Nanoparticle-Based Antioxidants in Stress Signaling and Programmed Cell Death in Breast Cancer Treatment.

Breast cancer (BC) is a complex and heterogeneous disease, and oxidative stress is a hallmark of BC. Oxidative stress is characterized by an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms. ROS has been implicated in BC development and progression by inducing DNA damage, inflammation, and angiogenesis. Antioxidants have been shown to scavenge ROS and protect cells from oxidative damage, thereby regulating signaling pathways involved in cell growth, survival, and death. Plants contain antioxidants like ascorbic acid, tocopherols, carotenoids, and flavonoids, which have been found to regulate stress signaling and PCD in BC. Combining different antioxidants has shown promise in enhancing the effectiveness of BC treatment. Antioxidant nanoparticles, when loaded with antioxidants, can effectively target breast cancer cells and enhance their cellular uptake. Notably, these nanoparticles have shown promising results in inducing PCD and sensitizing breast cancer cells to chemotherapy, even in cases where resistance is observed. This review aims to explore how nanotechnology can modulate stress signaling and PCD in breast cancer. By summarizing current research, it underscores the potential of nanotechnology in enhancing antioxidant properties for the treatment of breast cancer.

Antioxidant p-terphenyl compound, isolated from edible mushroom, Boletopsis leucomelas.

A new acetyl p-terphenyl derivative, boletopsin 15, was isolated from the ethyl acetate extract of fruit bodies of the Basidiomycete Boletopsis leucomelas, together with 4 known compounds. The structures of these compounds were elucidated by spectral analysis as well as by directly comparing the spectral data of the new compound with those of known compounds. The free radical-scavenging activity of the compounds was assayed using the 2,2-diphenyl-1-picrylhydrazyl scavenging method. The results showed that compounds 1 and 2 exhibited significant antioxidant activity (1: EC50 = 2.1 µm and 2: EC50 = 6.6 µm).

Structure elucidation of a new bicoumarin derivative from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm.

A new bicoumarin derivative, bidysoxyletine (1), was isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm. The structure of 1 was elucidated by analysis of NMR, UV, IR, HR-ESITOFMS, and DDFT approach using the B3LYP exchange-correlation function for 13 C NMR and UV spectroscopic data. The results indicated that the structure of 1 possessed a dibenzonapthyrone skeleton.

ß-Resorcylic Acid Derivatives, with Their Phytotoxic Activities, from the Endophytic Fungus Lasiodiplodia theobromae in the Mangrove Plant Xylocarpus granatum.

Nine new ß-resorcylic acid derivatives, (15S)-de-O-methyllasiodiplodin (1), (13S,15S)-13-hydroxy-de-O-methyllasiodiplodin (2), (14S,15S)-14-hydroxy-de-O-methyllasiodiplodin (3), (13R,14S,15S)-13,14-dihydroxy-de-O-methyllasiodiplodin (4), ethyl (S)-2,4-dihydroxy-6-(8-hydroxynonyl)benzoate (5), ethyl 2,4-dihydroxy-6-(8-hydroxyheptyl)benzoate (6), ethyl 2,4-dihydroxy-6-(4-methoxycarbonylbutyl)benzoate (7), 3-(2-ethoxycarbonyl-3,5-dihydroxyphenyl)propionic acid (8), and isobutyl (S)-2,4-dihydroxy-6-(8-hydroxynonyl)benzoate (9), together with a known ethyl 2,4-dihydroxy-6-(8-oxononyl)benzoate (10) were obtained from Lasiodiplodia theobromae GC-22. The structures of these compounds were elucidated by extensive spectroscopic analyses. Compounds 1, 3, and 6 showed growth inhibitory effects against Digitaria ciliaris. Conversely, treatment with compounds 5, 6, 7, 9, and 10 stimulated elongation activity toward the root of Lactuca sativa. These data expand the repertoire of new ß-resorcylic acid derivatives that may function as lead compounds in the synthesis of new agrochemical agents.

Towards halal pharmaceutical: Exploring alternatives to animal-based ingredients.

Halal is a crucial concept for Muslim consumers regarding consumed products, including pharmaceutical ingredients, which are essential in modern medicine. To address the issue of using porcine-sourced ingredients in pharmaceuticals, it is essential to search for halal alternatives derived from poultry, animal by-products from meat processing, marine sources, and plants. However, the complexity of this problem is further compounded by the rapid advances in innovation and technology, which can lead to adulteration of ingredients derived from pigs. Other challenges include the sustainability of alternative materials, management of waste or by-products practice, halal awareness, certification, government policies, religious adherence of consumers, food suppliers, marketers, and purchasing of products. The importance of halal and non-halal problems, specifically in the context of pharmaceutical materials, is still rarely discussed, including alternatives derived from poultry, animal by-products, marine sources, and plants. Due to the increasing global population, there is a growing need to increase awareness and concern among Muslim consumers for halal products, including pharmaceuticals. Therefore, this research aimed to investigate the importance of halal and non-halal issues in pharmaceutical ingredients, the potential impact on the Muslim community, as well as opportunities and challenges in the search for alternative ingredients.

