Aloin alleviates pathological cardiac hypertrophy via modulation of the oxidative and fibrotic response

Syed, Abu Mohammad; Kundu, Sourav; Ram, Chetan; Kulhari, Uttam; Kumar, Akhilesh; Mugale, Madhav Nilakanth; Murty, Upadhyayula Suryanarayana; Sahu, Bidya Dhar

doi:10.1016/j.lfs.2021.120159

Cited by 14 publications

(3 citation statements)

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“…ISO is a non-selective β 1 and β 2 adrenergic receptor agonist and has been widely used to induce cardiac hypertrophy in mice and rats. It has been reported in the literature that consecutive administration of ISO at a certain dose through mini-osmotic pump implantation, intraperitoneal, or subcutaneous injection over two to four weeks could generate a hypertrophic response in most rats [19][20][21]. In this study, intraperitoneal injection of ISO at 30 mg/kg thrice daily for 14 consecutive days resulted in increases in cross-sectional cardiomyocytes area, ratios of HW/BW, LVW/BW, and RVW/BW, as well as reactivation of fetal genes; however, treatment with Re ameliorated most of these hypertrophic responses, which is in line with a previous study [15].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Qiu,

Xie,

Ding

et al. 2024

Cureus

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Background and objectivesGinsenoside Re (Re), a protopanaxatriol-type saponin extracted from ginseng, is known to have potential cardioprotective effects; however, the mechanisms of Re in improving cardiac hypertrophy have not been fully elucidated. This study aimed to investigate the therapeutic effects and underlying mechanism of Re on isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro. MethodsRats were intraperitoneally injected with ISO 30 mg/kg thrice daily for 14 consecutive days to induce cardiac hypertrophy, and these rats were treated with atorvastatin (ATC, 20 mg/kg) or Re (20 mg/kg or 40 mg/kg) once daily for three days in advance until the end of the experiment. Heart weight index, hematoxylin and eosin staining, and hypertrophy-related fetal gene expression were measured to evaluate the effect of Re on cardiac hypertrophy in vivo. Meanwhile, the rat H9c2 cardiomyocyte hypertrophy model was induced by ISO 10 μM for 24 hours. Cell surface area and hypertrophy-related fetal gene expression were determined to assess the effect of Re on ISO-induced cardiomyocyte hypertrophy in vitro. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in both serum and cardiomyocytes were detected by enzymatic colorimetric assays. Furthermore, we chose cholesteryl ester transfer protein (CETP) as a target to explore the influence of Re on CETP expression in vivo and in vitro through real-time polymerase chain reaction, western blot, and enzymelinked immunosorbent assay. ResultsIntraperitoneal administration of ISO into rats resulted in increases in cross-sectional cardiomyocyte area, the ratio of heart weight to body weight, the ratio of left ventricular weight to body weight, and the ratio of right ventricular weight to body weight, as well as reactivation of fetal genes; however, treatment with Re or ATC ameliorated most of these hypertrophic responses. Similarly, Re pronouncedly alleviated ISO-induced cardiomyocyte hypertrophy, as evidenced by a decreased cell surface area and downregulation of fetal genes. Moreover, our in vivo and in vitro data revealed that Re reduced TC, TG, and LDL-C levels, and enhanced HDL-C levels. Re improved cardiac hypertrophy mainly associated with the inhibition of mRNA level and protein expression of CETP, to an extent comparable to that of the classical CETP inhibitor, anacetrapib. ConclusionsOur research found that CETP inhibition contributes to the protection of Re against ISO-induced cardiac hypertrophy, which provides evidence for the application of Re for cardiovascular disease treatments.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Qiu,

Xie,

Ding

et al. 2024

Cureus

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“…In Vitro Oxidative Stress-Induced Cell Viability Assessment Using Flow Cytometry. Intracellular H 2 O 2 -induced ROS (reactive oxygen species) generation in the H9c2 cells was evaluated using a fluorescent probe DCFH-DA as reported by Syed et al 52 with slight modifications. The H9c2 cells were plated at a concentration of 2 × 10 4 cells per well in a sterile 12-well plate and incubated for 24 h. The cells were treated with hydrogen peroxide (H 2 O 2 ) at a concentration of 0.3 mmol/L for 3 h alone or along with two safe doses of CVD-NLPs (10 and 20 μg/mL), QC-NLPs (5 and 10 μg/mL), and dual combination CVD/QC-NLPs [i.e., 4.88 and 3.91 μg/mL of CVD and QC and 9.77 and 7.81 μg/mL of CVD and QC as low and high doses] for 20 h. Cells treated with H 2 O 2 alone were considered as the positive control.…”

Section: Ex Vivo Permeation Studymentioning

confidence: 99%

Intranasal Delivery of Carvedilol- and Quercetin-Encapsulated Cationic Nanoliposomes for Cardiovascular Targeting: Formulation and In Vitro and Ex Vivo Studies

Kar,

Das,

Kundu

et al. 2024

ACS Appl. Bio Mater.

