Dinia Rizqi Dwijayanti’s research while affiliated with Ritsumeikan University and other places

Deoxycorticosterone acetate (DOCA) and N-nitro-L-arginine methyl ester (L-NAME) hydrochloride have been well-reported as pre-eclampsia inducers due to their ability to mimic hypertension, endothelial dysfunction, and inflammatory response. However, no study has compared the two inducers in developing a mice model of preeclampsia characterized by proinflammatory and anti-inflammatory parameters. The aim of this study was to investigate the efficacy of DOCA and L-NAME hydrochloride in inducing pre-eclampsia in pregnant mice, focusing on the expression of regulatory T cells (Tregs), macrophages, anti-inflammatory cytokines TGF-β, and pro-inflammatory cytokines (IL-6 and IL-1β). Twenty-seven female BALB/c mice were grouped into three groups (n=9): healthy pregnant mice (NP), pregnant mice induced with DOCA (PD), and pregnant mice induced with L-NAME hydrochloride (PL). L-NAME hydrochloride was orally given to the pregnant mice at 4.464 mg/30 g body weight (BW) every day after five days of gestation. DOCA was injected subcutaneously in 0.1 mL of corn oil at 0.74 mg/30 g BW before mating and 0.38 mg/30 g BW once a week until dissection. Drinking water for PD and PL groups was replaced with 0.9% saline. On day 16 of pregnancy, the lymphocytes were isolated from the spleen to determine the profile of Tregs, macrophages, TGF-β, IL-6, and IL-1β using flow cytometry analysis. The results showed that administering L-NAME hydrochloride in pregnant mice exhibited a significant increase in the relative number of IL-1β and macrophages compared to DOCA (p<0.05). L-NAME hydrochloride significantly reduced the production of TGF-β compared to DOCA (p<0.05). Both DOCA and L-NAME hydrochloride could decrease Tregs and IL-6 levels. This study also found that L-NAME hydrochloride was more effective in inducing pre-eclampsia in pregnant BALB/c mice than DOCA indicated by the highest increase in pro-inflammatory cytokines and macrophage activity and a low anti-inflammatory cytokine. The present study provides a foundation for understanding the pathophysiological mechanisms of preeclampsia in the inflammatory pathway; however, further exploration of other mechanisms, markers, and target proteins can deepen insights into its development.

Puji syukur kita panjatkan ke hadirat Tuhan Yang Maha Esa, atas segala rahmat dan karunia-Nya sehingga buku ini yang berjudul “Khasiat, Manfaat, dan Kajian Biologis Tapak Liman (Elephantopus scaber L.)” dapat selesai dengan baik. Buku ini hadir sebagai hasil dari proses penelitian yang mendalam mengenai salah satu tumbuhan yang banyak ditemukan di Indonesia. Tapak Liman, telah lama dikenal dalam pengobatan tradisional masyarakat. Namun, potensi tanaman ini masih banyak yang perlu digali lebih lanjut dari segi biologis, farmakologi, dan aplikasinya dalam dunia kesehatan. Penulisan buku ini bertujuan untuk mengintegrasikan pengetahuan tradisional dengan hasil-hasil penelitian ilmiah terkini mengenai kandungan senyawa bioaktif, aktivitas farmakologis, serta potensi pengembangan Tapak Liman sebagai sumber obat alami. Kami berharap buku ini dapat menjadi referensi yang bermanfaat bagi para peneliti, akademisi, praktisi kesehatan, serta masyarakat umum yang tertarik untuk memahami lebih dalam mengenai tanaman obat.

Blumea balsamifera (Bb) is a plant used as herbal medicine in Southeast Asia, and it has been used due to its antibacterial, antiinflammatory, anticancer, etc. However, there is currently limited evidence that Bb leaf extract from Batu, Indonesia, contains beneficial compounds against breast cancer. Hence, this study evaluates the active compounds in extract and their potential as therapeutic agents for breast cancer. The total phenolic and flavonoid content was determined based on quantified colourimetry analysis followed by DPPH assay to evaluate antioxidant activity and phytochemicals screening in the extract, which was characterised by LC-HRMS analysis. Furthermore, computational methods are used to predict the pharmacological properties of compounds in the extract, particularly against breast cancer. The results showed a total phenolic content of 103.85+1.5 mgGAE/g and a total flavonoid content of 225.99+17.68 mgQE/g, with an antioxidant activity of 255.17+13.11µg/mL. 11 compounds were identified, but only four (Aurantio-obtusin, Isorhamnetin, Quercetin, and Hemiphloin) were computationally analysed. Molecular docking and dynamics simulation indicate that these phytochemicals bind to their target, possibly limiting their activity. Therefore, Bb has potential as a natural product remedy for breast cancer and contributes significantly to our knowledge of the plant by providing essential data for its future development.

