Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

Components from Curcuma longa (Turmeric) Against Hepatobiliary Diseases Based on Gut-Liver Axis: Pharmacotherapeutic Properties and Potential Clinical Applications.

Turmeric is widely used worldwide, and there are many examples of its use in treating hepatobiliary diseases. The gut-liver axis is a bidirectional relationship between gut microorganisms and the liver that is closely related to the pathogenesis of hepatobiliary diseases. This review systematically summarizes the components of turmeric. It links the studies on turmeric affecting gut microorganisms to its effects on liver and biliary diseases to explain the potential mechanism of turmeric's regulation of the gut-liver axis. Besides, ethnopharmacology, phytochemicals, and clinical adverse events associated with turmeric have been researched. Furthermore, turmeric is a safe agent with good clinical efficacy and without apparent toxicity at a certain amount. By summarizing the influence of turmeric on the liver by regulating the gut-liver axis, especially the gut microbiota, it provides a preclinical basis for using turmeric as a safe and effective therapeutic agent for the prevention and treatment of hepatobiliary diseases based on the gut-liver axis. However, more efforts should be made to exploit its clinical application further.

Modulating Effects of Turmeric Polysaccharides on Immune Response and Gut Microbiota in Cyclophosphamide-Treated Mice.

Turmeric, a traditional medicinal herb, is commonly used as a dietary and functional ingredient. This study aimed to investigate the effect of turmeric polysaccharides (TPs) on intestinal immunity and gut microbiota in cyclophosphamide (Cy)-induced immunosuppressed BALB/c mice. We verified that the oral administration of TPs-0 and TPs-3 (200 and 400 mg/kg, bw) improved thymus and spleen indexes, increased the whole blood immune cells (WBC) and lymph count index, and stimulated the secretion of serum immunoglobulin IgG. More importantly, TPs-0 and TPs-3 could repair intestinal immune damage and reduce intestinal inflammation. The specific mechanism is ameliorating the intestinal pathological damage, promoting CD4+ T cell secretion, regulating the expression of related cytokines, and reducing the level of critical proteins in the NF-κB/iNOS pathway. Interestingly, the intake of TPs-0 and TPs-3 significantly increased the content of short-chain fatty acids (SCFAs). Moreover, TPs-0 and TPs-3 relieved the intestinal microbiota disorder via the proliferation of the abundance of Lactobacillus and Bacteroides and the inhibition of Staphylococcus. Cumulatively, our study suggests that TPs-0 and TPs-3 can relieve intestinal immune damage by repairing the immune barrier and regulating intestinal flora disorders. TPs have potential applications for enhancing immunity as a functional food.

The Association Between Dietary Magnesium Intake with Chronic Obstructive Pulmonary Disease and Lung Function in US Population: a Cross-sectional Study.

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV1 [ß = 0.21 (95% CI 0.12, 0.30)] and FVC [ß = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40-60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD.

