Author(s): Evgeny E. Buyko, Artem M. Guryev, Olga A. Kaidash, Kseniya I. Rovkina, Sergei V. Krivoshchekov, Elena A. Kiseleva, Olga Y. Rybalkina, Vladimir V. Ivanov, Konstantin S. Brazovskii, Mikhail V. Belousov

Email(s): mvb63@mail.ru

DOI: 10.52711/0974-360X.2026.00109   

Address: Evgeny E. Buyko1,2, Artem M. Guryev1, Olga A. Kaidash1, Kseniya I. Rovkina1, Sergei V. Krivoshchekov1, Elena A. Kiseleva3, Olga Y. Rybalkina1,3, Vladimir V. Ivanov1, Konstantin S. Brazovskii1,2, Mikhail V. Belousov1,2*
1Siberian State Medical University, Moskovsky Trakt, 2, 634050, Tomsk, Russia.
2Tomsk Polytechnic University, Lenina Ave., 30, 634050, Tomsk, Russia.
3Goldberg Research Institute of Pharmacology and Regenerative Medicine, Lenina Ave, 3, 634028, Tomsk, Russia.
*Corresponding Author

Published In:   Volume - 19,      Issue - 2,     Year - 2026


ABSTRACT:
This study aimed to elucidate the lipid-lowering mechanisms of L-rhamnopyranosyl-6-alkyl-D-galacturonan (L-RDG) – a polysaccharide from Betula pendula leaves – focusing on bile acid (BA) sequestration and modulation of cholesterol metabolism. L-RDG was extracted, purified, and structurally characterized (FTIR, GC, HPSEC). In vivo efficacy was assessed in 48 hyperlipidemic Wistar rats fed a high-fat diet (HFD) divided into: HFD control (n=12), HFD + L-RDG (3 g/100g diet, n=12), HFD + cholestyramine (2 g/100g diet, n=12), and normal diet control (n=12). BA-binding capacity was evaluated in vitro; molecular dynamics simulations explored L-RDG-BA interactions. Hepatic CYP7A1 and LDLR mRNA expression was analyzed via RT-PCR. L-RDG significantly reduced serum and hepatic lipid levels in HFD-fed rats. L-RDG reduced serum LDL-C by 42.1% (p<0.001) and hepatic triglycerides by 32.5% (p=0.005), matching cholestyramine (p>0.05). It demonstrated selective BA-binding (highest affinity for deoxycholic acid, p=0.004) and increased fecal BA excretion by 135.8% (p<0.001). Molecular simulations identified hydrogen bonding as the primary interaction mechanism. L-RDG upregulated CYP7A1 (p<0.001) and LDLR (p<0.001) expression. L-RDG demonstrates potent lipid-lowering activity through BA sequestration and modulation of cholesterol metabolism pathways. Its efficacy parallels cholestyramine, with dual mechanisms involving fecal BA excretion and transcriptional regulation of key hepatic genes. These findings position L-RDG as a promising natural candidate for dyslipidemia management, warranting further clinical evaluation. The actual work was carried out within the framework of state task number 056-00065-25-03.


Cite this article:
Evgeny E. Buyko, Artem M. Guryev, Olga A. Kaidash, Kseniya I. Rovkina, Sergei V. Krivoshchekov, Elena A. Kiseleva, Olga Y. Rybalkina, Vladimir V. Ivanov, Konstantin S. Brazovskii, Mikhail V. Belousov. Insights into the Hypolipidemic Action Mechanism of a Birch-derived Polysaccharide: From Molecular Dynamics to In vivo Efficacy. Research Journal of Pharmacy and Technology. 2026;19(2):756-3. doi: 10.52711/0974-360X.2026.00109

Cite(Electronic):
Evgeny E. Buyko, Artem M. Guryev, Olga A. Kaidash, Kseniya I. Rovkina, Sergei V. Krivoshchekov, Elena A. Kiseleva, Olga Y. Rybalkina, Vladimir V. Ivanov, Konstantin S. Brazovskii, Mikhail V. Belousov. Insights into the Hypolipidemic Action Mechanism of a Birch-derived Polysaccharide: From Molecular Dynamics to In vivo Efficacy. Research Journal of Pharmacy and Technology. 2026;19(2):756-3. doi: 10.52711/0974-360X.2026.00109   Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-2-38


