Compound-level identification of sasang constitution type-specific personalized herbal medicine using data science approach.

Introduction: Sasang Constitutional Medicine (SCM) is a type of traditional Korean medicine where patients are classified as one of four Sasang constitution types (Sasang type) and medications consisting of medicinal herbs are prescribed according to the Sasang type. Despite the importance of personalized medicine, the operation mechanism is largely unknown. To gain a better understanding, we investigated the compound information that composes Sasang type-specific personalized herbal medicines on both multivariate and univariate levels. Methods: Five machine learning classifiers including extremely randomized trees (ERT) were trained to investigate whether the Sasang type can be explained by compound information at the multivariate level. Hierarchical clustering was conducted to determine whether compounds are processed distributedly or specifically. Taxonomic and biosynthetic analyses were conducted on these compounds. A univariate level statistical test was conducted to provide more robust Sasang type-specific compound information. Results: Using the trained ERT classifier, sixty important compounds were extracted. The sixty compounds were clustered into three groups, corresponding to each Sasang type-prominent compounds, suggesting that most compounds have specific preference for the Sasang type. Structural and biosynthetic characteristics of these Sasang type-prominent compounds were determined based on taxonomy and pathway analyses. Fourteen compounds showed statistically significant relevance with the Sasang type. Additionally, we predicted the Sasang type of unknown herbs, which were confirmed by their biological effects in functional assays. Conclusion: This study investigated the personalized herbal medicines of the SCM using compound information. This study provided information on the chemical characteristics of the compounds that are essential for classifying the Sasang type of medicinal herbs, as well as predictions regarding the Sasang type of the commonly used but unidentified medicinal herbs.

A Machine Learning Approach for Recommending Herbal Formulae with Enhanced Interpretability and Applicability.

Herbal formulae (HFs) are representative interventions in Korean medicine (KM) for the prevention and treatment of various diseases. Here, we proposed a machine learning-based approach for HF recommendation with enhanced interpretability and applicability. A dataset consisting of clinical symptoms, Sasang constitution (SC) types, and prescribed HFs was derived from a multicenter study. Case studies published over 10 years were collected and curated by experts. Various classifiers, oversampling methods, and data imputation techniques were comprehensively considered. The local interpretable model-agnostic explanation (LIME) technique was applied to identify the clinical symptoms that led to the recommendation of specific HFs. We found that the cascaded deep forest (CDF) model with data imputation and oversampling yielded the best performance on the training set and holdout test set. Our model also achieved top-1 and top-3 accuracies of 0.35 and 0.89, respectively, on case study datasets in which clinical symptoms were only partially recorded. We performed an expert evaluation on the reliability of interpretation results using case studies and achieved a score close to normal. Taken together, our model will contribute to the modernization of KM and the identification of an HF selection process through the development of a practically useful HF recommendation model.

Investigating the Biomarkers of the Sasang Constitution via Network Pharmacology Approach.

Sasang constitutional (SC) medicine classifies people into Soeum (SE), Soyang (SY), Taeeum (TE), and Taeyang (TY) types based on psychological and physical traits. However, biomarkers of these types are still unclear. We aimed to identify biomarkers among the SC types using network pharmacology methods. Target genes associated with the SC types were identified by grouping herb targets that preserve and strengthen the requisite energy (Bomyeongjiju). The herb targets were obtained by constructing an herb-compound-target network. We identified 371, 185, 146, and 89 target genes and their unique biological processes related to SE, SY, TE, and TY types, respectively. While the targets of SE and SY types were the most similar among the target pairs of the SC types, those of TY type overlapped with only a few other SC-type targets. Moreover, SE, SY, TE, and TY were related to "diseases of the digestive system," "diseases of the nervous system," "endocrine, nutritional, and metabolic diseases," and "congenital malformations, deformations, and chromosomal abnormalities," respectively. We successfully identified the target genes, biological processes, and diseases related to each SC type. We also demonstrated that a drug-centric approach using network pharmacology analysis provides a deeper understanding of the concept of Sasang constitutional medicine at a phenotypic level.

Efficacy of traditional herbal medicine for psychological sequelae in COVID-19 survivors: A protocol for systematic review and meta-analysis.

