Ligularia fischeri ethanol extract: An inhibitor of alpha-melanocyte-stimulating hormone-stimulated melanogenesis in B16F10 melanoma cells.

BACKGROUND: Ligularia fischeri is a perennial herb isolated from plants of the Asteraceae family. Ligularia fischeri is distributed throughout Korea, Japan, eastern Siberia, and China. AIMS: The aim of this study is to examine the intracellular inhibitory effect of Ligularia fischeri ethanol extract on melanin synthesis and expression of tyrosinase and tyrosinase-related protein 1 and 2. In addition, we analyzed the mitogen-activated protein kinase signaling pathway and microphthalmia-associated transcription factor in alpha-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells. METHODS: To assess the inhibition of melanogenesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells, the expression of melanogenesis-related genes was investigated by quantitative real-time polymerase chain reaction, while western blotting was performed to determine protein expression levels. RESULTS: We confirmed that the ethanol extract of Ligularia fischeri inhibited melanin synthesis in vitro by decreasing tyrosinase and tyrosinase-related protein 1 and 2 expression. Furthermore, we revealed that tyrosinase expression was regulated by the suppression of microphthalmia-associated transcription factor expression and activation of extracellular signal-regulated kinase phosphorylation. The ethanol extract of Ligularia fischeri inhibited melanogenesis by activating extracellular signal-regulated kinase phosphorylation and suppressing microphthalmia-associated transcription factor and tyrosinase expression. CONCLUSIONS: Ligularia fischeri ethanol extract may be used as an effective skin whitening agent in functional cosmetics.

Changes in pharmaceutical market and "fake drug" problem in the Qing period.

Since ancient times, fake drugs have been on the market in Chinese society. However, during the Ming-Qing Dynasty, this problem intensified as the size of the pharmaceutical market grew, the collection and distribution structure of pharmaceutical products became increasingly complex, and the phenomenon of separation between the prescription and distribution of drugs advanced. Additionally, the government did not manage the manufacturing or quality of drugs and there was no law or institution designed to solve the problem of fake drugs. Furthermore, social opinion also criticized the widespread problem of fake drugs, and patients and doctors had to rely on various pharmacognostic books and medical knowledge to find reliable drugs in the drug market. Meanwhile, as merchants participated and invested commercial capital in the pharmaceutical industry, large reputable pharmacies began to emerge in large cities and produced drugs. With the commercialization of the pharmaceutical market, the public gained interest in drugs and consumed drugs produced by these pharmacies. Moreover, there were frequent problems in the market as fake drugs imitating popular drugs were distributed and the names of famous pharmacies were stolen. Although fake drugs were a universal social problem, the Qing government was reluctant to strictly control them tried to solve this issue by enforcing banning and punishment through local governments. Prominent pharmacies filed several lawsuits against the government over the theft of fake drugs and drug names. They also advertised the legitimacy and authenticity of drugstore to the public and customers. Doctors and merchants responded to the problem of fake drugs by following occupational morality, developing drug discrimination, cracking down on organizational discipline, filing complaints with government offices, and advertising their authenticity. However, the fake medicines did not easily disappear despite such a response, as there was no state control or legislation. Evidently, the pharmaceutical market was already highly commercialized and its structure were complex. Moreover, the financial benefits of fake drugs, competition in the pharmaceutical market, and public demand for drugs with similar effects at low prices also affected the popularity of fake drugs. Hence, the distribution of fake medicine in the Qing society can be seen as a phenomenon of separation between the prescription and distribution of drugs, commercialization and consumption of drugs, and competition on the medical market.

Effect of black ginseng and silkworm supplementation on obesity, the transcriptome, and the gut microbiome of diet-induced overweight dogs.

