Author(s):
Chase Yost, Mark Vincent C. Dela Cerna, Savita Chaurasia
Email(s):
schaurasia@bellarmine.edu , mdelacerna@georgiasouthern.edu
DOI:
10.52711/0974-360X.2025. 00860
Address:
Chase Yost1, Mark Vincent C. Dela Cerna2, Savita Chaurasia1*
1Biochemistry and Molecular Biology Program, Department of Chemistry, Bellarmine University, Louisville, KY 40205, USA.
2Department of Biochemistry, Chemistry and Physics, Georgia Southern University, Savannah, GA 31419, USA.
*Corresponding Author
Published In:
Volume - 18,
Issue - 12,
Year - 2025
ABSTRACT:
Protein tyrosine phosphatase 1B (PTP1B) is a therapeutic target for diabetes, obesity, and cancers. Despite several promising inhibitors, none have progressed to the clinic, emphasizing the need for continued identification of novel inhibitors. This study demonstrates the potential of Eriodictyon californicum ethanolic leaf extract (ECE) as a source of PTP1B inhibitors. Through in vitro assays, we observed a strong, dose-dependent inhibition of PTP1B by ECE, ranging from 21.3 ± 8.7% at 1.3 µg/ml to 101.8 ± 1.9% at 50 µg/ml with an IC50 of 4.19 µg/ml. Preliminary kinetic analysis revealed an apparent mixed inhibition, with changes in both Vmax and Km values. Molecular docking of known bioactive compounds in the plant showed modest binding energies. Most compounds, particularly flavonones, are predicted to bind to the catalytic site of PTP1B, exhibiting potential hydrogen bonding and hydrophobic interactions with critical active site residues. This study is the first to demonstrate the inhibitory potential of ECE against PTP1B, positioning E. californicum as a promising source of PTP1B inhibitors, further expanding the role of nature-based therapies for diseases associated with PTP1B dysregulation.
Cite this article:
Chase Yost, Mark Vincent C. Dela Cerna, Savita Chaurasia. Eriodictyon californicum Extract Inhibits Therapeutically Relevant Protein Tyrosine Phosphatase 1B. Research Journal Pharmacy and Technology. 2025;18(12):5949-7. doi: 10.52711/0974-360X.2025. 00860
Cite(Electronic):
Chase Yost, Mark Vincent C. Dela Cerna, Savita Chaurasia. Eriodictyon californicum Extract Inhibits Therapeutically Relevant Protein Tyrosine Phosphatase 1B. Research Journal Pharmacy and Technology. 2025;18(12):5949-7. doi: 10.52711/0974-360X.2025. 00860 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-12-50
REFERENCES:
1. Cohen P, Cross D, Jänne PA. Kinase drug discovery 20 years after imatinib: progress and future directions. Nature Reviews Drug Discovery. 2021 May 20. 551-569. doi: 10.1038/s41573-021-00195-4
2. Xie Z, Yang X, Duan Y, Han J, Liao C. Small-Molecule Kinase Inhibitors for the Treatment of Nononcologic Diseases. Journal of Medicinal Chemistry. 2021 Jan 22. 64, 3, 1283-1345. doi: 10.1021/acs.jmedchem.0c01511
3. Turdo A, D’Accardo C, Glaviano A, Porcelli G, Colarossi C, Colarossi L, Mare M, Faldetta N, Modica C, Pistone G, Bongiorno MR, Todaro M, Stassi G. Targeting Phosphatases and Kinases: How to Checkmate Cancer. Frontiers in Cell and Developmental Biology. 2021 Oct 27. 9:690306. doi: 10.3389/fcell.2021.690306
4. Teimouri M, Hosseini H, ArabSadeghabadi Z, Babaei-Khorzoughi R, Gorgani-Firuzjaee S, Meshkani R. The role of protein tyrosine phosphatase 1B (PTP1B) in the pathogenesis of type 2 diabetes mellitus and its complications. Journal of Physiology and Biochemistry. 2022 Jan 6. 78(2):307-322. doi: 10.1007/s13105-021-00860-7
5. Vieira MN, Lyra e Silva NM, Ferreira ST, De Felice FG. Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer's Therapy? Frontiers in Aging Neuroscience. 2017 Jan 31. 9:7. doi: 10.3389/fnagi.2017.00007