INTRODUCTION: This study is the protocol for a systematic review to evaluate the efficacy of herbal medicine on COVID-19 survivors with psychological sequelae. Currently, there are many COVID-19 survivors with psychological sequelae as COVID-19 has widely spread all over the world. However, there is no critically appraised evidence of the benefit of herbal medicine for COVID-19 survivors with psychological sequelae. MATERIALS AND METHODS: We will search 11 electronic databases from inception to December, 2022: 4 English databases, MEDLINE, PubMed, Excerpta Medica database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL); 3 Chinese databases, the Chinese National Knowledge Infrastructure, the Chinese Scientific Journal database, and the Wan Fang database; and 4 Korean databases, the Oriental Medical Advanced Searching Integrated System, the Korean Studies Information Service System, the National Digital Science Links, and the Research Information Sharing Service. We will include randomized controlled trials (RCTs), non-RCTs, and quasi-RCTs for all formations of TRADITIONAL herbal medicine versus conventional drug, placebo, and no treatment for COVID-19 survivors. We will only include the COVID-19 survivors with psychiatric symptoms lasting at least 1 month, regardless of their race, sex, and age. DISCUSSION AND CONCLUSIONS: This systematic review will be published in a peer-reviewed journal. The findings will provide evidence and treatment directions for clinicians. This protocol does not need ethical approval because it will be based on published research. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020210592.

Stilbenes contribute to the anticancer effects of Rheum undulatum L. through activation of apoptosis.

Rheum undulatum L. (R. undulatum) is a medicinal plant used for the treatment of inflammatory diseases in East Asian countries. Numerous stilbenes isolated from R. undulatum have been revealed to possess anticancer effects. The aim of the present study was to evaluate the effect of extracts and compounds isolated from R. undulatum on human gastric cancer cell viability and to elucidate their molecular mechanism of action on the apoptosis pathway. The results demonstrated that aloe-emodin and chrysophanol 1-O-ß-D-glucopyranoside, isolated from the methanolic extract of dried rhizomes of R. undulatum, exhibited anti-proliferative effects on the human gastric carcinoma cell line AGS, with IC50 values of 84.66±0.44 and 68.28±0.29 µM, respectively. The percentage of apoptotic cells increased significantly following treatment with each compound at a concentration of 100 µM, compared with that in the non-treated group in the image-based cytometry assay. Western blot analysis revealed that these compounds activated the caspase cascade and inhibited B-cell lymphoma-2, an anti-apoptotic protein.

Herbal medicine for the management of postoperative pain: A protocol for the systematic review of randomized controlled trials.

BACKGROUND: Postoperative pain is caused by surgical trauma and poses a significant challenge for health care providers. Opioid analgesics are commonly used to control postoperative pain. However, these drugs are associated with a number of negative side effects. This review will assess the clinical evidence for and against the use of herbal medicine formulas as a treatment for postoperative pain, especially after musculoskeletal surgery. METHODS: Twelve databases will be searched from inception to March 2019. We will include randomized controlled trials (RCTs) assessing herbal medicine decoctions used to treat any type of postoperative pain. All RCTs of decoctions or modified decoctions will be included. The methodologic qualities of the RCTs will be assessed using the Cochrane Collaboration tool for assessing risk of bias, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation method. CONCLUSION: This systematic review will be published in a peer-reviewed journal and disseminated electronically and in print. The review will be updated to inform and guide health care practices.Registration number: CRD42018094897.

Herbal medicine for benign prostatic hyperplasia: A protocol for a systematic review of controlled trials.

BACKGROUND: Herbal medicine has been used to manage benign prostatic hyperplasia (BPH) and the associated lower urinary tract symptoms, but its effects are not yet fully understood. The purpose of this review is to assess the efficacy and safety of herbal medicine as a treatment for BPH. METHODS AND ANALYSIS: Thirteen databases will be searched for relevant studies from inception to the present date. We will include randomized controlled trials assessing herbal medicine for the treatment of BPH. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print.

Bioactivity-based analysis and chemical characterization of anti-inflammatory compounds from Curcuma zedoaria rhizomes using LPS-stimulated RAW264.7 cells.

Inflammation is not only a self-defense response of the innate immune system, but also the pathogenesis mechanism of multiple diseases such as arthritis, neurodegeneration, and cancer. Curcuma zedoaria Roscoe (Zingiberaceae), an indigenous plant of India, has been used traditionally in Ayurveda and folk medicine. As part of our ongoing efforts to screen traditional medicinal plants exhibiting pharmacological potential and to characterize the compounds involved, we examined the anti-inflammatory effects of the MeOH extract of C. zedoaria rhizomes using lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells and found that MeOH extract inhibited the synthesis of nitric oxide (NO) in a dose-dependent manner (IC50: 23.44 ±â€¯0.77 µg/mL). In our efforts to characterize the compounds responsible for these anti-inflammatory effects, bioactivity-guided fractionation of the MeOH extract and chemical investigation of its active hexane-soluble fraction led to the successful isolation of five sesquiterpenes (1-5), the structures of which were elucidated by NMR spectroscopic analysis and LC/MS analysis. Among them, curcuzedoalide (5) exhibited potent inhibitory effects on NO synthesis (IC50: 12.21 ±â€¯1.67 µM) and also suppressed pre-inflammatory protein expression of iNOS and COX-2. Curcuzedoalide (5) was thus determined to be a contributor to the anti-inflammatory effect of C. zedoaria rhizomes and could be a potential candidate for therapeutic applications.

