Effects of Physalis angulata L. Fruit Extract on Endothelial Cell Migration and VEGF Concentration during Wound Healing under Hyperglycemic Conditions: An in vitro Study
Main Article Content
Abstract
Diabetes mellitus cases and complications, including difficult-to-heal wounds, are increasing worldwide. Diabetic wounds frequently exhibit impaired angiogenesis due to hyperglycemia, which disrupts many factors that promote angiogenesis, including the release of vascular endothelial growth factor (VEGF). Physalis angulata L, an herb in the Solanaceae family, is used as a herbal medicine for many ailments, such as treating wounds. The fruit of P. angulata is rich in lupeol, a compound that can enhance wound healing by upregulating the expression of certain growth factors. This study aimed to determine the effect of P. angulata fruit extract on endothelial cell migration and VEGF concentration in wound healing in hyperglycemic endothelial cell cultures. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (22 mM/dL) for 6 and 24 h with or without 0.025%, 0.05%, and 0.1% concentrations of P. angulata fruit extract. Cell migration was examined in HUVECs by scratching and measuring the distance. VEGF concentration was measured using enzyme-linked immunosorbent assay methods. P. angulata fruit extract at a concentration of 0.025% for 24 h significantly stimulated cell migration and VEGF concentration in HUVECs exposed to hyperglycemia. P. angulata fruit extract is a promising herb for treating diabetic wounds.
Downloads
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
WHO. Diabetes. France: World Health Organization. 2021.
Zheng SY, Wan XX, Kambey PA, Luo Y, Hu XM, Liu YF, Shan JQ, Chen YW, Xiong K. Therapeutic role of growth factors in treating diabetic wound. World J Diabetes. 2023; 14(4): 364-395. doi:10.4239/wjd.v14.i4.364
Zubair M, Ahmad J. Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review. Rev Endocr Metab Disord. 2019; 20(2): 207–217. doi:10.1007/s11154-019-09492-1
Ciechanowska A, Gora I, Sabalinska S, Foltynski P, Ladyzynski P. Effect of glucose concentration and culture substrate on HUVECs viability in in vitro cultures: A literature review and own results. Biocybern Biomed Eng. 2021; 41(4):1390–1405.https://doi.org/10.1016/j.bbe.2021.04.010
Zhou J, Ni M, Liu X, Ren Z, Zheng Z. Curcumol promotes vascular endothelial growth factor (VEGF)-Mediated diabetic wound healing in streptozotocin-induced hyperglycemic rats. Med Sci Monit. 2017; 23: 555–562. doi:10.12659/msm.902859
Setiawan E, Purwanto B, Wasita B, Putra A. Locally injected mesenchymal stem cells optimize angiogenesis by regulating VEGF and CD31 expression in duodenal perforation. Ann Med Surg (Lond). 2022; 82:104529. doi:10.1016/j.amsu.2022.104529
Wiszniak S, Schwarz Q. Exploring the intracrine functions of VEGF-A. Biomolecules 2021; 11(1): 1–13. doi:10.3390/biom11010128
Guerra A, Belinha J, Natal Jorge R. A preliminary study of endothelial cell migration during angiogenesis using a meshless method approach.