Herb pairs containing Curcumae Rhizoma (Ezhu): A review of bio-active constituents, compatibility effects and t-copula function analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: An herbal pair is a classic form of clinical dispensing in Traditional Chinese Medicine (TCM), often used in prescriptions to enhance the effect or reduce potential side effects. It is the smallest component unit of Chinese medicine prescription and an essential bridge between Chinese medicine and prescription. Curcumae Rhizoma (called Ezhu in Chinese) is a representative TCM herb that promotes blood circulation and removes blood stasis. It has been used in Chinese medicine for thousands of years. Ezhu is generally used in clinical applications as a part of a "drug pair" to treat heartburn, stomach pain, tumour, amenorrhea and abdominal pain caused by blood stasis, qi stagnation and injury. AIMS OF THE REVIEW: This review aims to summarize the latest and comprehensive situation of the biological activity and clinical application of drug pairs containing Ezhu, find the law of Ezhu compatibility application, and discuss the rationalization of Ezhu drug compatibility. For Ezhu, herb pairs to provide a theoretical basis for clinical research in TCM and serve as a research foundation for developing new drugs. MATERIALS AND METHODS: Using a self-built prescription database and Apriori algorithm for association rule mining. A systematic search for studies on herb pairs containing Ezhu was carried out by using the internet databases of PubMed, CNKI, Baidu Scholar, Google Scholar and Web of Science, as well as other relevant textbooks, reviews and documents (e.g. Chinese Pharmacopoeia, 2020 edition, Chinese herbal classic books and PhD and MSc theses, etc.). Among them with keywords including "Curcumae Rhizoma", "Ezhu", "herb pairs", "clinical application", etc. and their combinations. Moreover, the t-copula function was used to analyse the dose-coupling effect of five drug pairs, including Ezhu. RESULTS: The preliminary statistical analysis retrieved Ezhu prescriptions from self-built prescription database and internet databases. The results showed that the compatibility frequency of Ezhu with the other five Chinese medicines was high. Most of these selected herbal combinations are used to treat internal diseases. In this paper, the progress of the ethnopharmacology of Ezhu was reviewed, emphasizing the changes in bioactive components and compatibility of Chinese traditional medicine combinations such as Ezhu and Astragalus Curcuma (Sparganium stoloniferum Buch. -Ham; called Sanleng in Chinese), Ezhu and Astragali Radix (Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Astragalus membranaceus (Fisch.) Bge.; called Huangqi in Chinese). Some other varieties, such as Ezhu and Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.; called Chuanxiong in Chinese), Trionycis Carapax (Trionyx sinensis Wiegmann; called Biejia in Chinese), and Coptidis Rhizoma (Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, Coptis teeta Wall.; called Huanglian in Chinese), are also recorded in ancient books but rarely researched. The dose of Ezhu is strongly correlated with the amount of Sanleng, Huangqi, Biejia, Chuanxiong and Huanglian, respectively. Furthermore, there was a positive correlation between them. CONCLUSIONS: The bioactive components and compatibility effects of Ezhu herb pairs were studied in detail using data mining and t-copula function analysis. Ezhu and Astragalus Curcuma (Sanleng) mainly treat gynecological disorders by activating blood circulation and relieving congestion. Ezhu and Astragali Radix (Huangqi) drug pair and Ezhu and Trionycis Carapax (Biejia) drug pair are all commonly used in the clinical treatment of tumors, the former is mainly used clinically for the treatment of digestive tract-related inflammation and tumors, liver cancer and gynecological tumors, and the latter is commonly used for the treatment of malignant tumors, such as liver cancer and mammary cancer.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells.

Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future.

Study on the mechanism of Huangqin Decoction on rats with ulcerative colitis of damp-heat type base on mtDNA, TLR4, p-PI3K, p-Akt protein expression and microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin decoction (HQD), composed of Scutellaria(Huangqin), Peony(Shaoyao), Liquorice(Gancao) and Jujube(Dazao), is a traditional Chinese medicine prescription, originated from treatise on Febrile Diseases, has the functions of clearing heat, stopping benefits and relieving pain. It is the original prescription for treating heat and relieving dysentery, and is commonly used in clinic for diarrhea and other diseases. In ulcerative colitis, damp-heat syndrome is the most common. However, its mechanism of action is not completely clear. AIMS OF THE REVIEW: The purpose of the research is to investigate the protective effect of HQD on ulcerative colitis rats and the regulation effect of mitochondrial DNA, TLR4, p-Akt, p-PI3K protein and microbiota. MATERIALS AND METHODS: The effects of HQD anti-UC were investigated by fluorescence quantitative PCR, cytokine level and histopathological analysis in DSS-induced ulcerative colitis (UC) rats. The content of mtDNA in colon epithelial cells of rats in each group was detected by fluorescence quantitative PCR, p-PI3K, p-Akt and TLR4 protein expressions in colon tissues of rats in each group were detected by Western blotting. IL-6, IL-17 and IL-23 inflammatory factors were detected by ELISA. The effect of HQD on intestinal microbiota of rats with ulcerative colitis was studied by high-throughput sequencing technology, and the correlation between mtDNA level and inflammatory factors as well as protein expression in colonic epithelium of rats with ulcerative colitis was analyzed by SPSS23.0. RESULTS: HQD significantly alleviated UC symptoms by improving the mucosal intestinal epithelial cell structure, mental state, hair gloss, fecal occult blood, lamina propria intestinal glands and inflammatory cell infiltration. And HQD reduced the pro-inflammatory cytokines in the colonic epithelium of UC rats Production of IL-6, IL-17 and IL-23. The HE stained section of colon tissue showed a complete intestinal epithelial mucosal layer structure. The structure of epithelial cells was more normal and abundant. There were more goblet cells in lamina propria adenoma, which improved the infiltration of inflammatory cells. HQD significantly inhibited the mtDNA content in rat colonic epithelial tissue, and significantly inhibited the expression of TLR4, p-PI3K and p-Akt inflammatory signaling pathways. The results of the microbiota experiment showed that the abundance of HQD in the phylum Firmicutes increased, and the number of Bacteroides phylum decreased (p < 0.05). At the genus level, HQD significantly increased Lactobacillus and Firmicutes Bacteroides, while Treponema and Bacteroides were significantly reduced (p < 0.05). CONCLUSION: HQD has a certain protective effect on rats with damp heat ulcerative colitis. Its mechanism may be related to regulating the expression of p-PI3K, p-Akt and TLR4 proteins, mitochondrial DNA as well as microbiota.

