacopoeia. Plant names were verified by "The Plant List" (http://www.theplantlist.org). The literature cited in this review can be traced back to 1878 to 2021. RESULTS: More than 290 chemical constituents have been isolated from the genus Aralia, including triterpenoid saponins, terpenoids, organic acids, flavonoids, polyacetylenes, phenylpropanoids and other constituents. Pharmacological studies have shown that the extracts and compounds of Aralia have a wide range of pharmacological activities, including anti-inflammation, analgesic, anti-tumor, liver protection, protection of cardiovascular and nervous system, regulating substance metabolism, antibacterial, antiviral and antioxidation. CONCLUSIONS: The genus Aralia is not only an excellent traditional herbal medicine, but also a source of bioactive molecules with good application prospects. However, the structure-activity relationship, in vivo activity and action mechanism of its bioactive components need to be further studied. In addition, more toxicological and quality control studies are essential to evaluate the efficacy and safety of Aralia as medicine.

Successful treatment of restless leg syndrome with the traditional herbal medicines Dangguijakyak-san and Shihogyeji-tang: A case report (CARE-compliant).

RATIONALE: Dopamine replacement is currently the standard treatment for restless leg syndrome (RLS); however, various adverse effects are associated with long-term therapy, and the benefits disappear upon discontinuation. To overcome these limitations, interest in traditional East Asian medicine has increased. PATIENT CONCERNS: A 72-year-old Asian woman originally admitted for an intracerebral hemorrhage presented with complaints of an unpleasant sensation throughout the body that appeared at night. DIAGNOSES: The patient was diagnosed with chronic persistent RLS based on the 2012 Revised International Restless Leg Syndrome Study Group Diagnostic Criteria. INTERVENTIONS: The patient was treated with extracts of the traditional herbal medicines Dangguijakyak-san (DS) and Shihogyeji-tang (ST). After 47 days of therapy, all herbal medicines were discontinued, and symptoms had not returned by the last follow-up 244 days after the initial treatment. OUTCOMES: One week after initiating herbal treatment with DS and ST, the RLS symptoms began to improve, and the total hours of sleep had increased from 2 to 9 hours by day 21, with a Korean version of the international restless legs scale score of 11 points. On day 36, ST was discontinued, given the continued improvement of symptoms. On day 47, symptoms had disappeared (Korean version of the international restless legs scale score: 0), and sleep disturbances caused by RLS had completely resolved. After day 47, DS was also discontinued. There were no adverse effects associated with the administration of DS and ST, and the symptoms had not recurred by the last follow-up on day 244. LESSONS: In this case, RLS related symptoms, which had been present for approximately 60 years, were improved using only the traditional herbal medicines DS and ST (without dopamine replacement), and no symptoms recurred for 244 days. This case suggests that if replacement therapy is difficult or not desired, herbal medicinal therapies may be an effective alternative. This also suggests that the effect of herbal medicine on RLS might be semi-permanent. Further investigations, including clinical trials, are needed to confirm these effects.

