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All Journal Jurnal Riset Kesehatan Quagga Biology, Medicine, & Natural Product Chemistry PENA SAINS Journal of Natural Sciences and Mathematics Research Jurnal Ilmiah Universitas Batanghari Jambi Jurnal SOLMA JURNAL KESEHATAN PERINTIS Prosiding Seminar Nasional Multidisiplin Jurnal Inovasi Farmasi Indonesia Abdimas Galuh: Jurnal Pengabdian Kepada Masyarakat Jurnal Abdimas Ilmiah Citra Bakti (JAICB) SIMBIOSA Indonesian Journal of Natural Science Education Jumat Ekonomi: Jurnal Pengabdian Masyarakat PHARMACOLOGY, MEDICAL REPORTS, ORTHOPEDIC, AND ILLNESS DETAILS (COMORBID) BIO-CONS: Jurnal Biologi dan Konservasi Gema Kesehatan Journal of Engineering Science and Technology Management Journal for Quality in Public Health Komunita: Jurnal Pengabdian dan Pemberdayaan Masyarakat Jurnal Kesehatan Metro Sai Wawai Jurnal Mahasiswa Kesehatan Jurnal Bioteknologi & Biosains Indonesia (JBBI) Jurnal Cendekia Ilmiah Joong-Ki Jurnal Bioteknologi & Biosains Indonesia
Lisa Savitri
Universitas Kadiri, Jawa Timur, Indonesia
Religion Agriculture, Biological Sciences & Forestry Arts Humanities Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Civil Engineering, Building, Construction & Architecture Computer Science & IT Control & Systems Engineering Decision Sciences, Operations Research & Management Economics, Econometrics & Finance Education Electrical & Electronics Engineering Energy Environmental Science Health Professions Immunology & microbiology Languange, Linguistic, Communication & Media Law, Crime, Criminology & Criminal Justice Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Neuroscience Nursing Physics Public Health Social Sciences Other

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Kadar Fenolik, Flavonoid Total dan Aktivitas Antioksidan Ekstrak Etanol Daun Calathea Silver Plate: Total of Phenolic, Flavonoid Content and Antioxidant Activity of Calathea Silver Plate Leaves Extract Datin An Nisa Sukmawati; Lisa Savitri; Firdania Firdaus Rosyida; Khoirul Ngibad; Hanifah Delima Nuardani
Jurnal Inovasi Farmasi Indonesia (JAFI) Vol. 7 No. 1 (2025): Volume 7 No 1 2025
Publisher : Universitas Kadiri

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30737/jafi.v7i1.7316

Abstract

Daun Calatea Silver Plate (CSP) merupakan tanaman hias yang memiliki karakteristik daun berwarna ungu pada bagian atasnya dan perak pada bagian bawahnya yang mengindikasikan adanya potensi bioaktivitas sebagai antioksidan. Sehingga, tujuan penelitian ini adalah untuk mengetahui dan menganalisis kadar fenolik, flavonoid total dan mengukur aktivitas antioksidan ekstrak etanol CSP. Uji kadar fenolik total menggunakan metode folin-ciocalteu dengan menggunakan asam galat sebagai senyawa standar. Sedangkan untuk uji kadar flavonoid total menggunakan metode kolorimetri dengan menggunakan AlCl3 dan senyawa kuersetin sebagai standar. Untuk uji aktivitas antioksidan menggunakan metode DPPH dan ABTS. Adapun hasil dari penelitian ini adalah ekstrak CSP mengandung senyawa fenolik dengan kadar 203,89 mg GEA/g, senyawa flavonoid dengan kadar 446 mg QE/g, memiliki aktivitas antioksidan dengan nilai IC50  75,78±2,1 terhadap DPPH dan nilai IC50 87,75±3,0 terhadap ABTS. Berdasarkan hasil tersebut dapat disimpulkan bahwa ekstrak CSP memiliki potensi sebagai antioksidan alami.
Modulation of Th1/Th2 Cytokine Balance by Extract of Male Papaya Leaves (Carica papaya L.) in an Experimental Autoimmune Disease Model Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo
Biology, Medicine, & Natural Product Chemistry Vol 15, No 1 (2026)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2026.151.1543-1548

