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Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities.
J Ethnopharmacol. 2020 Jun 28; 256:112821.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Genus Trigonella has a history of folkloric medicinal uses in China, Japan, Egypt and India. There are a variety of therapeutic actions of Trigonella including hypocholesterolemia, hypoglycemia, antibacterial, antiviral, anti-inflammatory activities, antioxidants and appetite stimulant.

AIM OF THE STUDY

The prevalence of diabetes mellitus is increasing annually. The present study aims at investigating the protective effects of Trigonella stellata against the adverse effects of diabetes mellitus through investigation of the changes in phase I & II drug-metabolizing enzyme activities, protein expression of cytochrome P450 isoenzymes [CYP2E1 & 3A4], oxidative stress, antioxidant enzymes as well as histopathology of both liver and kidney tissues.

METHODS

GC-MS and MALDI-TOF were used to analyze the main constituents of the aqueous and the ethanolic extract of Trigonella stellata. Western immunoblotting technique used to show the protein expression of CYP450 isozymes in different groups. Spectrophotometric- and fluorophotometric techniques were also used for assessment of different hepatic integrity enzymes. Histopathological techniques used to illustrate the changes in the tissues of both livers and kidneys after different treatments.

RESULTS

Trigonelline was found to be the main constituent of both aqueous and ethanolic extract of Trigonella stellata. Administration of the aqueous and/or the ethanolic extracts of Trigonella stellata to the diabetic rats was found to decrease the blood glucose level, the biochemical markers of both liver (transaminases activities, Lactate dehydrogenase, gamma-glutamyl transferase) and the renal functions (urea, creatinine and bilirubin) which were increased in diabetic-treated rats relative to their normal levels. Diabetes mellitus potentially induced the oxidative stress, and also activities of dimethylnitrosamine N-demethylase I, cytochrome c-reductase, ethoxyresourfin O-deethylase, and the total hepatic content of cytochrome P450. On the other hand, the activity of catalase [CAT], superoxide dismutase [SOD], glutathione S-transferase [GST], glutathione reductase [GR], glutathione peroxidase [GPx] and levels of reduced glutathione [GSH] were potentially inhibited in diabetic rats compared to the control rats. However, treatments of diabetic rats with either aqueous and/or ethanolic extracts of Trigonella stellata restored such changes caused by diabetes almost nearly to their normal levels compared to the control group. Supporting the activity of dimethyl nitrosamine N-demethylase I activity, the protein expression of CYP2E1 was also induced in diabetic rats. However, the aqueous extract of Trigonella stellata was more effective than ethanolic extract in restoring the changes in the protein expression of CYP2E. On the other hand, the protein expression of CYP3A4 was markedly decreased in diabetic rats, and this decrease was partially restored to its normal level after treatment of diabetic rats with aqueous and/or ethanolic extracts. In addition, Trigonella stellata extracts alleviated the histopathological changes in livers and kidneys caused by diabetes mellitus.

CONCLUSION

It is concluded that diabetes mellitus induced changes in oxidative stress, phase I & II drug-metabolizing enzymes, and antioxidant enzymes activities, whereas both extracts of Trigonella stellata alleviated such changes. Alterations in cytochrome P450 system should be considered when therapeutic drugs are administered to diabetic patients since most of xenobiotic are mainly metabolized by this system.

Authors+Show Affiliations

Department of Clinical Biochemistry, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia; Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. Electronic address: ssheweita@yahoo.com.Department of Biochemistry, Faculty of Pharmacy, Pharos University, Egypt.Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32251758