The traditional and modern uses of Selaginella tamariscina (P.Beauv.) Spring, in medicine and cosmetic: Applications and bioactive ingredients.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of the plant Selaginella tamariscina (P.Beauv.) Spring (spike moss) are used for a long time in Asia, for the treatment of multiple diseases and conditions. Aqueous and alcoholic leave extracts are used by local communities. In China, the plant (Juan bai) is listed on the Pharmacopoeia. In South Korea, the use of this plant (Kwon Baek) is mentioned in the book Dongui-Bogam (Heo Jun 1613), at the origin of the Hyungsang medicine. S. tamariscina is traditionally used in Vietnam (mong lung rong), Thailand (dok hin), Philippines (pakong-tulog) and other Asian countries. AIM OF THE STUDY: To provide an analysis of the multiple traditional and current uses of S. tamariscina extracts (STE) in the field of medicine and cosmetic. The review is also intended at identifying the main natural products at the origin of the many pharmacological properties reported with these extracts (anti-inflammatory, antioxidant, antidiabetic, antibacterial, antiallergic, anticancer effects). METHODS: Extensive database retrieval, such as SciFinder and PubMed, was performed by using keywords like " Selaginella tamariscina", "spike moss", "Selaginellaceae ". Relevant textbooks, patents, reviews, and digital documents were consulted to collate all available scientific literature and to provide a complete science-based survey of the topic. RESULTS: Different solvents and methods are used to prepare STE. The process can largely modify the natural product content and properties of the extracts. STE display a range of pharmacological effects, useful to treat metabolic disorders, several inflammatory diseases and various cancers. A specific carbonized extract (S. tamariscina carbonisatus) has shown hemostatic effects, whereas standard STE can promote blood circulation. Many patented STE-containing cosmetic preparations are reviewed here. Several biflavonoids (chiefly amentoflavone) and phenolic compounds (selaginellin derivatives) are primarily responsible for the observed pharmacological properties. Potent inhibitors of protein tyrosine phosphatase 1 B (PTP1B), phosphodiesterase-4 (PDE4), and repressor of pro-inflammatory cytokines expression have been identified from STE. CONCLUSION: The traditional use of STE supports the research performed with this plant. There are robust experimental data, based on in vitro and in vivo models, documenting the use of STE to treat type 2 diabetes, several inflammatory diseases, and some cancers (in combination with standard chemotherapy). Selaginella tamariscina (P.Beauv.) is a prime reservoir for amentoflavone, and many other bioactive natural products. The interest of the plant in medicine and cosmetic is amply justified.

The Extracts of Angelica sinensis and Cinnamomum cassia from Oriental Medicinal Foods Regulate Inflammatory and Autophagic Pathways against Neural Injury after Ischemic Stroke.

The study indicates inflammation and autophagy are closely related to neural apoptosis in the pathology of ischemic stroke. In the study, we investigate the effects and mechanisms of the extracts of Angelica sinensis and Cinnamomum cassia (AC) from oriental medicinal foods on inflammatory and autophagic pathways in rat permanent middle cerebral artery occlusion model. Three doses of AC extract were, respectively, administered for 7 days. It suggests that AC extract treatment ameliorated scores of motor and sensory functions and ratio of glucose utilization in thalamic lesions in a dose-dependent manner. Expression of Iba1 was decreased and CD206 was increased by immunofluorescence staining, western blotting results showed expressions of TLR4, phosphorylated-IKKß and IκBα, nuclear P65, NLRP3, ASC, and Caspase-1 were downregulated, and Beclin 1 and LC3 II were upregulated. Low concentrations of TNF-α, IL-1ß, and IL-6 were presented by ELISA assay. Additionally, caspase 8 and cleaved caspase-3 expressions and the number of TUNEL positive cells in ipsilateral hemisphere were decreased, while the ratio of Bcl-2/Bax was increased. Simultaneously, in LPS-induced BV2 cells, it showed nuclear P65 translocation and secretion of proinflammatory cytokines were suppressed by AC extract-contained cerebrospinal fluid, and its intervened effects were similar to TLR4 siRNA treatment. Our study demonstrates that AC extract treatment attenuates inflammatory response and elevates autophagy against neural apoptosis, which contributes to the improvement of neurological function poststroke. Therefore, AC extract may be a novel neuroprotective agent by regulation of inflammatory and autophagic pathways for ischemic stroke treatment.

