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Aims: Inflammatory cytokines contribute to proximal tubular cell (PTC) injury leading to the deterioration of renal function and acute kidney injury (AKI) development. They also stimulate cyclo‑oxygenase-2 (COX-2)- dependent production and release to the extracellular medium of prostaglandin E2 (PGE2), a mediator of PTC injury. However, in several settings PGE2 re-uptake by prostaglandin transporter (PGT) is critical for PGE2- mediated PTC injury. Here we investigated several deleterious effects of pro-inflammatory cytokines in PTC and their prevention by PGT targeting. Main methods: In human kidney-2 (HK-2) PTC exposed to an inflammatory cytokine cocktail, consisting of interleukins (IL) IL-1α, IL-1β and IL-2, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were determined the changes in several parameters related to PTC injury, their dependency on PGE2 (through modulation by antagonists of PGE2 receptors) and the preventive effect of PGT inhibitor bromosulfophthalein. Key findings: The cytokine cocktail induced a COX-2-dependent increase in intracellular PGE2 (iPGE2) and cell death, together to a decrease in cell number and cell proliferation. There was also loss of adherent cells to collagen IV, changes in actin cytoskeleton and loss of monolayer integrity, together to an increase in paracellular permeability. All the changes were sensitive to antagonist of PGE2 receptors AH6809 and were fully prevented by bromosulfophthalein. Significance: These results indicate that PGT-, iPGE2-dependent mechanisms mediate inflammatory cytokineinduced HK-2 cell injury and suggest that treatment with PGT inhibitors might help to prevent AKI induced by sepsis, renal ischemia/reperfusion and other pathological conditions in which inflammatory cytokines contribute to PTC damage, This work was supported by a grant COVID-19 2021 2020/00003/ 016/001/009 from the Universidad de Alcala and a grant Ayudas a la Investigacion ´ Departamento de Biología UAM. This research is part of the project on COVID-19 and diabetes (REACT UE-CM2021-02) funded by the Community of Madrid in agreement with the University of Alcala, ´ and co-funded with REACT-EU resources from the European Regional Development Fund “A way to make Europe”

Ethno-pharmacological relevance The scientific proof and clinical validation of Chinese herbal medicine (CHM) require a rigorous approach that includes chemical standardization, biological assays, animal studies and clinical trials. Aim of the study To assess the experimental design of animal studies on the activity of CHM by selection and scrutinizing of a series of papers in some major disease areas. Materials and methods We have analyzed the English publications reported in MEDLINE (ISI web of knowledge). Results Our data showed that (i) research of CHM during the last 10 years had been highly intensified and become more accessible worldwide through increased publications in English, although still most authors had Chinese names; (ii) English journals publishing animal research of CHM were comparable to those publishing animal studies of non-Chinese phytotherapy in terms of impact factor; and (iii) published data on authentication and quality control of CHM, as well as research design of animal studies were far from sufficient to meet the criteria needed to support their reproducibility and reliability. Conclusions and perspectives The recent decade witnessed an increase in CHM research activities and CHM English publications. Based on common problems identified in publications on CHM animal studies, we have proposed a checklist that could help in preliminary selection of publications lacking the most common problems and thus would be useful for a quick search of reproducible CHM regimens that are likely to be effective in a given context. The second application of this checklist is to help avoid the most common problems when designing experiments.