Excessive inflammation, driven by macrophage activation and nitric oxide (NO) production, underlies various diseases. This study investigates the anti-inflammatory potential of bungur (Lagerstroemia speciosa L.) leaf extract. We characterized its phytochemical profile and evaluated the effects using in silico approaches. Bungur leaves (L. speciosa L.) were extracted using MAE extraction and subjected to phenol, flavonoid, terpenoid, alkaloid content and antioxidant DPPH assay. The compound profile was analyzed using LC-HRMS. Identified compounds were screened in silico for drug-likeness, bioactivity, and membrane permeability. Molecular docking and molecular dynamics simulations were conducted to evaluate the interaction and stability of selected compounds with TLR4/MD2 complex. This study demonstrated that bungur leaf extract exhibited higher levels of phenolic and flavonoid compounds than terpenoids and alkaloids. This finding was confirmed by the LC-HRMS analysis, which revealed a dominance of phenolic and flavonoid compounds in the extract. The extract also showed excellent DPPH antioxidant activity, as evidenced by its low IC50 value. In silico studies identified luteolin, luteolin 7-sulfate, and quercetin as the three best compounds, which acted as potent competitive inhibitors of TLR4 activation. Therefore, compounds contained in bungur leaf exhibited promising anti-inflammatory activity through TLR4 inhibition.

Obesity, which is characterized by excessive body fat accumulation and energy imbalance, is a major risk factor for type 2 diabetes mellitus. Boesenbergia rotunda rhizomes (known as fingerroots) exhibit a variety of pharmacological activities and are used in traditional medicine. Pinostrobin was identified as a major constituent of Boesenbergia rotunda rhizome (BR) extract and suppressed nitric oxide production in interleukin 1β-treated hepatocytes. Next, we investigated the anti-obesity effects of BR extract in ob/ob mice, a type 2 diabetes mellitus model. The ob/ob mice were treated with or without 1% BR extract for 14 days and then analyzed for serum insulin and triglyceride levels, liver histology, and liver mRNA expression. The administration of BR extract significantly decreased blood glucose concentrations and increased serum insulin concentrations in ob/ob mice. In addition, this treatment reduced triglyceride levels in both the serum and liver and decreased lipid accumulation in hepatocytes. Microarray analysis revealed that hepatic mRNA affected the expression of genes involved in inflammation, lipid metabolism, lipid synthesis, and insulin signaling, leading to improvements in obesity. Because BR extract has hypoglycemic and antidiabetic effects on ob/ob mice, it might be a promising candidate for addressing obesity and related metabolic disorders.

Breast cancer is a type of cancer that has a high rate of diagnosis and mortality in the world. Lagerestroemia speciosa is a herb that has anticancer activity. This study aims to analyze the compounds in L. speciosa that most act as anticancer of the breast. The compounds in L. speciosa were selected based on drug-likeness, physicochemical properties, ability to penetrate the lipid bilayer and toxicity. The Lagerstroemin target related to Lagestroemin breast cancer was predicted using DisGeNET, SWISS Target Prediction and cBioportal. Molecular docking between Lagerstroemin and AURKA, EGFR and SRC was performed using AutoDock Vina. The interaction stability of each complex was analyzed by molecular dynamic simulation using YASARA with parameters of RMSD protein, RMSD ligand, number of hydrogen bonds and molecular dynamic binding energy. Of the 22 compounds, Quercetin, Caffeic acid, Lagerstroemin and Dypirone were predicted to have good ADME properties and can easily penetrate lipid membranes. Therefore, Quercetin, Caffeic acid and Lagerstroemin were predicted to have anti-breast cancer bioactivity. Of the 3 compounds, Lagerstroemin had the lowest toxicity. Lagerstroemin was predicted to interact with breast cancer-related proteins AURKA, EGFR and SRC. Molecular docking and dynamics showed that Lagerestroemin interacted stably at the ATP binding site of the 3 proteins, so it was very potential as an inhibitor of these 3 proteins. Therefore, Lagerstroemin was predicted to be the compound in L. speciosa with the most potential breast anticancer agent by targeting AURKA, EGFR and SRC. HIGHLIGHTS Quercetin, Caffeic acid and Lagerstroemin from Lagerstroemia speciosa show promising anticancer properties for breast cancer treatment. Lagerstroemin stands out with low toxicity and potent anticancer activity, suggesting its safety and effectiveness as a therapeutic agent. Lagerstroemin interacts stably with breast cancer-related proteins AURKA, EGFR and SRC, indicating its potential as a powerful inhibitor targeting key pathways in breast cancer. GRAPHICAL ABSTRACT