Phytochemistry and pharmacological activities of Arundina graminifolia (D.Don) Hochr. And other common Orchidaceae medicinal plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Arundina graminifolia (Orchidaceae) has been widely used for heat clearance and detoxification, anti-inflammatory diuretic, and anti-microbes for two thousand years in national minorities, especially among the Dai people. It was known as "Zhuyelan" (Chinese: ), "Wenshanghai" (Chinese: ) and "Baiyangjie" (Chinese: ) in the Dai nationality, and mainly used as antidote, which is characterized by "relieving the poison before getting sick and treating illness". Therefore, it has been typically applied in the treatment of food poisoning, snake bites, rheumatism, stomachache and traumatic injuries. It is also used to treat bronchitis, tuberculosis and pneumonia in the Bulang and the Wa ethnic people. AIM OF THIS REVIEW: This review aims to provide up-to-date information about the botanical characterization, traditional uses, phytochemistry, and pharmacology of A. graminifolia, and the related importantly medicinal plants (e.g. Bletilla striata, Cremastra appendiculata, and Dendrobium officinale) of the same Orchidaceae family. Our work aims to further promote scientific cognition, basic research and in-depth discovery of potential drug candidates for Minority Medicine of our nation. MATERIALS AND METHODS: Relevant information was obtained via piles of resources including classic books about Chinese herbal medicine, and worldwide accepted scientific databases including Web of Science, Pubmed, Google Scholar, SciFinder, Elsevier, Springer, NCBI, ACS Publications, CNKI and Wanfang data. RESULTS: Phytochemical investigations have been intensively performed for these two decades, over 134 compounds, mainly include stilbenoids, phenanthrenes, quinones, ketones, phenolic acids, and glycosides, have been isolated and identified from A. graminifolia. The literature surveys exhibited that the ethnomedicinal uses of A. graminifolia, such as detoxification, anti-inflammation and the ability to cure trauma and pain associated with infections, are correlated with its modern pharmacological activities, including antibacterial, anti-oxidation, anti-lipid peroxidation. Stilbenoids and phenanthrenes have been regarded as the main active substances, among which stilbenoids with open ring style have superior antitumor activity. Furthermore, phytochemical investigations, biological activities, as well as the main molecular mechanism involved the coexisted stilbenoids and phenanthrenes from other most common used medicinal plants of the same Orchidaceae family were presented, compared and discussed together. CONCLUSIONS: This review presents the current research findings of A. graminifolia and three other related medicinal plants of the same family. Some of the traditional uses of A. graminifolia have been assessed by pharmacological studies. Despite A. graminifolia is used as an antidote and anti-aging dote, a few unsolved problems including the molecular mechanism underlying biological activities, pharmacokinetics, and in vivo detoxification tests still need to be settled extensively. Therefore, it is necessary to conduct a comprehensive survey and collect investigation information on A. graminifolia.

Traditional uses, phytochemistry, pharmacology and toxicology of the genus Gynura (Compositae): A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura cass., belonging to the tribe Senecoineae of the family Compositae, contains more than 40 accepted species as annual or perennial herbs, mainly distributed in Asia, Africa and Australia. Among them, 11 species are distributed in China. Many of the Gynura species have been used as traditional herbal medicines for the treatment of diabetes mellitus, rheumatism, eruptive fever, gastric ulcer, bleeding, abscesses, bruises, burning pains, rashes and herpes zoster infection in tropical Asia countries such as China, Thailand, Indonesia, Malaysia, and Vietnam. Some of the species have been used as vegetables, tea beverage or ornamental plants by the local people. AIM OF THE STUDY: A more comprehensive and in-depth review about the geographical distribution, traditional uses, chemical constituents and pharmacological activities as well as safe and toxicity of Gynura species has been summarized, hoping to provide a scientific basis for rational development and utilization as well as to foster further research of these important medicinal plant resources in the future. MATERIALS AND METHODS: A review of the literature was performed based on the existing peer-reviewed researches by consulting scientific databases including Web of Science, PubMed, Elsevier, Google Scholar, SciFinder and China National Knowledge Infrastructure. RESULTS: Many of the Gynura species have been phytochemically studied, which led to the isolation of more than 338 compounds including phenolics, flavonoids, alkaloids, terpenoids, steroids, cerebrosides, aliphatics and other compounds. Pharmacological studies in vitro and in vivo have also confirmed the various bioactive potentials of extracts or pure compounds from many Gynura plants, based on their claimed ethnomedicinal and anecdotal uses, including antioxidant, anti-inflammation, anticancer, antidiabetic, antihypertension, antibacterial and other activities. However, pyrrolizidine alkaloids (PAs) pose a threat to the medication safety and edible security of Gynura plants because of toxicity issues, requiring the need to pay great attention to this phenomenon. CONCLUSION: The traditional uses, phytochemistry and pharmacology of Gynura species described in this review demonstrated that these plants contain a great number of active constituents and display a diversity of pharmacological activities. However, the mechanism of action, structure-activity relationship, potential synergistic effects and pharmacokinetics of these components need to be further elucidated. Moreover, further detailed research is urgently needed to explain the mechanisms of toxicity induced by PAs. In this respect, effective detoxification strategies need to be worked out, so as to support the safe and reasonable utilization of Gynura plant resources in the future.

