Evaluation of the antiplasmodial and anti-Toxoplasma activities of several Indonesian medicinal plant extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria, caused by Plasmodium parasites, remains a significant global health challenge, particularly in tropical and subtropical regions. At the same time, the prevalence of toxoplasmosis has been reported to be 30% worldwide. Traditional medicines have long played a vital role in discovering and developing novel drugs, and this approach is essential in the face of increasing resistance to current antimalarial and anti-Toxoplasma drugs. In Indonesian traditional medicine, various plants are used for their therapeutic properties. This study focuses on eleven medicinal plants from which nineteen extracts were obtained and screened for their potential medicinal benefits against malaria and toxoplasmosis. AIMS OF THE STUDY: The aim of this study was to evaluate the efficacy of extracts from Indonesian medicinal plants to inhibit Plasmodium falciparum, a parasite responsible for malaria, and Toxoplasma gondii, an opportunistic parasite responsible for toxoplasmosis. METHODS: Nineteen extracts from eleven plants were subjected to in vitro screening against P. falciparum 3D7 (a chloroquine-sensitive strain) and the T. gondii RH strain. In vitro treatments were conducted on P. falciparum 3D7 and K1 (multidrug-resistant strains) using the potent extracts, and in vivo assessments were carried out with mice infected with P. yoelii 17XNL. LCMS analysis was also conducted to identify the main components of the most effective extract. RESULTS: Seven extracts showed significant antiplasmodial activity (>80% inhibition) at a concentration of 100 µg/ml. These extracts were obtained from Dysoxylum parasiticum (Osbeck) Kosterm., Elaeocarpus glaber (Bl.) Bijdr., Eleutherine americana Merr., Kleinhovia hospita L., Peronema canescens Jack, and Plectranthus scutellarioides (L.) R.Br. Notably, the D. parasiticum ethyl acetate extract exhibited high selectivity and efficacy both in vitro and in vivo. Herein, the key active compounds oleamide and erucamide were identified, which had IC50 values (P. falciparum 3D7/K1) of 17.49/23.63 µM and 32.49/51.59 µM, respectively. CONCLUSIONS: The results of this study highlight the antimalarial potential of plant extracts collected from Indonesia. Particularly, extracts from D. parasiticum EtOH and EtOAc stood out for their low toxicity and strong antiplasmodial properties, with the EtOAc extract emerging as a notably promising antimalarial candidate. Key compounds identified within this extract demonstrate the complexity of extracts' action against malaria, potentially targeting both the parasite and the host. This suggests a promising approach for developing new antimalarial strategies that tackle the multifaceted challenges of drug resistance and disease management. Future investigations are necessary to unlock the full therapeutic potential of these extracts.

Molecular Docking Study of Phytosterols in Lygodium microphyllum Towards SIRT1 and AMPK, the in vitro Brine Shrimp Toxicity Test, and the Phenols and Sterols Levels in the Extract.

Background: Lygodium microphyllum is a fern plant with various pharmacological activities, and phytosterols were reported contained in the n-hexane and ethyl acetate extract of this plant. Phytosterols are known to inhibit steatosis, oxidative stress, and inflammation. Sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are the key proteins that control lipogenesis. However, information about L. microphyllum on SIRT1 and AMPK is still lacking. Purpose: This study aims to investigate the binding mode of phytosterols in L. microphyllum extract towards AMPK and SIRT1, and the toxicity of the extract against brine shrimp (Artemia salina) larvae, and to determine the phenols and sterols levels in the extract. Methods: The molecular docking was performed towards SIRT1 and AMPK using AutoDock v4.2.6, the toxicity of the extract was assayed against brine shrimp (Artemia salina) larvae, and the phytosterols were analyzed by employing a thin layer chromatography densitometry, and the total phenols were by spectrophotometry. Results: The molecular docking study revealed that ß-sitosterol and stigmasterol could occupy the active allosteric-binding site of SIRT1 and AMPK by binding to important residues similar to the protein's activators. The cold extraction of the plant yields 15.86% w/w. Phytochemical screening revealed the presence of phenols, steroids, flavonoids, alkaloids, and saponins. The total phenols are equivalent to 126 mg gallic acid (GAE)/g dry extract, the total sterols are 954.04 µg/g, and the ß-sitosterol level is 283.55 µg/g. The LC50 value of the extract towards A. salina larvae is 203.704 ppm. Conclusion: Lygodium microphyllum extract may have the potential to be further explored for its pharmacology activities, particularly in the discovery of plant-based anti-dyslipidemic drug candidates. However, further studies are needed to confirm their roles in alleviating lipid disorders.

