Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Network Pharmacology and Experimental Verifications to Discover Scutellaria baicalensis Georgi's Effects on Joint Inflammation, Destruction, and Pain in Osteoarthritis.

Osteoarthritis is the most common type of arthritis, characterized by joint pain and a decline in physiological function. Scutellaria baicalensis Georgi (SB) is potentially effective against osteoarthritis because of its wide range of anti-inflammatory pharmacological activities. This study aimed to identify the mode of action of SB against osteoarthritis using network pharmacology prediction and experimental verification. Networks were constructed to key compounds, hub targets, and pathways essential for SB's effectiveness against osteoarthritis. Additionally, in vivo and in vitro tests were performed, including investigations on weight bearing in hind limbs, the acetic acid-induced writhing response, lipopolysaccharide-stimulated RAW264.7 cells, and serum cytokine responses. We identified 15 active compounds and 14 hub targets, supporting the anti-osteoarthritis effects of SB. The Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that fluid shear stress, atherosclerosis, phosphatidylinositol 3-kinase-Akt signaling, and cellular senescence pathways were important. SB showed substantial anti-inflammatory, analgesic, and joint tissue-protective effects against osteoarthritis. Our study shows that SB has the potential value to be further investigated as a candidate material for the treatment of osteoarthritis in the future.

Stem of Sorbus commixta Hedl. Extract Inhibits Cartilage Degradation and Arthritic Pain in Experimental Model via Anti-Inflammatory Activity.

Osteoarthritis (OA) is a widespread joint disease that affects millions of people worldwide. Conventional treatments for OA, including non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, have a risk of various adverse events, including liver, gastrointestinal, cardiovascular, and kidney disease, which are unsatisfactory in their effectiveness. In this study, Sorbus commixta Hedl. Stem extracts (SCE) were evaluated in animal models as potential inhibitors for the progression of OA. Sorbus commixta Hedl., which was found to have substantial anti-inflammatory and antioxidant activities in earlier investigations, has shown potential as a candidate for OA treatment. To mimic human OA symptoms, male rats were injected using sodium iodoacetate (MIA) in their knee joints. SCE significantly reduced MIA-induced weight-bearing loss in rats after the MIA injection and alleviated cartilage degradation and subchondral bone injury caused by MIA. In addition, SCE administration reduced levels of TNF-α and IL-1ß such as pro-inflammatory cytokines in serum, as well as the levels of matrix metalloproteinases (MMPs) such as MMP-1, -3, -8 and -13 in the joint cartilage. SCE significantly inhibited the writhing responses in acetic acid-administered mice and was used to quantify pain. In lipopolysaccharide (LPS)-activated RAW264.7, SCE suppressed NO production and reduced the expression of TNF-α, PGE2, IL-6, IL-1ß, MMP1, MMP3, MMP8, and MMP-13. Our study showed that SCE alleviated inflammation and cartilage degradation in arthritis through its anti-inflammatory activities on multiple targets.

Efficacy and Key Materials of East Asian Herbal Medicine Combined with Conventional Medicine on Inflammatory Skin Lesion in Patients with Psoriasis Vulgaris: A Meta-Analysis, Integrated Data Mining, and Network Pharmacology.

Psoriasis is a chronic inflammatory disease that places a great burden on both individuals and society. The use of East Asian herbal medicine (EAHM) in combination with conventional medications is emerging as an effective strategy to control the complex immune-mediated inflammation of this disease from an integrative medicine (IM) perspective. The safety and efficacy of IM compared to conventional medicine (CM) were evaluated by collecting randomized controlled trial literature from ten multinational research databases. We then searched for important key materials based on integrated drug data mining. Network pharmacology analysis was performed to predict the mechanism of the anti-inflammatory effect. Data from 126 randomized clinical trials involving 11,139 patients were used. Compared with CM, IM using EAHM showed significant improvement in the Psoriasis Area Severity Index (PASI) 60 (RR: 1.4280; 95% CI: 1.3783-1.4794; p < 0.0001), PASI score (MD: -3.3544; 95% CI: -3.7608 to -2.9481; p < 0.0001), inflammatory skin lesion outcome, quality of life, serum inflammatory indicators, and safety index of psoriasis. Through integrated data mining of intervention data, we identified four herbs that were considered to be representative of the overall clinical effects of IM: Rehmannia glutinosa (Gaertn.) DC., Isatis tinctoria subsp. athoa (Boiss.) Papan., Paeonia × suffruticosa Andrews, and Scrophularia ningpoensis Hemsl. They were found to have mechanisms to inhibit pathological keratinocyte proliferation and immune-mediated inflammation, which are major pathologies of psoriasis, through multiple pharmacological actions on 19 gene targets and 8 pathways in network pharmacology analysis. However, the quality of the clinical trial design and pharmaceutical quality control data included in this study is still not optimal; therefore, more high-quality clinical and non-clinical studies are needed to firmly validate the information explored in this study. This study is informative in that it presents a focused hypothesis and methodology for the value and direction of such follow-up studies.

