Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva

Aims of the study

We recently reported the potential antioxidant and anti-inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from the whole plants of Angelica decursiva. In this study, we elucidated the anti-inflammatory mechanisms of UMC in vitro and in vivo.

Methods

The inhibitory effects of UMC on the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α), the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear factor kappa B (NF-κB) were evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)-induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of UMC was evaluated using carrageenan induced mouse paw edema model.

Results

UMC dose-dependently inhibited NO and PGE₂ production by down-regulating iNOS and COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also suppressed the production of the proinflammatory cytokine TNF-α in LPS stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC dose-dependently prevented LPS-induced nuclear translocation of NF-κB in RAW 264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t-BHP-induced ROS generation in RAW 264.7 cells with an IC₅₀ value of 705.1 μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25 mg/kg body weight, respectively.

Conclusion

The combined results of this study indicate that UMC is an important anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect was due to its ability to inhibit the production of inflammatory mediators via inhibition of NF-κB activation pathway.     

Modulatory effects of the acid polysaccharide fraction from one of anamorph of Cordyceps sinensis on Ana-1 cells

Ethnopharmacological relevance

Cordyceps sinensis has been used as a precious herbal medicine for thousands of years in China. Its polysaccharide fraction has been confirmed possessing immunomodulatory function and we have reported the acid polysaccharide fraction (APSF), from an anamorph of C. sinensis, has stimulating activity on macrophages. The mechanism still needs to be further elucidated.

Materials and methods

In order to investigate the effects of APSF on macrophage's phenotypes, Ana-1 mouse macrophages were polarized to M2 phenotype by culturing the cells with culture supernatant of H22 cells. M2 phenotype was determined by measuring the expression of TNF-α and checking cell surface markers mannose receptor (MR) and scavenger receptor (SR). After cultured with H22 supernatant for 72 h, the TNF-α level of Ana-1 cells was decreased while the SR and MR expressions were up-regulated, suggesting that Ana-1 cells were polarized towards M2 macrophages. Then the effects of APSF on M2 macrophages were investigated by measuring mRNA levels of TNF-α, inducible nitric oxide synthase (iNOS), IL-12 and IL-10. Nuclear NF-κB was detected by Western blotting.

Results

APSF treatment increased the expressions of TNF-α, IL-12 and iNOS, and reduced the expression of IL-10 of Ana-1 cells. Besides, the expressions of SR and MR were down-regulated by APSF. And the result of Western blotting showed NF-κB level was decreased in M2 macrophages and up-regulated after APSF treatment.

Conclusions

APSF may convert M2 macrophages to M1 phenotype by activating NF-κB pathway.     

Herbal medicines for the prevention of alcoholic liver disease: A review

Ethnopharmacological relevance

Long-term excess alcohol exposure leads to alcoholic liver disease (ALD)—a global health problem without effective therapeutic approach. ALD is increasingly considered as a complex and multifaceted pathological process, involving oxidative stress, inflammation and excessive fatty acid synthesis. Over the past decade, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of ALD, due to their multiple targets and less toxic side effects. Several herbs, such as Cnidium monnieri (L.) Cusson (Apiaceae), Curcuma longa L. (Zingiberaceae) and Pueraria lobata (Willd.) Ohwi (Leguminosae), etc., have been shown to be quite effective and are being widely used in China today for the treatment of ALD when used alone or in combination.

Aim of the review

To review current available knowledge on herbal medicines used to prevent or treat ALD and their underlying mechanisms.

Materials and methods

We used the pre-set searching syntax and inclusion criteria to retrieve available published literature from PUBMED and Web of Science databases, all herbal medicines and their active compounds tested on ALD induced by both acute and chronic alcohol ingestion were included.

Results

A total of 40 experimental studies involving 34 herbal medicines and (or) active compounds were retrieved and reviewed. We found that all reported extracts and individual compounds from herbal medicines/natural plants could be beneficial to ALD, which might be attributed to regulate multiple critical targets involved in the pathways of oxidation, inflammation and lipid metabolism.

Conclusions

Screening chemical candidate from herbal medicine might be a promising approach to drug discovery for the prevention or treatment of ALD. However, further studies remain to be done on the systematic assessment of herbal medicines against ALD and the underlying mechanisms, as well as their quality control studies.     

参附注射液对心肌缺血再灌注老年大鼠NF-κB p65及COX-2表达的影响

目的：探讨参附注射液对心肌缺血再灌注老年大鼠心肌组织NF-κB p65及COX-2的影响。方法：健康Wistar老年大鼠30只,18月龄,随机分为3组,假手术组（S组）、缺血再灌注组（I/R组）、参附注射液组（SF组）,每组10只。采用结扎左冠状动脉前降支制备心肌缺血再灌注模型。观察参附注射液对缺血再灌注老年大鼠血清中肌酸激酶同工酶（CK-KB）、天门冬氨基转移酶（AST）、乳酸脱氢酶（LDH）溢出量的影响;运用免疫组化法观察心肌缺血再灌注后心肌组织细胞中NF-κB p65的活性及COX-2的蛋白表达。结果：参附注射液能显著减少I/R老年大鼠血清中CK-KB、AST、LDH的溢出量。与S组比较,I/R组心肌组织NF-κB p65的活性增高,COX-2的蛋白表达明显增加（P〈0.05）。SF组中NF-κB p65、COX-2显著下降（P〈0.05）。结论：NF-κB p65和COX-2在心肌缺血再灌注中均有高水平表达,提示炎症参与了心肌缺血再灌注,机制可能是NF-κB p65通过对COX-2的转录调控发挥了重要作用;参附注射液可抑制NF-κB p65活性,降低COX-2的蛋白表达水平,减轻I/R心肌炎症反应,对心肌起保护作用。     

降脂瘦身汤对非酒精性脂肪肝大鼠脂代谢及核转录因子-κB蛋白表达影响的实验研究

目的:研究降脂瘦身汤对非酒精性脂肪肝(NFALD)大鼠脂代谢及核转录因子-κB(NF-κB)蛋白表达的影响.方法:将32只SD大鼠随机分为正常组、模型组、降脂瘦身汤组,除正常组外,其余两组采用高脂饲料喂养8周建立非酒精性脂肪肝大鼠模型.造模成功后,降脂瘦身汤组给予相应的药物水溶液,正常组和模型组给予等量0.9％氯化钠溶...     

Identification of biomarkers for essential hypertension based on metabolomics

AimEssential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases.Data synthesisThis review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0.Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development.ConclusionsThis study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.