Curcumae rhizoma and its major constituents against hepatobiliary disease: Pharmacotherapeutic properties and potential clinical applications.

BACKGROUND: Hepatobiliary disease currently serves as an urgent health issue in public due to health-modulating factors such as extension of life expectancy, increasingly sedentary lifestyles and over-nutrition. A definite treatment remains lacking owing to different stages of the disease itself and its intricate pathogenesis. Traditional Chinese medicine (TCM) has been gradually popularized in clinic with the satisfactory efficacy and good safety. Curcumae Rhizoma (called E Zhu, EZ in Chinese) is a representative herb, which has been used to treat hepatobiliary disease for thousands of years. PURPOSE: To systematically summarize the recent research advances on the pharmacological activities of EZ and its constituents, explain the underlying mechanisms of preventing and treating hepatobiliary diseases, and assess the shortcomings of existing work. Besides, ethnopharmacology, phytochemicals, and toxicology of EZ have been researched. METHODS: The information about EZ was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG using keywords given below and terms like pharmacological and phytochemical details of this plant. RESULTS: The chemical constituents isolated and identified from EZ, such as terpenoids including ß-elemene, furanodiene, germacrone, etc. and curcuminoids including curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. prove to have hepatoprotective effect, anti-liver fibrotic effect, anti-fatty liver effect, anti-liver neoplastic effect, and cholagogic effect through TGF-ß1/Smad, JNK1/2-ROS, NF-κB and other anti-inflammatory and antioxidant signaling pathways. Also, EZ is often combined with other Chinese herbs in the treatment of hepatobiliary diseases with good clinical efficacy and no obvious adverse reactions. CONCLUSION: It provides a preclinical basis for the efficacy of EZ as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases. Even so, the further studies still needed to alleviate hepatotoxicity and expand clinical application.

Isatidis Radix and Isatidis Folium: A systematic review on ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Isatidis Radix (called Banlangen, BLG in Chinese) and Isatidis Folium (called Daqingye, DQY in Chinese) are common traditional edible-medicinal herbs in detoxifying for thousands of years, have been traditionally applied in traditional Chinese medicine for centuries. Both of them are bitter in taste, coolness in nature, acting on the heart and stomach channels. They are often used to treat influenza and other viral infectious diseases in clinic, as well as could treat fever, dizziness, and cough and sore throat caused by lung heat. AIMS OF THE REVIEW: This review aimed at summarizing the latest and comprehensive information of BLG and DQY on the ethnopharmacology, phytochemistry, pharmacology, toxicity and clinical application to explore the therapeutic potential of them. In addition, outlooks and perspective for possible future researches that related are also discussed. MATERIALS AND METHODS: Related information concerning BLG and DQY were gathered from the internet database of Google Scholar, PubMed, Baidu Scholar, GeenMedical, CNKI and Web of Science, as well as other relevant textbooks, reviews, and documents (e.g., Chinese Pharmacopoeia, 2020 edition, Chinese herbal classic books and PhD and MSc thesis, etc.). Among of them with the keywords including "Isatis indigotica" "Isatidis Radix", "Isatidis Folium", "phytochemistry", "pharmacology", "toxicology", "clinical application" etc. and their combinations. RESULTS: To date, 39 Chinese patent medicines containing BLG and/or DQY have been developed on basis of the data of NMPA. Besides, 304 and 142 compounds have been found in BLG and DQY, respectively. The main chemical differences between BLG and DQY were concentrated on alkaloids and lignans, such as indican, indirubin, (R, S)-epigoitrin, 4(3H)-quinazolinone, clemastanin B and isatindigotindolines A-D. In 2020 Edition ChP, (R, S)-goitrin and indirubin are now used as the official marker to monitor the quality of BLG and DQY, respectively. Modern pharmacology has mainly studied some monomer components such as 4(3H)-quinazolinone, clemastanin B, erucic acid and adenosine, etc., all of which have shown good effects. These active compounds can resist various viruses, such as influenza virus, respiratory syncytial virus, herpes simplex virus, etc.. By regulating the level of immunity and a variety of inflammatory factors, inhibit the growth and reproduction of the virus. At the same time, it is worth noting that different components of BLG and DQY lead to BLG is more powerful in antiviral and immunomodulatory activity than DQY, while DQY possesses a higher intensity than BLG in anti-oxidant activity. CONCLUSION: By collecting and collating a large number of literature and various data websites, we concluded that the common compounds are mainly alkaloids. Recent findings regarding the phytochemical and pharmacological properties of BLG and DQY have confirmed their traditional uses in antiviral, antibacterial and treatment immune diseases. Without doubt, their significant differences on ethnopharmacology, phytochemistry and pharmacology can be used as evidence of separate list of BLG and DQY. For shortcomings, some comprehensive studies should be well designed for further utilization of BLG and DQY.

