Abstract
The needle powder of Taxus wallichiana is in use for the management of diabetes and inflammation-related complications in the Indian and Chinese Systems of Traditional Medicine but the lack of proper pharmacological intervention has prompted us to investigate the pharmacological mechanism against inflammation-induced insulin resistance in high-fat diet-fed C57BL/6 mice. Hexane (Tw-H), chloroform (Tw-C), and ethyl acetate (Tw-EA) extracts were prepared from a needle of T. wallichiana and its effect on glucose uptake against TNF-α-induced insulin resistance in skeletal muscle cells was studied. Among all, Tw-EA extract has shown promising glucose uptake potential. Tw-EA treatment is also able to decrease the lipid accumulation in adipocytes. Chemical signature of Tw-EA using HPLC showed the presence of taxoids. Efficacy of taxoids-rich extract from T. wallichiana (Tw-EA) was further validated in in vivo system against high-fat diet (HFD)-induced insulin resistance in C57BL/6 mice. Oral treatment of Tw-EA showed significant reduction in blood glucose, pro-inflammatory cytokine production and body weight gain when compared with vehicle-treated HFD-induced insulin resistance in C57BL/6 mice. Histopathology and immunohistochemistry study in skeletal muscle and adipose tissue revealed that oral treatment of Tw-EA is able to reduce the infiltration of inflammatory cells in skeletal muscles, ameliorate the hypertrophy in adipose tissue and upregulate the GLUT4 protein expression. Treatment with Tw-EA significantly up-regulated mRNA expression of insulin signaling pathway (IRS-1, PI3K, AKT, GLUT 4). This study suggested the beneficial effect of taxoids-rich extract from Taxus wallichiana against the inflammation-associated insulin resistance condition.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Enquiries about data availability should be directed to the authors.
Abbreviations
- IR:
-
Insulin resistance
- T2D:
-
Type 2 diabetes mellitus
- PI3K:
-
Phosphatidylinositol-3-kinase
- HFD:
-
High-fat diet
- FBG:
-
Fasting blood glucose
- DMSO:
-
Dimethyl sulfoxide
- Akt:
-
Protein kinase B
- GOD–POD:
-
Glucoxidase–peroxidase
- ITT:
-
Insulin tolerance test
- GLUT 4:
-
Glucose transporter
- Met:
-
Metformin
- IRS:
-
Insulin receptor substrate
- TwN :
-
Taxus wallichiana needles
- OGTT:
-
Oral glucose tolerance test
- 10-DAB:
-
10-Deacetylbaccatin
- BRE:
-
Brevifoliol
References
Abel ED, Peroni O, Kim JK et al (2001) Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409(6821):729–733. https://doi.org/10.1038/35055575
Akinrinde A, Koekemoer T, Venter MV, Bradley G (2018) In vitro investigation of potential antidiabetic activity of the corm extract of Hypoxis argentea Harv. Ex Baker. Acta Pharm 68(4):389–407. https://doi.org/10.2478/acph-2018-0023
Bala S, Uniyal GC, Chattopadhyay SK et al (1999) Analysis of taxol and major taxoids in Himalayan yew, Taxus wallichiana. J Chromatogr A 858(2):239–244. https://doi.org/10.1016/s0021-9673(99)00841-9
Baloglu E, Kingston DG (1999) The taxane diterpenoids. J Nat Prod 62(10):1448–1472. https://doi.org/10.1021/np990176i
Bhukya B, Fatima K, Nagar A et al (2020) Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway. Chem Biol Drug Des 95(1):150–161. https://doi.org/10.1111/cbdd.13631
Cai Z, Huang Y, He B (2022) New insights into adipose tissue macrophages in obesity and insulin resistance. Cells 11(9):1424. https://doi.org/10.3390/cells11091424
Dang PH, Nguyen HX, Duong TTT et al (2017) α-Glucosidase inhibitory and cytotoxic taxane diterpenoids from the stem bark of Taxus wallichiana. J Nat Prod 80(4):1087–1095. https://doi.org/10.1021/acs.jnatprod.7b00006
de Alvaro C, Teruel T, Hernandez R, Lorenzo M (2004) Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappa B kinase in a p38 MAPK-dependent manner. J Biol Chem 279(17):17070–17078. https://doi.org/10.1074/jbc.M312021200
DeFronzo RA, Tripathy D (2009) Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32(Suppl 2):S157–S163. https://doi.org/10.2337/dc09-S302
Fazakerley DJ, Krycer JR, Kearney AL, Hocking SL, James DE (2019) Muscle and adipose tissue insulin resistance: malady without mechanism? J Lipid Res 60(10):1720–1732. https://doi.org/10.1194/jlr.R087510
Ghanbari M, Momen Maragheh S, Aghazadeh A, Mehrjuyan SR, Hussen BM, Abdoli Shadbad M, Dastmalchi N, Safaralizadeh R (2021) Interleukin-1 in obesity-related low-grade inflammation: from molecular mechanisms to therapeutic strategies. Int Immunopharmacol 96:107765. https://doi.org/10.1016/j.intimp.2021.107765
Giani JF, Mayer MA, Muñoz MC et al (2009) Chronic infusion of angiotensin-(1–7) improves insulin resistance and hypertension induced by a high-fructose diet in rats. Am J Physiol Endocrinol Metab 296(2):E262–E271. https://doi.org/10.1152/ajpendo.90678.2008
