Prinsepia utilis Royle leaf extract: Ameliorative effects on allergic inflammation and skin lesions in allergic contact dermatitis and polyphenolic profiling through UPLC-MS/MS coupled to chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic contact dermatitis (ACD) is a common allergic inflammatory disease that is concomitant with skin swelling, redness, dry itching, and relapses. Prinsepia utilis Royle, a Chinese and Indian folk medicine, is rich in polyphenols with potential anti-inflammatory and skin-protective activities. However, the underlying mechanism of P. utilis leaf (PUL) in the treatment of ACD and its functional basis remains unclear. AIM OF THE STUDY: This study is aimed to explore and reveal the active substances and mechanism of PUL against ACD. MATERIALS AND METHODS: Hyaluronidase inhibitory assay and fluorescein isothiocyanate (FITC)-induced ACD mouse model were performed to assess the antiallergic effects of PUL in vitro and in vivo. Different solvents were applied to obtain multiple PUL extracts. The extracts were further tested for total phenolic content (TPC) and total flavonoid content (TFC) by using spectrophotometric assays. Polyphenolic profiles were analyzed by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), and a simultaneous quantification method was established using UPLC-QTrap-MS/MS through multiple reaction monitoring (MRM) and applied to analyze the pharmacokinetics of the multiple major polyphenols of PUL in mice. RESULTS: The water extract of PUL with the highest TPC/TFC exhibited the strongest antihyaluronidase effect (IC50 = 231.93 µg/mL). In vivo assays indicated that the oral administration of PUL water extract dose-dependently attenuated ACD-like symptoms by decreased interleukin (IL)-4, IL-5, IL-13, IL-33, thymic stromal lymphopoietin, and IgE production, suppressed eosinophil and basophil secretion, and increasing the expression of tight junction (TJ) proteins (claudin-1 [CLDN-1] and occludin). Concomitantly, UPLC-QTOF-MS/MS analysis enabled the identification of 60 polyphenols and the pharmacokinetic parameters of seven quantified constituents of PUL were characterized. Four compounds, trans-p-coumaric acid 4-O-ß-D-glucopyranoside (11), vicenin-2 (21), isoschaftoside (31), and kaempferol 3-O-(2″,6″-di-O-α-L-rhamnopyransoyl)-ß-D-glucopyranoside (38) which displayed satisfactory pharmacokinetic features, were considered as potential effective substances in PUL. CONCLUSIONS: PUL water extract ameliorated the allergic inflammation of ACD by repairing the epithelial barrier and alleviating Th2-type allergic inflammation. The anti-allergic effect of PUL is closely related to its phenolic substances, and compounds 11, 21, 31, and 38 were the active substances of PUL. It revealed that P. utilis could be developed as a new source of antiallergic agents for ACD therapy.

Oral Chinese Herbal Medicine for Depressive Disorder in Patients after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness and safety of oral Chinese herbal medicines (CHMs) on post-percutaneous coronary intervention (PCI) patients with depressive disorder in coronary heart disease (CHD). METHODS: A literature search was conducted through databases including PubMed, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Chinese Biomedical Literature Database (SinoMed), Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and Wanfang Database up to August 2018. Randomized controlled trials (RCTs) comparing CHMs with placebo or no additional treatments on the basis of standard conventional pharmacological therapies were included. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 software was used to synthesize the results. RESULTS: A total of 16 RCTs enrolling 1,443 participants were included in this systematic review. When compared with antidepressants alone, CHMs showed similar benefits with less side effects [risk ratio=0.54, 95% confidence interval (CI) 0.43 to 0.69, 582 patients]; meanwhile, the combination therapy may have more advantages than antidepressants alone [mean difference (MD)=-1.03, 95%CI-1.81 to-0.25, 267 patients). When identified with placebo, CHMs seem to have more advantages in relieving depressive symptoms (MD=-19.00, 95%CI-20.02 to-17.98, 189 patients). However, when compared with basic treatment of post- PCI, CHMs showed different results in two trials. In terms of post-PCI related clinical symptoms, CHMs seem to have more advantages in relieving chest pain and other general clinical symptoms. However, the heterogeneity in this review was generally high, it may be caused by different interventions used in each trial and the low quality of the trials. CONCLUSIONS: In total, CHMs showed potentially beneficial effects on depressive symptoms and post-PCI related clinical symptoms. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.

Increased Chondrocyte Apoptosis in Kashin-Beck Disease and Rats Induced by T-2 Toxin and Selenium Deficiency.

OBJECTIVE: To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model. METHODS: Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and mRNA levels were determined by real-time reverse transcription polymerase chain reaction. RESULTS: Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and mRNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. CONCLUSION: T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.

Efficacy of Chinese eye exercises on reducing accommodative lag in school-aged children: a randomized controlled trial.

