Delving into the Latest Updates on Nobiletin with Synapse

Overview

Basic Info

Drug Type

Herbal medicine

Synonyms

NOB, nobiletin, 川陈皮素

Target

PDE4B

Action

inhibitors

Mechanism

PDE4B inhibitors(Phosphodiesterase 4B inhibitors)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesCardiovascular Diseases+ [5]

Active Indication

Arthritis, GoutyPulmonary Arterial HypertensionParkinson Disease+ [2]

Inactive Indication

Neoplasms

Originator Organization

Nanjing Shenzhou Jiamei Pharmaceutical Co., Ltd.

Active Organization

Ocean University of China

Tanta UniversityHubei Provincial Hospital of TCM

+ [2]

Inactive Organization

Nanjing Shenzhou Jiamei Pharmaceutical Co., Ltd.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC21H24O8

InChIKeyLTRBUBSPQISFFL-UHFFFAOYSA-N

CAS Registry67549-69-3

The impaired reabsorption of kidney tubules is a critical early event in drug-induced kidney injury (DIKI), making real-time monitoring of human serum albumin (HSA) endocytosis essential for assessing renal function and screening nephroprotective agents. Inspired by the specific warfarin-HSA interactions, a novel coumarin-derived near-infrared (NIR) fluorogenic sensor, NCBP, was engineered based on a twisted intramolecular charge transfer (TICT) mechanism. Under physiological conditions, NCBP rapidly and stably bound to subdomain IIA of HSA with 1:1 stoichiometry, triggering a 79-fold fluorescence enhancement at 665 nm. NCBP integrated multiple advantages for detecting HSA, including instantaneous response, high physicochemical stability, ultrahigh sensitivity, and excellent selectivity. Furthermore, NCBP enabled in situ spatiotemporal imaging of HSA reabsorption in living nephrocytes and renal tissues, which was then used for screening nephroprotective agents to mitigate cisplatin-induced nephrotoxicity (CINT). Nobiletin (NOB) and 4',7-dimethoxyisoflavone (DIF) were identified as promising lead compounds capable of restoring renal uptake function and mitigating cisplatin-induced oxidative stress. In CINT mice, both NOB and DIF significantly improved renal function and attenuated tubular injury, confirming their nephroprotective potentials. Collectively, a TICT-based NIR sensor was developed for in situ imaging of HSA reabsorption, offering a robust phenotypic platform for spatiotemporal mapping of cellular HSA trafficking and discovering nephroprotective agents.

01 May 2026·CELLULAR SIGNALLING

Anti-fibrotic activity of nobiletin and nintedanib: In vitro and in vivo evidence in pulmonary fibrosis models

Article

Author: Wang, Yuanru ; Li, Luyao ; Yang, Xue ; Li, Xuejun ; Li, Huifang ; Zhang, Xiaoqian ; Cao, Yajun ; Lei, Qiqi ; Liu, Jie ; Xiang, Liuyan

BACKGROUND:

Pulmonary fibrosis, a well-known chronic and progressive lung disease, primarily impacts the interstitial tissues of the lungs, with a lack of effective therapies. Nobiletin is a polymethoxyflavonoid that exhibits characteristics of BH3 mimetics. It is mainly extracted from citrus peels and is known for its diverse pharmacological activities. Given the unsatisfactory clinical trial results of nintedanib, a combined treatment approach may represent a viable strategy for combating pulmonary fibrosis.

METHODS:

An in vitro pulmonary fibrosis model was established by inducing MRC-5 cells with transforming growth factor-β1 (TGF-β1). The impact of nobiletin combined with nintedanib on the migration of MRC-5 cells was assessed by wound healing and Transwell assays. Immunofluorescence and Western blot analyses were employed to assess the effect of drug combination on fibrosis-related markers, while Co-Immunoprecipitation (Co-IP) experiments were performed to assess the effects on autophagy. The anti-fibrotic effects and potential mechanisms of the combination of nobiletin and nintedanib were further explored using a bleomycin-induced pulmonary fibrosis model in C57BL/6 J mice.

