Pharmacology of bioactive compounds from plant extracts for improving non-alcoholic fatty liver disease through endoplasmic reticulum stress modulation: A comprehensive review.

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with significant clinical implications. Emerging research indicates endoplasmic reticulum (ER) stress as a critical pathogenic factor governing inflammatory responses, lipid metabolism and insulin signal transduction in patients with NAFLD. ER stress-associated activation of multiple signal transduction pathways, including the unfolded protein response, disrupts lipid homeostasis and substantially contributes to NAFLD development and progression. Targeting ER stress for liver function enhancement presents an innovative therapeutic strategy. Notably, the natural bioactive compounds of plant extracts have shown potential for treating NAFLD by reducing the level of ER stress marker proteins and mitigating inflammation, stress responses, and de novo lipogenesis. However, owing to limited comprehensive reviews, the effectiveness and pharmacology of these bioactive compounds remain uncertain. Objectives: To address the abovementioned challenges, the current review categorizes the bioactive compounds of plant extracts by chemical structures and properties into flavonoids, phenols, terpenoids, glycosides, lipids and quinones and examines their ameliorative potential for NAFLD under ER stress. Methods: This review systematically analyses the literature on the interactions of bioactive compounds from plant extracts with molecular targets under ER stress, providing a holistic view of NAFLD therapy. Results: Bioactive compounds from plant extracts may improve NAFLD by alleviating ER stress; reducing lipid synthesis, inflammation, oxidative stress and apoptosis and enhancing fatty acid metabolism. This provides a multifaceted approach for treating NAFLD. Conclusion: This review underscores the role of ER stress in NAFLD and the potential of plant bioactive compounds in treating this condition. The molecular mechanisms by which plant bioactive compounds interact with their ER stress targets provide a basis for further exploration in NAFLD management.

Convallatoxin induces HaCaT cell necroptosis and ameliorates skin lesions in psoriasis-like mouse models.

Psoriasis is considered an immune-mediated inflammatory skin disorder that affects the quality of life of nearly four percent of the world population. Considering the side effects of existing therapeutic drugs and the urgent need for new drug development, we screened more than 250 traditional Chinese medicine compounds to identify drugs that significantly reduced the viability of human HaCaT keratinocytes, a psoriasis-related model cell line. Convallatoxin (CNT) was found to be a highly effective inhibitor of HaCaT cell viability. Subsequent mechanistic studies revealed that CNT induced HaCaT cell death by necroptosis rather than by apoptosis. CNT destroyed the membrane integrity of HaCaT cells, as detected by nuclear propidium iodide (PI) staining and lactate dehydrogenase (LDH) release. Additionally, the intercellular levels of adenosine triphosphate (ATP) were lower in HaCaT cells treated with CNT than in control HaCaT cells, and typical necroptosis-associated characteristics were observed by electron microscopy in cells treated with CNT. Furthermore, compared with control HaCaT cells, CNT-treated HaCaT cells produced more reactive oxygen species (ROS), but this effect was inhibited by the antioxidants N-acetyl-cysteine (NAC), diphenyleneiodonium chloride (DPI), and apocynin and the necroptosis inhibitor Nec-1. In addition, antioxidant treatment attenuated necroptotic cell death, suggesting that CNT-induced HaCaT necroptosis is mediated by oxidative stress. More importantly, CNT ameliorated skin lesions and inflammation in imiquimod (IMQ)- and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced psoriasis-like mouse models. In conclusion, our results demonstrate that CNT is cytotoxic against HaCaT cells in vitro and exerts antipsoriatic activities in two mouse models of psoriasis in vivo, making CNT a potential promising candidate drug for future research.

Safety Concerns of Traditional Chinese Medicine Injections Used in Chinese Children.

