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Cantleyoside (CA) is a kind of iridoid glycosides in Pterocephalus hookeri (C. B. Clarke) Höeck. The purpose of this study was to investigate the effects of CA on human rheumatoid arthritis fibroblast synovial cells (HFLS-RA). Cell proliferation of HFLS-RA was assessed by CCK-8. ELISA was used to detect cytokines NO, TNF-α, IL-1β/6, MCP-1, MMP-1/3/9 and metabolism-related ATPase activities and ATP levels. JC-1, DCFH-DA, Fluo-3 AM and Calcein AM probes were used to detect mitochondrial membrane potential (MMP), reactive oxygen species (ROS), Ca2+ and mitochondrial permeability conversion pore (MPTP), respectively. Isolated mitochondria assay was used to detect mitochondrial swelling. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and real-time ATP production were measured using a Seahorse analyzer. Apoptosis was detected by TUNEL and Hoechst staining. Western blot was used to detect the expressions of AMPK/p-AMPK, Sirt 1, IκBα, NF-κB p65/p-NF-κB p65, Bcl-2 and Bax. Cytoplasmic nuclear isolation was also performed to detect the translocation of NF-κB. CA significantly suppressed cell proliferation and the levels of NO, TNF-α, IL-1β/6, MCP-1 and MMP-1/3/9 in HFLS-RA. In addition, CA promoted the apoptosis of HFLS-RA by increasing TUNEL and Hoechst positive cells and the ratio of Bax/Bcl-2. Inhibition of energy metabolism in HFLS-RA by CA reduced OCR, ECAR and real-time ATP generation rate. Importantly, CA promoted p-AMPK and Sirt 1 expression, inhibited IκBα degradation to reduce p-NF-κB and translocation. The results suggest that CA activates the AMPK/Sirt 1/NF-κB pathway by promoting mitochondrial dysfunction, thereby exerting anti-inflammatory and pro-apoptotic effects. [Display omitted] • CA could inhibit inflammatory responses by weakening the expression of inflammatory cytokines, chemokines and MMPs. • CA could induce mitochondrial dysfunction by overloading intracellular ROS and Ca2+ in HFLS-RA. • CA could reduce mitochondrial energy metabolism by restraining OCR, ECAR and real-time ATP production rates in HFLS-RA. • CA could promote apoptosis of HFLS-RA by the activation of AMPK/Sirt 1/NF-κB pathway. [ABSTRACT FROM AUTHOR]

• We summarized and analyzed the prescriptions, herbs and identified compounds of TCM on the treatment of DR from the aspects of anti-inflammation, anti-oxidative stress, anti-angiogenesis and anti-apoptosis. • The detailed mechanisms and involved network pathways of herbs-compounds-targets of TCM in treating DR were reviewed and visualized by Cytoscape software. • We discussed the limitations or deficiencies of TCM on the treatment of DR, and gave the further suggestions. As a common ocular complication and microangiopathy of type 2 diabetic mellitus, diabetic retinopathy (DR) can lead to vision loss or even blindness in diabetic patients. At present, the treatment methods of DR mainly include laser and anti-VEGF therapies. Nevertheless, the higher cost and obvious side effects seriously disturb the normal life of DR patients. Promisingly, traditional Chinese medicine (TCM) has been demonstrated to be effective in treating DR by tonifying Qi and nourishing Yin, as well clearing heat and breeding body fluids, thus activating blood and removing blood stasis. Therefore, we screened the literatures on TCM treatment of DR through the web of science, ScienceDirect, PubMed, Google scholar and CNKI online databases. The representative prescriptions, herbs and extracts, and identified compounds for treatment of DR were further summarized and analyzed. Moreover, the detailed mechanisms and involved network pathways of herbs-compounds-targets were visualized by Cytoscape software. Meanwhile, we discussed the existing limitations and deficiencies of TCM on treatment of DR and gave corresponding measures. In conclusion, TCM could significantly ameliorate DR via anti-inflammation, anti-oxidative stress, anti-angiogenesis and anti-apoptosis. [ABSTRACT FROM AUTHOR]

Inflammation and renal tubular injury are major features of acute kidney injury (AKI). Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI)-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ)-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling) showed lower levels of blood urea nitrogen (BUN) in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI. [ABSTRACT FROM AUTHOR]

Gallic acid (GA), also known as 3,4,5-trihydroxybenzoic acid, is a natural secondary metabolite and widely isolated from various fruits, plants and nuts. In recent years, GA has received increasing attention for its powerful anti-inflammatory properties. The purpose of this review is to clearly illuminate the pharmacological activities and related molecular mechanisms of GA in inflammatory diseases. After consulting a large number of literatures, we made a comprehensive exposition on the chemical characteristics, plant origins, pharmacokinetics and toxicity of GA, especially its pharmacological activities and mechanisms of action. Although the plant source of GA is very rich, its lower extraction rate limits the application of GA in development. It is worth mentioning that GA can not only be separated from many plants, but also be produced in large quantities through biological and chemical synthesis. According to pharmacokinetic studies, the absorption and elimination of GA after oral administration are fast, while the structural optimization or dosage form adjustment of GA is beneficial to increase its bioavailability. Promisingly, toxicity studies have shown that GA scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials. The results show that the anti-inflammatory mechanisms of GA mainly involved MAPK and NF-κB signaling pathways. It thus weakens the inflammatory response by reducing the release of inflammatory cytokines, chemokines, adhesion molecule and cell infiltration. Due to its excellent pharmacological activities, GA is expected to be a potential candidate for the treatment of various inflammation-related diseases. This paper will provide theoretical basis for the clinical application of GA and guide the future research and medicinal development of GA. [ABSTRACT FROM AUTHOR]