PURPOSE: To evaluate the efficacy of Chinese eye exercises on reducing accommodative lag in children by a randomized, double-blinded controlled trial. METHODS: A total of 190 children aged 10 to 14 years with emmetropia to moderate myopia were included. They were randomly allocated to three groups: standard Chinese eye exercises group (trained for eye exercises by doctors of traditional Chinese medicine); sham point eye exercises group (instructed to massage on non-acupoints); and eyes closed group (asked to close their eyes without massage). Primary outcome was change in accommodative lag immediately after intervention. Secondary outcomes included changes in corrected near and distant visual acuity, and visual discomfort score. RESULTS: Children in the standard Chinese eye exercises group had significantly greater alleviation of accommodative lag (-0.10 D) than those in sham point eye exercises group (-0.03 D) and eyes closed group (0.07 D) (P = 0.04). The proportion of children with alleviation of accommodative lag was significantly higher in the standard Chinese eye exercises group (54.0%) than in the sham point eye exercises group (32.8%) and the eyes closed group (34.9%) (P = 0.03). No significant differences were found in secondary outcomes. CONCLUSION: Chinese eye exercises as performed daily in primary and middle schools in China have statistically but probably clinically insignificant effect in reducing accommodative lag of school-aged children in the short-term. Considering the higher amounts of near work load of Chinese children, the efficacy of eye exercises may be insufficient in preventing myopia progression in the long-term. TRIAL REGISTRATION: ClinicalTrials.gov NCT01756287.

Anti-fibrotic effect of PF2401-SF, a standardized fraction of Salvia miltiorrhiza, in thioacetamide-induced experimental rats liver fibrosis.

We previously reported the in vitro and in vivo hepatoprotective and anti-fibrotic effects of PF2401-SF, a standardized fraction of Salvia miltiorrhiza, against acute and subacute liver injury. The aim of this study was to investigate the effect of PF2401-SF on liver fibrosis induced by thioacetamide (TAA), a chronic liver injury model (12 weeks) that closely resembles fibrosis and cirrhosis in humans. Hepatoprotective activity was indicated by low serum levels of the markers aspartate amino transferase and alanine amino transferase .In addition, compared to the TAA-group livers, the PF2401-SF-treated liver tissues showed no fibrous tissue deposition in the portal areas, hepatocyte morphology more closely resembling normal tissue morphology, and significantly reduced collagen deposition. Furthermore, downregulation of collagen 1(α) and tissue inhibitor of metalloproteinase (TIMP)1 protein and mRNA expression also supports PF2401-SF's anti-fibrotic effect. We also observed reduced expression of α-smooth muscle actin (α-SMA), an important marker of hepatic stellate cells (HSCs) activation. From these results, we conclude that PF2401-SF's anti-fibrotic mechanism in the TAA model involves reduced HSC activation, and may be mediated by downregulation of central markers of fibrosis, including collagen 1(α), TIMP1, and α-SMA.

Effects of moniliformin and selenium on human articular cartilage metabolism and their potential relationships to the pathogenesis of Kashin-Beck disease.

OBJECTIVE: To investigate the effects of mycotoxin moniliformin (MON) on the metabolism of aggrecan and type II collagen in human chondrocytes in vitro and the relationship between MON and Kashin-Beck disease (KBD). METHODS: Human chondrocytes were isolated and cultured on bone matrix gelatin to form an artificial cartilage model in vitro with or without MON toxin. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of aggrecan and type II collagen in the cartilage was determined using immunocytochemical staining. RESULTS: MON toxin inhibited chondrocyte viability in dose-dependent and time-dependent manners. MON reduced aggrecan and type II collagen syntheses in the tissue-engineered cartilage. MON also increased the expression of matrix metalloproteinase-1 (MMP-1), MMP-13, BC4 epitopes, and CD44 in cartilages. However, the expression of 3B3(-) epitopes in cartilages was inhibited by MON. Selenium partially alleviated the damage of aggrecan induced by MON toxin. CONCLUSION: MON toxin promoted the catabolism of aggrecan and type II collagen in human chondrocytes.

Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect.

OBJECTIVE: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD), the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. METHODS: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA), soluble CD44 (sCD44), IL-1beta and TNF-alpha levels in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was determined by flow cytometry (FCM). CD44, hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13, 3-B-3(-) and 2-B-6 epitopes in the cartilage reconstructed in vitro. RESULTS: T-2 toxin inhibited CD44, HAS-2, and aggrecan mRNA expressions, but promoted aggrecanase-2 mRNA expression. Meanwhile, CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition, ELISA results indicated that there were higher sCD44, IL-1beta and TNF-alpha levels in T-2 toxin group. Similarly, higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore, using monoclonal antibodies BC-13, 3-B-3 and 2-B-6, strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin, whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. CONCLUSION: T-2 toxin could inhibit aggrecan synthesis, promote aggrecanases and pro-inflammatory cytokines production, and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage, inducing aggrecan loss in the end, which may be the initiation of the cartilage degradation.