Metabolomics combined with network pharmacology to study the mechanism of Shentong Zhuyu decoction in the treatment of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong Zhuyu decoction (STZYD) was first recorded in the classic of "Yilin Gaicuo" written by Wang Qingren, and recognized by the Chinese National Administration of Traditional Chinese Medicine as one of the 100 classic formulas. The formula has been widely used in the treatment of rheumatoid arthritis (RA) with significant clinical effects. However, its mechanism of action is not completely clear. AIM OF THE STUDY: This study aimed to explore the mechanism of STZYD in the treatment of RA by network pharmacology and metabolomics. MATERIALS AND METHODS: The effects of STZYD anti-RA were investigated by paw swelling, arthritis score, cytokine level, histopathological and micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The chemical constituents of STZYD and absorbed constituents in AIA rat serum were analyzed by UPLC-Q-Exactive MS/MS. Based on the characterized chemical components, the network pharmacology was used to find potential targets and signaling pathways of STZYD in RA treatment. Meanwhile, the predicted pathway was determined by the Western blot (WB). Subsequently, non-targeted metabolomics of serum was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of STZYD in the treatment of RA based on LC-MS technology. RESULTS: STZYD significantly alleviated RA symptoms by improving paw redness and swelling, bone and cartilage damage, synovial hyperplasia, and infiltration of inflammatory cells, and decreased the generation of pro-inflammatory cytokines IL-1ß, IL-6, IL-17A and TNF-α in AIA rats. Totally, 59 chemical components of STZYD and 24 serum migrant ingredients were identified. A total of 655 genes of potential bioactive components in STZYD and 1025 related genes of RA were obtained. TNF signaling pathway was considered to one of the main signaling pathways of STZYD anti-RA by KEGG analysis, including a wide range intracellular signaling pathways. NF-κB signaling pathway regulates inflammation and immunity in the TNF signaling pathway. STZYD markedly inhibited the expression of NF-κB signaling pathway. Ten potential biomarkers were found in metabolomics based on LC-MS technology. Alanine, aspartate and glutamate metabolism, arachidonic acid metabolism are the most related pathways of STZYD anti-RA. CONCLUSION: The study based on serum pharmacochemistry, network pharmacology and metabolomics indicated that STZYD can improve RA through regulating inflammation and immunity related pathways, and provided a new possibility for treatment of RA.

Gastroprotective Effect of Ethanol Extracts from Bark of Magnolia officinalis on Ethanol-Induced Gastric Mucosal Damage in Rats.

Background. Magnolia officinalis Rehd. and Wils. is widely used in Asian countries because of its multiple pharmacological effects. This study investigated the gastroprotective effect and mechanisms of the ethanol extracts from the bark of Magnolia officinalis (MOE) against ethanol-induced gastric mucosal damage in rats. Methods. MOE was prepared by reflux extraction with 70% ethanol, and its main compounds were analyzed by UPLC-Q-Exactive Orbitrap-MS. DPPH, ABTS, and FRAP methods were used to evaluate the antioxidant capacity of MOE in vitro. The gastroprotective effects of MOE were evaluated by the area of gastric injury, H&E (hematoxylin-eosin), and PAS (periodic acid-Schiff). The mechanism was explored by measuring the levels of cytokines and protein in the NF-κB signaling pathway. Results. 30 compounds were identified from MOE, mainly including lignans and alkaloids. MOE presented a high antioxidant activity in several oxidant in vitro systems. Gastric ulcer index and histological examination showed that MOE reduced ethanol-induced gastric mucosal injury in a dose-dependent manner. MOE pretreatment significantly restored the depleted activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzymes, reduced malondialdehyde (MDA), and prostaglandin E2 (PGE2) levels in the gastric tissue in rats. In addition, MOE also inhibited the activation of nuclear factor kappa B (NF-κB) pathway and decreased the production of proinflammatory cytokines. Conclusions. The gastroprotective effect of MOE was attributed to the inhibition of oxidative stress and the NF-κB inflammatory pathway. The results provided substantial evidence that MOE could be a promising phytomedicine for gastric ulcer prevention.