Like humans, weight control in overweight dogs is associated with a longer life expectancy and a healthier life. Dietary supplements are one of the best strategies for controlling obesity and obesity-associated diseases. This study was conducted to assess the potential of black ginseng (BG) and silkworm (SW) as supplements for weight control in diet-induced overweight beagle dogs. To investigate the changes that occur in dogs administered the supplements, different obesity-related parameters, such as body condition score (BCS), blood fatty acid profile, transcriptome, and microbiome, were assessed in high energy diet (HD) and HD with BG + SW supplementation (HDT) groups of test animals. After 12 weeks of BG + SW supplementation, total cholesterol and triglyceride levels were reduced in the HDT group. In the transcriptome analysis, nine genes (NUGGC, EFR3B, RTP4, ACAN, HOXC4, IL17RB, SOX13, SLC18A2, and SOX4) that are known to be associated with obesity were found to be differentially expressed between the ND (normal diet) and HD groups as well as the HD and HDT groups. Significant changes in some taxa were observed between the HD and ND groups. These data suggest that the BG + SW supplement could be developed as dietary interventions against diet-induced obesity, and obesity-related differential genes could be important candidates in the mechanism of the anti-obesity effects of the BG + SW supplement.

Anti-Inflammatory Effects of Fermented Lotus Root and Linoleic Acid in Lipopolysaccharide-Induced RAW 264.7 Cells.

Inflammation is a protective response of the innate immune system. However, aberrant inflammatory responses lead to various diseases. Lotus root, the edible rhizome of Nelumbo nucifera, is a popular traditional herbal medicine in East Asia. In a previous study, we reported that fermented lotus root (FLR) alleviated ethanol/HCl-induced gastric ulcers in rats by modulating inflammation-related genes. However, the mechanisms underlying the anti-inflammatory effects of FLR and its major constituent, linoleic acid (LA), are still largely unknown. In this study, we investigated the anti-inflammatory effects of FLR and LA on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 murine macrophages. We found that FLR inhibited LPS-induced expression of inflammatory mediators through down-regulation of NF-κB activity. Similarly, LA also attenuated LPS-induced inflammatory responses and reduced LPS-induced phosphorylation of proteins associated with NF-κB signaling, such as ERK, JNK, and p38. Overall, our results suggested that FLR and LA may effectively ameliorate inflammatory diseases.

The Effects of Irvingia gabonensis Seed Extract Supplementation on Anthropometric and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Background: It has been hypothesized that Irvingia gabonensis can promote weight loss by increasing fatty acid breakdown and inhibiting fatty acid synthesis.Objective: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Irvingia gabonensis seed extract supplementation on weight-related health outcomes.Methods: Literature searches were conducted in 4 databases from January 2018 to identify randomized controlled trials (RCTs) investigating the effects of Irvingia gabonensis seed extract supplementation on anthropometric measures and cardiovascular biomarkers. Two investigators independently performed abstract screenings, full-text screenings, data extraction, and risk of bias (ROB) assessments. Random effects meta-analyses were performed when 3 or more RCTs reported the same outcome.Results: Five RCTs met the eligibility criteria for this systematic review. Four of the 5 RCTs were rated as having a high ROB, and only one RCT was rated as having a low ROB. Random-effects meta-analysis of the 5 RCTs showed that a significant decrease in body weight, body fat, and waist circumference was observed in relation to Irvingia gabonensis seed extract supplementation. However, the only one low-ROB trial did not have significantly different outcomes. Meta-analysis also showed beneficial effects of Irvingia gabonensis seed extract supplementation on total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Only the low-ROB trial showed a trend of increasing HDL-cholesterol levels (net percent change = 11.61%; 95% confidence interval (CI: -6.12%, 29.34%) and decreasing triglyceride levels (net percent change = -29%; 95% CI: -76%, 19%). The reported adverse events were minor in these 5 RCTs.Conclusions: Overall efficacy of Irvingia gabonensis seed extract supplementation on weight loss seems positive but is limited due to poor methodological quality and the insufficient reporting of the clinical trials. Further high quality RCTs are needed to determine the effectiveness of Irvingia gabonensis seed extract supplement on the weight-related health outcomes.

Social Perceptions of Quack in Qing Dynasty and Its Transformation in the Late Qing Period.

