Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats

Ahmed, Lamiaa A.; Obaid, Al Arqam Z.; Zaki, Hala F.; Agha, Azza M.

doi:10.1016/j.ejphar.2014.07.026

Cited by 55 publications

(40 citation statements)

References 49 publications

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“…These mechanisms could be responsible for the observed changes in the RV of the MCT group in our study (Figure ). Other studies also observed an increase in antioxidant enzymes during hypertrophy, leukocyte infiltration even during early stages of the MCT syndrome, and increased local expression and concentration of TNF‐α and IL‐1β . The alleviation of some of these changes in our treated groups (Figure ) can be attributed to the antioxidant properties of the used symmetric 2,6‐bis(2‐R‐benzylidene) cyclohexanone derivatives, allowing them to directly quench reactive species, thereby inhibiting their influence on signaling pathways.…”

Section: Discussionsupporting

confidence: 64%

“…Increased lipid peroxidation has previously been observed during chronic pressure overload of the heart . Our finding that increased enzymatic antioxidant activity in MCT‐injected rats is not sufficient to prevent oxidative stress leading to lipid peroxidation (Figure , Table ) suggests an altered capacity of the nonenzymatic antioxidant system.…”

Section: Discussionmentioning

confidence: 57%

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Antioxidant and anti‐inflammatory effects of the monocarbonyl curcumin analogs B2BRBC and C66 in monocrotaline‐induced right ventricular hypertrophy

Hadzi‐Petrushev

Angelovski

Rebok

et al. 2019

J Biochem & Molecular Tox

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For 22 days after monocrotaline injection two groups of rats received either of the monocarbonyl curcumin analogs (2E,6E)‐2,6‐bis(2‐bromobenzylidene)cycloxehanone (B2BrBC) and (2E,6E)‐2,6‐bis([2‐triﬂuoromethyl]benzylidene)cyclohexanone (C66), and their right ventricle parameters were compared to those from the control and the monocrotaline injected animals. B2BrBC and C66 treatments did not prevent the monocrotaline‐induced right ventricular hypertrophy but attenuated the changes in antioxidant enzyme activities and reduced inflammation. The level of thiol‐based nonenzymatic antioxidants did not change in the function of monocrotaline or curcumin analogs treatment. However, due to its stronger antioxidant properties, only B2BrBC treatment was effective in the reduction of monocrotaline‐associated lipid peroxidation. The obtained results suggest that increasing the levels of antioxidant enzymes may not be sufficient to reduce oxidative stress and chronic inflammation optimally and our current study supports the potential of compounds with more than one beneficial biological activity as a promising treatment against the progression of cardiac hypertrophy.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 57%

Antioxidant and anti‐inflammatory effects of the monocarbonyl curcumin analogs B2BRBC and C66 in monocrotaline‐induced right ventricular hypertrophy

Hadzi‐Petrushev

Angelovski

Rebok

et al. 2019

J Biochem & Molecular Tox

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“…A previous study demonstrated that factors other than hypoxia may enhance HIF-1α mRNA expression, as the HIF-1 level did not increase in direct correlation to oxygen concentration (22). Accumulating evidence suggests that oxidative stress is involved in the regulation of HIF-1 expression and activity (23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

“…muscle contraction (23). Previous research demonstrated that augmenting SOD2-increased hydrogen peroxide-mediated redox signaling inhibited HIF-1α activity and reduced pulmonary artery smooth muscle cell proliferation (24). Recent studies have reported that oxidative stress regulates the expression of HIF-1α at both the protein and mRNA levels (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Effects of 17β-estradiol and 2-methoxyestradiol on the oxidative stress-hypoxia inducible factor-1 pathway in hypoxic pulmonary hypertensive rats

Wang

Zheng

Yuan

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to investigate the effects of 17β-estradiol (E2) and 2-methoxyestradiol (2ME) on the oxidative stress-hypoxia inducible factor-1 (OS-HIF-1) pathway in hypoxic pulmonary hypertensive rats. Female Sprague-Dawley rats were divided randomly into 4 groups, as follows: i) Control (Group A); ii) ovariectomy (OVX) + hypoxia (Group B); iii) OVX + hypoxia + E2 injection (Group C); and iv) 2ME injection (Group D). The rats were maintained under hypoxic conditions for 8 weeks, and mean pulmonary artery pressure (mPAP) and pulmonary arteriole morphology were measured. The reactive oxygen species, superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (Cu/ZnSOD) levels in serum were also measured. MnSOD and HIF-1α expression levels in lung tissue were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. The mPAP and arterial remodeling index were significantly elevated following chronic hypoxia exposure; however, experimental data revealed a reduced response in E2 and 2ME intervention rats. Compared with Group A, Group B had significantly elevated oxidative stress levels, as illustrated by increased serum ROS levels, decreased serum SOD and MnSOD levels and decreased MnSOD mRNA and protein expression levels in lung tissue. Furthermore, HIF-1α mRNA and protein expression in Group B was significantly elevated compared with Group A. E2 and 2ME intervention significantly attenuated the aforementioned parameter changes, suggesting that E2 and 2ME partially ameliorate hypoxic pulmonary hypertension. The underlying mechanism of this may be associated with the increase in MnSOD activity and expression and reduction in ROS level, which reduces the levels of transcription and translation of HIF-1α.

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“…In fact, diosgenin treatment preserved hemodynamic changes and alleviated oxidative stress, inflammatory, and apoptotic markers induced by monocrotaline. This protective effect could be mediated through preserving eNOS expression together with inhibition of iNOS overexpression [49]. …”

Section: Pharmacology: Recent Datamentioning

confidence: 99%

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology

Jesus

Martins

Gallardo

et al. 2016

Journal of Analytical Methods in Chemistry

194

125

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Diosgenin, a steroidal sapogenin, occurs abundantly in plants such as Dioscorea alata, Smilax China, and Trigonella foenum graecum. This bioactive phytochemical not only is used as an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry, but has revealed also high potential and interest in the treatment of various types of disorders such as cancer, hypercholesterolemia, inflammation, and several types of infections. Due to its pharmacological and industrial importance, several extraction and analytical procedures have been developed and applied over the years to isolate, detect, and quantify diosgenin, not only in its natural sources and pharmaceutical compositions, but also in animal matrices for pharmacodynamic, pharmacokinetic, and toxicological studies. Within these, HPLC technique coupled to different detectors is the most commonly analytical procedure described for this compound. However, other alternative methods were also published. Thus, the present review aims to provide collective information on the most recent pharmacological data on diosgenin and on the most relevant analytical techniques used to isolate, detect, and quantify this compound as well.

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Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats

Cited by 55 publications

References 49 publications

Antioxidant and anti‐inflammatory effects of the monocarbonyl curcumin analogs B2BRBC and C66 in monocrotaline‐induced right ventricular hypertrophy

Antioxidant and anti‐inflammatory effects of the monocarbonyl curcumin analogs B2BRBC and C66 in monocrotaline‐induced right ventricular hypertrophy

Effects of 17β-estradiol and 2-methoxyestradiol on the oxidative stress-hypoxia inducible factor-1 pathway in hypoxic pulmonary hypertensive rats

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology

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