Vinegar-processed Curcuma phaeocaulis promotes anti-angiogenic activity and reduces toxicity in zebrafish and rat models.

CONTEXT: Processing with vinegar could enhance the efficacy and reduce the toxicity of Curcuma phaeocaulis Valeton. (Zingiberaceae), a Chinese herbal medicine with anti-inflammatory and antitumor activities. OBJECTIVE: This study investigated the vinegar processing effects by evaluating anti-angiogenic effect and toxicity of C. phaeocaulis through zebrafish and rat models. MATERIALS AND METHODS: Zebrafish embryos (AB and FLk-GFP strain) were applied to evaluate toxicity, cardiotoxicity and anti-angiogenic activity of volatile oil, and water decoction of the raw and vinegar-processed C. phaeocaulis. Meanwhile, a blood stasis syndrome rat model was applied to study the toxicity by measuring the ovarian and uterine coefficient. RESULTS: Curcuma phaeocaulis volatile oil and its vinegar-processed products in zebrafish had an LC50 of 67.315 and 95.755 µg/mL, respectively. Curcuma phaeocaulis water decoction and its vinegar-processed products had an LC50 of 161.440 and 206.239 µg/mL, respectively. The toxicity of vinegar-processed products was significantly lower than the raw, and the development characteristic of zebrafish embryos at different times confirmed these results. The volatile oil of vinegar-processed products could inhibit the growth of intersegmental blood vessels at the dose of 20 µg/mL, while the raw materials did not exhibit such effect at the same concentration. The rat experiment also confirmed that the volatile oil could reduce toxicity of ovarian and uterine. DISCUSSION AND CONCLUSIONS: The study indicated that processing using vinegar could decrease toxicity and increase anti-angiogenic activity of C. phaeocaulis, which could be applied for clinical treatment. Further in-depth study on the synergism and detoxification mechanism of vinegar processing technology is needed.

Essential oil from the raw and vinegar-processed Rhizoma Curcumae ameliorate CCl4-induced liver fibrosis: integrating network pharmacology and molecular mechanism evaluation.

Liver fibrosis, caused by multiple chronic liver injuries, is a known contributor to cirrhosis and even liver cancer. As a Traditional Chinese Medicine (TCM), Rhizoma curcumae has been extensively used in the treatment of liver fibrosis with satisfying therapeutic effects; however, its mechanism is unclear. The essential oil is the main bioactive component. The purpose of this study was to investigate the chemical profile and the pharmacological mechanisms of the essential oil of Rhizoma curcumae (EORC) against liver fibrosis by combining network pharmacology and transcriptomic technologies. A total of 37 active compounds were identified using the GC/MS system and literature mining, and the corresponding putative targets were predicted. Then, network pharmacology method was applied to identify the 168 candidate targets of EORC-alleviated liver fibrosis. String database and Cytoscape software were used to build the herb-compound-target network and protein-protein interactions (PPIs) network. Functional and pathway enrichment analysis indicated that EORC significantly influenced TGF-ß1/Smads and PI3K/AKT pathways. Experimentally, we verified that EORC attenuated the severity and pathological changes during liver fibrosis progression based on the CCl4-induced liver fibrosis rat model. Transcriptomic technologies demonstrated that EORC ameliorated liver fibrosis partially by regulating the TGF-ß1/Smads and PI3K/AKT pathways. In addition, the effect of vinegar-processed EORC was more significant than that of the raw one. Therefore, EORC can alleviate the severity of liver fibrosis through mechanisms predicted by network pharmacology and provide a basis for the further understanding of the application of EORC in the treatment of liver fibrosis.

Modulation of adenine phosphoribosyltransferase-mediated salvage pathway to accelerate diabetic wound healing.