"Yong-yi" means "quack" in English, which generally refers to a doctor who does not have good medical skills. In the Ming and Qing dynasties in China, various criticism about "Yong-yi" became popularized, and by the late Qing period, "quacks" had become a serious social issue. The theory of traditional Chinese medicine was developed during the Ming and Qing dynasties, and local medical resources also increased. Moreover, the prevalence of medical book publishing led to the openness and generalization of medical knowledge. As a result, not only the number of doctors increased, but also the number of doctors who lack medical knowledge and clinical experience increased. However, at the outset, "Yong-yi" did not only mean doctors with poor medical skills. "Yong-yi" also reflected conflicts and contradictions between doctors. Doctors consistently criticized quacks in an attempt to maintain their identity as a "good" doctor or a Confucian doctor. In this sense, "Yong-yi" was used among physicians as an expression of discrimination and exclusion. The concept of "quackery" was also determined by the relationship between patients and doctors. In general, itinerant doctors, midwives and shaman doctors were regarded as "Yong-yi"; however, they served the medical needs of various patients. Thus, to some extent, "Yong-yi" were also useful medical resources. On the contrary, in certain situations, "shiyi," physicians who serviced a family for generations and were generally believed to be reliable and as trustworthy doctors, were also labelled as quacks, especially when the patient did not trust them or was not satisfied with the treatment. Therefore, doctors' thoughts about "Yong-yi" did not always coincide with patients' thoughts about "Yong-yi." However, by the late Qing period, the description of quacks in media reports found a singular connotation, and the divergent social image of quacks disappeared. By this time, quacks were uniformly described as ignorant and irresponsible Chinese medicine practitioners. Specifically, in one murder case in which a "Yong-yi" was accused as the murderer, the report unilaterally reported the patient's claims. Consequently, Chinese medicine practitioners who failed in their treatment of patients became labeled as "quack" doctors. In newspaper reports, "Yong-yi" no longer simply referred to individual cases of "quacks" but had come to represent the entirety of the Chinese medicine practitioner community. On the contrary, Western medical doctors who replaced the status of traditional doctors were positively portrayed. Pictorials also had similar perspectives with newspapers, supporting the narrative of the news with ironic drawings and articles. Overall, media reports regarding "Yong-yi" did not focus on reporting facts, but they had the purpose of making quacks a serious social problem.

Piscroside C inhibits TNF-α/NF-κB pathway by the suppression of PKCδ activity for TNF-RSC formation in human airway epithelial cells.

BACKGROUND: Piscroside C, isolated from Pseudolysimachion rotundum var. subintegrum, is a novel iridoid glycoside with therapeutic efficacy in a mouse model of chronic obstructive pulmonary disease (COPD). Piscroside C has been reported as a constituent of YPL-001 (under Phase 2a study, ClinicalTrials.gov identifier NCT02272634). PURPOSE: To investigate the mechanisms behind piscroside C therapeutic effects on COPD in human airway epithelial NCI-H292 cells. METHODS: We tested if piscroside C effectively suppresses MUC5AC gene expression and TNF-RSC/IKK/NF-κB cascades in TNF-α-stimulated NCI-H292 cells by employing, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, luciferase reporter assays, chromatin immunoprecipitation assays and immunoprecipitation. RESULTS: Piscroside C markedly suppressed the expression of TNF-α-induced MUC5AC mucus protein by inhibiting the transcriptional activity of NF-κB in NCI-H292 cells. Indeed, piscroside C negatively regulated the function of TNF receptor 1 signaling complex (TNF-RSC, an upstream regulator of the NF-κB pathway) without affecting its extracellular interaction with the TNF-α ligand. This inhibitory effect by piscroside C is mediated by the inactivation of protein kinase C (PKC), an essential regulator of TNF-RSC. PKC inactivation by piscroside C results in decreased PKCδ binding to a TRAF2 subunit of TNF-RSC and subsequent reduced IKK phosphorylation, resulting in NF-κB inactivation. CONCLUSION: We propose that piscroside C is a promising therapeutic constituent of YPL-001 through its inhibition of PKCδ activity in the TNF-RSC/IKK/NF-κB/MUC5AC signaling cascade.