Herrada AA, Olate-Briones A, Rojas A, Liu C, Escobedo N, Piesche M (2021) Adipose tissue macrophages as a therapeutic target in obesity-associated diseases. Obese Rev 22(6):e13200. https://doi.org/10.1111/obr.13200
Johnson AM, Olefsky JM (2013) The origins and drivers of insulin resistance. Cell 152:673–684. https://doi.org/10.1016/j.cell.2013.01.041
Jorquera G, Russell J, Monsalves-Álvarez M et al (2021) NLRP3 inflammasome: potential role in obesity related low-grade inflammation and insulin resistance in skeletal muscle. Int J Mol Sci 22(6):3254. https://doi.org/10.3390/ijms22063254
Juyal D, Thawani V, Thaledi S, Joshi M (2014) Ethnomedical properties of taxus wallichiana zucc. (Himalayan yew). J Tradit Complement Med 4(3):159–161. https://doi.org/10.4103/2225-4110.136544
Khan I, Nisar M, Shah MR et al (2011) Anti-inflammatory activities of Taxusabietane A isolated from Taxus wallichiana Zucc. Fitoterapia 82(7):1003–1007. https://doi.org/10.1016/j.fitote.2011.06.003
Lange BM, Conner CF (2021) Taxanes and taxoids of the genus Taxus - a comprehensive inventory of chemical diversity. Phytochemistry 190:112829. https://doi.org/10.1016/j.phytochem.2021.112829
Li Z, Zhu Y, Li C et al (2018) Liraglutide ameliorates palmitate-induced insulin resistance through inhibiting the IRS-1 serine phosphorylation in mouse skeletal muscle cells. J Endocrinol Invest 41(9):1097–1102. https://doi.org/10.1007/s40618-018-0836
Nisar M, Khan I, Ahmad B, Ali I, Ahmad W, Choudhary MI (2008) Antifungal and antibacterial activities of Taxus wallichiana Zucc. J Enzyme Inhib Med Chem 23(2):256–260. https://doi.org/10.1080/14756360701505336
Qayum M, Nisar M, Shah MR et al (2012) Analgesic and anti-inflammatory activities of taxoids from Taxus wallichiana Zucc. Phytother Res 26(4):552–556. https://doi.org/10.1002/ptr.3574
Rehman K, Akash MS (2016) Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J Biomed Sci 23(1):87. https://doi.org/10.1186/s12929-016-0303-y
Sharma H, Garg M (2015) A review of traditional use, phytoconstituents and biological activities of Himalayan yew, Taxus wallichiana. J Integr Med 13(2):80–90. https://doi.org/10.1016/S2095-4964(15)60161-3
Shi QW, Li ZP, Zhao D, Gu JS, Kiyota H (2006) Isolation and structure revision of 10- deacetyltaxinine from the seeds of the Chinese yew, Taxus mairei. Nat Prod Res 20(1):47–51. https://doi.org/10.1080/14786410500111184
Singh R, Trivedi P, Bawankule DU, Ahmad A, Shanker K (2012) HILIC quantification of oenotheralanosterol A and B from Oenothera biennis and their suppression of IL-6 and TNF-α expression in mouse macrophages. J Ethnopharmacol 141(1):357–362. https://doi.org/10.1016/j.jep.2012.02.046
Son M, Wu J (2019) Egg white hydrolysate and peptide reverse insulin resistance associated with tumor necrosis factor-α (TNF-α) stimulated mitogen-activated protein kinase (MAPK) pathway in skeletal muscle cells. Eur J Nutr 58(5):1961–1969. https://doi.org/10.1007/s00394-018-1753-7
Wang C, Chen L, Sun Y, Guo W, Taouil AK, Ojima I (2022) Design, synthesis and SAR study of fluorine-containing 3rd-generation taxoids. Bioorg Chem 119:105578. https://doi.org/10.1016/j.bioorg.2021.105578
Xiao L, Lao WG, Tan Y, Qu X (2012) In vitro investigation of anti-diabetic effect of Taxus cuspidate extracts by ultrasound assisted method. Am J Chin Med 40(6):1205–1215. https://doi.org/10.1142/S0192415X12500899
Yang WX, Zhao ZG, Wang LH, Yu SJ, Liang ZS (2012) Control of hypertension in rats using volatile components of leaves of Taxus chinensis var. mairei. J Ethnopharmacol 141(1):309–313. https://doi.org/10.1016/j.jep.2012.02.036
Yu S, Guo X, Li G, Yang H, Zheng L, Sun Y (2021) Lymphocyte to high-density lipoprotein ratio but not platelet to lymphocyte ratio effectively predicts metabolic syndrome among subjects from rural China. Front Cardiovasc Med 8:583320. https://doi.org/10.3389/fcvm.2021.583320
Zatterale F, Longo M, Naderi J et al (2020) Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Front Physiol 10:1607. https://doi.org/10.3389/fphys.2019.01607
Acknowledgements
The authors are grateful to the Indian Council of Medical Research (ICMR), New Delhi under project GAP-234 for providing fellowship to first author and Director, CSIR-CIMAP, Lucknow, India for providing essential research facilities and support.
Funding
The study was financially supported by the Council of Scientific and Industrial Research (CSIR), New Delhi under project HCP-0007.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Authors declare no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Binwal, M., Babu, V., Israr, K.M. et al. Taxoids-rich extract from Taxus wallichiana alleviates high-fat diet-induced insulin resistance in C57BL/6 mice through inhibition of low-grade inflammation. Inflammopharmacol 31, 451–464 (2023). https://doi.org/10.1007/s10787-022-01119-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-022-01119-3