Exploring the Antidiarrheal Properties of Papaya Leaf: Insights In Vivo Study in Mice-Model and In Silico Analysis at M3 Muscarinic Acetylcholine Receptor Interaction.

Diarrhea caused by gut motility involves 5-HT3 serotonin receptor (5-HT3R) antagonist, M3 muscarinic acetylcholine receptor (M3-AchR), and H1 histamine receptor (H1R) via their respective agonist. Papaya (Carica papaya L.) leaf is an herbal medicine to treat diarrhea in Indonesia, though this has not yet been proven scientifically. This study aimed to determine the antidiarrheal properties of papaya leaf through in vivo and in silico studies. In the mice model, papaya leaves were infused with distilled water and subjected to in vivo antidiarrheal study using castor oil-induced diarrhea. In silico molecular docking study of nineteen secondary metabolites was carried out on the M3-AchR (PDB ID: 5ZHP) using AutoDock Tools 1.5.6, while ADMET was predicted by pre-ADMET. The results showed that papaya leaf infusion caused a decrease in the total number of feces, an increase in the onset time of diarrhea, a reduction in the frequency of diarrhea, and an increase in the percentage of inhibition of diarrhea. Quercetin 3-rutinoside, a flavonoid glycoside, is potentially an antidiarrheal remedy at M3-AchR. ADMET prediction showed good distribution on the target and was not toxic, but absorption needed to be considered. We concluded that the antidiarrheal activity of papaya leaf infusion was dose-dependent. Based on a molecular docking study, the flavonoid glycoside was very effective as an antidiarrheal remedy. ADMET prediction showed a specific distribution to the target and was not toxic.

Cassia alata L.: A Study of Antifungal Activity against Malassezia furfur, Identification of Major Compounds, and Molecular Docking to Lanosterol 14-Alpha Demethylase.

Empirically, in Indonesia, the leaves of Cassia alata L. (candle bush or ketepeng cina) have been used as a topical antifungal agent. Malassezia furfur is a natural microorganism found in the human body. It is among the factors contributing to conditions such as pityriasis versicolor, a common, benign, superficial fungal infection of the skin that is closely associated with seborrheic dermatitis and dandruff. This study aimed to explore C. alata leaves, starting from determining antifungal activity against M. furfur and the identification of major compounds in the ethyl acetate and n-hexane fractions, and then we carried out molecular docking of the major compounds in the n-hexane fraction to lanosterol 14-alpha demethylase. The method was the disc diffusion technique to test antifungal activity, LC-MS/MS for major compound identification, and homology modeling through Swiss Models for molecular docking. The fractions of ethyl acetate and n-hexane extract showed concentration-dependent antifungal activity against M. furfur. The LCMS/MS analysis revealed five major compounds in the ethyl acetate and n-hexane fractions. The molecular docking demonstrated the highest binding affinity with stearidonic acid at -7.2 kcal/mol. It can be concluded that the compounds in the n-hexane fraction have antifungal activity against M. furfur, as supported by both in vitro and in silico studies.