Abstract

Autoimmune diseases are characterized by dysregulated immune responses, particularly involving an imbalance between T helper 1 (Th1) and T helper 2 (Th2) cytokines. This imbalance contributes to chronic inflammation and progressive tissue damage. Modulation of Th1/Th2 balance has emerged as a promising therapeutic strategy; however, current treatments are often associated with significant side effects. This study aimed to evaluate the immunomodulatory effects of male papaya (C. papaya L.) leaf extract on Th1/Th2 cytokine balance in an experimental autoimmune disease model. An experimental approach was conducted using in vivo autoimmune models and ex vivo immune assays. Male papaya leaves were extracted using 70% ethanol and analyzed for phytochemical content. Experimental animals were induced with autoimmune disease and treated with different doses of the extract. Cytokine levels, including interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10), were measured using ELISA. Gene expression of transcription factors T-bet and GATA-3 was analyzed using qRT-PCR. Histopathological examination was performed to assess tissue inflammation and damage. The results showed that the extract significantly reduced Th1 cytokines (IFN-gamma and IL-2) and increased Th2 cytokines (IL-4 and IL-10), leading to normalization of the IFN-gamma/IL-4 ratio. The extract also downregulated T-bet expression and upregulated GATA-3, indicatingtranscriptional modulation. Histological findings confirmed reduced inflammatory infiltration and improved tissue structure in treated groups. In conclusion, male papaya leaf extract demonstrates significant potential as a natural immunomodulatory agent capable of restoring Th1/Th2 balance in autoimmune conditions. These findings provide a scientific basis for the development of plant-based therapies targeting immune regulation.
Antiviral Immunological Potential of Male Papaya (Carica papaya L.) Leaf Extract Through Activation of the Type I Interferon Pathway Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo
Biology, Medicine, & Natural Product Chemistry Vol 15, No 1 (2026)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2026.151.1515-1521

Abstract

Viral infections remain a major global health challenge, highlighting the need for novel host-directed antiviral strategies. Activation of the type I interferon pathway represents a critical component of innate antiviral immunity. Male papaya (Carica papaya L.) leaves have been traditionally used to enhance immunity; however, their antiviral immunological mechanisms remain insufficiently characterized. This study aimed to investigate the antiviral immunologic potential of male papaya leaf extract by activating the type I interferon signaling pathway. Male papaya leaves were extracted using 70% ethanol, and phytochemical screening was performed. The immunomodulatory activity of the extract was evaluated in RAW 264.7 and THP-1 cells stimulated with polyinosinic-polycytidylic acid [poly(I:C)] as a viral mimic. Cytotoxicity was assessed using the MTT assay. Type I interferon production (IFN-alpha and IFN-beta) was quantified by ELISA, while activation of interferon signaling was evaluated by analysis of interferon-stimulated gene expression using quantitative real-time PCR and signaling protein activation by Western blot. The extract showed no significant cytotoxicity at concentrations up to 200 µg/mL. Treatment with male papaya leaf extract significantly enhanced IFN-alpha and IFN-beta production in poly(I:C)-stimulated cells in a dose-dependent manner. This increase was accompanied by activation of IRF3 and STAT1 signaling and robust upregulation of interferon-stimulated genes, including MX1, OAS1, and ISG15. These findings indicate that the extract enhances antiviral immune responses by amplifying type I interferon-mediated signaling. In conclusion, male papaya leaf extract exhibits significant antiviral immunological activity through activation of the type I interferon pathway. This host-directed immunomodulatory mechanism supports its potential development as a complementary therapeutic agent for viral infections.
Effects of Extract of Male Papaya Leaves (Carica papaya L.) on Macrophage Polarization (M1/M2) in Chronic Inflammation and Cancer Models Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo
Biology, Medicine, & Natural Product Chemistry Vol 15, No 1 (2026)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2026.151.1523-1529

