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Virtual Prediction of Lycopene and Quercetin Effects on Angiogenesis Through VEGFR-2 Pathway Samoedra, Rizky Senna; Sari, Fikriya Novita; Pratama, Setyaki Kevin
JSMARTech: Journal of Smart Bioprospecting and Technology Vol 2, No 1 (2020)
Publisher : JSMARTech

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jsmartech.2020.002.01.7

Angiogenesis is a complex process that is required for cancer cells to perform metastasis. The binding of a growth factor such as VEGF to its receptor is one of the factors to trigger angiogenesis through VEGFR-2 pathway. This study is conducted to analyze the effect of lycopene and quercetin, which are compounds found in watermelon (Citrullus lanatus) on angiogenesis through VEGFR-2 pathway. The study was carried out in silico. Ligands were obtained from PubChem and prepared using PyRx while the protein was obtained from PDB and prepared using BIOVIA Discovery Studio 2019. The docking was done by using HEX 8.0.0 and the results were visualized using BIOVIA Discovery Studio 2019. Lycopene and quercetin were able to bind with VEGFR-2 to interrupt the binding of VEGFA. The presence of lycopene and quercetin also lowers the binding strength of VEGFA with VEGFR-2 as they can affect interactions between VEGFA and VEGFR-2 at 4 and 5 amino acid residues by changing the type of interactions to make the binding strength weaker. The binding of lycopene and quercetin have the potential to interrupt the downstream pathway of angiogenesis through VEGFR-2 pathway.

The effect of Phyllanthus niruri and Catharanthus roseus on Macrophage Polarization in Breast Cancer Mice Model: The Effect of P. niruri and C. roseus in Breast Cancer Mice Model Sakti, Sefihara Paramitha; Sari, Fikriya Novita; Rachmawati, Farida; Widyarti, Sri; Rahayu, Sri; Soewondo, Aris; Jatmiko, Yoga Dwi; Rifa'i, Muhaimin
Journal of Tropical Life Science Vol. 14 No. 1 (2024)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.14.01.03

Cancer death cases have increased yearly, and there are estimated to be 21.6 million cancer cases in 2030. Studies of herbal compounds for cancer treatment alternatives are essential because cancer treatment is relatively expensive and has adverse effects. Phyllanthus niruri (Pn) and Catharanthus roseus (Cr) are plants that are known as herbal medicines. Combining the two plants is expected to prevent and enhance the immune system in breast cancer cases. This study aims to analyze the anti-cancer and immunomodulatory effects of P. niruri and C. roseus extract (PCE) in modulating macrophage polarization in breast cancer mice. Experimental animals are divided into six groups and there is healthy control (normal mice), cancer (DMBA-induced mice), cancer mice with cisplatin administration, cancer mice with PCE administration with three different doses, including dose 1 (500 mg/kg Pn + 15 mg/kg Cr), dose 2 (1000 mg/kg Pn + 75 mg/kg Cr), and dose 3 (2000 mg/kg Pn + 375 mg/kg Cr). The mice were injected with DMBA once a week for six weeks to induce cancer in mice. The breast cancer mice model was administered with PCE orally for 14 days. The expression of CD11b+IL-10+ and CD11b+IFN-γ+ demonstrated macrophage polarization. The results showed that breast cancer induction using DMBA increased the level of IL-10 and decreased the level of IFN-γ significantly compared to the normal group (p < 0.05). In specific doses, administration of PCE could reduce IL-10 levels and increase the level of IFN-γ significantly (p < 0.05). PCE can modulate the polarization of macrophages by suppressing the M2-like macrophage and increasing the M1-like macrophage. The ability of PCE to modulate macrophage polarization indicates that the combination of P. niruri and C. roseus has activity as an anti-cancer.

Antioxidant Activity of Baby Java Citrus Peel Extract Promotes Lung Tissue Repair in Mice Challenged by Lipopolysaccharides: Antioxidant Activity of BJE Promotes Lung Tissue Repair Rachmawati, Farida; Sari, Fikriya Novita; Sakti, Sefihara Paramitha; Sakti, Muhammad Wisam Wira; Rahayu, Sri; Soewondo, Aris; Rifa'i, Muhaimin
Journal of Tropical Life Science Vol. 14 No. 2 (2024)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.14.02.03

Acute lung injury tends to be induced by infection or sepsis that disrupt alveolar and vascular permeability, neutrophil influx, and edema. Those impairments are worsened by the increase of oxidative stress along with hyperinflammation response. Oxidative stress in lung tissue could be indicated by malondialdehyde (MDA) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. This research aimed to evaluate the efficacy of Baby Java citrus peel extract (BJE) in suppressing oxidative stress and preventing lung injury in lipopolysaccharides (LPS)-induced mice. Twenty-five male BALB/c mice were divided into five groups consisting of untreated (N), LPS (A), and LPS-induced followed by treatment using BJE at various doses: 75 mg/kg BW (BJE-1), 105 mg/kg BW (BJE-2), and 150 mg/kg BW (BJE-3). Lungs were isolated for histopathological analysis also detection of MDA and Nrf2 using flow cytometry. BJE at the dose of 105 mg/kg BW could inhibit the alteration of lung histology following LPS challenge including alveolar and interstitial neutrophil infiltration, proteinaceous debris, and septal thickening. The same dose also showed good potency in suppressing MDA and Nrf2 levels as oxidative stress indicators. Our findings demonstrated protective effects of Baby Java citrus peel in acute lung injury and oxidative stress prevention after LPS exposure.