REFERENCES: 
1.    Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP. Heart Disease and Stroke Statistics - 2020 Update: A Report From the American Heart Association. Circulation. 2020; 141(9): E139–596. Doi:10.1161/CIR.0000000000000757.
2.    Sridevi CH, Azreen A, Shekinah B, Sarika B, Priyamsha B. A Study on Assessment of Risk Factors, Prescribing Patterns, and Role of Statins in Coronary Artery Disease patients. Research Journal of Pharmacy and Technology. 2024; 17(3): 1342-5. Doi: 10.52711/0974-360X.2024.00211
3.    Sakhare SS, Chavan MA. Formulation aspects of Solid Dispersions of Simvastatin. Research Journal of Pharmacy and Technology. 2016; 9(8): 1023-1026. Doi: 10.5958/0974-360X.2016.00193.1
4.    Ranjitha R, Elango K, Devi Damayanthi R, Sahul Hameed Niyaz U. Formulation and Evaluation of Lovastatin Loaded Nanosponges for the treatment of Hyperlipidemia. Research Journal of Pharmacy and Technology. 2021; 14(11): 5653-0. Doi: 10.52711/0974-360X.2021.00983
5.    Al-Deresawi TS, Habeeb AA. The side effects of the Atorvastatin on liver of Hyperlipidemia Patients. Research Journal of Pharmacy and Technology. 2019; 12(9): 4310-4312. Doi: 10.5958/0974-360X.2019.00741.8
6.    Sowmya A, Ananthi T. Hypolipidemic activity of Mimosa pudica Linn on Butter Induced Hyperlipidemia in Rats. Asian J. Res. Pharm. Sci. 2011; 1(4): 123-126.
7.    Tomar H, Shukla VK, Arora K, Tomar N, Roy S, Kumar V. Curcuma longa: Review of Advances in Pharmacology. Research Journal of Pharmacy and Technology. 2012; 5(9): 1141-1144.
8.    Giri RK, Kanungo SK, Patro SK, Sahoo M, Panda DS. Hypolipidemic effect of prepared Polyherbal formulations in Wistar albino rats. Research Journal of Pharmacy and Technology. 2021; 14(8): 4314-0. Doi: 10.52711/0974-360X.2021.00749
9.    Zhang M, Xie Z, Gao W, Pu L, Wei J, Guo C. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats. Nutr Res. 2016; 1; 36(3): 271–9. Doi:10.1016/j.nutres.2015.11.019.
10.    Xu Y, Zhang X, Yan XH, Zhang JL, Wang LY, Xue H. Characterization, hypolipidemic and antioxidant activities of degraded polysaccharides from Ganoderma lucidum. Int J Biol Macromol. 2019; 15; 135: 706–16. Doi:10.1016/j.ijbiomac.2019.05.166
11.    Yang JX, Wu S, Huang XL, Hu XQ, Zhang Y. Hypolipidemic Activity and Antiatherosclerotic Effect of Polysaccharide of Polygonatum sibiricum in Rabbit Model and Related Cellular Mechanisms. Evidence-Based Complement Altern Med. 2015; 2015(1): 391065. Doi:10.1155/2015/391065
12.    Favier ML, Rémésy C, Moundras C, Demigné C. Effect of cyclodextrin on plasma lipids and cholesterol metabolism in the rat. Metabolism. 1995; 44(2): 200–6. Doi:10.1016/0026-0495(95)90265-1 
13.    Rastogi S, Pandey MM, Rawat AKS. Medicinal plants of the genus Betula - Traditional uses and a phytochemical–pharmacological review. Journal of Ethnopharmacology, 2015; 159: 62-83. Doi:10.1016/j.jep.2014.11.010
14.    Rovkina KI, Krivoshchekov SV, Guriev AM, Yusubov MS, Belousov MV. Development of methods for obtaining polysaccharides from birch leaves (Betula Pendula Roth., Betula pubescens Ehrh.). Khimiya Rastit Syr’ya. 2019; (3): 23–31. Doi:10.14258/jcprm.2019035420.
15.    Blakeney AB, Harris PJ, Henry RJ, Stone BA. A simple and rapid preparation of alditol acetates for monosaccharide analysis. Carbohydr Res. 1983; 113(2): 291–9. Doi:10.1016/0008-6215(83)88244-5)
16.    Golovchenko VV, Khlopin VA, Patova OA, Feltsinger LS, Bilan MI, Dmitrenok AS, et al. Pectin from leaves of birch (Betula pendula Roth.): Results of NMR experiments and hypothesis of the RG-I structure. Carbohydr Polym. 2022; 284: 119186. Doi:10.1016/j.carbpol.2022.119186.
17.    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–75. 
