Abstract
Conflicting reports of HRT necessitates exploration of therapeutic interventions with the least side effects to preserve metabolic homeodynamics in women later in life. The current study was designed to elucidate the cumulative effects of aging and/or high fat diet (HFD) on some metabolic indicators and their management by Tinospora cordifolia stem powder (TCP) using middle-aged acyclic and young adult cyclic female rats as the model system. Animals were fed on either normal chow or HFD supplemented with or without TCP. Blood and liver tissue were collected for biochemical, and histological studies as well as for expression of proteins regulating lipid metabolism. Animals fed with TCP supplemented normal chow feed showed bodyweight management over 12-weeks despite their high feed and calories intake compared to young and age-matched controls as well as HFD-fed animals. TCP dose used was not toxic and rather prevented age-associated liver dysfunctions and ameliorated dyslipidemia and oxidative stress, normalized blood glucose, insulin, leptin, and secretary pro-inflammatory cytokines. Further, bodyweight management effect of TCP was observed to target AMPK signalling pathway as the mediator of lipogenesis, sterol biosynthesis, lipolysis, and β-oxidation of fatty acids. These findings suggest that TCP supplementation in diet may be a potential interventional strategy to ameliorate aging-associated hepatic and metabolic dysfunctions and to promote healthy aging.
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Abbreviations
- ACC:
-
Acetyl-CoA carboxylase
- ALT:
-
Alanine transaminase
- AMPK:
-
AMP-activated protein kinase
- AST:
-
Aspartate aminotransferase
- ATGL:
-
Adipose triglyceride lipase
- B-TCE:
-
Butanol extract of Tinospora cordifolia
- ERβ:
-
Estrogen receptor beta
- FAS:
-
Fatty acid synthase
- GSH:
-
Glutathione
- HDL:
-
High-density lipoprotein
- HFD:
-
High fat diet
- HM:
-
Middle-aged acyclic female rats fed on 30% high fat diet
- HMG-CoA reductase:
-
3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase
- HRP:
-
Horseradish peroxidase
- HRT:
-
Hormone replacement therapy
- HTM:
-
Middle-aged acyclic female rats fed on TCP supplemented 30% high fat diet
- IDV:
-
Integrated density value
- IL-1β:
-
Interleukin1 beta
- IL-6:
-
Interleukin 6
- KCl:
-
Potassium chloride
- LM:
-
Middle-aged acyclic female rats fed on normal chow feed
- LTM:
-
Middle-aged acyclic female rats fed on TCP supplemented chow feed
- LY:
-
Young cyclic female rats fed on normal chow feed
- MCP-1:
-
Monocyte chemotactic protein-1
- PAI-1:
-
Plasminogen activator inhibitor1
- PPARs:
-
Peroxisome proliferator-activated receptors
- PVDF:
-
Polyvinylidene difluoride
- SAG:
-
Superoxide-anion generation
- SDS-PAGE:
-
Sodium dodecyl sulphate–Polyacrylamide gel electrophoresis
- SREBP1:
-
Sterol regulatory element-binding transcription factor 1
- TBARS:
-
Thiobarbituric acid reactive substances
- TBST:
-
Tris-buffered saline and Tween-20
- TCE:
-
Aqueous extract of Tinospora cordifolia
- TCP:
-
Dry stem powder of Tinospora cordifolia
- TG:
-
Triglycerides
- TNF-α:
-
Tumour necrosis factor alpha
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Funding
The current study was funded by the Department of Science & Technology under Cognitive Science Research Initiative- DST-CSRI, GOI grant to Prof. Gurcharan Kaur (DST/CSRI/2018/99). Anmol Bhandari is thankful to DST for the fellowship from this grant during the course of this work. This funding agency has no role in study designing, manuscript writing, and data interpretation.
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AB, AS and GK conceptualized the study; GK obtained the funding; experimentation was carried out by AB performed diet-induced obesity, bodyweight, caloric intake record, western blotting; AK, and AS performed liver function tests, oxidative stress markers, and histology study; HS helped in western blotting; AB, GK, and AS analysed the data and participated in the preparation of the manuscript. All authors have read and approved the final manuscript.
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Protocols for animal experimentation were approved (Reg. no. 266/2020/12) by the Institutional Animal Ethical Committee of Guru Nanak Dev University, Amritsar, India, and performed in compliance with the guidelines of ‘Animal Care and Use’ laid down by Institutional Animal Ethical Committee, Guru Nanak Dev University.
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Bhandari, A., Sharma, A.K., Singh, H. et al. Aging-related changes in metabolic indicators in female rats and their management with Tinospora cordifolia. Biogerontology 23, 363–380 (2022). https://doi.org/10.1007/s10522-022-09962-1
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DOI: https://doi.org/10.1007/s10522-022-09962-1