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.

Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix-Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology.

The Astragali Radix-Cinnamomi Ramulus herb-pair (ACP) has been widely used in the treatment of diabetic peripheral neuropathy (DPN) as part of East Asian herbal medicine (EAHM). Eligible randomized controlled trials (RCTs) were identified by searching 10 databases. The outcomes investigated were response rate, sensory nerve conduction velocity (SNCV), and motor nerve conduction velocity (MNCV) in four regions of the body. The compounds in the ACP and their targets of action, disease targets, common targets, and other relevant information were filtered using network pharmacology. Forty-eight RCTs, with 4308 participants, and 16 different interventions were identified. Significant differences were observed in the response rate, MNCV, and SNCV, as all EAHM interventions were superior to conventional medicine or lifestyle modification. The EAHM formula containing the ACP ranked highest in more than half of the assessed outcomes. Furthermore, major compounds, such as quercetin, kaempferol, isorhamnetin, formononetin, and beta-sitosterol, were found to suppress the symptoms of DPN. The results of this study suggest that EAHM may increase therapeutic efficacy in DPN management, and EAHM formulations containing the ACP may be more suitable for improving treatment response rates to NCV and DPN therapy.

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.

Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain.

Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1ß, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-ß. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation.

Positive short term effects of an integrative korean medicine treatment package for low back pain caused by motor vehicle accidents: A retrospective chart review of real - world practice data.

Backgrounds No standard treatment exist for reducing symptoms related to sequelae of motor vehicle accidents (MVAs). In Korea, comprehensive Korean Medicine (KM) treatment that includes botanical drugs (herbal medicine), acupuncture, pharmacopuncture, tuina, moxibustion, and cupping is covered by automobile insurance and increasingly used to help alleviate such pain. This study aimed to analyze real-world data and to evaluate the effectiveness and safety of comprehensive KM treatment for low back pain caused by MVAs. Methods We conducted a retrospective chart review of patients who received KM treatment during hospitalization. Records that lacked follow-up outcome assessments were excluded. The Verbal Numerical Rating Scale (VNRS), the Korean version of the Oswestry Disability Index (K-ODI) and the Korean version of the Roland-Morris Disability Questionnaire (K-RMDQ) were evaluated at admission and discharge. Adverse events were also analyzed. A paired t-test was used to identify the effectiveness of KM treatment. Results A total of 50 patients, 30 males and 20 females, were included in the analysis. The mean age of the patients was 40.72 ± 13.31 years and the average treatment period was 7.22 ± 3.84 days. After treatment, VNRS, K-ODI and K-RMDQ were significantly improved (p < 0.001). There was a decrease from 5.06 ± 1.60 to 3.40 ± 1.81 in VNRS, 33.38 ± 16.88 to 24.54 ± 13.63 in K-ODI, and 6.84 ± 6.27 to 4.14 ± 4.38 in K-RMDQ. During this period, a total of two adverse events were reported. Discussion Although this retrospective chart review looked into the short term effects only, comprehensive KM treatment might be an effective and safe therapeutic option to reduce acute low back pain especially after MVA. Prospective research data is needed to support this hypothesis.

Safety of acupotomy in a real-world setting: A prospective pilot and feasibility study.

OBJECTIVE: Acupotomy is a modern acupuncture method that includes modern surgical methods. Since acupotomy is relatively more invasive than filiform acupuncture treatment, it is important to establish the safety profile of this practice. To justify further large-scale prospective observational studies, this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events (AEs). METHODS: This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting. The feasibility (call response rate, drop-out rate, response rate for each variable and recruitment per month) and safety profile (incidence, type, severity and causality of AEs, and factors potentially associated with AEs) were measured. RESULTS: A total of 28 participants joined the study from January to May 2018. A follow-up assessment was achieved in 258 (1185 treatment points) out of 261 sessions (1214 treatment points). The response rate via telephone on the day after treatment was 87.3%. There were 8 systemic AEs in all the sessions (8/258; 3.11%) and 27 local AEs on the total points treated (27/1185; 2.28%). Severe AEs did not occur. Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point. CONCLUSION: The findings suggest that it could be feasible to analyze the safety of acupotomy in a real-world setting. Moreover, the primary data on some relevant AEs could be determined. We are planning large-scale prospective studies based on these findings. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0002849 (https://cris.nih.go.kr/cris/search/detailSearch.do/11487).