A Japanese traditional medicine Hochuekkito promotes negative conversion of vancomycin-resistant Enterococci.

Vancomycin-resistant enterococci (VRE) are prominent causes of nosocomial infections. Japanese traditional (Kampo) medicine promotes intestinal immunity and protects against bacterial infections. We assessed potential differences in the clinical course of VRE-positive patients, based on their characteristics and treatment with Kampo medicines. This retrospective observational study collected data from VRE-positive patients from August 2018 to July 2019 at a tertiary-care hospital in Japan. The data of 122 consecutive VRE-positive inpatients were analyzed. Sixty-nine patients were treated with probiotics, among whom, 18 were further treated with Kampo medicines. Twenty-six of the 122 patients subsequently died. In univariate analyses, subsequent VRE negative conversion significantly reduced the mortality of VRE-detected patients (p = .0003). Administration of probiotics (p = .0065) and Kampo medicines with probiotics (p = .0002), especially of the Kampo medicine hochuekkito (p = .0014), and a higher serum albumin level positively contributed to the subsequent VRE negative conversion. Multivariate analyses demonstrated that Kampo medicines and body mass index contributed to VRE negative conversion. Hochuekkito shortened the time needed for VRE negative conversion (p = 0.0485). Administration of Kampo medicines, especially of hochuekkito, in addition to probiotics in VRE patients may promote VRE negative conversion.

Traditional East Asian herbal medicines for the treatment of poststroke constipation: A protocol for systematic review and meta analysis.

BACKGROUND: Post-stroke constipation is a major complication of stroke and increases the incidence of poor neurological outcomes and infectious complications and, therefore, warrants active and prompt treatment. In East Asian countries, several types of herbal medicines have been used for the treatment of post-stroke constipation because they are considered safer than existing pharmacotherapies. However, no systematic review has investigated the efficacy and safety of traditional East Asian herbal medicine in the treatment of post-stroke constipation. With this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of traditional East Asian herbal medicines for the treatment of post-stroke constipation. METHODS AND ANALYSIS: Eight electronic databases will be searched for relevant studies published from inception to April 2021. Only randomized controlled trials (RCTs) that assess the efficacy and safety of traditional East Asian herbal medicines for the treatment of post-stroke constipation will be included in this study. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool. After screening the studies, a meta-analysis of the RCTs will be performed, if possible. RESULTS: This study is expected to generate high-quality evidence of the efficacy and safety of herbal medicines to treat post-stroke constipation. CONCLUSION: Our systematic review will provide evidence to determine whether herbal medicines can be effective interventions for patients with post-stroke constipation. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study was based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: Research registry reviewregistry1117.

Medicinal plants from the Himalayan region for potential novel antimicrobial and anti-inflammatory skin treatments.

