Safety and efficacy test of a cream combination containing jujube (Ziziphus mauritiana L.) and perilla (Perilla frutescens L. Britton) leaf extracts
Abstract
Excessive free radicals accelerate skin degradation by causing oxidative damage to keratinocytes and fibroblasts, leading to structural protein breakdown (collagen, elastin, keratin), lipid peroxidation, and DNA damage. This process compromises skin barrier integrity, reduces elasticity, and promotes premature aging. Antioxidants play a crucial role in protecting the skin by neutralizing reactive oxygen species (ROS) and preventing lipid peroxidation. This study aimed to develop a topical cream containing jujube (Ziziphus mauritiana L.) and perilla (Perilla frutescens L. Britton) leaf extracts and evaluate its antioxidant activity and dermal safety. Extracts were obtained through kinetic maceration using 70% ethanol and formulated into oil-in-water creams at two concentration levels. The creams were assessed for physical characteristics (organoleptic properties, cream type, pH, homogeneity, spreadability, rheology, viscosity), stability under room and accelerated conditions (40°C for 4 weeks), antioxidant activity via DPPH assay, and irritation potential using albino rabbits. All formulations exhibited good physical properties, stability, and homogeneity. Irritation testing showed no erythema or edema, confirming the cream’s safety for topical application. Antioxidant testing revealed strong free radical scavenging activity, with IC50 values of 119.705 ppm (F1) and 66.938 ppm (F2). Accelerated storage slightly reduced antioxidant activity, while higher extract concentrations enhanced antioxidant effects compared to the base formulation. These findings indicate that jujube (Ziziphus mauritiana L.) and perilla (Perilla frutescens L. Britton) leaf extracts synergistically enhance antioxidant activity in a safe topical cream formulation, demonstrating potential as a natural preparation for skin protection against oxidative damage.
References
[2] S. Zhang, S. Lu, Y. Wang, J. Ni, and G. Xiao, “The efficacy of a novel tomato extracts formulation on skin aging and pigmentation: A randomized, double-blind, parallel-controlled trial,” J. Dermatologic Sci. Cosmet. Technol., vol. 1, 2024, doi: 10.1016/j.jdsct.2024.100005.
[3] A. M. Muddathir, K. Yamauchi, I. Batubara, E. A. M. Mohieldin, and T. Mitsunaga, “Anti-tyrosinase, total phenolic content and antioxidant activity of selected Sudanese medicinal plants,” South African J. Bot., vol. 109, pp. 9–15, 2017, doi: 10.1016/j.sajb.2016.12.013.
[4] N. Ariani, 5 Herbal bermanfaat bagi kesehatan kandungan perempuan. Jambi: PT Sonpedia Publishing Indonesia, 2024.
[5] N. S. Gunarti et al., Kumpulan tanaman obat di Kecamatan Tirtajaya. Yogyakarta: Jejak Pustaka, 2023.
[6] G. Adam et al., “Applications of Perilla frutescens extracts in clinical practice,” Antioxidants, vol. 12, no. 727, pp. 1–17, 2023, doi: 10.3390/antiox12030727.
[7] M. L. Mintoro, F. L. Darsono, and S. Wijaya, “Formulasi sediaan pelembab ekstrak buah melon orange (Cucumis melo L. var. reticulatus) dalam bentuk krim,” J. Ilmu Kefarmasian Indones., vol. 20, no. 2, pp. 291–301, 2022, doi: 10.35814/jifi.v20i2.1164.
[8] L. Lamsari, S. Taurhesia, and R. Djamil, “Formulasi dan uji aktivitas antioksidan krim kombinasi ekstrak biji kopi hijau (Coffea canephora var Robusta) dan ekstrak daun teh hijau (Camellia sinensis (L.)),” J. Farm. Sains dan Terap., vol. 10, no. 2, pp. 99–107, 2023, doi: 10.33508/jfst.v10i2.5082.
[9] Y. Yahia, M. A. Benabderrahim, N. Tlili, M. Bagues, and K. Nagaz, “Bioactive compounds, antioxidant and antimicrobial activities of extracts from different plant parts of two Ziziphus Mill. Species,” PLoS One, vol. 15, no. 5, pp. 1–16, 2020, doi: 10.1371/journal.pone.0232599.
[10] W. Punfa, C. Khanaree, K. Pintha, O. Chumphukam, M. Suttajit, and P. Tantipaiboonwong, “Protective effect of Perilla leaf extract against ROS formation and inflammation induced by TNF-α in A549 human lung carcinoma cell line,” Songklanakarin J. Sci. Technol., vol. 44, no. 2, pp. 361–369, 2022.
[11] A. Arifin, N. Jummah, and M. Arifuddin, “Formulasi dan evaluasi krim daun teh hijau (Camellia sinensis (L.) Kuntze) dengan kombinasi emulgator,” Pharm. J. Farm. Indones., vol. 19, no. 1, pp. 56–65, 2022, doi: 10.30595/pharmacy.v19i1.10841.
[12] M. Taufiqurrahman, F. Faizatun, and S. Setyahadi, “Pengembangan krim ekstrak dedak padi (Rice Bran) dan susu kuda sumbawa sebagai antihiperpigmentasi,” J. Ilm. Kesehat., vol. 20, no. 3, pp. 127–134, 2021, doi: 10.33221/jikes.v20i3.1462.
[13] N. Kamaruzaman and S. M. Yusop, “Determination of stability of cosmetic formulations incorporated with water-soluble elastin isolated from poultry,” J. King Saud Univ. - Sci., vol. 33, no. 6, pp. 1–7, 2021, doi: 10.1016/j.jksus.2021.101519.
[14] BPOM RI, “Peraturan badan pengawas obat dan makanan No 10 Tahun 2022 Tentang pedoman uji toksisitas praklinik secara ın vivo,” pp. 117–124, 2022.
[15] V. Rosiana, S. Taurhesia, and R. Djamil, “Synergistic effect on tyrosinase inhibition of Cassia fistula flower with gynura procumbens leaf extracts,” South African J. Bot., vol. 170, pp. 172–176, 2024, doi: 10.1016/j.sajb.2024.05.033.
[16] T. Saras, Daun bidara: Kekuatan alamiah untuk kesehatan dan kecantikan. Semarang: Tiram Media, 2024.
[17] W. Preedalikit, K. Pintha, P. Tantipaiboonwong, N. Aunsri, P. Vivattanaseth, and L. Mungmai, “Inhibitory effect of Perilla frutescens L. leaves extract on melanogenesis and skin whitening efficacy in the underarm whitening product application,” Key Eng. Mater., vol. 859, pp. 166–171, 2020, doi: 10.4028/www.scientific.net/KEM.859.166.
[18] Nurkhasanah, M. S. Bachri, and S. Yuliani, Antioksidan dan Stres Oksidatif. Yogyakarta: UAD Press, 2023.

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Licencing
All articles in Jurnal Ilmu Kefarmasian Indonesia are an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted non-commercial used, distribution and reproduction in any medium.
This licence applies to Author(s) and Public Reader means that the users mays :
- SHARE:
copy and redistribute the article in any medium or format - ADAPT:
remix, transform, and build upon the article (eg.: to produce a new research work and, possibly, a new publication) - ALIKE:
If you remix, transform, or build upon the article, you must distribute your contributions under the same license as the original. - NO ADDITIONAL RESTRICTIONS:
You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
It does however mean that when you use it you must:
- ATTRIBUTION: You must give appropriate credit to both the Author(s) and the journal, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
You may not:
- NONCOMMERCIAL: You may not use the article for commercial purposes.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.



Tools
