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Carvedilol (CVD), an adrenoreceptor blocker, is a hydrophobic Biopharmaceutics Classification System class II drug with poor oral bioavailability due to which frequent dosing is essential to attain pharmacological effects. Quercetin (QC), a polyphenolic compound, is a potent natural antioxidant, but its oral dosing is restricted due to poor aqueous solubility and low oral bioavailability. To overcome the common limitations of both drugs and to attain synergistic cardioprotective effects, we formulated CVD-and QCencapsulated cationic nanoliposomes (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. We designed CVD-and QC-loaded cationic nanoliposomal (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. In vitro drug release studies of CVD/QC-L.O.F. (16.25%) exhibited 18.78 ± 0.57% of QC release and 91.38 ± 0.93% of CVD release for 120 h. Ex vivo nasal permeation studies of CVD/QC-L.O.F. demonstrated better permeation of QC (within 96 h), i.e., 75.09% compared to in vitro drug release, whereas CVD permeates within 48 h, indicating the better interaction between cationic NLPs and the negatively charged biological membrane. The developed nasal gel showed a sufficient mucoadhesive property, good spreadability, higher firmness, consistency, and cohesiveness, indicating suitability for membrane application and intranasal administration. CVD-NLPs, QC-NLPs, and CVD/QC-NLPs were evaluated for in vitro cytotoxicity, in vitro ROS-induced cell viability assessment, and a cellular uptake study using H9c2 rat cardiomyocytes. The highest in vitro cellular uptake of CVD/QC-cationic NLPs by H9c2 cells implies the benefit of QC loading within the CVD nanoliposomal carrier system and gives evidence for better interaction of NLPs carrying positive charges with the negatively charged biological cells. The in vitro H 2 O 2 -induced oxidative stress cell viability assessment of H9c2 cells established the intracellular antioxidant activity and cardioprotective effect of CVD/QC-cationic NLPs with low cytotoxicity. These findings suggest the potential of cationic NLPs as a suitable drug delivery carrier for CVD and QC combination for the intranasal route in the treatment of various cardiovascular diseases like hypertension, angina pectoris, etc. and for treating neurodegenerative disorders.

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“…64 Here, aloin upregulated the expression of Nrf2/HO-1 pathway but repressed the level of the TGFβ/Smad2/3 axis in OVA-induced mice. Aloin was shown to activate Nrf2/HO-1 pathway in pathological cardiac hypertrophy, 65 and myocardial ischemia/reperfusion injury. 17 Besides, the effect of aloe on Nrf2/HO-1 signaling pathway has been documented in the experimental models of other immunological diseases, such as acute colitis and non-alcoholic steatohepatitis.…”

Section: Aloin Regulated Nrf2/ho-1 and Tgf-β/smad2/3 Pathways In Asth...mentioning

confidence: 99%

Protective effects of aloin on asthmatic mice by activating Nrf2/HO-1 pathway and inhibiting TGF-β/Smad2/3 pathway

Xia

Yang

et al. 2023

Allergol Immunopathol

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Background: Asthma is a severe chronic respiratory disease affecting all age groups with increasing prevalence. Anti-inflammatory strategies are promising options for the treatment of asthma. Although the inhibitory effect of aloin on inflammation has been demonstrated in various diseases, its effect on asthma remains unknown. Methods: A mice asthma model was established by treating with ovalbumin (OVA). The effects and mechanism of aloin on the OVA-treated mice were determined by enzyme-linked-immunosorbent serologic assay, biochemical examination, hematoxylin and eosin and Masson's staining, and Western blot assay. Results: OVA treatment in mice significantly increased the number of total cells, neutrophils, eosinophils, and macrophages and the concentration of interleukin (IL)-4, IL-5, and IL-13, which were attenuated with the administration of aloin. The content of malondialdehyde was enhanced in OVA-treated mice, with the decreased levels of superoxide dismutase and glutathione, which were reversed with aloin treatment. Aloin treatment reduced the airway resistance of OVA-induced mice. The inflammatory cell infiltration around small airways was accompanied by the thickening and contraction of bronchial walls and pulmonary collagen deposition in OVA-treated mice; however, these conditions were ameliorated with aloin treatment. Mechanically, aloin upregulated the expression of nuclear factor erythroid 2-related fac-tor 2 (Nrf2)—heme oxygenase 1 (HO-1) pathway but inhibited the level of transforming growth factor beta–SMAD2/3 genes (TGF-β/Smad2/3) axis in OVA-induced mice. Conclusion: Aloin treatment lessened airway hyperresponsiveness, airway remodeling, inflammation, and oxidative stress in OVA-treated mice, and was closely related to the activation of Nrf2/HO-1 pathway and the weakening of TGF-β/Smad2/3 pathway.

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Aloin alleviates pathological cardiac hypertrophy via modulation of the oxidative and fibrotic response

Cited by 14 publications

References 47 publications

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Intranasal Delivery of Carvedilol- and Quercetin-Encapsulated Cationic Nanoliposomes for Cardiovascular Targeting: Formulation and In Vitro and Ex Vivo Studies

Protective effects of aloin on asthmatic mice by activating Nrf2/HO-1 pathway and inhibiting TGF-β/Smad2/3 pathway

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