Clinical evidence construction of East Asian herbal medicine for inflammatory pain in rheumatoid arthritis based on integrative data mining approach.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to a significant social burden. East Asian herbal medicine (EAHM) has long been used to treat RA. Therefore, a systematic study of how EAHM treatments can be developed into new drugs using specific materials is needed. METHODS: Eleven databases containing literature in English, Korean, Chinese, and Japanese were searched for randomized controlled trials comparing EAHM with conventional medicine (CM). A meta-analysis was performed on the variable data to assess their effects on inflammatory pain. Subsequently, we searched for core materials and combinations of core material-based data mining methods. RESULTS: A total of 186 trials involving 19,716 patients with RA met the inclusion criteria. According to the meta-analysis, EAHM had a significantly superior effect on continuous pain intensity, tender joint count, and response rate. Patients treated with EAHM had a significantly reduced incidence of adverse events compared with those treated with CM. Based on additional analysis of the EAHM formula data included in this meta-analysis, 21 core materials and five core herbal combinations were identified. CONCLUSION: EAHM remedies for RA have the adequate potential for use as candidate materials for treating inflammatory pain in RA. The candidate core herbs evaluated in this study act on multiple pathways and are expected to provide pain relief, sustained inflammation suppression, immune regulation, and prevention of joint destruction. It seems worthwhile to conduct follow-up research on drug development using the core materials derived from this review.

Oral Administration of East Asian Herbal Medicine for Inflammatory Skin Lesions in Plaque Psoriasis: A Systematic Review, Meta-Analysis, and Exploration of Core Herbal Materials.

Psoriasis is an inflammatory autoimmune skin disease with various clinical manifestations. The aim of this review was to systematically evaluate the efficacy and safety of oral administration of East Asian herbal medicine (EAHM) for inflammatory skin lesions in psoriasis and to explore core herbal materials for drug discovery. A comprehensive search was conducted in 10 electronic databases for randomized controlled trials from their inception until 29 July 2021. Statistical analysis was performed in R version 4.1.2 and R studio. When heterogeneity in studies was detected, the cause was identified through sensitivity analysis, meta-regression, and subgroup analysis. Methodological quality was independently assessed using the revised tool for risk of bias in randomized trials. A total of 56 trials with 4966 psoriasis patients met the selection criteria. Meta-analysis favored EAHM monotherapy on Psoriasis Area Severity Index (PASI) 70 (RR: 1.2845; 95% CI: 1.906 to 1.3858, p < 0.0001), PASI 60 (RR: 1.1923; 95% CI: 1.1134 to 1.2769, p < 0.0001), continuous PASI score (MD: −2.3386, 95% CI: −3.3068 to −1.3704, p < 0.0001), IL-17, IL-23, TNF-α, and Dermatology Life Quality Index. Patients treated with EAHM monotherapy had significantly reduced adverse events incidence rate. In addition, based on additional examination of the herb data included in this meta-analysis, 16 core materials were identified. They are utilized in close proximity to one another, and all have anti-inflammatory properties. The findings in this study support that oral EAHM monotherapy may be beneficial for inflammatory skin lesions in psoriasis. Meanwhile, the identified core materials are expected to be utilized as useful drug candidate hypotheses through follow-up studies on individual pharmacological activities and synergistic effects.

Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin.

Streptomyces rapamycinicus NRRL 5491 is a well-known producer of rapamycin, a secondary metabolite with useful bioactivities, including antifungal, antitumor, and immunosuppressive functions. For the enhanced rapamycin production, a rapamycin-overproducing strain SRMK07 was previously obtained as a result of random mutagenesis. To identify genomic changes that allowed the SRMK07 strain's enhanced rapamycin production, genomes of the NRRL 5491 and SRMK07 strains were newly sequenced in this study. The resulting genome sequences of the wild-type and SRMK07 strains showed the size of 12.47 Mbp and 9.56 Mbp, respectively. Large deletions were observed at both end regions of the SRMK07 strain's genome, which cover 17 biosynthetic gene clusters (BGCs) encoding secondary metabolites. Also, genes in a genomic region containing the rapamycin BGC were shown to be duplicated. Finally, comparative metabolic network analysis using these two strains' genome-scale metabolic models revealed biochemical reactions with different metabolic fluxes, which were all associated with NADPH generation. Taken together, the genomic and computational approaches undertaken in this study suggest biological clues for the enhanced rapamycin production of the SRMK07 strain. These clues can also serve as a basis for systematic engineering of a production host for further enhanced rapamycin production.