Abstract

Chronic inflammation plays a central role in the pathogenesis of various diseases, including cancer, and is closely associated with dysregulated macrophage polarization. Macrophages exhibit high plasticity and can differentiate into pro-inflammatory (M1) or anti-inflammatory/tumor-promoting (M2) phenotypes. Targeting macrophage polarization has emerged as a promising therapeutic strategy to restore immune balance and inhibit tumor progression. This study aimed to investigate the effects of male papaya (C. papaya L.) leaf extract on macrophage polarization (M1/M2) in models of chronic inflammation and cancer. An experimental approach was employed using both in vitro and in vivo models. Male papaya leaves were extracted using 70% ethanol and subjected to phytochemical analysis. In vitro studies were conducted using RAW 264.7 macrophages induced into M1 (LPS/IFN-gamma) and M2 (IL-4) phenotypes, followed by treatment with varying concentrations of the extract. Macrophage polarization was assessed through gene and protein expression of specific markers (iNOS, TNF-alpha, IL-6, Arg-1, CD206, IL-10), nitric oxide (NO) production, and analysis of signaling pathways (NF-kB, STAT1/STAT6, PI3K/Akt). A macrophage–cancer cell co-culture system was used to evaluate effects on cancer cell proliferation, migration, and apoptosis. In vivo studies were performed using mouse models of chronic inflammation and tumor induction. The results demonstrated that male papaya leaf extract contains significant levels of phenolic and flavonoid compounds and exerts a dose-dependent immunomodulatory effect. The extract reduced M1-associated pro-inflammatory markers and nitric oxide production while also suppressing excessive M2 polarization markers, indicating a rebalancing effect on macrophage phenotypes. Mechanistically, these effects were associated with the inhibition of NF-kB and modulation of STAT1/STAT6 and PI3K/Akt signaling pathways. In cancer models, extract-treated macrophages reduced tumor cell proliferation and migration while increasing apoptosis. In vivo findings further confirmed reduced tumor growth and a shift toward anti-tumor macrophage activity. In conclusion, male papaya leaf extract exhibits significant potential as a natural immunomodulatory agent by regulating macrophage polarization in chronic inflammation and cancer. These findings provide a scientific basis for the development of plant-based therapeutic strategies targeting immune regulation. Further studies are needed to isolate active compounds and evaluate clinical applications.
In Vivo validation of the Neuroprotective Effects of Acalypha indica leaf extract in an Aluminum Chloride-Induced Alzheimer's Disease mouse model Lisa Savitri; Elfred Rinaldo Kasimo; Rochmad Krissanjaya
Journal of Natural Sciences and Mathematics Research Vol. 12 No. 1 (2026): June
Publisher : Faculty of Science and Technology, Universitas Islam Negeri Walisongo Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21580/jnsmr.v12i1.30610

Abstract

Neurodegenerative disorders, particularly Alzheimer’s disease, are closely associated with cholinergic dysfunction and oxidative stress. A. indica L. is a medicinal plant traditionally used for neurological disorders and has been reported to contain phytochemicals with potential acetylcholinesterase (AChE) inhibitory activity. This study aimed to evaluate the neuroprotective effects of the ethanolic extract of A. indica in a scopolamine-induced cognitive impairment model. Thirty male Wistar rats were randomly divided into five groups (n = 6): normal control, scopolamine control, donepezil-treated, and two extract-treated groups (100 and 300 mg/kg body weight). Animals received oral treatment for 14 days, and cognitive impairment was induced by scopolamine (1 mg/kg). Spatial learning and memory were assessed using the Morris Water Maze test, followed by biochemical and histopathological analyses. Scopolamine significantly impaired cognitive performance, increasing escape latency from 21.4 ± 3.2 s to 45.8 ± 5.6 s and reducing time spent in the target quadrant from 32.6 ± 4.1 s to 14.3 ± 2.8 s (p < 0.05). Treatment with A. indica extract at 300 mg/kg significantly improved cognitive performance, reducing escape latency to 26.2 ± 3.5 s and increasing target quadrant retention time to 29.4 ± 3.9 s (p < 0.05 versus scopolamine). The extract also reduced brain AChE activity from 1.78 ± 0.19 to 1.02 ± 0.12 μmol/min/mg protein, decreased malondialdehyde levels from 3.11 ± 0.34 to 1.48 ± 0.21 nmol/mg protein, and increased superoxide dismutase activity from 4.02 ± 0.51 to 7.98 ± 0.71 U/mg protein (all p < 0.05). Histopathological examination demonstrated preservation of hippocampal neuronal architecture in extract-treated animals. The neuroprotective effects of the high-dose extract were comparable to those of donepezil. These findings indicate that the ethanolic extract of A. indica exerts significant neuroprotective effects through cholinergic modulation and antioxidant mechanisms, supporting its potential as a natural therapeutic candidate for the management of neurodegenerative disorders.
Inhibition of NF-kB Signaling by Extract of Male Papaya Flowers (Carica papaya L.) in Chronic Inflammatory Disease Models Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo
Biology, Medicine, & Natural Product Chemistry Vol 15, No 1 (2026)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2026.151.1667-1676