The Cytotoxic Activity of Dammarane-Type Triterpenoids Isolated from the Stem Bark of Aglaia cucullata (Meliaceae).

The Aglaia genus, a member of the Meliaceae family, is generally recognized to include a number of secondary metabolite compounds with diverse structures and biological activities, including triterpenoids. Among the members of this genus, Aglaia cucullata has been reported to have unique properties and thrives exclusively in mangrove ecosystems. This plant is also known to contain various metabolites, such as flavaglines, bisamides, and diterpenoids, but there are limited reports on the isolation of triterpenoid compounds from its stem bark. Therefore, this research attempted to isolate and elucidate seven triterpenoids belonging to dammarane-type (1-7) from the stem bark of Aglaia cucullata. The isolated compounds included 20S,24S-epoxy-3α,25-dihydroxy-dammarane (1), dammaradienone (2), 20S-hydroxy-dammar-24-en-3-on (3), eichlerianic acid (4), (20S,24RS)-23,24-epoxy-24-methoxy-25,26,27-tris-nor dammar-3-one (5), 3α-acetyl-cabraleahydroxy lactone (6), and 3α-acetyl-20S,24S-epoxy-3α,25-dihydroxydammarane (7). Employing spectroscopic techniques, the chemical structures of the triterpenoids were identified using FTIR, NMR, and HRESITOF-MS. The cytotoxic activity of compounds 1-7 was tested with the PrestoBlue cell viability reagent against MCF-7 breast cancer, B16-F10 melanoma, and CV-1 normal kidney fibroblast cell lines. The results displayed that compound 5 had the highest level of bioactivity compared to the others. Furthermore, the IC50 values obtained were more than 100 µM, indicating the low potential of natural dammarane-type triterpenoids as anticancer agents. These findings provided opportunities for further studies aiming to increase their cytotoxic activities through semi-synthetic methods.

Sesquiterpenoids and sesquiterpenoid dimers from the stem bark of Dysoxylum parasiticum (osbeck) kosterm.

Two undescribed sesquiterpenoids, namely dysoticans A and B, and three undescribed sesquiterpenoid dimers, namely dysoticans C-E, together with six analogs, were isolated from the stem bark of Dysoxylum parasiticum (Osbeck) Kosterm. (Meliaceae), growing in West Java, Indonesia. Their structures were elucidated based on extensive spectroscopic analysis and theoretical simulations of ECD spectra and 13C NMR shifts. Dysoticans A and B possessed undescribed cadinanes with minor modifications, while C and D featured unprecedented pseudo-sesquiterpenoid dimers through O-ether linkages of cadinanes and guaianes, respectively. Dysotican E was also characterized as the true-sesquiterpenoid dimer featuring eudesmane-germacrene hybrid framework from the Meliaceae family. Furthermore, A-C and E showed moderate activities against the human breast cancer MCF-7 and cervical cancer HeLa cell lines with IC50 values ranging from 22.15 to 45.14 µM. D selectively exhibited significant cytotoxicity against the HeLa cell line with an IC50 value of 13.00 ± 0.13 µM.

Role of the AMPK/SIRT1 pathway in non­alcoholic fatty liver disease (Review).

Non­alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP­activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.

Dipeptidyl peptidase IV inhibition of phytocompounds from Artocarpus champeden (Lour.) Stokes: In silico molecular docking study and ADME-Tox prediction approach.

