Abstract
The current study aimed to investigate statin (HMG-CoA reductase inhibitor) mimic and free radical scavenging potential of phytoconstituents of the methanolic extract of Prosopis cineraria pod by in vitro, in silico, and in vivo assessments. The phytoconstituents of the chosen extract were screened out by using the LCMS and GCMS analyses. The in vitro assessment of the extract shown 78.3% (IC50 1.7786 μg/ml) inhibition of HMG-CoA reductase as compared with pravastatin (positive control). The administration of the extract made considerable (P ≤ 0.001) improvements in lipid profile, atherogenic indices and oxidative stress. The in silico studies of molecular docking revealed significant binding energy of key identified compounds obtained in test extracts, i.e., cinnerin C, prosogerin A, prosogerin B, prosopine, spicegrin, quercetin, alpha-d-mannofuranoside, methyl, undecanoic acid and l-gala-l-iodo-octose with target enzymes. The quercetin showed significant interaction with the target protein (HMG-CoA reductase) compared to atorvastatin with − 8.4 kcal/mol binding energy. Further, validations of ligands-protein interactions were examined by molecular dynamics at 100 ns through RSMD, RSMF, SASA and MMPBSA, which revealed the significant interactions of quercetin and atorvastatin with HMGCR. ADMET predictions shown significant pharmacokinetic profiles of phytoconstituents. The phytoconstituents of Prosopis cineraria pod of methanolic extract contains potent phytochemicals like quercetin which may be concerned to the inhibition of HMG-CoA reductase and free radical scavenging activities.
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References
Abell L, Levy B, Kendall E, Brodie B (1952) A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 1952(195):357–366
Ambade VN, Sharma Y, Somani B (2017) Methods for estimation of blood glucose: a comparative evaluation. Med J Armed Forces India 54(2):131–133. https://doi.org/10.1016/s0377-1237(17)30502-6
Banach M, Surma S, Reiner Z, Katsiki N, Penson PE, Fras Z, Sahebkar A, Paneni F, Rizzo M, Kastelein J (2022) Personalized management of dyslipidemias in patients with diabetes—it is time for a new approach (2022). Cardiovasc Diabetol 21(1):1–10. https://doi.org/10.1186/s12933-022-01684-5
Bhardwaj S, Bhattacharjee J, Bhatnagar MK, Tyagi S (2013). Atherogenic index of plasma, castelli risk index and atherogenic coeficent—new parameters in assessing cardiovascular risk. Int J Pharm Biol Sci 3(3):359–364. https://www.ijpbs.com/ijpbsadmin/upload/ijpbs_526938e855804.pdf
Busher JT (1990) Serum albumin and globulin. Clinical methods: the history, physical, and laboratory examinations, pp 497–499
Chugh A, Sehgal I, Khurana N, Verma K, Rolta R, Vats P, Salaria D, Fadare OA, Awofisayo O, Verma A, Phartyal R, Verma M (2023) Comparative docking studies of drugs and phytocompounds for emerging variants of SARS-CoV-2. 3 Biotech 13(1):1–17. https://doi.org/10.1007/s13205-022-03450-6
Hirano T, Nohtomi K, Koba S, Muroi A, Ito Y (2008) A simple and precise method for measuring HDL-cholesterol subfractions by a single precipitation followed by homogenous HDL-cholesterol assay. J Lipid Res 49(5):1130–1136. https://doi.org/10.1194/jlr.D700027-JLR200
Isah M, Rosdi RA, Wan Abdul Wahab W-N-A, Abdulla H, Sul’ain MD, Ishak WRW (2023) Phytoconstituents and biological activities of Melaleuca cajuputi Powell: a scoping review. J Appl Pharm Sci 13(01):10–23. https://doi.org/10.7324/japs.2023.130102
Jaipal N, Ram H, Charan J, Dixit A, Singh G, Singh BP, Kumar A, Panwar A (2022) HMG-CoA reductase inhibition medicated hypocholesterolemic and antiatherosclerotic potential of phytoconstituents of an aqueous pod extract of Prosopis cineraria (L.) Druce: in silico, in vitro, and in vivo studies. Efood 3(6):1–16. https://doi.org/10.1002/efd2.42
Kabir MT, Tabassum N, Uddin MS, Aziz F, Behl T, Mathew B, Rahman MH, Akter R, Rauf A, Aleya L (2021) Therapeutic potential of polyphenols in the management of diabetic neuropathy. Evid Based Complement Altern Med 2021:1–20. https://doi.org/10.1155/2021/9940169
Katiyar C, Kanjilal S, Gupta A, Katiyar S (2012) Drug discovery from plant sources: an integrated approach. AYU 33(1):10–19. https://doi.org/10.4103/0974-8520.100295