6. Wiede F, Lu KH, Du X, Zeissig MN, Xu R, Goh PK, Xirouchaki CE, Hogarth SJ, Greatorex S, Sek K, Daly RJ, Beavis PA, Darcy PK, Tonks NK, Tiganis T. PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity. Cancer Discovery. 2022 Mar 1. 12(3):752-773. doi: 10.1158/2159-8290.CD-21-0694
7. Jadhav GB, Athare CL, Saudagar RB. Synthesis of Novel Protein Tyrosine Phosphatases 1b inhibitors 2, 5-disubsituted oxadiazole. Asian Journal of Pharmacy and Technology. 2014 Apr 28. 4(2):43-49
8. Liu R, Mathieu C, Berthelet J, Zhang W, Dupret JM, Rodrigues Lima F. Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives. International Journal of Molecular Sciences. 2022 Jun 24. 23(13):7027. doi: 10.3390/ijms23137027
9. Bai X, Fan W, Luo Y, Liu Y, Zhang Y, Liao X. Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing. Molecules. 2022 Nov 15. 27(22):7896. doi: 10.3390/molecules27227896
10. Kapojos MM, Walean M, Abdjul DB. PTP1B Inhibitors from Indonesian Plants and Its Structure-Activity Relationship: A Review. Tropical Journal of Natural Product Research. 2024 Jun 5. 8(3):6480–6486. doi: 10.26538/tjnpr/v8i3.2
11. Kapojos MM, Abdjul DB, Yamazaki H, Yagi A, Uchida R. Screening of Indonesian Edible Plants for Bioactive Constituents and a New Protein Tyrosine Phosphatase 1B Inhibitory Acylbenzene Derivative from Leaves of Indonesian Syzygium polyanthum. Chemical and Pharmaceutical Bulletin. 2020. 68(9):903-906. doi: 10.1248/cpb.c20-00457
12. Pitschmann A, Zehl M, Atanasov AG, Dirsch VM, Heiss E, Glasl S. Walnut leaf extract inhibits PTP1B and enhances glucose-uptake in vitro. Journal of Ethnopharmacology. 2014 Mar 28. 152(3):599-602. doi: 10.1016/j.jep.2014.02.017
13. Zhang Y, Liu H, Lv T, Xiao M, Gao G. Protein Tyrosine Phosphatase 1B Inhibitors of Pueraria lobata Based on the Spectrum-Effect Relationship by Q-Marker Selection. Molecules. 2024 Jun 8. 29(12):2731. doi: 10.3390/molecules29122731
14. Rasoanaivo P, Wright CW, Willcox ML, Gilbert B. Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malaria Journal. 2011 Mar 15. 10 Suppl 1(Suppl 1):S4. doi: 10.1186/1475-2875-10-S1-S4
15. Singh N, Zalma K, Khatri M, Ven P, Singh A. Screening and Validation of Natural Products for Drug Discovery: Key Points and Approaches. Asian Journal of Pharmaceutical Research. 2024 Apr 20. 14(2):162-168. doi: 10.52711/2231-5691.2024.00027
16. Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K. Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. International Journal of Molecular Sciences. 2018 May 25. 19(6):1578. doi: 10.3390/ijms19061578
17. Kansal P, Shukla A. Anti-diabetic and Anti-inflammatory activities of Various Green Solvent Extracts of Ficus drupacea Leaves. 2025 Jan 28. 18(2):619-624. doi: 10.52711/0974-360X.2025.00092
18. Amari S, Karbab A, Charef N, Arrar L. Antioxidant, Antimicrobial activities and Phytochemical analysis of Erica arborea L. stem extracts. Research Journal of Pharmacy and Technology. 2025 Jan 28. 18(2):757-764. doi: 10.52711/0974-360X.2025.00112
19. Khare E, Sharma A, Chowdhury A, Narwariya SS. Potential of Natural Products for Chemoprevention of Breast Cancer. Research Journal of Pharmacognosy and Phytochemistry. 2023 Aug 25. 2023 Aug 25. doi: 10.52711/0975-4385.2023.00048
20. Yadav AR, Mohite SK. Anticancer Activity of Psidium guajava Leaf Extracts on Breast Cancer Cell Line. Research Journal of Pharmaceutical Dosage Forms and Technology. 2020 Jul 20. 12(4):298-300. doi: 10.5958/0975-4377.2020.00049.X
21. Anderson M. Tending the Wild: Native American Knowledge and the Management of California's Natural Resources. University of California Press. 2005.
