# A Nuphar lutea plant active ingredient, 6,6′-dihydroxythiobinupharidine, ameliorates kidney damage and inflammation in a mouse model of chronic kidney disease

**Authors:** Daniel Landau, Jannat Khalilia, Eden Arazi, Ana Foigelman Tobar, Daniel Benharroch, Avi Golan-Goldhirsh, Jacob Gopas, Yael Segev

PMC · DOI: 10.1038/s41598-024-58055-1 · Scientific Reports · 2024-03-30

## TL;DR

A compound from the Nuphar lutea plant reduces kidney damage and inflammation in a mouse model of chronic kidney disease.

## Contribution

The study identifies DTBN as a novel compound that ameliorates CKD symptoms through anti-inflammatory mechanisms.

## Key findings

- DTBN significantly reduced serum urea and creatinine levels in CKD mice.
- DTBN decreased kidney macrophage infiltration and TGF-β levels in CKD mice.
- DTBN reduced inflammation markers IL-1β, IL-6, and P-STAT3 in CKD mice.

## Abstract

Chronic Kidney Disease (CKD) associated complications are associated with increased inflammation through the innate immune response, which can be modulated with anti-inflammatory agents. An active ingredient derived from the Nuphar lutea aquatic plant, 6,6′-dihydroxythiobinupharidine (DTBN) has anti-inflammatory properties, mainly through the inhibition of NF-κB. We tested the effects of DTBN on mice with CKD. After preliminary safety and dosing experiments, we exposed 8 weeks old male C57BL/6J mice to adenine diet to induce CKD. Control and CKD animals were treated with IP injections of DTBN (25 μg QOD) or saline and sacrificed after 8 weeks. Serum urea and creatinine were significantly decreased in CKD-DTBN Vs CKD mice. Kidney histology showed a decrease in F4/80 positive macrophage infiltration, damaged renal area, as well as decreased kidney TGF-β in CKD-DTBN Vs CKD mice. Kidney inflammation indices (IL-1β, IL-6 and P-STAT3) were significantly decreased in CKD-DTBN as compared to CKD mice. DTBN treatment showed no apparent damage to tissues in control mice, besides a decrease in weight gain and mild hypoalbuminemia without proteinuria. Thus, DTBN significantly improved renal failure and inflammation indices in CKD mice. Therefore, this and similar substances may be considered as an additional treatment in CKD patients.

## Linked entities

- **Proteins:** NFKB1 (nuclear factor kappa B subunit 1), TGFB1 (transforming growth factor beta 1), IL1B (interleukin 1 beta), IL6 (interleukin 6), Adgre1 (adhesion G protein-coupled receptor E1)
- **Chemicals:** 6,6′-dihydroxythiobinupharidine (PubChem CID 73834258), adenine (PubChem CID 190)
- **Diseases:** Chronic Kidney Disease (MONDO:0005300)

## Full-text entities

- **Genes:** Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Adgre1 (adhesion G protein-coupled receptor E1) [NCBI Gene 13733] {aka DD7A5-7, EGF-TM7, Emr1, F4/80, Gpf480, Ly71}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}
- **Diseases:** inflammation (MESH:D007249), renal failure (MESH:D051437), CKD (MESH:D051436), proteinuria (MESH:D011507), weight gain (MESH:D015430), Kidney inflammation (MESH:D007674), hypoalbuminemia (MESH:D034141)
- **Chemicals:** adenine (MESH:D000225), creatinine (MESH:D003404), 6,6'-dihydroxythiobinupharidine (-), urea (MESH:D014508)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10981724/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC10981724/full.md

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Source: https://tomesphere.com/paper/PMC10981724