In cell development, the cell cycle is crucial, and the cycle progression’s main controllers are endogenous CDK inhibitors, cyclin-dependent kinases (CDKs), and cyclins. In response to the mitogenic signal, cyclin D is produced and retinoblastoma protein (Rb) is phosphorylated due to activated CDK4/CDK6. This causes various proteins required in the cell cycle progression to be generated. In addition, complexes of CDK1-cyclin A/B, CDK2-cyclin E/A, and CDK4/CDK6-cyclin D are required in each phase of this progression. Cell cycle dysregulation has the ability to lead to cancer. Based on its role in the cell cycle, CDK has become a natural target of anticancer therapy. Therefore, understanding the CDK structures and the complex formed with the drug, helps to foster the development of CDK inhibitors. This development starts from non-selective CDK inhibitors to selective CDK4/CDK6 inhibitors, and these have been applied in clinical cancer treatment. However, these inhibitors currently require further development for various hematologic malignancies and solid tumors, based on the results demonstrated. In drug development, the main strategy is primarily to prevent and asphyxiate drug resistance, thus a determination of specific biomarkers is required to increase the therapy’s effectiveness as well as patient selection suitability in order to avoid therapy failure. This review is expected to serve as a reference for early and advanced-stage researchers in designing new molecules or repurposing existing molecules as CDK4/CDK6 inhibitors to treat breast cancer.

The G1 phase of cell cycle progression is regulated by Cyclin-Dependent Kinase 4 (CDK4) as well as Cyclin-Dependent Kinase 6 (CDK6), and the acivities of these enzymes are regulated by the catalytic subunit, cyclin D. Cell cycle control through selective pharmacological inhibition of CDK4/6 has proven to be beneficial in the treatment of estrogen receptor-positive (ER-positive) breast cancer, particularly improving the progression-free survival of patients. Thus, targeting specific inhibition on CDK4/6 is bound to increase therapeutic efficiency. This study aimed to obtain CDK4/6 inhibitors through a pharmacophore-based virtual screening of the ZINC15 purchasable compound database using the in silico method. The pharmacophore model was designed based on the FDA-approved cdk4/6 inhibitor structures, and molecular docking was performed to further screen the hit compounds obtained. A total of eight compounds were selected based on docking results and interactions with CDK4 and CDK6, using palbociclib as the reference drug. According to the results, the compounds of ZINC585292724 and ZINC585291674 were the best compounds based on free binding energy, as well as hydrogen bond stability, and, therefore, exhibit potential as starting points in the development of CDK4/6 inhibitors.

Atherosclerosis is a chronic inflammatory disease that begins with endothelial dysfunction, it caused fat accumulation and plaque growth in the inner arteries walls. Endothelial dysfunction will activate the Mitogen Activated Protein Kinase (MAPK) pathway involving ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, as well as the Nuclear Factor Kappa B (NF-kB) pathway involving IKK proteins. Terpinen-4-ol is constituent found in the bangle rhizome. The purpose of this study were to determine the affinity and mechanisms of terpinen-4-ol against ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins as anti-inflammatory in atherosclerosis performed using molecular docking method. The study was conducted exploratively with several steps such as preparation and optimization of terpinen-4-ol structure, preparation of 3D ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, validation method of molecular docking, and docking terpinen-4-ol in these proteins. The docking result are assessed from the binding energy and hydrogen bonds formed between terpinen-4-ol and proteins. The smaller value of binding energy terpinen-4-ol with target proteins showed the complex that form more stable. The result showed that terpinen-4-ol and has activity in inhibiting the inflammatory process because it is able to disturb ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins with respective bond energy values -5,12; -5,24; -5,08; -5,88; and -4,99 Kcal/mol. The molecular mechanism in inhibiting the activity of ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins is through the formation of hydrogen bonds in these proteins. These results show that terpinen-4-ol have the potential to inhibit inflammatory process and the formation of atherosclerotic plaque can be obstructed. Keywords : atherosclerosis, terpinen-4-ol, molecular docking, in silico

Phenol compound in Piper betle leaves has several pharmacology activities such as antibacteria, antifungi and antioxidant. The pharmacology activities of a herbal drug are influenced by the phytochemistry content, so in order to do a quality determination that provides phytochemistry profile and consistent pharmacology activities, a standardization is required. Fingerprint is the main standard to perform quality control for herbal drug. TLC-spectrophotodensitometry was used as the method in order to provide fingerprint profile of phenol compound. In this experiment, Piper betle leaves samples were extracted by reflux method using ethanol 96% as the solvent. Identification of phenol compound was done using TLC-spectrophotodensitometry with Silica gel 60 F254 as the stationary phase, toluena: ethyl acetate (93:7 v/v) as the mobile phase, FeCl3 and Folin-Ciocalteau as the reagent. The fingerprint profile of phenol compund was shown in Rf value 0,19; 0,42; and 0,62. Positive results of phenol compound are black spot on FeCl3 colour test and dark blue spot on Folin-Ciocalteau colour test. Maximum wavelength of phenol compound was 283 nm.