18.    Usov AI, Bilan MI, Klochkova NG. Polysaccharides of Algae 48. Polysaccharide Composition of Several Calcareous Red Algae: Isolation of Alginate from Corallina pilulifera P. Et R. (Rhodophyta, Corallinaceae). Bot Mar. 1995; 38(1–6): 43–52. https://doi.org/10.1515/botm.1995.38.1-6.43 
19.    Zhang GH, Cong AR, Xu GB, Li CB, Yang RF, Xia TA. An enzymatic cycling method for the determination of serum total bile acids with recombinant 3α-hydroxysteroid dehydrogenase. Biochem Biophys Res Commun. 2004; 326(1): 87–92. Doi:10.1016/j.bbrc.2004.11.005.
20.    Folch J, Lees M, Sloane GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226: 497–509. 
21.    Park SJ, Lee J, Patel DS, Ma H, Lee HS, Jo S et al. Glycan Reader is improved to recognize most sugar types and chemical modifications in the Protein Data Bank. Bioinformatics. 2017; 33(19): 3051–7. Doi:10.1093/bioinformatics/btx358.
22.    Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, et al.  GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1–2:19–25. Doi:10.1016/j.softx.2015.06.001 .
23.    Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Research. 2001; 29(9): e45. Doi:10.1093/nar/29.9.e45.
24.    Kačuráková M, Mathlouthi M. FTIR and laser-Raman spectra of oligosaccharides in water: characterization of the glycosidic bond. Carbohydrate research. 1996; 284(2): 145-157. Doi:10.1016/0008-6215(95)00412-2
25.    Gnanasambandam R, Proctor AJFC. Determination of pectin degree of esterification by diffuse reflectance Fourier transform infrared spectroscopy. Food chemistry. 2000; 68(3): 327-332. Doi:10.1016/S0308-8146(99)00191-0.
26.    Rini TDP, Sangande F, Agustini K, Bahtiar A. Identification and Analysis of Ardisia humilis as Potential Antihyperlipidemic by Network Pharmacology Followed by Molecular Docking. Research Journal of Pharmacy and Technology. 2024; 17(5): 2009-7. Doi: 10.52711/0974-360X.2024.00318
27.    Verma P, Sutrakar SK. Dyslipidemic and Antioxidant activity of Piper longum extract in hyperlipemic rats. Research Journal of Pharmacy and Technology. 2015; 8(12): 1609-1614. Doi: 10.5958/0974-360X.2015.00288.7
28.    Jyoti S, Kumar PP, Kaur CD. Effect of Quisqualis indica extract on cholesterol diet induced hyperlipidemia in rats. Research J. Pharmacology and Pharmacodynamics. 2013; 5(6): 317-320.
29.    Samal PK. Assessment of Hypolipidemic Effect of Ardisia solanacea in high fat diet induced rats. Research J. Pharmacology and Pharmacodynamics. 2013; 5(3): 147-150.
30.    Ebrahimi Y, Hasanvand A, Valibeik A, Ebrahimi F, Abbaszadeh S. Natural Antioxidants and Medicinal Plants Effective on Hyperlipidemia. Research Journal of Pharmacy and Technology. 2019; 12(3): 1457-1462. Doi: 10.5958/0974-360X.2019.00242.7
31.    Xu Z, Deng P, Tang S, Li J. Fluorescent molecularly imprinted polymers based on 1, 8-naphthalimide derivatives for efficiently recognition of cholic acid. Materials Science and Engineering: C. 2016; 58: 558-567. Doi:10.1016/j.msec.2015.08.060
32.    Alagumanivasagam G, Veeramani P. A review on medicinal plants with hypolipidemic activity. International Journal of Pharmacy and Analytical Research. 2015; 4(2): 129-34. Doi:10.61096/ijpar.v4.iss2.2015.129-134.
33.    Cariello M, Piglionica M, Gadaleta RM, Moschetta A. The enterokine fibroblast growth factor 15/19 in bile acid metabolism. Bile Acids and Their Receptors. 2019; 73-93.  Doi:10.1007/164_2019_235.
34.    Chiang JY, Ferrell JM. Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis. Liver research. 2020; 4(2): 47-63. Doi:10.1016/j.livres.2020.05.001.


Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.52711/0974-360X 

1.3
2021CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank

Journal Policies & Information


Recent Articles




Tags


Not Available