Adenine phosphoribosyltransferase (APRT) is the key enzyme involved in purine salvage by the incorporation of adenine and phosphoribosyl pyrophosphate to provide adenylate nucleotides. To evaluate the role of APRT in the repair processes of cutaneous wounds in healthy skin and in diabetic patients, a diabetic mouse model (db/db) and age-matched wild-type mice were used. Moreover, the topical application of adenine was assessed. In vitro studies, analytical, histological, and immunohistochemical methods were used. Diabetic mice treated with adenine exhibited elevated ATP levels in organismic skin and accelerated wound healing. In vitro studies showed that APRT utilized adenine to rescue cellular ATP levels and proliferation from hydrogen peroxide-induced oxidative damage. HPLC-ESI-MS/MS-based analysis of total adenylate nucleotides in NIH-3T3 fibroblasts demonstrated that adenine addition enlarged the cellular adenylate pool, reduced the adenylate energy charge, and provided additional AMP for the further generation of ATP. These data indicate an upregulation of APRT in skin wounds, highlighting its role during the healing of diabetic wounds through regulation of the nucleotide pool after injury. Furthermore, topical adenine supplementation resulted in an enlargement of the adenylate pool needed for the generation of ATP, an important molecule for wound repair.

Terpenoids from Curcumae Rhizoma: Their anticancer effects and clinical uses on combination and versus drug therapies.

Cancer is a fatal disease with high mortality and low survival rate worldwide. At present, there is still no known cure for most cancers. Traditional Chinese medicine (TCM) represents a noteworthy reservoir for anticancer agents in drug discovery and development. Curcumae Rhizoma (called Ezhu in Chinese) is widely prescribed in TCM for anticancer therapy owing to its broad-spectrum antineoplastic activities. Especially, the terpenoids isolated from the essential oil of Curcumae Rhizoma form an integral part of cancer research and are well established as a potential anticancer agent. For example, ß-elemene has been developed into a new drug for the treatment of solid tumors in China, and is currently undergoing clinical trials in the United States. The review aims to systematically summarize the recent advances on the anticancer effects and related molecular mechanisms of Curcumae Rhizoma, and its terpenoids (ß-elemene, Furanodiene, Furanodienone, Germacrone, Curcumol, Curdione). In addition, we evaluated and compared the anticancer efficacy and clinical use of the terpenoids with combination therapies and traditional therapies. Therefore, this review provides sufficient evidence for the anticancer therapeutic potential of Curcumae Rhizoma and its terpenoids, and will contribute to the development of potential anticancer drugs.

[Research progress of effect of Rhei Radix et Rhizoma and its anthraquinone in treatment of autoimmune diseases].

Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.

Integrating Network Analysis and Metabolomics to Reveal Mechanism of Huaganjian Decoction in Treatment of Cholestatic Hepatic Injury.

Huaganjian decoction (HGJD) was first recorded in the classic "Jing Yue Quan Shu" during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.

Usage of Chinese Herbs in Cancer Patients in Southern China: A Survey.

OBJECTIVE: To study the use of Chinese medicine (CM) in cancer patients in southern China. METHODS: A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. RESULTS: The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. CONCLUSION: This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.

Synergistic Actions of Benzyl Isothiocyanate with Ethylenediaminetetraacetic Acid and Efflux Pump Inhibitor Phenylalanine-Arginine ß-Naphthylamide Against Multidrug-Resistant Escherichia coli.

The aim of this study was to assess the efficacy of benzyl isothiocyanate (BITC) in combination with efflux inhibitors and metal chelators against multidrug-resistant Escherichia coli. In vitro synergism between testing molecules was observed based on the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), fractional inhibitory concentration index (FICI), bactericidal kinetics, and growth inhibition assay. BITC alone exhibited moderate antibacterial activity against E. coli strains with MIC and MBC values of 0.625-1.25 µM and 1.25-2.5 µM, respectively. In contrast, double and triple combinations of BITC, ethylenediaminetetraacetic acid (EDTA), and phenylalanine-arginine ß-naphthylamide (PAßN) resulted in synergistic activities with FICI values between 0.18 and 0.5, whereas combination of BITC with carbonyl cyanide m-chlorophenyl hydrazone or 2, 2'-dipyridyl revealed additive or indifference effect with FICI values of 0.75-1.5 and 1-1.5, respectively. Results of bactericidal kinetics and growth inhibition assays also supported the synergistic effects of EDTA and PAßN with BITC against E. coli strains. Our data demonstrate the possible use of adjuvant agents, such as the chelating agent EDTA and the efflux inhibitor PAßN to improve the antibacterial potential of isothiocyanate and may help to develop an alternative strategy for reducing the occurrence of multidrug resistance.