Data Mining Study on Prescription Patterns of Different Dosage Forms of Chinese Herbal Medicines for Treating and Improving Immune-Inflammatory Indices in Patients with Rheumatoid Arthritis.

OBJECTIVE: To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices. METHODS: Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups. RESULTS: (1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions. CONCLUSIONS: The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.

Antidepressant Effect of Blue Light on Depressive Phenotype in Light-Deprived Male Rats.

Blue light has been previously reported to play a salient role in the treatment of seasonal affective disorder. The present study aimed to investigate whether blue light had antidepressant effect on light-deprivation-induced depression model, and the underlying visual neural mechanism. Blue light mitigated depression-like behaviors induced by light deprivation as measured by elevated sucrose preference and reduced immobility time. Blue light enhanced melanopsin expression and light responses in the retina. We also found the upregulation of serotonin and brain derived neurotrophic factor expression in the c-fos-positive areas of rats treated with blue light compared with those maintained in darkness. The species gap between nocturnal albino (Sprague-Dawley rat) and diurnal pigmented animals (human) might have influenced extrapolating data to humans. Blue light has antidepressant effect on light-deprived Sprague-Dawley rats, which might be related to activating the serotonergic system and neurotrophic activity via the retinoraphe and retinoamygdala pathways. Blue light is the effective component of light therapy for treatment of depression.

Sparstolonin B: A Unique Anti-Inflammatory Agent.

Toll-like receptors are transmembrane proteins which sense and transmit infectious and inflammatory responses to the cells expressing them. Therapeutic strategies for the blockade of excessive Toll-like receptor signaling are being actively pursued for several diseases. Recently, Sparstolonin B, isolated from Chinese herb, which suppresses selectively Toll-like receptors has been studied in various inflammatory models. The objective of this review is to summarize the current literature regarding the use of Sparstolonin B in various in vitro and in vivo studies and to provide an overview regarding the potential use of this agent in different inflammatory diseases. Additionally, the current knowledge regarding the role of Toll-like receptors in inflammatory disease and the usage of various Toll-like receptor antagonists will be summarized. Based on our review, we believe Sparstolonin B could serve as a potential therapeutic agent for treatment of Toll-like receptor-mediated inflammatory disorders.

Protective effects of glutathione on oxidative injury induced by hydrogen peroxide in intestinal epithelial cells.

BACKGROUND: Reactive oxygen species are increased in multiple gastrointestinal diseases and contribute to their pathogenesis. glutathione (GSH) is an antioxidant that helps to prevent reactive oxygen species-mediated mucosal damage. This study examines the mechanisms by which GSH attenuates hydrogen peroxide (H2O2)-induced injury in intestinal epithelial cells. METHODS: IEC-6 cells were cultured and treated with H2O2 ± GSH. Inflammation was measured by nuclear factor kappa-B (NF-κB) P65 expression, NF-κB nuclear translocation, iκBα phosphorylation, and interleukin 1 beta secretion. Terminal deoxynucleotidyl transferase-mediated UTP end-labeling staining and cleaved caspase-3 were used to assess apoptosis. The role of P38 mitogen-activated protein kinase (P38 MAPK) signaling was examined using the P38 MAPK agonist U46619 and inhibitor SB203580 in H2O2 and GSH-treated cells. Phosphorylated and total P38 MAPKs and cleaved caspase-3 were measured by Western blot. Data are means ± standard deviation, statistical significance P < 0.05 by student's t-test, or one-way analysis of variance. RESULTS: Pretreatment with GSH attenuates the activation of NF-κB and P38 MAPK signaling pathways by H2O2. GSH also decreased H2O2-mediated increases in interleukin 1 beta secretion, cleaved caspase-3 activation, and apoptosis in IEC-6 cells. SB203580 attenuated the increase in apoptosis and cleaved caspase-3 in H2O2-treated cells. The increase in apoptotic index and cleaved caspase-3 observed in U46619-treated cells was also diminished by GSH. CONCLUSIONS: GSH appears to ameliorate oxidative injury in intestinal epithelial cells by attenuating H2O2-mediated activation of NF-κB and P38 MAPK signaling pathways that regulate intestinal inflammation and apoptosis.

Synthetic small molecule GLP-1 secretagogues prepared by means of a three-component indole annulation strategy.

Rational assembly of small molecule libraries for purposes of drug discovery requires an efficient approach in which the synthesis of bioactive compounds is enabled so that numerous structurally related compounds of a similar basic formulation can be derived. Here, we describe (4 + 3) and (3 + 2) indole annulation strategies that quickly generate complex indole heterocycle libraries that contain novel cyclohepta- and cyclopenta[b]indoles, respectively. Screening of one such library comprised of these indoles identifies JWU-A021 to be an especially potent stimulator of glucagon-like peptide-1 (GLP-1) secretion in vitro. Surprisingly, JWU-A021 is also a potent stimulator of Ca(2+) influx through TRPA1 cation channels (EC50 ca. 200 nM), thereby explaining its ability to stimulate GLP-1 release. Of additional importance, the available evidence indicates that JWU-A021 is one of the most potent non-electrophilic TRPA-1 channel agonists yet to be reported in the literature.

Stimulation of expression of the intestinal glutamine transporter ATB0 in tumor-bearing rats.

BACKGROUND: Glutamine supplementation ameliorates host catabolic response in tumor bearing states. The purpose of this in vivo study was to investigate intestinal glutamine transport and expression of glutamine transporter ATB(0) in methyl-cholanthrene (MCA)-sarcoma bearing rats. METHODS: Fisher-344 rats underwent subcutaneous flank implantation of MCA-sarcoma cells (saline as control) and were pair-fed an equal quantity of chow as controls, to account for tumor-induced anorexia, until tumors reached 10 or 20% body weight. Intestinal mucosal brush border membrane [3H]-Glutamine transport was measured. Glutamine transporter ATB(0) mRNA and protein levels were measured by real-time PCR and western blot techniques, respectively. RESULTS: Glutamine transport activity across the intestinal brush border membrane (BBM) was 3.7-fold higher in tumor-bearing rats (TBR) than in controls (TBR 153 +/- 22.6 vs. Control 41.9 +/- 9.7 pmol/mg protein/10s, P < .01). Transporter ATB(0) mRNA levels were 1.4-fold higher in tumor-bearing rats (Relative value TBR .61 +/- .12 vs. Control .43 +/- .1, P < .05). A 1.4-fold increase in transporter ATB(0) protein levels was observed in the tumor-bearing rats (Relative value TBR .52 +/- .07 vs. Control .37 +/- .04, P < .05). Circulating aortic plasma glutamine levels were 1.3-fold higher in tumor bearing rats ([Glutamine] = .63 +/- .02 Control vs. [Glutamine] = .74 +/- .01 mmol/l TBR, P < .0001). Portal venous plasma glutamine levels were also higher in tumor bearing rats ([Glutamine] = .47 +/- .01 Control vs. [Glutamine] = .60 +/- .02 mmol/l TBR, P < .0001). CONCLUSION: Intestinal brush border membrane glutamine transport activity, transporter ATB(0) mRNA and protein levels are up-regulate in tumor-bearing rats.