22. Moerman D. Native American Medicinal Plants: And Ethnobotanical Dictionary. Timber Press. 2009.
23. Timbrook J. Chumash Ethnobotany: Plant Knowledge Among the Chumash People of Southern California. Heyday Books. 2007.
24. Fletcher JN, Kinghorn AD, Slack JP, McCluskey TS, Odley A, Jia Z. In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31. Journal of Agricultural and Food Chemistry. 2011 Nov 8. 59(24):13117-21. doi: 10.1021/jf204359q
25. Ley JP, Krammer G, Reinders G, Gatfield IL, Bertram HJ. Evaluation of bitter masking flavanones from Herba Santa (Eriodictyon californicum (H. and A.) Torr., Hydrophyllaceae). Journal of Agricultural and Food Chemistry. 2005 Jun 22. 53(15):6061-6. doi: 10.1021/jf0505170
26. United States Food and Drug Administration, Module 19. Botanicals Generally Recognized As Safe. https://s10.lite.msu.edu/res/msu/botonl/b_online/library/dr-duke/gras.htm [Accessed April 15, 2023]. 2022.
27. Mödinger Y, Schön C, Wilhelm M, Pickel C, Grothe T. A Food Supplement with Antioxidant Santa Herba Extract Modulates Energy Metabolism and Contributes to Weight Management. Journal of Medicinal Food. 2021 Nov 17. 24(11): 1235-1242. doi: 10.1089/jmf.2021.0016
28. Fischer W, Currais A, Liang Z, Pinto A, Maher P. Old age-associated phenotypic screening for Alzheimer's disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa. Redox Biology. 2019 Feb. 21:101089. doi: 10.1016/j.redox.2018.101089
29. Liu YL, Ho DK, Cassady JM, Cook VM, Baird WM. Isolation of potential cancer chemopreventive agents from Eriodictyon californicum. Journal of Natural Products. 1992 March 1. 55(3):357-63. doi: 10.1021/np50081a012
30. Maher P, Fischer W, Liang Z, Soriano-Castell D, Pinto AFM, Rebman J, Currais A. The Value of Herbarium Collections to the Discovery of Novel Treatments for Alzheimer's Disease, a Case Made With the Genus Eriodictyon. Frontiers in Pharmacology. 2020 March 9. 11:208. doi: 10.3389/fphar.2020.00208
31. Richards A, Chaurasia S. Antioxidant Activity and Reactive Oxygen Species (ROS) Scavenging Mechanism of Eriodictyon californicum, an Edible Herb of North America. Journal of Chemistry. 2022 Oct 4. doi: 10.1155/2022/6980121
32. Shin SY, Yong Y, Hong DS, Lee DH, Lee DH, Lee YH. Identification of flavonoids from Eriodictyon californicum and their cytotoxicity against HCT116 colon cancer cells. Journal of the Korean Society for Applied Biological Chemistry. 2015 Jan 24. 58:77-81. doi:10.1007/s13765-015-0015-0
33. Choy MS, Li Y, Machado LESF, Kunze MBA, Connors CR, Wei X, Lindorff-Larsen K, Page R, Peti W. Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery. Molecular Cell. 2017 Feb 16. 65(4):644-658.e5. doi: 10.1016/j.molcel.2017.01.014
34. Fang L, Cao J, Duan L, Tang Y, Zhao Y. Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities of Schinsandra chinensis (Turcz.) Baill. Journal of Functional Foods. 2014 July. 9:264-270. doi: 10.1016/j.jff.2014.04.017