Temporal Dynamics of TNF-α Expression and Cell Viability in LPS-Stimulated Peripheral Blood Mononuclear Cells Cahyani, Dini; Hidayah, Nurul; Sari, Fikriya Novita
International Journal of Cell and Biomedical Science Vol 3 No 7 (2024)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v3i7.49

Background: Lipopolysaccharide (LPS), a key component of Gram-negative bacterial membranes, activates innate immune responses through Toll-like receptor 4 (TLR4) signaling in peripheral blood mononuclear cells (PBMCs). This study aimed to evaluate the temporal dynamics of TNF-α expression and cell viability in LPS-stimulated PBMCs to understand the inflammatory and cytotoxic effects of prolonged LPS exposure. Methods: Human PBMCs were treated with increasing concentrations of LPS (10, 30, and 50 ng/mL) for 4, 8, 12, and 24 hours. TNF-α mRNA expression was analyzed using quantitative PCR, while cell viability was assessed via CCK-8 assay and microscopic imaging. Results: LPS stimulation induced a robust, dose-dependent upregulation of TNF-α expression, peaking at 4 hours and gradually declining over time. Concurrently, PBMC viability remained stable up to 12 hours post-stimulation but significantly decreased at 24 hours, particularly at higher LPS concentrations (30–50 ng/mL). Microscopic analysis revealed increased cellular aggregation and morphological changes consistent with immune activation and cytotoxic stress. Conclusion:LPS triggers early TNF-α expression in PBMCs through TLR4-mediated activation of the NF-κB pathway. However, prolonged exposure to LPS results in decreased cell viability, likely due to sustained inflammatory signaling and oxidative stress. These findings provide insight into the dual-phase response of PBMCs to LPS and underscore the importance of tightly regulated inflammation in innate immunity.

The effect of Phyllanthus niruri and Catharanthus roseus on Macrophage Polarization in Breast Cancer Mice Model: The Effect of P. niruri and C. roseus in Breast Cancer Mice Model Sakti, Sefihara Paramitha; Sari, Fikriya Novita; Rachmawati, Farida; Widyarti, Sri; Rahayu, Sri; Soewondo, Aris; Jatmiko, Yoga Dwi; Rifa'i, Muhaimin
Journal of Tropical Life Science Vol. 14 No. 1 (2024)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.14.01.03

Cancer death cases have increased yearly, and there are estimated to be 21.6 million cancer cases in 2030. Studies of herbal compounds for cancer treatment alternatives are essential because cancer treatment is relatively expensive and has adverse effects. Phyllanthus niruri (Pn) and Catharanthus roseus (Cr) are plants that are known as herbal medicines. Combining the two plants is expected to prevent and enhance the immune system in breast cancer cases. This study aims to analyze the anti-cancer and immunomodulatory effects of P. niruri and C. roseus extract (PCE) in modulating macrophage polarization in breast cancer mice. Experimental animals are divided into six groups and there is healthy control (normal mice), cancer (DMBA-induced mice), cancer mice with cisplatin administration, cancer mice with PCE administration with three different doses, including dose 1 (500 mg/kg Pn + 15 mg/kg Cr), dose 2 (1000 mg/kg Pn + 75 mg/kg Cr), and dose 3 (2000 mg/kg Pn + 375 mg/kg Cr). The mice were injected with DMBA once a week for six weeks to induce cancer in mice. The breast cancer mice model was administered with PCE orally for 14 days. The expression of CD11b+IL-10+ and CD11b+IFN-γ+ demonstrated macrophage polarization. The results showed that breast cancer induction using DMBA increased the level of IL-10 and decreased the level of IFN-γ significantly compared to the normal group (p < 0.05). In specific doses, administration of PCE could reduce IL-10 levels and increase the level of IFN-γ significantly (p < 0.05). PCE can modulate the polarization of macrophages by suppressing the M2-like macrophage and increasing the M1-like macrophage. The ability of PCE to modulate macrophage polarization indicates that the combination of P. niruri and C. roseus has activity as an anti-cancer.