Int J Numer Method Biomed Eng. 2020; 36(11):e3393. doi:10.1002/cnm.3393
Pitulescu ME, Schmidt I, Giaimo BD, Antoine T, Berkenfeld F, Ferrante F, Park H, Ehling M, Biljes D, Rocha SF, Langen UH, Stehling M, Nagasawa T, Ferrara N, Borggrefe T, Adams RH. Dll4 and Notch signalling couples sprouting angiogenesis and artery formation. Nat Cell Biol. 2017; 19(8):915–927. doi:10.1038/ncb3555
Darwin E and Tomic-Canic M. Healing chronic wounds: Current challenges and potential solutions. Curr Dermatol Rep. 2018; 7(4):296–302. doi:10.1007/s13671-018-0239-4
Li W, Kandhare AD, Mukherjee AA, Bodhankar SL. Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats: Role of TGF-B/SMADS and ANG-1/TIE-2 signaling pathways. Excli J. 2018;17: 399–419. doi:10.17179/excli2018-1036
AbdulNasirDeen AY, Boakye YD, Osafo N, Agyare C, Boamah D, Boamah VE and Agyei EK: Antiinflammatory and wound healing properties of methanol leaf extract of Physalis angulata L. S Afr J Bot.2020; 133: 124131. Corpus ID: 225213819
Brar R, Chand Gupta R. Phytochemical analysis of two cytotypes (2x and 4x) of Physalis angulata an important medicinal plant, collected from Rajasthan. Biochem Mol Biol J. 2017; 3(3):15. doi: 10.21767/2471-8084.100040
Liu Y, Li Z, Li W, Chen X, Yang L, Lu S, Zhou S, Li M, Xiong W, Zhang X, Liu Y, Zhou J. Discovery of β-sitosterol’s effects on molecular changes in rat diabetic wounds and its impact on angiogenesis and macrophages. Int Immunopharmacol. 2024; 126:111283. doi:10.1016/j.intimp.2023.111283
Qian K, Zheng XX, Wang C, Huang WG, Liu XB, Xu SD, Liu DK, Liu MY, Lin CS. β-sitosterol inhibits rheumatoid synovial angiogenesis through suppressing VEGF signaling pathway. Front Pharmacol. 2022;12: 816477. doi: 10.3389/fphar.2021.816477
Wang K, Ge Y, Yang Y, Li Z, Liu J, Xue Y, Zhang Y, Pang X, Ngan AHW, Tang B. Vascular endothelial cellular mechanics under hyperglycemia and its role in tissue regeneration. Regen Biomater.2024;11: rbae004. doi:10.1093/rb/rbae004
Pereira Beserra F, Sérgio Gushiken LF, Vieira AJ, Augusto Bérgamo D, Luísa Bérgamo P, Oliveira de Souza M, Alberto Hussni C, Kiomi Takahira R, Henrique Nóbrega R, Monteiro Martinez ER, John Jackson C, Lemos de Azevedo Maia G, Leite Rozza A, Helena Pellizzon C. From inflammation to cutaneous repair: Topical application of lupeol improves skin wound healing in rats by modulating the cytokine levels, NF-κB, Ki-67, growth factor expression, and distribution of collagen fibers. Int J Mol Sci. 2020; 21(14):1–22.doi:10.3390/ijms21144952
Ghasemzadeh F, Darzi GN, Mohammadi M. Extraction and purification of ursolic acid from the apple peel and in vitro assessment of the biochemical antibacterial, antioxidant and wound healing characteristics. Appl Food Biotechnol. 2022; 9(1):17–30.https://doi.org/10.22037/afb.v9i1.34756
Akbarian M, Bertassoni LE, Tayebi L. Biological aspects in controlling angiogenesis. Current progress. Cell Mol Life Sci. 2022;79(7): 349.doi:10.1007/s00018-022-04348-5
Catar R, Moll G, Hosp I, Simon M, Luecht C, Zhao H, Wu D, Chen L, Kamhieh-Milz J, Korybalska K, Zickler D, Witowski J. Transcriptional regulation of thrombin‐induced endothelial VEGF induction and proangiogenic response. Cells. 2021;10(4):910. doi:10.3390/cells10040910
Kaewsrisung S, Sukpat S, Issarasena N,Patumraj S, Somboonwong J. The effects of oral Aloe vera on the efficacy of transplanted human endothelial cells and the expression of matrix metalloproteinases in diabetic wound healing. Heliyon2021; 7(12):e08533. doi:10.1016/j.heliyon.2021.e08533
Beserra FP, Vieira AJ, Gushiken LF, de Souza EO, Hussni MF, Hussni CA, Nóbrega RH, Martinez ER, Jackson CJ, de Azevedo Maia GL, Rozza AL, Pellizzon CH. Lupeol, a dietary triterpene, enhances wound healing in streptozotocin-induced hyperglycemic rats with modulatory effects on inflammation, oxidative stress, and angiogenesis.Oxid Med Cell Longev.2020;2020: 3252696. doi: 10.1155/2020/3252696
Kiran MS, Viji RI, Sameer Kumar VB, Sudhakaran PR. Modulation of angiogenic factors by ursolic acid. Biochem Biophys Res Commun. 2008; 371(3): 556–560.https://doi.org/10.1016/j.bbrc.2008.04.108
Nguyen TQ, Vo TS. Investigation of the anti-diabetic and antioxidant activities of Physalis angulata extract. Trop J Nat Prod Res.2020; 4(6):243-248.doi.org/10.26538/tjnpr/v4i6.6
Hammour WMA, Oran SA, Darwish RM. In vivo evaluation of the wound healing potential of the aerial parts of Globularia arabica aqueous and methanol extracts grown in Jordan. Trop J Nat Prod Res. 2023; 7(3):2611-2617.http://www.doi.org/10.26538/tjnpr/v7i3.22