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In Vitro Assessment of the Antibacterial Activity of Sapindus rarak (Lerak) and Its Influence on Cellular Immune Markers During Escherichia coli Infection Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo; Rochmad Krissanjaya
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.2026.151.209-213

Abstract

Antibiotic-resistant Escherichia coli remains a major public health concern, prompting interest in plant-derived compounds with both antimicrobial and immunomodulatory functions. This study evaluated the antibacterial activity of Sapindus rarak (lerak) extract and its influence on macrophage cytokine responses during E. coli stimulation. Lerak pericarp extract was prepared using 70% ethanol and tested against E. coli ATCC 25922 using broth microdilution. Immunomodulatory effects were assessed in RAW 264.7 macrophages exposed to heat-killed E. coli, followed by treatment with sub-MIC concentrations of the extract. The results showed moderate antibacterial activity, with a minimum inhibitory concentration of 250 microgram/mL and a minimum bactericidal concentration of 500 microgram/mL. Cell viability exceeded 90% at 50–100 microgram/mL, confirming suitability for immunological assays. Lerak significantly reduced TNF-alpha and IL-6 production while increasing IL-10 levels, indicating suppression of excessive inflammation and enhancement of regulatory responses. These findings suggest that S. rarak possesses dual antibacterial and immunomodulatory properties, highlighting its potential as a complementary therapeutic candidate for managing E. coli infections where inflammation contributes to disease severity.
IMMUNOLOGY OF INFECTION: MECHANISM OF IMMUNE RESPONSE AND IMPLICATION FOR THERAPEUTIC Lisa Savitri; Elfred Rinaldo Kasimo; Rochmad Krissanjaya
JURNAL PENA SAINS Vol 13, No 1 (2026): Jurnal Pena Sains
Publisher : Program Studi Pendidikan IPA, Fakultas Ilmu Pendidikan, Universitas Trunojoyo Madura

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21107/jps.v13i1.29979

Abstract

Infectious diseases, caused by pathogens such as bacteria, viruses, fungi, and parasites, continue to represent a significant global health challenge. The immune system plays a pivotal role in recognizing and eliminating these pathogens, but pathogens have evolved various mechanisms to evade immune responses, resulting in chronic infections and disease progression. This review aims to explore the mechanisms of immune responses to infections, focusing on innate and adaptive immune cells, pathogen recognition, and immune evasion strategies. The review also discusses the therapeutic implications of these findings, highlighting potential targets for developing new treatments. The innate immune response, which includes pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), serves as the first line of defense. In contrast, the adaptive immune response involves T cells and B cells recognizing specific antigens on pathogens. Despite the immune system's defense mechanisms, pathogens can evade immune detection through antigenic variation and suppression of immune functions. Recent research has provided new insights into immune modulation and therapeutic targets, such as enhancing the innate immune response and targeting specific immune cell subsets. Vaccines remain a critical strategy for preventing infectious diseases. Continued advancements in immunology are crucial for developing more effective interventions to control and treat infectious diseases.
Anticancer Immunomodulatory Activity of Male Papaya Leaf Extract (Carica papaya L.) Through PD-1/PD-L1 Pathway Modulation: An In Silico and In Vitro Study Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo; Rochmad Krissanjaya
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.2026.151.1255-1263

Abstract

Cancer immunotherapy targeting the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway has shown remarkable clinical success; however, high costs and immune-related adverse effects remain major challenges. Natural products with immunomodulatory properties offer a promising alternative approach. Male papaya leaves (Carica papaya L.) are traditionally used in herbal medicine, yet their potential role in immune checkpoint modulation remains largely unexplored. This study aimed to investigate the anticancer immunomodulatory activity of male papaya leaf extract through PD-1/PD-L1 pathway modulation using integrated in silico and in vitro approaches. Molecular docking analysis was performed to evaluate the interaction between major phytochemical compounds and PD-1/PD-L1 proteins. In vitro cytotoxic activity was assessed using the MTT assay on cancer cell lines, while immunomodulatory effects were evaluated by measuring interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) levels using ELISA. PD-L1 protein expression in treated cancer cells was analyzed by Western blotting. The docking results demonstrated strong binding affinities of flavonoid compounds, particularly quercetin, toward PD-L1, involving key residues at the active binding site. The extract exhibited dose-dependent cytotoxic effects with moderate IC50 values. Treatment with male papaya leaf extract significantly increased IFN-gamma and IL-2 secretion in immune cells and markedly downregulated PD-L1 protein expression in cancer cells. In conclusion, male papaya leaf extract exhibits promising anticancer immunomodulatory activity by modulating the PD-1/PD-L1 immune checkpoint pathway. These findings highlight the potential of male papaya leaves as a natural source of immune checkpoint modulators and support further investigation for their development as complementary agents in cancer immunotherapy.
Immunomodulatory Effects of Male Papaya Leaf Extract (Carica papaya L.) on Interferon-gamma and Interleukin-6 Levels in an In Vivo Viral Infection Model Lisa Savitri; Kharisul Ihsan; Elfred Rinaldo Kasimo; Rochmad Krissanjaya
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.2026.151.1139-1143