Antioxidant Activity of Baby Java Citrus Peel Extract Promotes Lung Tissue Repair in Mice Challenged by Lipopolysaccharides: Antioxidant Activity of BJE Promotes Lung Tissue Repair Rachmawati, Farida; Sari, Fikriya Novita; Sakti, Sefihara Paramitha; Sakti, Muhammad Wisam Wira; Rahayu, Sri; Soewondo, Aris; Rifa'i, Muhaimin
Journal of Tropical Life Science Vol. 14 No. 2 (2024)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.14.02.03

Acute lung injury tends to be induced by infection or sepsis that disrupt alveolar and vascular permeability, neutrophil influx, and edema. Those impairments are worsened by the increase of oxidative stress along with hyperinflammation response. Oxidative stress in lung tissue could be indicated by malondialdehyde (MDA) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. This research aimed to evaluate the efficacy of Baby Java citrus peel extract (BJE) in suppressing oxidative stress and preventing lung injury in lipopolysaccharides (LPS)-induced mice. Twenty-five male BALB/c mice were divided into five groups consisting of untreated (N), LPS (A), and LPS-induced followed by treatment using BJE at various doses: 75 mg/kg BW (BJE-1), 105 mg/kg BW (BJE-2), and 150 mg/kg BW (BJE-3). Lungs were isolated for histopathological analysis also detection of MDA and Nrf2 using flow cytometry. BJE at the dose of 105 mg/kg BW could inhibit the alteration of lung histology following LPS challenge including alveolar and interstitial neutrophil infiltration, proteinaceous debris, and septal thickening. The same dose also showed good potency in suppressing MDA and Nrf2 levels as oxidative stress indicators. Our findings demonstrated protective effects of Baby Java citrus peel in acute lung injury and oxidative stress prevention after LPS exposure.

Human-Umbilical Cord-Mesenchymal Stem Cells (hUC-MCSs) Therapy with Extravesicles (EVs) Booster Improves Recovery in Type 2 Diabetes Mellitus with Cardiovascular Disease Nugraha, Dendi Krisna; Jutadi; Anggoro, Naufal Sebastian; Sari, Fikriya Novita; Ardani, Yanuar
International Journal of Cell and Biomedical Science Vol 4 No 10 (2025)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v4i10.66

Background: Type 2 diabetes (T2DM) is a chronic metabolic disorder characterized by insulin resistance and β-cell dysfunction, leading to persistent hyperglycemia and complications. Studies have explored mesenchymal stem cell (MSC)-based therapies and their extracellular vesicles (EVs) as novel approaches for metabolic regulation and tissue repair. Case: A 43-year-old male patient exhibited symptoms including excessive thirst and hunger, frequent urination, fatigue, and intermittent blurry vision. He had type 2 diabetes and recently worsened symptoms. The obese patient had elevated blood glucose, HbA1c, triglycerides, and uric acid. He received umbilical cord-derived mesenchymal stem cells (161,6 × 106 cells), followed by seven intramuscular EV injections (1.5 cc each), along with diet and antioxidant supplements. Results: Three months after the conclusion of treatment, laboratory test showed significant improvement, with fasting glucose levels measuring at 91 mg/dL, HbA1c levels at 5,1%, triglyceride levels at 151 mg/dL, uric acid levels at 4,9 mg/dL, and an erythrocyte sedimentation rate of 12 mm/hr. The clinical symptoms such as nocturia, fatigue, and neuropathic pain, demonstrated a substantial improvement, as well as led to the resolution of skin xerosis and heel fissures. Conclusion: This case suggests that combined UC-MSC and EV therapy, complemented by lifestyle modification, may contribute to metabolic stabilization and symptomatic relief in T2DM patients.

Therapeutic Role of MSC-Secretome in Type 2 Diabetic Models: Correlation between Improved HOMA-IR and Attenuated Pancreatic-Hepatic Structural Alterations Wulandari, Putri Karenina Amalia; Sari, Fikriya Novita; Ardianto, Okky; Widyatmoko, Agus
International Journal of Cell and Biomedical Science Vol 4 No 10 (2025)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v4i10.69

Background: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction, and chronic hyperglycemia leading to multiorgan complications. Conventional therapies primarily target glycemic control but often fail to prevent progressive pancreatic and hepatic injury. This study investigated the therapeutic potential of hypoxic mesenchymal stem cell (MSC) secretome in improving insulin resistance and restoring tissue integrity in T2DM rat models. Methods: Male Wistar rats were induced with T2DM using a high-fat diet followed by streptozotocin–nicotinamide administration and subsequently treated intraperitoneally with MSC-secretome for four weeks. Fasting blood glucose, serum insulin levels, and HOMA-IR index were assessed, followed by histopathological evaluation of hepatic and pancreatic tissues. Results: The results showed that T2DM was significantly associated with elevated insulin levels and HOMA-IR values compared to the normal group, confirming insulin resistance. Treatment with MSC-secretome markedly reduced both parameters (p < 0.001), suggesting improved insulin sensitivity. Histological analyses revealed substantial hepatic and pancreatic degeneration in untreated diabetic rats, characterized by hepatocellular vacuolization, steatosis, and islet necrosis. Conclusion: Conversely, MSC-secretome treatment demonstrated remarkable restoration of lobular architecture, reduced lipid accumulation, and regeneration of pancreatic islets. These reparative effects are attributed to the secretome’s bioactive components that regulate oxidative stress, inflammation, and cellular regeneration. In conclusion, hypoxic MSC-secretome administration effectively ameliorates insulin resistance and attenuates hepatic and pancreatic damage in T2DM rats, underscoring its potential as a novel non-cell-based therapeutic strategy for metabolic disorders.

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