Citation

Sheweita, Salah A., et al. "Trigonella Stellata Reduced the Deleterious Effects of Diabetes Mellitus Through Alleviation of Oxidative Stress, Antioxidant- and Drug-metabolizing Enzymes Activities." Journal of Ethnopharmacology, vol. 256, 2020, p. 112821.
Sheweita SA, ElHady SA, Hammoda HM. Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities. J Ethnopharmacol. 2020;256:112821.
Sheweita, S. A., ElHady, S. A., & Hammoda, H. M. (2020). Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities. Journal of Ethnopharmacology, 256, 112821. https://doi.org/10.1016/j.jep.2020.112821
Sheweita SA, ElHady SA, Hammoda HM. Trigonella Stellata Reduced the Deleterious Effects of Diabetes Mellitus Through Alleviation of Oxidative Stress, Antioxidant- and Drug-metabolizing Enzymes Activities. J Ethnopharmacol. 2020 Jun 28;256:112821. PubMed PMID: 32251758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities. AU - Sheweita,Salah A, AU - ElHady,Sara A, AU - Hammoda,Hala M, Y1 - 2020/04/03/ PY - 2019/11/13/received PY - 2020/03/26/revised PY - 2020/03/28/accepted PY - 2020/4/7/pubmed PY - 2021/1/28/medline PY - 2020/4/7/entrez KW - Antioxidant enzymes KW - Cytochrome P(450) KW - Diabetes mellitus KW - Glutathione-metabolizing enzymes KW - Oxidative stress KW - Trigonella stellata SP - 112821 EP - 112821 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 256 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Genus Trigonella has a history of folkloric medicinal uses in China, Japan, Egypt and India. There are a variety of therapeutic actions of Trigonella including hypocholesterolemia, hypoglycemia, antibacterial, antiviral, anti-inflammatory activities, antioxidants and appetite stimulant. AIM OF THE STUDY: The prevalence of diabetes mellitus is increasing annually. The present study aims at investigating the protective effects of Trigonella stellata against the adverse effects of diabetes mellitus through investigation of the changes in phase I & II drug-metabolizing enzyme activities, protein expression of cytochrome P450 isoenzymes [CYP2E1 & 3A4], oxidative stress, antioxidant enzymes as well as histopathology of both liver and kidney tissues. METHODS: GC-MS and MALDI-TOF were used to analyze the main constituents of the aqueous and the ethanolic extract of Trigonella stellata. Western immunoblotting technique used to show the protein expression of CYP450 isozymes in different groups. Spectrophotometric- and fluorophotometric techniques were also used for assessment of different hepatic integrity enzymes. Histopathological techniques used to illustrate the changes in the tissues of both livers and kidneys after different treatments. RESULTS: Trigonelline was found to be the main constituent of both aqueous and ethanolic extract of Trigonella stellata. Administration of the aqueous and/or the ethanolic extracts of Trigonella stellata to the diabetic rats was found to decrease the blood glucose level, the biochemical markers of both liver (transaminases activities, Lactate dehydrogenase, gamma-glutamyl transferase) and the renal functions (urea, creatinine and bilirubin) which were increased in diabetic-treated rats relative to their normal levels. Diabetes mellitus potentially induced the oxidative stress, and also activities of dimethylnitrosamine N-demethylase I, cytochrome c-reductase, ethoxyresourfin O-deethylase, and the total hepatic content of cytochrome P450. On the other hand, the activity of catalase [CAT], superoxide dismutase [SOD], glutathione S-transferase [GST], glutathione reductase [GR], glutathione peroxidase [GPx] and levels of reduced glutathione [GSH] were potentially inhibited in diabetic rats compared to the control rats. However, treatments of diabetic rats with either aqueous and/or ethanolic extracts of Trigonella stellata restored such changes caused by diabetes almost nearly to their normal levels compared to the control group. Supporting the activity of dimethyl nitrosamine N-demethylase I activity, the protein expression of CYP2E1 was also induced in diabetic rats. However, the aqueous extract of Trigonella stellata was more effective than ethanolic extract in restoring the changes in the protein expression of CYP2E. On the other hand, the protein expression of CYP3A4 was markedly decreased in diabetic rats, and this decrease was partially restored to its normal level after treatment of diabetic rats with aqueous and/or ethanolic extracts. In addition, Trigonella stellata extracts alleviated the histopathological changes in livers and kidneys caused by diabetes mellitus. CONCLUSION: It is concluded that diabetes mellitus induced changes in oxidative stress, phase I & II drug-metabolizing enzymes, and antioxidant enzymes activities, whereas both extracts of Trigonella stellata alleviated such changes. Alterations in cytochrome P450 system should be considered when therapeutic drugs are administered to diabetic patients since most of xenobiotic are mainly metabolized by this system. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/32251758/Trigonella_stellata_reduced_the_deleterious_effects_of_diabetes_mellitus_through_alleviation_of_oxidative_stress_antioxidant__and_drug_metabolizing_enzymes_activities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(19)34464-2 DB - PRIME DP - Unbound Medicine ER -