BACKGROUND AND OBJECTIVES: Adequate treatment of wounds remains one of the major medical needs globally, most notably in the regions with poor or limited access to health care. In many local and traditional systems of medicine, plants are often widely used for treating infected wounds. AIM AND OBJECTIVES: The overarching aim of this project was selection of potential species for use in a future treatment by combining with plant resources with aspects of antimicrobial photodynamic therapy (aPDT). Specifically, we focussed on species used locally in the Himalayan region for the treatment of skin disorders and then assessed the existing pharmacological evidence for key species based on the published evidence available. METHODS: Database searches were performed to identify relevant publications describing local and traditional uses of plants in the Himalayan region of Bhutan, PR China, India, Nepal and Pakistan. Using the Global Biodiversity Information Facility (GBIF), species were researched in terms of their distribution including in different climatic regions, focussing on species mostly found in higher climatic zones (based on the Köppen-Geiger climate classification). For species used in three or more countries and restricted to the higher altitudes, data on safety, pharmacology, as it relates to dermatological conditions, and phytochemistry were retrieved. KEY FINDINGS: The study identified a total of 606 species that are used in the treatment of various skin conditions often associated with infections reported in 84 articles. Common weeds like Ageratum conyzoides and Bidens pilosa, widely used and cultivated species like Centealla asiatiaca and Prunus armenica were excluded. This ultimately led to the identification of a core group of five widely used species restricted to the Himalayan region (Cedrus deodara, Nardostachys jatamansi, Pinus wallichiana, Pinus roxburghii and Valeriana jatamansi). CONCLUSIONS: Here we apply a novel approach comprising an assessment of the published information on the use of medicinal plants (i.e. local and traditional knowledge) in the context of their potential to be used in a biomedical form of clinical treatment - aPDT. Then, once sustainable sourcing based on access and benefit-sharing arrangements is in place, these species are investigated for their potential in wound treatment. Ultimately, the goal is to develop a new baseline for primary health care in some of the regions of the world with poor or limited access to health care.

Adverse events from pharmacopuncture treatment in Korea: A protocol for systematic review and meta analysis.

BACKGROUND: Pharmacopuncture is a combination of acupuncture and herbal medicine, which involves the injection of herbal extracts into acupuncture points (acupoints). Pharmacopuncture has become one of the major therapeutic tools used in Korea; however, safety is one of the major concerns associated with it. We aim to systematically review clinical studies on the adverse events of pharmacopuncture in Korea. METHODS: To collect data on the incidence and characteristics of adverse events (AEs) and to evaluate pharmacopuncture safety, 2 or more researchers will conduct a comprehensive search of pertinent English and Korean databases using the keywords "pharmacopuncture" and "adverse events." Regardless of the participants' conditions or treatment types, we will include clinical studies on the AEs of pharmacopuncture. Studies that were not conducted in Korea, and acupoint injections containing Western medications, vitamins, or autologous serum will be excluded from this study. The severity of AEs will be classified using the common terminology criteria for adverse events, and the causality between pharmacopuncture and AEs will be assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality scale. The quality of identifying and reporting the AEs will be assessed using the McHarm scale. The risk of selection bias will be assessed using the Cochrane risk of bias and the risk of bias for non-randomized studies tools. Studies will be assessed for heterogeneity utilizing Higgins's I2 statistics, and the risk of publication bias will be assessed and expressed in the form of a contour-enhanced funnel plot. RESULTS AND CONCLUSION: Comprehensive investigation of all types of clinical studies in Korea will provide clearer evidence of the safety of pharmacopuncture. The results of this study will be useful for traditional medical doctors and patients who use such treatments and interventions.Systematic Review Registration: Open Science Foundation (osf.io/umhyz).

Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality.

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

Extract of high hydrostatic pressure-treated danshen (Salvia miltiorrhiza) ameliorates atherosclerosis via autophagy induction.

Danshen (Salvia miltiorrhiza) is a traditional medicinal plant widely used in Asian countries for its pharmacological activities (e.g., amelioration of cardiovascular diseases). In this study, we investigated the anti-atherosclerotic activity of raw danshen root extract prepared using high hydrostatic pressure (HHP) at 550 MPa for 5 min and hot water extraction. This method was useful for elimination of bacteria from cultured danshen plants and for better extraction yield of active principles. The HHPtreated danshen extract (HDE) inhibited proliferation of human umbilical vein endothelial cells (HUVECs) and induced autophagy that was assessed by LC3 conversion and p62 degradation. HDE suppressed foam cell formation in oxLDL-induced RAW264.7 macrophages; lysosomal activity simultaneously increased, measured by acridine orange staining. HDE also reduced atherosclerotic plaque development in vivo in apolipoprotein E knock-out (ApoE-/-) mice fed a high cholesterol diet. Taken together, these results indicated that HDE exhibited anti-atherosclerotic activity via autophagy induction. [BMB Reports 2020; 53(12): 652-657].