Molecular Insight into the Pharmacological Potential of Clerodendrum minahassae Leaf Extract for Type-2 Diabetes Management Using the Network Pharmacology Approach.

Background and Objectives: The increasing occurrence and prevalence of type-2 diabetes mellitus (T2DM) have led to a growing interest in researching available treatment alternatives. Clerodendrum minahassae, a native plant species of North Sulawesi, has been a focus of ethnopharmacological studies due to its significance contributions to drug development, particularly its potential antidiabetic properties. This study investigated the pharmacological potential of Clerodendrum minahassae (CM) leaf extract for managing type-2 diabetes (T2DM) using a network pharmacology approach. Materials and Methods: Active compounds were extracted from CM leaves, and their interactions with target proteins in T2DM were explored through various in silico analyses. Results: SAR analysis using Way2Drug Pass Online identified 29 bioactive CM leaf extract compounds with promise as T2DM treatments. Additionally, 26 of these met Ro5 criteria for favorable drug-likeness. Most compounds exhibited positive pharmacodynamic and pharmacokinetic profiles, with 22 considered safe, while 7 posed potential toxicity risks when ingested individually. CM leaf extract targeted 60 T2DM-related proteins, potentially affecting T2DM via cytokine regulation, particularly in proteins linked to metabolic processes, cellular response to angiotensin, and the sphingosine-1-phosphate signaling pathway. The network pharmacology analysis identified five genes targeted by CM leaf extract, namely, STAT3, MAPK1, ESR1, PIK3R1, and NFKB1. Among these genes, PIK3R1's interaction with the insulin receptor (INSR) positions it as a crucial candidate gene due to its pivotal role in insulin signal transduction during T2DM development. Conclusions: This research sheds light on the therapeutic potential of CM leaf extract for treating T2DM. This potential is attributed to the diverse array of bioactive compounds present in the extract, which have the capacity to interact with and inhibit proteins participating in the insulin signal transduction pathway crucial for the progression of T2DM. The findings of this study may open up possibilities for future applications of CM leaf extract in the development of novel T2DM treatments.

Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach.

In many countries, the fruit of betel (Piper betle Linn) is traditionally used as medicine for treating malaria. It is a fatal disease, and existing medications are rapidly losing potency, necessitating the development of innovative pharmaceutics. The current study attempted to determine the compounds in the n-hexane fraction of betel fruit extract and investigate the potential inhibition of bioactive compounds against aspartic protease plasmepsin 1 (PDB ID: 3QS1) and plasmepsin 2 (PDB ID: 1LEE) of Plasmodium falciparum using a computational approach. The ethanol extract was fractionated into n-hexane and further analyzed using gas chromatography-mass spectrometry (GC-MS) to obtain information regarding the compounds contained in betel fruit. Each compound's potential antimalarial activity was evaluated using AutoDock Vina and compared to artemisinin, an antimalarial drug. Molecular dynamics simulations (MDSs) were performed to evaluate the stability of the interaction between the ligand and receptors. Results detected 20 probable compounds in the n-hexane extract of betel fruit based on GC-MS analysis. The docking study revealed that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)- has the highest binding affinity for plasmepsin 1 and plasmepsin 2. The compound exhibits a similar interaction with artemisinin at the active site of the receptors. The compound does not violate Lipinski's rules of five. It belongs to class 5 toxicity with an LD50 of 3000 mg/kg. MDS results showed stable interactions between the compound and the receptors. Our study concluded that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)- from betel fruit has the potential to be further investigated as a potential inhibitor of the aspartic protease plasmepsin 1 and plasmepsin 2 of Plasmodium falciparum.

Data on the docking of phytoconstituents of betel plant and matcha green tea on SARS-CoV-2.

Betel (Piper betle L.) and green tea (Camellia sinensis (L) O. Kuntze) have been used for a long time as traditional medicine. The docking of phytoconstituents contained in the betel plant was evaluated against Mpro, and matcha green tea was evaluated against five target receptors of SARS-CoV-2 as follows: spike ectodomain structure (open state), receptor-binding domain (RDB), main protease (Mpro), RNA-dependent RNA polymerase (RdRp), dan papain-like protease (PLpro). The evaluation was carried out based on the value of binding-free energy and the types of interactions of the amino acids at the receptors that interact with the ligands.

Isolation and Identification of Arsenic-resistant Bacteria for Possible Application in Arsenic Bioremediation.

BACKGROUND AND OBJECTIVE: North Sulawesi is rich in minerals, among them gold is also present. The gold mining in the Buyat area produces heavy metal waste which can pollute the environment, among others is arsenic. Arsenic is a heavy metal that is very toxic to humans, so an agent is needed for the remediation process. The aim of this study was to isolate and identify arsenic-resistant bacteria from the Buyat estuary and beach to analyze the isolates' ability to detoxify arsenic. MATERIALS AND METHODS: Soil sediment samples were obtained from Buyat estuary and beach in North Sulawesi. Isolation of arsenic-resistant bacteria was carried out by growing the samples in LB broth media containing 100, 500 and 1000 ppm arsenite. Indentification of arsenic-resistant bacteria was carried out by microbiological, biochemical and biomolecular analysis. The ability to detoxify arsenite was analyzed by CVAFS. RESULTS: The study showed that there were 4 isolates of arsenic-resistant bacteria isolated from the soil samples. All isolates are rod-shaped, Gram-negative and non-motile bacteria. BLAST results showed that isolates A was Stenotrophomonas sp., isolate B was Stenotrophomonas maltophilia, isolate C was Pseudomonas sp. and isolate D was Pseudomonas putida. All isolates reduced the levels of arsenic in media by almost 100% within 72 h. CONCLUSION: The study suggested that Stenotrophomonas sp., S. maltophilia, Pseudomonas sp. and P. putida had the potentials to be used in the bioremediation of arsenic.