Anti-Obesity and Anti-Hyperglycemic Effects of Meretrix lusoria Protamex Hydrolysate in ob/ob Mice.

Meretrix lusoria (M. lusoria) is an economically important shellfish which is widely distributed in South Eastern Asia that contains bioactive peptides, proteins, and enzymes. In the present study, the extracted meat content of M. lusoria was enzymatic hydrolyzed using four different commercial proteases (neutrase, protamex, alcalase, and flavourzyme). Among the enzymatic hydrolysates, M. lusoria protamex hydrolysate (MLPH) fraction with MW ≤ 1 kDa exhibited the highest free radical scavenging ability. The MLPH fraction was further purified and an amino acid sequence (KDLEL, 617.35 Da) was identified by LC-MS/MS analysis. The purpose of this study was to investigate the anti-obesity and anti-hyperglycemic effects of MLPH containing antioxidant peptides using ob/ob mice. Treatment with MLPH for 6 weeks reduced body and organ weight and ameliorated the effects of hepatic steatosis and epididymal fat, including a constructive effect on hepatic and serum marker parameters. Moreover, hepatic antioxidant enzyme activities were upregulated and impaired glucose tolerance was improved in obese control mice. In addition, MLPH treatment markedly suppressed mRNA expression related to lipogenesis and hyperglycemia through activation of AMPK phosphorylation. These findings suggest that MLPH has anti-obesity and anti-hyperglycemic potential and could be effectively applied as a functional food ingredient or pharmaceutical.

Assessment of the Effects of Salt and Salicornia herbacea L. on Physiochemical, Nutritional, and Quality Parameters for Extending the Shelf-Life of Semi-Dried Mullets (Chelon haematocheilus).

Mullet, a coastal fish species, is commonly used as a salted dried fish in many countries, including Korea, Japan, and the southeastern United States. The purpose of this investigation was to develop high-quality products of salted semi-dried mullet (SSDM) using natural salt and Salicornia herbacea L. (SAL). The antioxidant activity of SAL was investigated by in vitro studies. The physicochemical and nutritional characteristics of fresh mullet (FM), salted control (SSDM-CON), and SAL-treated (SSDM-SAL) mullet groups were analyzed. The moisture, ash, and crude protein contents were significantly increased in the SSDM-SAL group, whereas the salinity was decreased when compared with the SSDM-CON group. Lipid oxidation occurred in the FM and SSDM groups, as indicated by the increase in peroxide (PV), acid (AV), and thiobarbituric acid reactive substance (TBARS) values during the storage period. The protein pattern on the sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed similarities between the groups, while the amino acid and fatty acid contents also varied in the FM and SSDM groups depending on their processing methods. Initially, the total bacterial count was significantly higher in the SSDM groups than in the FM group. However, the SSDM-SAL group had a markedly lower total bacteria count than the FM and SSDM-CON groups during 21 days of refrigerated storage. This result indicates that SAL treatment can improve mullet's safety from microorganisms, includes beneficial biochemical parameters, and can extend their shelf-life through refrigerated storage.

Oral administration of East Asian herbal medicine for rheumatoid arthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, and painful joint disease. The aim of this review is to systematically evaluate the efficacy and safety of oral administration East Asian herbal medicine monotherapy for inflammatory pain of RA, and to explore core herb material information based on collected data. METHODS: A comprehensive literature search will be conducted in 11 electronic databases including PubMed, Cochrane Library, Cumulative Index to Nursing & Allied Health Literature, Excerpta Medica database, Korean Studies Information Service System, Research Information Service System Oriental Medicine Advanced Searching Integrated System, Korea Citation Index, Chinese National Knowledge Infrastructure Database, Wanfang data, citation information by NII for randomized controlled trials from their inception until October 13, 2021. Statistical analysis will be performed in the software R version 4.1.1. and R studio program using the default settings of the "meta" and "metafor" package. When heterogeneity in studies is detected, the cause will be identified through subgroup analysis. Methodological quality will be assessed independently using the revised tool for risk of bias in randomized trials (Rob 2.0). RESULTS: This study will provide more comprehensive and specific evidence of East Asian herbal medicine monotherapy for RA pain management. CONCLUSIONS: Based on the results of this review, it is expected that the efficacy and safety of East Asian herbal medicine for inflammatory pain of RA may be confirmed. In addition, it will be possible to derivation of a core herb material information related to this research topic through additional data mining. ETHICS AND DISSEMINATION: There are no ethical issues as there are no primary data collected by directly recruiting subjects. The results of this review will be reported in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42021273643.