Khan TJ, Ahmed YM, Zamzami MA, Mohamed SA, Khan I, Baothman OAS, Mehanna MG, Yasir M (2018) Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats. Sci Rep 8(1):1–9. https://doi.org/10.1038/s41598-017-19013-2
Klotzsch SG, McNamara JR (1990) Triglyceride measurements: a review of methods and interferences. Clin Chem 36(9):1605–1613. https://doi.org/10.1038/ncomms1953
Laka K, Makgoo L, Mbita Z (2022) Cholesterol-lowering phytochemicals: targeting the mevalonate pathway for anticancer interventions. Front Genet 13(March):1–22. https://doi.org/10.3389/fgene.2022.841639
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275. https://doi.org/10.1016/0304-3894(92)87011-4
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47(3):469–474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
Marques LR, Diniz TA, Antunes BM, Rossi FE, Caperuto EC, Lira FS, Gonçalves DC (2018) Reverse cholesterol transport: molecular mechanisms and the non-medical approach to enhance HDL cholesterol. Front Physiol 9(May):1–11. https://doi.org/10.3389/fphys.2018.00526
Mitchell RJ (1973) Improved method for specific determination of creatinine in serum and urine. Clin Chem 19(4):408–410. https://doi.org/10.1093/clinchem/19.4.408
Nurmaylindha V, Widodo GP, Herowati R (2020) Molecular docking analysis of Leucaena leucocephala and Trigonella foenum-graecum chemical constituents on antidiabetic macromolecular targets and prediction of the pharmacokinetic profiles. AIP Conf Proc. https://doi.org/10.1063/5.0006279
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358
Olamoyegun M, Oluyombo R, Asaolu S (2016) Evaluation of dyslipidemia, lipid ratios, and atherogenic index as cardiovascular risk factors among semi-urban dwellers in Nigeria. Ann Afr Med 15(4):194–199. https://doi.org/10.4103/1596-3519.194280
Othman ZA, Ghazali WSW, Noordin L, Yusof NAM, Mohamed M (2020) Phenolic compounds and the anti-atherogenic effect of bee bread in high-fat diet-induced obese rats. Antioxidants 9(1):1–12. https://doi.org/10.3390/antiox9010033
Pandey V, Patel S, Danai P, Yadav G, Kumar A (2023) Phyto-constituents profiling of Prosopis cineraria and in vitro assessment of antioxidant and anti-ulcerogenicity activities. Phytomedicine plus 3(3):100452. https://doi.org/10.1016/j.phyplu.2023.100452
Panth N, Paudel KR, Parajuli K (2016) Reactive oxygen species: a key hallmark of cardiovascular disease. Adv Med 2016:1–12. https://doi.org/10.1155/2016/9152732
Parasuraman S, Raveendran R, Kesavan R (2010) Blood sample collection in small laboratory animals. J Pharmacol Pharmacother 1(2):87–93. https://doi.org/10.4103/0976-500X.72350
Priyanka R, Ashok P, Karishma S, Heera R (2022) Atherosclerotic plaque regression and HMG-CoA reductase inhibition potential of curcumin: an integrative omics and in-vivo study. J Appl Biol Biotechnol 10(01):129–135. https://doi.org/10.7324/jabb.2021.100116
Rahman MF, Siddiqui MKJ, Jamil K (2000) Acid and alkaline phosphatase activities in a novel phosphorothionate (Rpr-11) treated male and female rats. Evidence of dose and time-dependent response. Drug Chem Toxicol 23(3):497–509. https://doi.org/10.1081/DCT-100100131
Ram H, Kumar P, Purohit A, Kashyap P, Kumar S, Kumar S, Singh G, Alqarawi AA, Hashem A, Abd-Allah EF, Al-Arjani ABF, Singh BP (2021) Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans. Nutr Metab 18(1):1–17. https://doi.org/10.1186/s12986-021-00547-2
Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56–63. https://doi.org/10.1093/ajcp/28.1.56
Riyad P, Purohit A, Sen K, Panwar A, Ram H (2023) HMG-CoA reductase inhibition mediated hypocholesterolemic potential of myricetin and quercetin: in-silico and in-vivo studies. CYTA J Food 21(1):115–125. https://doi.org/10.1080/19476337.2022.2162976
Salvamani S, Gunasekaran B, Shukor MY, Shaharuddin NA, Sabullah MK, Ahmad SA (2016) Anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities of Amaranthus viridis leaf extract as a potential treatment for hypercholesterolemia. Evid Based Complement Altern Med 2016:1–10. https://doi.org/10.1155/2016/8090841
Saran RP, Purohit A, Ram H (2016) A comparative patho-physiological study of diclofenac and meloxicam induced toxicity in Gallus domestics. Am J Pharm Health Res 4(11):71–84