35. Pawar RP, Rohane SH. Role of Autodock vina in PyRx Molecular Docking. Asian Journal of Research in Chemistry. 2020 Dec 16. 14(2):132-134. doi: 10.5958/0974-4150.2021.00024.9
36. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling. 2021 July 19. 61(8):3891-3898. doi: 10.1021/acs.jcim.1c00203
37. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry. 2010 Jan 30. 31(2):455-61. doi: 10.1002/jcc.21334
38. Hofmann J, Fayez S, Scheiner M, Hoffmann M, Oerter S, Appelt-Menzel A, Maher P, Maurice T, Bringmann G, Decker M. Sterubin: Enantioresolution and Configurational Stability, Enantiomeric Purity in Nature, and Neuroprotective Activity in Vitro and in Vivo. Chemistry A European Journal. 2020 May 2. 26:7299-7308. doi: 10.1002/chem.202001264
39. Wang M, Zhao J, Avula B, Lee J, Upton R, Khan IA. Chemical characterization and quantitative determination of flavonoids and phenolic acids in yerba santa (Eriodictyon spp.) using UHPLC/DAD/Q-ToF. Journal of Pharmaceutical and Biomedical Analysis. 2023 Sep 20. 234. doi: 10.1016/j.jpba.2023.115570
40. Chirgadze YN, Battaile KP, Likhachev IV, Balabaev NK, Gordon RD, Romanov V, Lin A, Karisch R, Lam R, Ruzanov M, Brazhnikov EV, Pai EF, Neel BG, Chirgadze NY. Signal transfer in human protein tyrosine phosphatase PTP1B from allosteric inhibitor P00058. Journal of Biomolecular Structure and Dynamics. 2022 Oct 27. 40(24):13823-13832. doi: 10.1080/07391102.2021.1994879
41. Iversen LF, Andersen HS, Möller KB, Olsen OH, Peters GH, Branner S, Mortensen SB, Hansen TK, Lau J, Ge Y, Holsworth DD, Newman MJ, Möller NPH. Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases. Biochemistry. 2001 Nov 15. 40(49):14812-20. doi: 10.1021/bi011389l
42. Newman DJ, Cragg GM. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. Journal of Natural Products. 2020 Mar 12. 83(3):770-803. doi: 10.1021/acs.jnatprod.9b01285
43. Pemovska T, Bigenzahn JW, Superti-Furga G. Recent advances in combinatorial drug screening and synergy scoring. Current Opinion in Pharmacology. 2018 Oct. 42:102-110. doi: 10.1016/j.coph.2018.07.008
44. Caesar LK, Cech NB. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Natural Product Reports. 2019 Jun 19. 36(6):869-888. doi: 10.1039/c9np00011a
45. Sachan AK, Rao ChV, Sachan NK. Determination of Antidiabetic Potential in Crude Extract of Caesalpinia bonducella Wild on normal and Streptozotocin Induced Diabetic Rats. Research Journal of Pharmacy and Technology. 2019 Sep 16. 13(2):857-861. doi: 10.5958/0974-360X.2020.00162.6
46. Rasyid SA, Bintang M, As’ad S, Miskad U, Minhajat R, Surya RA. Qualitative Phytochemical Screening and Effectiveness Analysis of Batissa violacea celebensis Martens 1897 Crude extract against Antioxidant and Cytotoxic Activity. Research Journal of Pharmacy and Technology. 2021 Jun 9. 15(1):263-269. doi: 10.52711/0974-360X.2022.00043
47. Rampadarath A, Balogun FO, Pillay C, Sabiu S. Identification of Flavonoid C-Glycosides as Promising Antidiabetics Targeting Protein Tyrosine Phosphatase 1B. Journal of Diabetes Research. 2022 Jun 24. 2022:6233217. doi: 10.1155/2022/6233217
