Shanghanlun (Treatise on Cold Damage Diseases) is the oldest document in the literature on clinical records of Traditional Asian medicine (TAM), on which TAM theories about symptoms-herbs relationships are based. In this study, we aim to quantitatively explore the relationships between symptoms and herbs in Shanghanlun. The text in Shanghanlun was converted into structured data. Using the structured data, Term Frequency - Inverse Document Frequency (TF-IDF) scores of symptoms and herbs were calculated from each chapter to derive the major symptoms and herbs in each chapter. To understand the structure of the entire document, principal component analysis (PCA) was performed for the 6-dimensional chapter space. Bipartite network analysis was conducted focusing on Jaccard scores between symptoms and herbs and eigenvector centralities of nodes. TF-IDF scores showed the characteristics of each chapter through major symptoms and herbs. Principal components drawn by PCA suggested the entire structure of Shanghanlun. The network analysis revealed a 'multi herbs - multi symptoms' relationship. Common symptoms and herbs were drawn from high eigenvector centralities of their nodes, while specific symptoms and herbs were drawn from low centralities. Symptoms expected to be treated by herbs were derived, respectively. Using measurable metrics, we conducted a computational study on patterns of Shanghanlun. Quantitative researches on TAM theories will contribute to improving the clarity of TAM theories.

Palmijihwang-tang is an herbal formula frequently used to treat many symptoms, such as lumbago, pollakiuria, cold hands and feet, nephritis, sterilitas virilis, and prostatic disorders. The aim of this study was to investigate the effects of Palmijihwang-tang on cisplatin-induced nephrotoxicity in rat kidney proximal tubular NRK-52E cells. NRK-52E cells were treated with Palmijihwang-tang in absence or presence of 30 µM cisplatin for 12 or 24 h. Palmijihwang-tang at concentrations of 50-800 ㎍/ml did not change the cell viability in NRK-52E cells, and showed no significant toxicity. Palmijihwang-tang at concentrations of 400 and 800 ㎍/ml significantly increased the cell viability and reduced apoptotic cells in NRK-52E cells exposed to cisplatin. Also, Palmijihwang-tang markedly inhibited cisplatin-induced caspase-3 activation, PARP cleavage, ROS production and p53 activation in NRK-52E cells. Furthermore, Palmijihwang-tang did not interfere with the antitumor activity of cisplatin in AGS and A549 cancer cells. Particularly, Palmijihwang-tang enhanced antitumor activity of cisplatin in A549 cells. Taken together, these results suggest that Palmijihwang-tang ameliorated cisplatin-induced nephrotoxicity through reduction of ROS production and p53 activation, and did not interrupt antitumor efficacy of cisplatin against cancer cells.

The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

This study was performed to find antibacterial substances contained in Scutellariae Radix (SR) using a systems pharmacological analysis method and to establish an effective strategy for the prevention and treatment of infectious diseases. Analysis of the main active ingredients of SR was performed using Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. 36 active compounds were screened by the parameter values of Drug-Likeness (DL), Oral Bioavailability (OB), and Caco-2 permeability (Caco-2), which were based on the drug absorption, distribution, metabolism, and excretion indicators. The UniProt database was used to obtain information on 159 genes associated with active compounds. The main active compounds with antibacterial effects were wogonin, β-sitosterol, baicalein, acacetin and oroxylin-A. Target proteins associated with the antibacterial action were chemokine ligand 2, interleukin-6, tumor necrosis factor, caspase-8,9 and mitogen-activated protein kinase 14. In the future, systems pharmacological analysis of traditional medicine will be able to make it easy to find the important mechanism of action of active substances present in natural medicines and to optimize the efficacy of medicinal effects for combinations of major ingredients to help treat certain diseases.

The purpose of this pilot study was to examine the effect of tongue color change due to food ingestion on tongue diagnosis by both Korean Medicine doctors and digital tongue diagnosis system. In order to obtain objective and quantitative data, we used digital camera to collect the data. Prior to our investigation, we conducted a brief survey of 26 Korean Medicine doctors and found out that tongue diagnosis is frequently used and food-stained tongue could be commonly observed in clinics. Depending on their color, viscosity, and amount of intake, various foods caused stains with different colors and thicknesses. Also, duration and amount of food stain on tongue were different from person to person. Since coffee-stained tongue was the most frequently observed one in clinics according to the survey, we used coffee to evaluate the effect of food-stained tongue on tongue diagnosis. Korean Medicine doctors tended to interpret coffee-stained tongue as having yellow tongue coat but their judgement on tongue body color did not differ in spite of the coffee stains. Meanwhile, tongue diagnosis system algorithm tended to judge coffee-stained tongue as having normal but yellowish tongue coat and reddish tongue body. Altogether, food color on tongue can influence tongue diagnosis outcomes. Further research is needed in order to develop more efficient tongue diagnosis algorithm and digital medical service system.

The effects of Gamisoyo-san (GMSYS) co-administration within 5 min on the pharmacokinetics (PK) of tamoxifen were observed. After 50 mg/kg of tamoxifen oral treatment, GMSYS 100 mg/kg was orally administered within 5 min to 7-wk old male SPF.VAF Outbred Crl:CD [Sprague-Dawley (SD)] rats. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, t1/2 and MRTinf of tamoxifen were analysis as compared with tamoxifen single administered rats. Although co-administration with GMSYS did not critically influenced on the pharmacokinetic parameters of oral tamoxifen, they induced increased trends of plasma tamoxifen concentrations, especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 hr after end of co-administration with GMSYS as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 10 mg/kg and GMSYS 100 mg/kg within 5 min. It is considered that pharmacokinetic studies should be tested like the effects of GMSYS on the pharmacokinetics of tamoxifen, when they were co-administered with prolonger intervals than Tmax of tamoxifen oral administration (about 2.5 hr-intervals), to achieve the optimal dosing regimen of GMSYS and tamoxifen co-administration.

The association of cold-heat (CH) pattern and anthropometry/body composition has been suggested in that they are related to thermoregulation. We aimed to study the association of CH pattern and anthropometry/body composition. A total of 1479 individuals aged 50-80 years were included in the study, and their CH pattern were evaluated by a self-administered questionnaire. After adjustment for age and sex, the CH score were significantly correlated with weight, BMI (body mass index), body surface area, waist-hip ratio, fat free mass, body fat mass, body cell mass, intracellular water, extracellular water, and basal metabolic rate; however, the correlation coefficients were mostly low (0.15-0.24). The selected variables for predicting CH score were various according to the methods used for variable selection; however, the adjusted R-squared of the final models were all around 0.12. Thus the most parsimonious model could be the one that includes sex and BMI. In conclusion, various anthropometry and body composition indices were associated with CH pattern. Future studies are necessary to improve the performance of the prediction model.