East Asian Herbal Medicine Combined with Conventional Therapy for Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis.

BACKGROUND: There is an increasing demand to improve personal health and reduce the social burden in children with autism spectrum disorder (ASD). A comprehensive review of ASD interventions from the point of view of efficacy, safety, and compliance is needed. The purpose of this study was to evaluate the efficacy and safety of East Asian Herbal Medicine (EAHM) in the treatment of ASD. MATERIALS AND METHODS: Eleven databases (PubMed, Cochrane Library, CINAHL, EMBASE, KISS, RISS, OASIS, KCI, CNKI, Wanfang data, and CiNii) were searched from their respective inception to July 2021. A search was conducted by combining the keywords Autism Spectrum Disorder and Herbal medicine. We included a randomized controlled trial in which oral administration of EAHM was combined with conventional treatment for pediatric ASD patients. The primary outcomes were the clinical efficacy rate and the improvement in Childhood Autism Rating Scale (CARS) score. RESULTS: A total of 7 studies involving 462 children with ASD were included. The results suggest that EAHM as part of a combined therapy enhances the CARS score (MD[95% confidential interval]=4.47[5.89,3.05], p<0.01) and the clinical efficacy rate (RR=1.31[1.14,1.51], p<0.01) in comparison to the control group using only conventional therapy. Safety information was reported in 4 of the 7 included studies, and there were no adverse events or the difference in the incidence of side effects between the two groups was not significant. CONCLUSION: This meta-analysis shows that EAHM may improves the clinical efficacy rate and CARS score in children with ASD. However, in that the quality of the included studies is not generally high and the numbers are difficult to be considered sufficient, larger scale and rigorously designed randomized controlled trials need to be conducted to strengthen the evidence.

Oral administration of East Asian herbal medicine for peripheral neuropathy: A protocol for systematic review and meta-analysis with using association rule analysis to identify core herb pattern.

BACKGROUND: Peripheral neuropathy (PN) is one of the most common medical problems encountered. Since the pathophysiology and symptom manifestation characteristics of PN are very diverse, it is difficult to provide an appropriate treatment. East Asian herbal medicine (EAHM) has long contributed to the treatment of neurological and pain disorders. The goal of this systematic review is to measure the efficacy and safety of EAHM for PN and to identify core herb patterns. In order to derive a more conservative result, a random effect model will be applied regardless of the significance of heterogeneity. METHODS: We will search 10 databases to identify suitable studies. There will be no restrictions regarding language or publication date. Primary outcomes will be nerve conduction velocity and response rate. Secondary outcomes will be any objective tool that can measure the efficacy of EAHM, and adverse events will be included. We will perform a meta-analysis of trials with the same intervention and outcome with comparator in a similar population. Meanwhile, in order to explore significant potential correlation in herb preparation, association rule analysis based on the Apriori algorithm will be performed on the collected composition data of herbal medicines. RESULTS: This study will provide scientific evidence for the treatment of EAHM for PN. CONCLUSIONS: Based on the results of this review, it is expected that the efficacy and safety of EAHM for PN can be confirmed. In addition, through additional analysis using data mining techniques, it will be possible to present a core herb pattern related to this research topic.

East Asian herbal medicine for cancer pain: A protocol for systematic review and meta-analysis with using association rule analysis to identify core herb pattern.

BACKGROUND: Cancer pain is an important factor in cancer management that affects a patient's quality of life and survival-related outcomes. The aim of this review is to systematically evaluate the efficacy and safety of oral administration East Asian herbal medicine (EAHM) for primary cancer pain, and to explore core herb patterns based on collected data. METHODS: A comprehensive literature search will be conducted in 10 electronic databases including PubMed, Cochrane Library, Cumulative Index to Nursing & Allied Health Literature, EMBASE, Korean Studies Information Service System, Research Information Service System Oriental Medicine Advanced Searching Integrated System, Korea Citation Index, Chinese National Knowledge Infrastructure Database (CNKI), CiNii for randomized controlled trials from their inception until August 19, 2021. Statistical analysis will be performed in the software R version 4.1.1. and R studio program using the default settings of the 'meta' package. When heterogeneity in studies is detected, the cause will be identified through meta regression and subgroup analysis. Methodological quality will be assessed independently using the revised tool for risk of bias in randomized trials (Rob 2.0). RESULTS: This study will provide more comprehensive and specific evidence of EAHM for cancer pain management. CONCLUSIONS: Based on the results of this review, it is expected that the efficacy and safety of East Asian herbal medicine for cancer pain may be confirmed. In addition, it will be possible to derivation of a core herb pattern related to this research topic through additional association rule mining analysis.