The present study examines the potential activity prediction based on free binding energy (ΔG) and interaction confirmation of phytocompounds from Artocarpus champeden (Lour.) Stokes with macromolecule protein receptor of dipeptidyl peptidase IV (DPP-IV) using in silico molecular docking studies and physicochemical and pharmacokinetic properties (ADME-Tox) prediction approaches. The active subsites of the DPP-IV receptor macromolecule protein Protein Data Bank (ID: 1 × 70) were docked using Autodock v4.2.6 (100 docking runs). A grid box of 52 × 28 × 26 Å points spaced by 0.37 Å was centered on the active site of x = 40.926 Å; y = 50.522 Å; z = 35.031 Å. For ADME-Tox prediction, Swiss ADME online-based application programs were used. The results show that 12 pythocompounds from A. champeden have the potential as DPP-IV inhibitors based on ΔG value and interaction conformation. There are five pythocompounds with lower ΔG values and inhibition constants than the native ligand and seven pythocompounds with ΔG values and inhibition constants close to the native ligand. The 12 compounds form an interaction conformation at the active subsites of the DPP-IV receptor. At the same time, the results of the ADME-Tox prediction analysis showed that the 12 compounds had different physicochemical and pharmacokinetic properties.

New dammarane-type triterpenoids from Aglaia elliptica (C.DC.) blume.

Three new dammarane-type triterpenoids, namely elliptaglin A-C (1-3) were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume along with three known derivatives, namely (20S)-hydroxydammar-24-en-3-on (4), cabralealactone (5), and E-25-hydroperoxydammar-23-en-20-ol-3-one (6). Subsequently, their chemical structures were determined using HR-ESI-MS, FTIR, 1D and 2D-NMR spectroscopic analysis as well as comparison with previous studies. The cytotoxicity activities of the isolated compounds against MCF-7 breast cancer and B16-F10 melanoma cell lines were then tested using PrestoBlue reagent. The analysis results showed that elliptaglin B (2) had the strongest activity against both cell lines with IC50 values of 60.98 and 51.83 µM, respectively.

Mitragyna Species as Pharmacological Agents: From Abuse to Promising Pharmaceutical Products.

Mitragyna is a genus belonging to the Rubiaceae family and is a plant endemic to Asia and Africa. Traditionally, the plants of this genus were used by local people to treat some diseases from generation to generation. Mitragyna speciosa (Korth.) Havil. is a controversial plant from this genus, known under the trading name "kratom", and contains more than 40 different types of alkaloids. Mitragynine and 7-hydroxymitragynine have agonist morphine-like effects on opioid receptors. Globally, Mitragyna plants have high economic value. However, regulations regarding the circulation and use of these commodities vary in several countries around the world. This review article aims to comprehensively examine Mitragyna plants (mainly M. speciosa) as potential pharmacological agents by looking at various aspects of the plants. A literature search was performed and information collected using electronic databases including Scopus, ScienceDirect, PubMed, directory open access journal (DOAJ), and Google Scholar in early 2020 to mid-2021. This narrative review highlights some aspects of this genus, including historical background and botanical origins, habitat, cultivation, its use in traditional medicine, phytochemistry, pharmacology and toxicity, abuse and addiction, legal issues, and the potential of Mitragyna species as pharmaceutical products.

Novel Amides Derivative with Antimicrobial Activity of Piper betle var. nigra Leaves from Indonesia.

Piper betle var. nigra is a tropical plant closely related to the common piper. P. betle has also been dubbed a promising source of natural antioxidants in herbal health products, antibacterial, antifungal, antimalarial, cytotoxic activity against the cancer cell lines K562 and HL-60, and antileishmanial. The aim of this study to observation Antimicrobial activity and isolation of chemical compound. The antimicrobial activity of P. betle extract was performed by well diffusion method against two oral pathogenic bacteria (Streptococcus mutans and Streptococcus sanguinis) and opportunistic pathogenic yeast (Candida albicans). The inoculum (bacterial and yeast suspension) was prepared from a 24-h culture on NB for bacterial suspension and on TSB for yeast suspension. Extraction and isolation using various method of chromatography. Isolated compounds were characterized by spectroscopic means. Our study showed antimicrobial activity from crude ethanol extract of leaves P. betle L. var. nigra against two oral pathogenic bacteria and opportunistic pathogenic yeast with concentration 0.5% and 1%. The first report of two new amides derivatives, piperenamide A (1) and piperenamide B (2) in P. betle L. var. nigra.