Abstract

Chronic inflammation is closely associated with persistent activation of Nuclear Factor-kappa B (NF-kB) signaling pathways, which regulate the expression of pro-inflammatory cytokines and inflammatory mediators involved in various chronic inflammatory diseases. The present study investigated the anti-inflammatory activity of male papaya flower (C. papaya L.) extract through inhibition of NF-?B signaling in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Male papaya flowers were extracted using 70% ethanol and subjected to phytochemical screening, total phenolic content (TPC), and total flavonoid content (TFC) analyses. Cytotoxicity was evaluated using the MTT assay, while anti-inflammatory activity was assessed through nitric oxide (NO) production, enzyme-linked immunosorbent assay (ELISA) for pro-inflammatory cytokines, western blot analysis, immunofluorescence staining, and DPPH radical scavenging assay. Phytochemical analysis revealed the presence of flavonoids, phenolics, alkaloids, tannins, saponins, and terpenoids. The extract demonstrated high TPC and TFC values of 186.42 ± 5.31 mg GAE/g extract and 97.25 ± 3.84 mg QE/g extract, respectively. Male papaya flower extract exhibited low cytotoxicity at concentrations below 200 µg/mL and significantly suppressed nitric oxide production, TNF-alpha, IL-1beta, and IL-6 secretion in LPS-induced macrophages (p < 0.05). Western blot analysis showed that the extract inhibited phosphorylation of NF-kB p65 and I?B? proteins while reducing COX-2 and iNOS expression. Immunofluorescence analysis further confirmed inhibition of NF-kB nuclear translocation. In addition, the extract demonstrated strong antioxidant activity with an IC50 value of 58.4 µg/mL in the DPPH assay. These findings suggest that male papaya flower extract possesses potent anti-inflammatory and antioxidant properties through suppression of NF-kB signaling pathways and may serve as a promising natural therapeutic candidate for chronic inflammatory diseases.
Co-Authors Afrilla, Rananda Agung Dwi Wahyu Widodo Agustanti, Khalimatus Nur Eka Akbar Nur Kholis Alimansur, Moh Alves, Silvina Sandra X. Amanda, Cornelia Aminah Alfiani Ana Retnowati Anjarwati, Aprilia Antoro, Ester Lianawati Apriana, Dita Arif Budi Setiawan Besan, Emma Jayanti Cornelia Amanda Datin An Nisa Sukmawati Datin An Nisa Sukmawati Dhony Hermanto Edda, Ilda Rambu Eka Wahyuningtiyas Elfred Rinaldo Kasimo Elfred Rinaldo Kasimo Elfred Rinaldo Kasimo Elfred Rinaldo Kasimo Elfred Rinaldo Kasimo Elfred Rinaldo Kasimo, Elfred Rinaldo Elly Megasari Ester Lianawati Antoro Ester Lianawati Antoro Ester Lianawati Antoro Ester Lianawati Antoro Evi Laela Sari Farabi, Meka Faizal Fendy Prasetyawan Firdania Firdaus Rosyida Fitri, Devi Nor Freitas, João Gregório Freitas, Maria Do Carmo Da Costa Hanifah Delima Nuardani Herman Herman Herman Hilmi, Mochammad Hanif Ida Septika Wulansari Ida Septika Wulansari Ida Septika Wulansari Ida Septika Wulansari Ihsan, Kharisul Imam Agus Faizal Indrayanti, Dian Iza Dwi Muslikha Juan Vega Mahardhika Juan Vega Mahardika Juwita, Syntia Tanu Kadir, Mujtahid Bin Abd Kadir, Mujtahid Bin And Kasimo, Elfred Khalimatus Nur Eka Agustanti Kharisma Rahmasari Kharisul Ihsan Kharisul Ihsan Kharisul Ihsan Khoirul Ngibad Kholis, Akbar Nur Kholis, Muhammad Akbar Nur Konradus Klala Mebung Laili, Nur Fahma La’ally Maula Lian Pandu Farendra Loviana, Novi Maria Do Carmo Da Costa Freitas Masyhuri, Aga Adi Mebung, Konradus Klala Megasari, Elly Meri, Meri Meri, Meri Mika Tri Kumala Swandari, Mika Tri Kumala Mila Putri Daniati Mochamad Hanif Hilmi Mochamad Hanif Hilmi Mohammad Firdaus Alshol Mosse1, Yosep Muhammad Nurul Fadel Muslikha, Iza Dwi Muttaqin, Saiful Neni Probosiwi Novirma Yanti Novirma Yanti Novyananda Salmasfattah Novyananda Salmasfattah Nur Fahma Laili Nur Fahma Laili Nurul Ismillayli Ornai, Andre Mario Sequeira Alves Rasyadan Taufiq Probojati Renaldi Umbu Ndamung Kale Restyana, Anggi Restyana, Anggy Retnowati, Ana Rochmad Krissanjaya Salmasfattah, Novyananda Sanjaya, Rochmad Kris Shinta Mayasari Shinta Mayasari Sueb Sugeng Santoso Syntia Tanu Juwita Syntia Tanu Juwita Syntia Tanu Juwita Syntia Tanu Juwita Syntia Tanu Juwita Syntia Tanu Juwita Tiyas, Eka Wahyuning Tridoso Sapto A Tsamrotul Ilmi Willy Sandhika Wulansari, Ida Septika Yanti, Novirma Yosep Mosse Yosep Mosse1 yunadi, frisca dewi Yuneka Saristiana