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.

Two new octahydronaphthalene derivatives, trichodermic acids C and D produced by Trichoderma sp. HN-1.1.

Two new octahydronaphthalene derivatives, trichodermic acid C (1) and trichodermic acid D (2), along with known analogs, trichodermic acid (3), trichodermic acid A (4) and trichodermic acid B (5), were isolated from an ethyl acetate extract of endophytic strain Trichoderma sp. HN-1.1. The structures of compounds 1 and 2 were elucidated using spectroscopic methods including UV, IR, HRESITOFMS, ECD, 1 D and 2 D NMR. The cytotoxic activity of the isolated compounds was evaluated on the rat hepatoma cell line H4IIE, using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. According to the results, only compound 3 showed a significant reduction of H4IIE cells from 75 to 21% (p < 0.01) with an IC50 value of 50% cell survival estimated as 143.1 µM, which indicated weak cytotoxic activity.

Integracide derivatives produced by endophyte Fusarium armeniacum M-3 isolated from Digitaria ciliaris.

Two new integracides, dedimethyl integracide B (1) and integracide K (2), were isolated from rice cultures of Fusarium armeniacum M-3, an endophyte isolated from Digitaria ciliaris, together with the known terpenoids, integracide B (3) and 2-deoxy-integracide B (4). Assignment of the signals in the 1H and 13C NMR spectra of 1 and 2 was achieved using DEPT, HMQC, HMBC, and NOESY spectra. Compound 2 exhibited moderate cytotoxicity against HeLa cells.

The 2,3-epoxy naphthoquinol produced by endophyte Arthrinium marii M-211.

A novel 2,3-epoxy naphthoquinol, named (6R,7R,8R)-theissenone A (1), possessing an oxatricyclo[5.4.0.03,5]undeca-trien-2-one skeleton, together with two known compounds, (6S,7R,8R)-theissenone (2) and arthrinone (3), were produced by an endophytic fungus, Arthrinium marii M-211, which was isolated from mangrove plants. The structure of 1, including the absolute stereochemistry, was elucidated by analysis of nuclear magnetic resonance (NMR) and mass spectrometry (MS) data and time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) spectra. Additionally, the absolute structure of 2 was deduced as a diastereomer of 1 using ECD spectral data analysis. Compounds 1, 2 and 3 exhibited cytotoxic activity against the H4IIE rat hepatoma cells, with IC50 values of 67.5, 46.6 and 13.4 µM, respectively.

Inhibition of bacillus spores germination by cinnamon bark, fingerroot, and moringa leaves extract.

This study was intended to discover the natural food preservatives by comparing the antibacterial effect of the ethanolic extract of cinnamon bark, finger root, and moringa leaves toward Bacillus cereus both the vegetative cells and spores. The antibacterial activities of the investigated extracts were assessed against cells using the agar diffusion method. Whereas the sporicidal test was performed by observing the colony growth, after various times of incubation (1, 3, and 5 h). The investigated extracts produced inhibition in a diameter ranging from 10.6 to 35.3 mm, and it can be classified that the extract of cinnamon bark was the most potent extract to inhibit the vegetative cells form, followed by fingerroot and the moringa leaves extract. Consistently, the ethanolic extract of cinnamon bark and fingerroot significantly yielded sporicidal activities higher than the moringa leaves extract. Both extracts exerted sporicidal activity within 1 h of contact time at the lowest test concentration of 5% w/v, whereas moringa leaves extract required a longer contact time (5 h) at higher concentration of 20% w/v. It can be concluded that cinnamon bark and fingerroot extract have great potential as effective food preservative candidates to inhibit the B. cereus growth than moringa leaves extract.

Bidysoxyphenols A-C, dimeric sesquiterpene phenols from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm.

Three new sesquiterpene phenol dimers, bidysoxyphenols A-C (2-4), along with two known compounds, namely sesquiterpene phenol (1) and ionone derivatives (5), were isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm. The structures of these new compounds, including their absolute configurations, were elucidated by nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, infrared spectroscopy, high-resolution electrospray ionization time-of-flight mass spectrometry, and electronic circular dichroism. Compounds 1 and 2 showed cytotoxicity against human promyelocytic leukemia cells, with IC50 values of 18.25 ± 1.52 and 39.04 ± 3.12 µM, respectively.

Cochlioquinone derivatives produced by coculture of endophytes, Clonostachys rosea and Nectria pseudotrichia.

Three new meroterpenoid derivatives, furanocochlioquinol (1) and furanocochlioquinone (2), as well as nectrianolin D (3), together with two known biogenetically related compounds 4 and 5 were isolated from a mixed culture of two mangrove-derived fungi, Clonostachys rosea B5-2 and Nectria pseudotrichia B69-1. The structures of 1-3 were deduced based on the interpretation of HRMS and NMR data. Compounds 1-5 exhibited cytotoxicity against human promyelocytic leukemia (HL60) cells with IC50 values ranging from 0.47 to 10.16 µM.