Platelet plays a crucial role in cardiovascular diseases (CVDs) development. Abnormalities in platelet aggregation provokes thromboembolism, eventually leading to death. In Indonesia, breadfruit (Artocarpus altilis) leaf is traditionally used to treat CVDs. This study aimed to evaluate the antiplatelet activity of A. altilis leaf extract (AAE) and to identify its active compound. A. altilis leaves were extracted with ethanol, and the antiplatelet activity was assessed using ADP-induced platelet aggregation. The major compound was isolated with column chromatography followed by preparative TLC, and the structure was determined on the basis of UV, MS, IR, and NMR spectra. The binding mode of the active compound to platelet receptors was characterized in in silico study. AAE exhibited an antiplatelet activity (IC50 of 252.23 µg/mL). A geranylated chalcone, 2-geranyl-2ʹ,3,3,4ʹ-tetrahydroxydihydrochalcone (GTDC) was identified as the antiplatelet compound (IC50 of 9.09 µM). GTDC actions with P2Y12 platelet receptor involving three amino acid residues.

Phosphodiesterase-1 (PDE1) is a versatile enzyme that has surprisingly received considerable attention as a possible therapeutic target in Alzheimer’s disease (AD) because it maintains the homeostasis of 3ʹ,5ʹ-cyclic adenosine monophosphate (cAMP) and 3ʹ,5ʹ-cyclic guanosine monophosphate (cGMP) in the brain. 3ʹ,5ʹ-cyclic adenosine monophosphate and 3ʹ,5ʹ-cyclic guanosine monophosphate are the two key second messengers that regulate a broad range of intracellular processes and neurocognitive functions, specifically memory and cognition, associated with Alzheimer’s disease. However, the lack of available selective drugs on the market poses challenges to identifying the beneficial effects of natural products. The present review focuses on Phosphodiesterase-1 and its isoforms, splicing variants, location, distribution, and function; the role of Phosphodiesterase-1 inhibitors in Alzheimer’s disease; and the use of vinpocetine and natural products as specific Phosphodiesterase-1 inhibitors. Moreover, it aims to provide ongoing updates, identify research gaps, and present future perspectives. This review indicates the potential role of Phosphodiesterase-1 inhibitors in the treatment of neurodegenerative disorders, such as Alzheimer’s disease. Certain clinical trials on the alleviation of Alzheimer’s disease in patients are still in progress. Among de novo outcomes, the employment of Phosphodiesterase-1 inhibitors to treat Alzheimer’s disease is an important advancement given the absence of particular therapies in the pipeline for this highly prevalent disease. To sum up, Phosphodiesterase-1 inhibition has been specifically proposed as a critical therapeutic approach for Alzheimer’s disease. This study provides a comprehensive review on the biological and pharmacological aspects of Phosphodiesterase-1, its role on the Alzheimer’s diseases and its significance as Alzheimer’s disease therapeutic target in drug discovery from natural products. This review will help clinical trials and scientific research exploring new entities for the treatment and prevention of Alzheimer’s disease.

In the last decade, Indonesia intensifies the efforts to reduce pharmaceutical imports. One of the initiatives is establishing a paracetamol production facility to start operating in 2024. Kinetics study is needed as a basis to design the paracetamol reactor. This study investigated the optimal temperature, reactant mole ratio, and agitation speed in the reactor for paracetamol production. In this study, aqueous solution of para-aminophenol was reacted with acetic anhydride. The mole ratio of para-aminophenol to acetic anhydride was varied to 1:1, 1:1.2, 1:1.5, and 1:2 while the temperature was varied to 80 °C, 90 °C, and 110 °C. However, due to uncontrolled heat of the reaction and limitation of the mixture’s boiling point, the actual reaction temperatures were 86 °C, 90 °C, and 108 °C. In addition, the agitation speed of 250 RPM and 350 RPM were also studied. Thin layer chromatography (TLC) and densitometry were used to determine the concentration of paracetamol in the reacting mixture. The optimum temperature, reactant mole ratio, and agitation speed in this study were 108 °C, 1:1.5, and 350 RPM, respectively. In addition, a reaction performed under those operating parameters gave the reaction rate constant of 1.95 L mol-1 min-1.Keywords: acetic anhydride; kinetics; para-aminophenol; paracetamol; pharmaceutical industry A B S T R A KDalam sepuluh tahun terakhir ini, Indonesia bertekad mengurangi impor bahan baku farmasi. Salah satu upaya yang dilakukan adalah membangun fasilitas produksi parasetamol yang akan mulai beroperasi pada tahun 2024. Studi kinetika diperlukan sebagai dasar perancangan reaktor parasetamol. Oleh karena itu, penelitian ini mengkaji kondisi operasi optimal pada reaksi produksi parasetamol yang akan dibutuhkan sebagai dasar perancangan pabrik. Pada percobaan ini, para-aminofenol direaksikan dengan anhidrida asetat dengan media air. Rasio mol para-aminofenol terhadap asetat anhidrida divariasikan 1:1 1:1,2, 1:1,5, dan 1:2 sedangkan temperatur divariasikan 80 °C, 90 °C, dan 110 °C. Akan tetapi, karena panas reaksi yang tidak dikontrol dan batasan berupa titik didih dari campuran reaksi, temperatur aktual reaksi menjadi 86 °C, 90 °C, dan 108 °C. Selain itu, kecepatan putaran pengadukan juga divariasikan pada angka 250 RPM dan 350 RPM. Kromatografi lapis tipis (KLT) dan densitometri digunakan untuk menentukan konsentrasi parasetamol dalam campuran reaksi. Temperatur, rasio mol reaktan, dan kecepatan putaran pengadukan yang optimum pada penelitian ini masing-masing adalah 110 °C, 1:1,5, dan 350 RPM. Selain itu, reaksi yang dilakukan dengan kondisi operasi tersebut menghasilkan konstanta laju reaksi 1,95 L mol-1 menit-1.Kata kunci: anhidrida asetat, industri farmasi, kinetika, para-aminofenol, parasetamol