Dalam tubuh manusia, radikal bebas dapat berasal dari dua sumber. Radikal bebas yang bersumber dari luar tubuh seperti polusi udara, asap rokok dan radiasi dari perangkat elektronik seperti ponsel dan televisi. Radikal bebas dari dalam tubuh dapat secara alami terjadi akibat proses oksidasi enzimatik maupun autooksidasi. Antioksidan merupakan senyawa kimia yang dapat tercipta dalam tubuh manusia secara alami atau diperoleh dari luar tubuh melalui makanan, yang dapat menjadikan radikal bebas menjadi bentuk yang lebih stabil. Senyawa metabolit sekunder seperti fenolik, flavonoid, atau asam organik yang berasal dari bahan alam seperti daun salam dapat menjadi sumber antioksidan dari luar tubuh. Daun salam (Syzygum polyanthum) memiliki berbagai kandungan metabolit sekunder salah satunya yakni flavonoid. Daun ini dapat ditemukan dengan mudah dalam keseharian. Pada review artikel ini akan dibahas terkait potensi daun salam sebagai sumber antioksidan untuk penangkal radikal bebas. Metode yang digunakan pada pembuatan artikel review ini adalah penelusuran literatur nasional maupun internasional dalam 5 tahun terakhir sebanyak 6 jurnal. Berbagai penelitian menunjukkan bahwa ekstrak daun salam (Syzygium polyanthum) memiliki aktivitas antioksidan karena polifenolnya. Berdasarkan skrining fitokimia senyawa bioaktif yang banyak terkandung di dalam daun salam adalah flavonoid. Flavonoid adalah senyawa polifenol yang memiliki manfaat salah satunya adalah sebagai antioksidan. Dengan demikian, daun salam (Syzygium polyanthum) dapat memiliki potensi sebagai sumber antioksidan untuk menangkal radikal bebas.

Aterosklerosis merupakan penyakit inflamasi kronis pada dinding arteri yang disebabkan oleh penumpukan lemak dan disfungsi endotel di dinding arteri sehingga menyebabkan penyempitan pembuluh darah dan mengganggu aliran darah. Terjadinya peradangan pembuluh darah dapat berkontribusi terhadap aterosklerosis. Salah satu inovasi dalam pengolahan bawang putih yaitu pengembangan bawang putih menjadi bawang hitam melalui proses fermentasi pada suhu tinggi (60- 70°C) dan kelembaban tinggi (80-90%) yang dikontrol selama periode waktu tertentu tanpa penambahan bahan tambahan. Hasil dari fermentasi bawang putih segar berwarna putih berubah menjadi hitam dan memiliki rasa manis, tekstur kenyal seperti jeli. Senyawa aktif dalam bawang hitam, seperti allicin dan S-allyl-cysteine (SAC), telah diteliti mampu meningkatkan kesehatan pembuluh darah dan mereduksi risiko aterosklerosis. Pada saat proses fermentasi pada suhu tinggi, senyawa aktif bawang putih diubah menjadi senyawa antioksidan. Kandungan antioksidan pada bawang hitam mampu meningkatkan profil lipid darah sehingga mencegah terjadinya aterosklerosis. Review artikel ini bertujuan untuk memberikan informasi mengenai potensi bawang hitam dalam menurunkan nilai kolesterol LDL dan berperan sebagai agen antiaterosklerosis. Metode yang digunakan dalam review artikel ini yaitu studi literatur dari berbagai hasil penelitian secara online pada jurnal nasional dan internasional dalam 5 tahun terakhir. Penelitian menunjukkan bahwa bawang hitam memiliki potensi untuk menurunkan nilai kolesterol LDL dan trigliserida yang merupakan faktor risiko utama dalam pembentukan plak aterosklerosis di pembuluh darah. Selain itu, bawang hitam dapat meningkatkan HDL pada tikus yang diinduksi diet tinggi lemak. Bawang hitam dapat disarankan karena berpotensi dalam menurunkan nilai kolesterol LDL dan berperan sebagai agen antiaterosklerosis.