OBJECTIVE: To explore risks underlying traditional Chinese medicine (TCM) injection-related adverse drug reactions (ADRs) in Chinese children, and to discuss the implications of postmarketing reevaluation studies. METHODS: We identified potential cases of exposure to TCM injections for children (<18 years of age) and adults (18 years and upwards) from database of ADRs. First, the associations between TCM injection-related ADRs and three administration routes (i.e., intravenous or intramuscular administration, oral administration, and external use) and the imbalance of TCM injection-related ADRs between the paediatric and adult populations were tested using the Chi-square (χ 2 ) test. Second, the proportional reporting ratio (PPR) was applied to identify statistically significant associations between drugs and anaphylactic shock in the paediatric population. RESULTS: The χ 2 test revealed that the highest frequency of paediatric ADRs was due to 5 types of herbal injections (i.e., Shuanghuanglian (SHL), Yuxingcao (YXC), Qingkailing (QKL), Xiyanping (XYP), and Reduning (RDN) herbal injections) (P<0.000), and the reports of ADRs attributed to the XYP and RDN herbal injections in children accounted for a greater proportion than the reports for adults (P<0.000). The PPR identified 5 types of herbal injections-anaphylactic shock pairs (i.e., the SHL, XYP, QKL, YXC, and Fufang Danshen herbal injections) that met the minimum criteria (i.e., a PPR of at least 2 and χ 2 of at least 4 and three or more cases), which suggested that TCM injections were significantly associated with anaphylactic shock. CONCLUSIONS: TCM injections pose graver risks to the paediatric population than the adult population. To achieve optimal benefits and minimal risk to children treated with TCM injections, we suggest reevaluating the effectiveness and safety, monitoring the risks, and promoting rational use of TCM injections in Chinese children.

A meta-analysis of randomized controlled trials: Efficacy of selenium treatment for sepsis.

BACKGROUND: To understand the clinical outcomes of selenium therapy in patients with sepsis syndrome, we conducted a meta-analysis of randomized controlled trials (RCT). METHODS: A total of 13 RCTs comparing selenium and placebo for patients with sepsis were reviewed systematically. RESULTS: However, we could not detect the association of selenium treatment with a decreased mortality at different time course (relative risk [RR] [95% confidence interval, CI]: 0.94 [0.82-1.06] at day 28; 0.73 [0.36-1.47] at day 90; 1.16 [0.78-1.71] at 6 months; respectively). Selenium supplementation did not show favorable efficacy in the incidence of renal failure, secondary infection or duration of mechanical ventilation (RR [95% CI]: 0.65 [0.41-1.03]; 0.96 [0.87-1.06]; standard mean difference [SMD] [95% CI]: 0.17 [-0.30-0.63]; respectively). Interestingly, we found that selenium therapy was benefit for sepsis patients with reduced duration of vasopressor therapy, staying time in intensive care unit and hospital, and incidence of ventilator-associated pneumonia (SMD [95% CI]: -0.75 [-1.37 to -0.13]; -0.15 [CI: -0.25 to -0.04]; -1.22 [-2.44 to -0.01]; RR [95% CI]: 0.61 [0.42-0.89]; respectively). CONCLUSION: Based on our findings, intravenous selenium supplementation could not be suggested for routine use.

Chromatogram-Bioactivity Correlation-Based Discovery and Identification of Three Bioactive Compounds Affecting Endothelial Function in Ginkgo Biloba Extract.

Discovery and identification of three bioactive compounds affecting endothelial function in Ginkgo biloba Extract (GBE) based on chromatogram-bioactivity correlation analysis. Three portions were separated from GBE via D101 macroporous resin and then re-combined to prepare nine GBE samples. 21 compounds in GBE samples were identified through UFLC-DAD-Q-TOF-MS/MS. Correlation analysis between compounds differences and endothelin-1 (ET-1) in vivo in nine GBE samples was conducted. The analysis results indicated that three bioactive compounds had close relevance to ET-1: Kaempferol-3-O-α-l-glucoside, 3-O-{2-O-{6-O-[P-OH-trans-cinnamoyl]-ß-d-glucosyl}-α-rhamnosyl} Quercetin isomers, and 3-O-{2-O-{6-O-[P-OH-trans-cinnamoyl]-ß-d-glucosyl}-α-rhamnosyl} Kaempferide. The discovery of bioactive compounds could provide references for the quality control and novel pharmaceuticals development of GRE. The present work proposes a feasible chromatogram-bioactivity correlation based approach to discover the compounds and define their bioactivities for the complex multi-component systems.

