Repurposing of digoxin in pain and inflammation: An evidence‐based study

Patel, Saraswati; Gururani, Ritika; Jain, Smita; Tripathi, Neetika; Paliwal, Swati; Paliwal, Sarvesh; Paliwal, Sunil; Sharma, Swapnil

doi:10.1002/ddr.21935

Cited by 16 publications

(3 citation statements)

References 45 publications

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“…Three-dimensional structure of muscarinic (M 3 ) and histaminic (H 1 ) receptors were retrieved from protein database (M3: 4u14 and H1: 3rze). Prior to analysis, water molecules and other unwanted residues were removed from all proteins using discovery studio 2.0 software [16,17].…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin‐induced allergic‐asthma model in guinea‐pigs: Evidences from ex vivo, in silico and in vivo studies

Gururani

Patel

Bisht

et al. 2023

Fundamemntal Clinical Pharma

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BackgroundTylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma. However, only few scientific studies have been performed in the past to validate its antiasthmatic potential.ObjectivesThe present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T. indica.MethodsThe most active fraction of T. indica leaves selected through bio‐guided activity was subjected to liquid chromatography‐mass spectrometry (LC–MS) analysis for chemical profiling. The binding affinity of identified compounds in fraction towards M3 and H1 receptors was determined by molecular docking study. F‐2 (chloroform fraction prepared from methanolic extract of T. indica leaves) was examined for its smooth muscle relaxant properties using isolated trachea of guinea‐pig. Further, F‐2 was evaluated through in vivo studies employing ovalbumin‐induced asthma model in guinea‐pigs.ResultsF‐2 was found most effective in bioassay‐guided fractionation. Characterization by LC–MS analysis revealed presence of five major bioactive compounds in F‐2 that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that F‐2 could significantly relax tracheal rings via targeting multiple signalling pathways videlicet, namely, noncompetitive antagonism of the histamine and muscarinic receptors, β2‐adrenergic stimulation and activation of soluble guanylyl cyclase. In in vivo studies, F‐2 ameliorated airway hyperresponsiveness and decreased broncho alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE).ConclusionThese results confirm the traditional use of T. indica as an antiasthmatic agent which are evidenced through ex vivo, in silico and in vivo studies.

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Section: Molecular Docking Studiesmentioning

confidence: 99%

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin‐induced allergic‐asthma model in guinea‐pigs: Evidences from ex vivo, in silico and in vivo studies

Gururani

Patel

Bisht

et al. 2023

Fundamemntal Clinical Pharma

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“…Inflammation plays an important role in IVDD ( 23 ). The anti-inflammatory properties of digoxin have been demonstrated in different diseases ( 24 ). However, it is unclear how digoxin affects IVDD.…”

Section: Introductionmentioning

confidence: 99%

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

Meng,

Liu,

Liu

et al. 2023

Front. Immunol.

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BackgroundIntervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.ObjectiveThis study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.MethodsWe exploited a rat needle model to investigate digoxin’s role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.ResultsDigoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.ConclusionThese findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.

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“…It goes by many names, including moringa, drumstick tree, horseradish tree, benzalum tree, and miracle tree (7). It grows in all tropical and subtropical regions such as Pakistan, Arabia, Central America, northern and southern Philippines (8The most popular of the 13 species of Moringa, Moringa is a member of the Moringa family (9). It is commonly used in perfumery and cosmetic oils and has a variety of medicinal and therapeutic uses (10).…”

Section: -1 Introductionmentioning

confidence: 99%

The Histological and Physiological Study of Moringa Oleifera

Mahdi FATHIL

2023

MINAR Journal

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The purpose of this study was to elucidate the effects of Moringa oleifera plants on physiological and histological indicators of animals from previous studies. Studies have shown that the moringa plant causes insignificant weight loss in rats. The study also showed that the Moringa plant affected kidney function, that the kidney capsules of the control group were wider than those of the treated mice, and that the results for urea and creatinine were not statistically significant in the experimental animal group compared to the control animal livers. Physiological studies of the enzymes showed no significant difference, as the moringa plant provided protection and maintained the functional integrity of liver cells, while other studies in mice showed that the moringa plant caused a significant increase in blood calcium and phosphorus in patients with bone Moringa oleifera increased levels of fertility hormones (testosterone, luteinizing hormone, follicle-stimulating hormone) in mice with porphyria and other studies. This study led to the need to increase awareness of the beneficial effects of this miracle tree (Moringa), the daily consumption of Moringa as a herb and even as a spice should be promoted, and the growing area in Iraq should be expanded. This should be considered for future nutritional research focusing on the use of moringa as a mineral supplement.It is too early to recommend Moringa leaves as a medicine for the prevention or treatment of diabetes, cardiovascular disease, dyslipidemia, cancer and infectious diseases.

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Repurposing of digoxin in pain and inflammation: An evidence‐based study

Cited by 16 publications

References 45 publications

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin‐induced allergic‐asthma model in guinea‐pigs: Evidences from ex vivo, in silico and in vivo studies

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin‐induced allergic‐asthma model in guinea‐pigs: Evidences from ex vivo, in silico and in vivo studies

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

The Histological and Physiological Study of Moringa Oleifera

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