Sargsyan K, Grauffel C, Lim C (2017) How molecular size impacts RMSD applications in molecular dynamics simulations. J Chem Theory Comput 13(4):1518–1524. https://doi.org/10.1021/acs.jctc.7b00028
Shin J, Seol I, Son C (2010) Interpretation of animal dose and human equivalent dose for drug development. J Korean Orient Med 31(3):1–7
Sözmen EY, Sözmen B, Delen Y, Onat T (2001) Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may implicate poor glycemic control. Arch Med Res 32(4):283–287. https://doi.org/10.1016/S0188-4409(01)00285-5
Tas S, Tas B, Bassalat N, Jaradat N (2018) In-vivo, hypoglycemic, hypolipidemic and oxidative stress inhibitory activities of Myrtus communis L. Fruits hydroalcoholic extract in normoglycemic and streptozotocin-induced diabetic rats. Biomed Res (India) 29(13):2727–2734. https://doi.org/10.4066/biomedicalresearch.29-18-708
Tian S, Wang J, Li Y, Li D, Xu L, Hou T (2015) The application of in silico drug-likeness predictions in pharmaceutical research. Adv Drug Deliv Rev 86:2–10. https://doi.org/10.1016/j.addr.2015.01.009
Toledo-Ibelles P, Mas-Oliva J (2018) Antioxidants in the fight against atherosclerosis: is this a dead end? Curr Atheroscler Rep 20(7):1–12. https://doi.org/10.1007/s11883-018-0737-7
Umeda R, Takanari H, Ogata K, Matsumoto S, Kitano T, Ono K, Tokumarukanari O, Ogata K, Matsumoto S, Kitano T, Ono K, Tokumaru O (2019) Direct free radical scavenging effects of water soluble HMG-CoA reductase inhibitors. J Clin Biochem Nutr 64(June):20–26. https://doi.org/10.3164/jcbn.18
Vettor R, Serra R (2018) Management of hypercholesterolemia, appropriateness of therapeutic approaches and new drugs in patients with high cardiovascular risk. Ital J Med 12(3):203–212. https://doi.org/10.4081/itjm.2018.1062
Villarreal-García D, Nair V, Cisneros-Zevallos L, Jacobo-Velázquez DA (2016) Plants as biofactories: postharvest stress-induced accumulation of phenolic compounds and glucosinolates in broccoli subjected to wounding stress and exogenous phytohormones. Front Plant Sci 7(February):1–11. https://doi.org/10.3389/fpls.2016.00045
Wang C, Greene D, Xiao L, Qi R, Luo R (2018) Recent developments and applications of the MMPBSA method. Front Mol Biosci 4(Jan):1–18. https://doi.org/10.3389/fmolb.2017.00087
Weydert CJ, Cullen JJ (2010) Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 5(1):51–66. https://doi.org/10.1038/nprot.2009.197
Wybenga DR, Di Giorgio J, Pileggi VJ (1971) Manual and automated methods for urea nitrogen measurement in whole serum. Clin Chem 17(9):891–895. https://doi.org/10.1093/clinchem/17.9.891
Xiao JF, Zhou B, Ressom HW (2012) Metabolite identification and quantitation in LC–MS/MS-based metabolomics. TrAC Trends Anal Chem 32:1–14. https://doi.org/10.1016/j.trac.2011.08.009
Yang X, Li Y, Li Y, Ren X, Zhang X, Hu D, Gao Y, Xing Y, Shang H (2017) Oxidative stress-mediated atherosclerosis: mechanisms and therapies. Front Physiol 8(Aug):1–16. https://doi.org/10.3389/fphys.2017.00600
Zhou Y, Wu WH, Zhao QB, Wang XY, Bao B (2015) Inhibition of HMG-CoA reductase by MFS, a purified extract from the fermentation of marine fungus Fusarium solani FG319, and optimization of MFS production using response surface methodology. Chin J Nat Med 13(5):346–354. https://doi.org/10.1016/S1875-5364(15)30025-X
Acknowledgements
We want to acknowledge the kind cooperation of AIIMS, Jodhpur, for the HMG-CoA reductase inhibition assay and the Department of Zoology for providing essential support for this study.
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HR and BPS—conceptualization, original drafting and supervision; NJ and PK—in vivo experimentations; JKC—in vitro study PK, and SC—in silico investigations; GS, AP and JC—editing, AP—molecular dynamics, SC and PK—phytochemistry.
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Jaipal, N., Ram, H., Kumar, P. et al. Statins mimic and free radical scavenging potential of phytoconstituents of methanolic pod extract of Prosopis cineraria (L.) Druce. Vegetos (2023). https://doi.org/10.1007/s42535-023-00677-3
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DOI: https://doi.org/10.1007/s42535-023-00677-3