Fractionation of oil palm empty fruit bunch by bisulfite pretreatment for the production of bioethanol and high value products.

In this work, fractionation of empty fruit bunch (EFB) by bisulfite pretreatment was studied for the production of bioethanol and high value products to achieve biorefinery of EFB. EFB was fractionated to solid and liquor components by bisulfite process. The solid components were used for bioethanol production by quasi-simultaneous saccharification and fermentation. The liquor components were then converted to furfural by hydrolysis with sulfuric acid. Preliminary results showed that the concentration of furfural was highest at 18.8g/L with 0.75% sulfuric acid and reaction time of 25min. The conversion of xylose to furfural was 82.5%. Furthermore, we attempted to fractionate the liquor into hemicellulose sugars and lignin by different methods for producing potential chemicals, such as xylose, xylooligosaccharide, and lignosulfonate. Our research showed that the combination of bisulfite pretreatment and resin separation could effectively fractionate EFB components to produce bioethanol and other high value chemicals.

[Effects of Yiqiyangyin recipe on the mRNA levels of TNF-α, TGF-ß1 and IFN-γ of lungs in rats with pulmonary interstitial fibrosis].

OBJECTIVE: To investigate the effects of Yiqiyangyin recipe on lung tissue morphological structure and mRNA levels of tumor necrosis factor α (TNF-α), transforming growth factor beta-1 (TGF-ß1) and interferon-γ (IFN-γ) in pulmonary interstitial fibrosis rat models. METHODS: The pulmonary interstitial fibrosis rat model was established by intrabronchial injection of bleomycin A5. After the model was set up, the rats were divided randomly into five groups, normal group, model group, prednisone acetate group, traditional Chinese medicine (TCM) group, and TCM plus prednisone acetate group. Twenty-eight days after modeling, all groups were subjected to gavage for another 28 days. Then the animals were executed in batch. Their lung tissues were separated and observed with HE staining and Masson staining. The mRNA levels of TNF-α, TGF-ß1 and IFN-γ were detected using in situ hybridization. RESULTS: The levels of TNF-α and TGF-ß1 mRNAs were enhanced and IFN-γ mRNA was weakened in the model group as compared with the other groups at the same time points. Compared with the prednisone acetate group and the TCM plus prednisone acetate group, the expression of TNF-α mRNA was reduced and IFN-γ mRNA was raised a little in the TCM group at the same time points. Compared with the prednisone acetate group at the same time points, the level of TGF-ß1 mRNA decreased slightly in the TCM group. CONCLUSION: Yiqiyangyin recipe could delay pulmonary fibrosis by reducing the mRNA levels of TNF-α and TGF-ß1 and increasing IFN-γ mRNA in lung tissues of pulmonary intestitial fibrosis rats.

Pretreatment of empty fruit bunch from oil palm for fuel ethanol production and proposed biorefinery process.

This study evaluates the effects of some pretreatment processes to improve the enzymatic hydrolysis of oil palm empty fruit bunch (EFB) for ethanol production. The experimental results show that the bisulfite pretreatment was practical for EFB pretreatment. Moreover, the optimum pretreatment conditions of the bisulfite pretreatment (180 °C, 30 min, 8% NaHSO3, 1% H2SO4) were identified. In the experiments, a biorefinery process of EFB was proposed to produce ethanol, xylose products, and lignosulfonates.