Retrospective case series on Gwakhyangjeonggi-san prescribed to patients with chronic urticaria.

INTRODUCTION: Chronic urticaria (CU) is characterized by repeated occurrence of wheals or itching for more than 6 weeks. When urticarial symptoms repeatedly occur despite taking western medicines such as antihistamines, herbal medicines have potential as an alternative for them. Among various herbal medications for CU, we mostly prescribe Gwakhyangjeonggi-san (GJS) made by Lee Je-ma, the founder of Sasang Constitutional Medicine (SCM) in Korea. The purpose of this study is to investigate whether GJS actually helps in treating CU. METHODS: We performed a retrospective review of the medical records of 30 patients to whom GJS was administered in order to compare the changes in urticaria activity scores (UAS) and in western medicines taken at the beginning of treatment of GJS and at 6 months after completion of the treatment. RESULTS: The UAS after 6 months from treatment (1.63 ± 2.06) with GJS for an average of 57.30 ± 35.88 days was significantly decreased compared to the score before treatment (5.10 ± 0.99), showing a statistically significant difference (p< 0.001). 46.67% of the patients (14/30 patients) reported that their symptoms were completely eliminated, and 66.67% of the patients taking anti-histamines (18/27 patients) were able to stop it completely. DISCUSSION: Based on the findings, GJS helps patients reduce taking western medicines such as anti-histamines, and we hypothesize that GJS improves symptoms of CU by the gastrointestinal protective activity and anti-oxidative/depressive effect. Further clinical study is warranted.

A simultaneous analysis method for Caihu-Dayuan-Yin using reversed-phase high-performance liquid chromatography coupled with pulsed amperometric detection.

A simultaneous analysis method was developed for Caihu-Dayuan-Yin decoction containing Bupleuri Radix, Glycyrrhizae Radix, and Ponciri fructus by reversed-phase (RP) HPLC coupled with pulsed amperometric detection (PAD). The analytes were separated in a RP column with 0.01 % phosphoric acid-acetonitrile gradient elution. The limits of detection (S/N = 3) and of quantification (S/N = 10) ranged 0.1-3.0, and 0.3-10 ng, respectively. The intra- and interday precisions (RSDs) were ≤15.15 % and the average recoveries were 94.6-98.3 %. Our RP-HPLC-PAD method showed 1.7-100 times higher sensitivity than the RP-HPLC-UV method.

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model.

The phosphorylation changes of nociceptive signaling proteins in the spinal cord dorsal horn (SCDH) are important in creating exaggerated pain following peripheral inflammation. Electroacupuncture (EA) has been widely used to relieve acute and chronic inflammatory pain in human and experimental pain models. In the present study, we performed a phosphoproteomic analysis to investigate whether EA alters protein phosphorylation in SCDH to attenuate pain development. Inflammatory hyperalgesia was induced by intraplantar injection of complete Freund's adjuvant (CFA) into the rat hind paw. EA treatment at ST36 and SP6 acupoints alleviated thermal hyperalgesia of the CFA-induced inflammatory pain model rats. The SCDH proteins from the control, inflammatory pain model and EA treatment rats were separated by 2-dimensional gel electrophoresis and the alterations in phosphoproteins were detected by Pro-Q Diamond staining. Eight proteins were differentially phosphorylated following EA treatment in the inflammatory pain model. Aldolase C, nascent polypeptide-associated complex α, stress-induced phosphoprotein 1 and heat shock protein 90 were identified as phosphoproteins whose expression was increased, whereas GDP dissociation inhibitor 1, thiamine triphosphatase, phosphoglycerate kinase 1 and 14-3-3 γ were phosphoproteins whose expression was decreased. This is the first phosphoproteomic screening study to elucidate the working mechanisms of EA analgesia. The results suggest that the regulation of cellular pathways in which the identified proteins are involved may be associated with an EA analgesic mechanism.

Reduced spatial focality of electrical field in tDCS with ring electrodes due to tissue anisotropy.

For effective stimulation with tDCS, spatial focality of induced electrical field (EF) is one of the important factors to be considered. Recently, there have been some studies to improve the spatial focality via different types of electrodes and their new configurations: some improvements using ring electrodes were reported over the conventional pad electrodes. However, most of these studies assumed isotropic conductivities in the head. In this work, we have investigated the effect of tissue anisotropy on the spatial focality of tDCS with the 4+1 ring electrode configuration via a 3-D high-resolution finite element (FE) head model with anisotropic conductivities in the skull and white matter. By examining the profiles of the induced EF from the head models with isotropic and anisotropic conductivities respectively, we found that the spatial focality of the induced EF significantly drops and get diffused due to tissue anisotropy. Our analysis suggests that it is critical to incorporate tissue anisotropy in the stimulation of the brain via tDCS.