RESULTS:

In vitro, the combination of nobiletin and nintedanib significantly inhibited MRC-5 cells' migration and extracellular matrix deposition, while simultaneously promoting apoptosis and autophagy. In addition, this combination exerted an anti-pulmonary fibrosis effect by regulating epigenetic mechanisms and the PI3K-AKT-mTOR signaling pathway. In vivo studies further revealed that the combination of nobiletin and nintedanib significantly reduced hydroxyproline levels in mice, attenuated lung inflammation, and helped to limit or prevent collagen accumulation.

CONCLUSIONS:

Our study demonstrates that the combination of nobiletin and nintedanib exhibits promising anti-fibrotic effects both in vitro and in vivo.

01 May 2026·JOURNAL OF ETHNOPHARMACOLOGY

Rapid antidepressant effects of Aurantii Fructus are mediated by hypoxanthine-caspase-4 axis in CUMS mice

Article

Author: Wu, Lei ; Zhu, Yaping ; Shao, Mengqi ; Tian, Liyuan ; Jiang, Yiran ; Lu, Chao ; Wei, Zixuan

ETHNOPHARMACOLOGICAL RELEVANCY:

Aurantii Fructus (AF)is a traditional Chinese medicine historically used to regulate Qi and alleviate emotional distress, suggesting potential psychotropic effects. This study investigates its therapeutic value for depression based on this traditional indication.

AIM OF THE STUDY:

To evaluate the rapid antidepressant-like effect of a single acute dose of AF extract in a chronic unpredictable mild stress (CUMS) mouse model and elucidate its underlying molecular mechanisms through integrated transcriptomic and metabolomic analyses.

MATERIALS AND METHODS:

AF flavonoid content was quantified by HPLC. Male mice underwent a 4-week CUMS protocol. A single oral dose of AF was administered 2 h prior to behavioral testing (NSF, TST, SPT, and OFT), with ketamine serving as a positive control. Hippocampal transcriptome analysis was performed by RNA sequencing, and serum metabolites were profiled via LC-MS in both positive and negative ion modes. Pearson correlation analysis assessed relationships between key targets and behavioral outcomes. Pathway involvement was functionally validated in a separate experiment using a hypoxanthine synthesis inhibitor.

RESULTS:

AF contained narirutin (1.32 mg/g), hesperidin (3.19 mg/g), neohesperidin (22.89 mg/g), naringenin (0.03 mg/g), and nobiletin (0.08 mg/g). Acute AF administration rapidly reversed CUMS-induced depressive-like behaviors, significantly decreasing latency to feed and increasing food consumption in the NSF test, reducing immobility time in the TST, and elevating sucrose preference in the SPT, without altering locomotor activity. Transcriptomic analysis revealed specific downregulation of hippocampal caspase-4 expression by AF. Metabolomic profiling showed AF normalized elevated serum hypoxanthine levels. Serum hypoxanthine levels negatively correlated with hippocampal caspase-4 expression and behavioral improvements, whereas caspase-4 expression positively correlated with behavioral deficits. Pharmacological inhibition of hypoxanthine synthesis abolished AF's antidepressant effects and prevented its normalization of hippocampal caspase-4, NF-κB, GDNF, and BDNF expression.

CONCLUSIONS:

Acute AF produces rapid, ketamine-like antidepressant effects by targeting the hypoxanthine-caspase-4 pathway. This study reveals a novel purinergic mechanism underlying AF's traditional use for emotional disorders and offers a promising therapeutic strategy for rapid-acting antidepressant development.

100 Deals associated with Nobiletin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	IND Application	China	Nanjing Shenzhou Jiamei Pharmaceutical Co., Ltd.	14 Sep 2006
Arthritis, Gouty	Preclinical	China	Wuhan University	01 Aug 2025
Pulmonary Arterial Hypertension	Preclinical	China	Hubei Provincial Hospital of TCM	29 Jun 2025
Parkinson Disease	Preclinical	Egypt	Tanta University	25 Jun 2025
Myocardial Infarction	Preclinical	United States	The University of Texas Health Science Center at Houston	23 Apr 2025
Asthma	Preclinical	China	Ocean University of China	27 Sep 2024