48. Proença C, Freitas M, Ribeiro D, Sousa JLC, Carvalho F, Silva AMS, Fernandes PA, Fernandes E. Inhibition of protein tyrosine phosphatase 1B by flavonoids: A structure - activity relationship study. Food and Chemical Toxicology. 2018 Jan. 111:474-481. doi: 10.1016/j.fct.2017.11.039
49. Salinas-Arellano E, Pérez-Vásquez A, Rivero-Cruz I, Torres-Colin R, González-Andrade M, Rangel-Grimaldo M, Mata R. Flavonoids and Terpenoids with PTP-1B Inhibitory Properties from the Infusion of Salvia amarissima Ortega. Molecules. 2020 Aug 1. 25(15):3530. doi: 10.3390/molecules25153530
50. Song YH, Uddin Z, Jin YM, Li Z, Curtis-Long MJ, Kim KD, Cho JK, Park KH. Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa. Journal of Enzyme Inhibition and Medicinal Chemistry. 2017 May 3. 32(1):1195-1202. doi: 10.1080/14756366.2017.1368502
51. To DC, Hoang DH, Tran MH, Pham MQ, Huynh NT, Nguyen PH. PTP1B Inhibitory Flavonoids From Orthosiphon stamineus Benth. and Their Growth Inhibition on Human Breast Cancer Cells. Natural Product Communications. 2020 Jan 17. doi: 10.1177/1934578X19899517
52. Choi JS, Ali MY, Jung HA, Oh SH, Choi RJ, Kim EJ. Protein tyrosine phosphatase 1B inhibitory activity of alkaloids from Rhizoma Coptidis and their molecular docking studies. Journal of Ethnopharmacology. 2015 Aug 2. 171:28-36. doi: 10.1016/j.jep.2015.05.020
53. Purwanti E, Hermanto FE, Prihanta W, Permana TI. Unfolding Biomechanism of Dolichos lablab Bean as A Dietary Supplement in Type 2 Diabetes Mellitus Management through Computational Simulation. Research Journal of Pharmacy and Technology. 2022 Jan 4. 15(7):3233-3240. doi: 10.52711/0974-360X.2022.00542
54. Ali MY, Jannat S, Rahman MM. Investigation of C-glycosylated apigenin and luteolin derivatives' effects on protein tyrosine phosphatase 1B inhibition with molecular and cellular approaches. Computational Toxicology. 2021 Feb. 17:100141. doi: 10.1016/j.comtox.2020.100141
55. Jiang CS, Liang LF, Guo YW. Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades. Acta Pharmacologica Sinica. 2012 Sep 3. 33(10):1217-45. doi: 10.1038/aps.2012.90
56. Saifudin A, Kadota S, Tezuka Y. Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal medicines and constituents of Cinnamomum burmannii and Zingiber aromaticum. Journal of Natural Medicine. 2012 May 30. 67(2):264-70. doi: 10.1007/s11418-012-0674-7
57. Yang SJ, Paudel P, Shrestha S, Seong SH, Jung HA, Choi JS. In vitro protein tyrosine phosphatase 1B inhibition and antioxidant property of different onion peel cultivars: A comparative study. Food Science and Nutrition. 2018 Dec 15. 7(1):205-215. doi: 10.1002/fsn3.863
58. Zhao BT, Nguyen DH, Le DD, Choi JS, Min BS, Woo MH. Protein tyrosine phosphatase 1B inhibitors from natural sources. Archives of Pharmacal Research. 2018 Dec 6. 41(2):130-161. doi: 10.1007/s12272-017-0997-8