Abstract

Viral infections pose a significant challenge to global health due to their ability to disrupt immune homeostasis and trigger excessive inflammatory responses. Immunomodulatory agents that enhance antiviral immunity while controlling inflammation are therefore essential. This study aimed to evaluate the immunomodulatory effects of male papaya leaf extract (Carica papaya L.) on Interferon-gamma (IFN-gamma) and Interleukin-6 (IL-6) levels in an in vivo viral infection model. Male papaya leaves were extracted using 70% ethanol and administered orally to virus-infected Wistar rats at two different doses for 14 days. Serum levels of IFN-gamma and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The results demonstrated that viral infection significantly decreased IFN-gamma levels and increased IL-6 levels compared to the normal control. Treatment with male papaya leaf extract resulted in a dose-dependent increase in IFN-gamma and a significant reduction in IL-6 levels compared to the negative control group. The high-dose extract group showed the most pronounced immunomodulatory effect, comparable to or exceeding that of the positive control. These findings indicate that male papaya leaf extract has potential as a natural immunomodulatory agent by enhancing antiviral immune responses and suppressing excessive inflammation. Further studies are recommended to explore its molecular mechanisms and therapeutic applications.
EDUKASI OBESITAS SEBAGAI UPAYA PREVENTIF PENYAKIT METABOLIK PADA USIA PRODUKTIF DI DESA POJOK KEDIRI Dita Apriana Dwi Astuti; Aprilia Anjarwati; Rochmad Krissanjaya; Saiful Muttaqin; Elfred Rinaldo Kasimo
Jurnal Edukasi Pengabdian Masyarakat Vol 5 No 3 (2026): JULI 2026
Publisher : FIP UNIRA MALANG

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36636/eduabdimas.v5i3.9648

Abstract

Obesity is one of the major risk factors for metabolic diseases such as type 2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease, particularly among the productive-age population. The increasing prevalence of obesity in the community indicates the need for promotive and preventive efforts through health education. This Community Service Program aimed to improve the knowledge and awareness of productive-age individuals regarding obesity as a risk factor for metabolic diseases and to encourage the adoption of healthy lifestyles in Pojok Village, Kediri. The program was conducted through health counseling, interactive discussions, and anthropometric assessments, including measurements of body weight, height, and Body Mass Index (BMI) calculation among 47 participants. The results showed that the majority of participants were female (72.3%). Based on BMI classification, 31 participants (65.96%) were categorized as obese, 11 participants (23.40%) as overweight, and only 5 participants (10.64%) had normal BMI status. These findings indicate a high risk of metabolic disorders among the productive-age population in the intervention area. The educational activities received positive responses and improved participants’ understanding of the importance of balanced nutrition, regular physical activity, and routine body weight monitoring. In conclusion, obesity education through the Community Service Program was effective as an initial preventive strategy to improve public health literacy and reduce the risk of metabolic diseases.
Pengenalan Metode Imunodiagnostik Dasar untuk Pencegahan Penyakit Menular di Peternakan Lisa Savitri; Elfred Rinaldo Kasimo; Rochmad Krissanjaya; Fendy Prasetyawan; Yuneka Saristiana; Cornelia Amanda; Konradus Klala Mebung
Abdimas Galuh Vol 8, No 1 (2026): Maret 2026
Publisher : Universitas Galuh

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25157/ag.v8i1.23354

Abstract

Penyakit menular pada ternak masih menjadi salah satu kendala utama dalam usaha peternakan rakyat karena dapat menurunkan produktivitas dan menyebabkan kerugian ekonomi. Salah satu upaya pencegahan yang dapat dilakukan adalah deteksi dini penyakit melalui metode imunodiagnostik dasar. Namun, tingkat pemahaman peternak mengenai prinsip kerja dan pemanfaatan metode imunodiagnostik masih relatif rendah. Kegiatan pengabdian kepada masyarakat ini bertujuan untuk meningkatkan pengetahuan dan pemahaman peternak mengenai pengenalan penyakit menular serta prinsip dasar metode imunodiagnostik sebagai langkah awal pencegahan penyakit di peternakan. Kegiatan dilaksanakan melalui penyuluhan interaktif, diskusi dua arah, serta demonstrasi penggunaan alat imunodiagnostik dasar berupa kit uji cepat. Sasaran kegiatan adalah peternak ternak rakyat di wilayah sasaran pengabdian. Evaluasi dilakukan melalui pengukuran tingkat pengetahuan peserta sebelum dan sesudah kegiatan serta observasi partisipasi aktif selama kegiatan berlangsung. Hasil kegiatan menunjukkan adanya peningkatan pemahaman peternak terkait jenis penyakit menular, prinsip reaksi antigen–antibodi, dan manfaat penggunaan metode imunodiagnostik dalam deteksi dini penyakit. Selain itu, peternak menunjukkan antusiasme dan partisipasi aktif selama proses penyuluhan dan demonstrasi. Kegiatan ini memberikan kontribusi positif dalam meningkatkan kesadaran peternak terhadap pentingnya pencegahan penyakit menular melalui pendekatan diagnostik sederhana yang aplikatif di tingkat peternakan rakyat.
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.